Психоактивные вещества

1. Breastfeed Med. 2019 Jun 18. doi: 10.1089/bfm.2019.0075. [Epub ahead of print]

Exposures Through Breast Milk: An Analysis of Exposure and Information Calls to

U.S. Poison Centers, 2001-2017.

Beauchamp GA(1), Hendrickson RG(2), Horowitz BZ(2), Spyker DA(2).

Author information:

(1)1 Lehigh Valley Health Network, Department of Emergency and Hospital Medicine,

Division of Medical Toxicology, University of South Florida Morsani College of

Medicine, Allentown, Pennsylvania.

(2)2 Department of Emergency Medicine/Oregon, Alaska and Guam Poison Center,

Oregon Health and Science University, Portland, Oregon.

Introduction: We described calls to U.S. poison centers (PCs) related to

potential exposure to substances through breast milk. Materials and Methods: We

analyzed National Poison Data System calls between 2001 and 2017 with "Exposure

through breast milk" or "Drug use during breastfeeding" as the coded scenario.

Data handling and descriptive statistics were carried out using SAS JMP 12.01.

Results: U.S. PCs received 76,416 information calls and 2,319 exposure calls

related to breast milk. Exposure calls were from a residence in 76% (n = 1,758),

from health care facilities (HCFs) in 15.5% (n = 360), and from a workplace in

0.6% (n = 15). A total of 466 exposures (20.1%) were subsequently managed at a

HCF: 269 were evaluated and released (58%), 38 were admitted to intensive care

unit (8.2%), and 53 were admitted to hospital floor (11%). Medical outcomes

included 1 death (0.04%), 8 major effect (0.3%), 43 moderate effect (1.9%), 170

minor effect (7.3%), and 390 no effect (16.8%). Exposure calls that reported

major effects involved opioids, benzodiazepines, ethanol, cyclobenzaprine,

insulin, and amphetamines. Exposure calls most commonly involved antibiotics,

antifungals, benzodiazepines, opioids, and selective serotonin reuptake

inhibitors (SSRIs). A total of 1,192 exposures (51.4%) had reported

signs/symptoms including drowsiness, agitation, rash, and vomiting/diarrhea.

Information calls most commonly involved systemic antibiotics, SSRIs,

antihistamines, corticosteroids, and benzodiazepines. Conclusions: Substances

common to both exposure and information calls included antibiotics,

benzodiazepines, and SSRIs. Most cases of severe toxicity included potential

exposures through breast milk to benzodiazepines and opioids. These data may help

inform educational outreach, risk assessment, and bedside care for breastfeeding

mothers.

DOI: 10.1089/bfm.2019.0075

PMID: 31211594

2. Addiction. 2019 Jun 10. doi: 10.1111/add.14706. [Epub ahead of print]

Mortality among people with regular or problematic use of amphetamines: a

systematic review and meta-analysis.

Stockings E(1), Tran LT(1), Santo T Jr(1), Peacock A(1), Larney S(1), Santomauro

D(2), Farrell M(1), Degenhardt L(1).

Author information:

(1)National Drug and Alcohol Research Centre (NDARC), UNSW Sydney, Sydney, 2052,

Australia.

(2)Queensland Centre for Mental Health Research and School of Public Health,

University of Queensland, Locked Bag 500, Archerfield, 4108, Australia.

BACKGROUND AND AIMS: Amphetamines are the second most commonly used class of

illicit drugs. We aimed to produce pooled estimates of mortality risks among

people with regular or dependent use of amphetamines, with a focus upon all-cause

mortality as well as specific causes of death.

DESIGN: Systematic review and meta-analysis of cohorts of people with problematic

use or dependence on amphetamines with data on all-cause or cause-specific

mortality.

SETTING AND PARTICIPANTS: Of 4,240 papers, 30 were eligible, reporting on 25

cohorts that measured all-cause mortality, drug poisoning, suicide, accidental

injuries, homicide and cardiovascular mortality. Cohorts (n=35-74,139) were in

North America, several Nordic countries, and Asia-Pacific.

MEASUREMENT: Titles/abstracts were independently screened by one reviewer and

excluded ones reviewed by a second. Full-text screening was by two reviewers with

discrepancies resolved via a third reviewer. We extracted data on crude mortality

rates (CMR) per 100-person-years (PY), standardised mortality ratios (SMRs). We

imputed SMRs where possible if not reported by study authors. We also calculated

mortality relative risks. Data were pooled using random-effects models; potential

reasons for heterogeneity were explored using subgroup analyses and

meta-regressions.

FINDINGS: Twenty-three cohorts contributed data for the pooled all-cause CMR:

1.11 per 100PY (95%CI 0.90-1.37). Pooled cause-specific mortality rates were:

drug poisoning, 0.14 per 100PY (95%CI: 0.06-0.34); cardiovascular disease, 0.13

per 100PY (95%CI: 0.06-0.55); suicide, 0.20 per 100PY (95%CI: 0.07-0.55);

accidental injury, 0.20 per 100PY (95%CI: 0.08-0.47) and homicide, 0.03 per 100PY

(95%CI: 0.02-0.06). There was substantial heterogeneity for all pooled CMR

estimates except homicide. The pooled all-cause SMR was 6.83 (95%CI: 5.27-8.84).

Pooled cause-specific SMRS were: poisoning, 24.70 (95%CI: 16.67, 36.58);

homicide, 11.90 (95%CI: 7.82-18.12); suicide, 12.20 (95%CI: 4.89-30.47);

cardiovascular disease, 5.12 (95%CI: 3.74-7.00) and accidental injury, 5.12

(95%CI: 2.88-9.08).

CONCLUSIONS: People with regular or dependent amphetamine use are at elevated

risk of a range of causes of mortality compared with people without regular or

dependent amphetamine use.

DOI: 10.1111/add.14706

PMID: 31180607

3. J Forensic Leg Med. 2019 Jul;65:101-104. doi: 10.1016/j.jflm.2019.05.011. Epub

2019 May 21.

The risk of emerging new psychoactive substances: The first fatal 3-MeO-PCP

intoxication in The Netherlands.

de Jong LAA(1), Olyslager EJH(2), Duijst WLJM(3).

Author information:

(1)Department of Clinical Pharmacy, Gelre Hospitals, P.O. Box 9014, 7300 DS,

Apeldoorn, the Netherlands. Electronic address: l.van.gendt@gelre.nl.

(2)Department of Clinical Pharmacy, Gelre Hospitals, P.O. Box 9014, 7300 DS,

Apeldoorn, the Netherlands.

(3)Maastricht University, Faculty of Law and Criminology, Minderbroedersberg 4-6,

6211 LK, Maastricht, the Netherlands.

Structural analogs of classic drugs, also called designer drugs, are a booming

market due to the easy accessibility on the internet and their legal status. One

of those 'legal highs' is an analog of phencyclidine, namely

3-methoxyphencyclidine (3-MeO-PCP). Very few fatalities have been reported where

3-MeO-PCP contributed to the death of an individual. We present the first fatal

case in the Netherlands and one of the few worldwide. Postmortem biological

samples and the presumed abused unknown substance, sold as ant poison, were

obtained. 3-MeO-PCP was detected, and the resulting concentration was 152 μg/l in

whole blood. The presumed taken unknown sample was identified as 3-MeO-PCP and

thus linked to the victim. The cause of death was a combination of 3-MeO-PCP,

amphetamine, and alcohol. Improved diagnostic skills are necessary to face these

emerging novel psychoactive substances also in light of public health and social

risks.

rights reserved.

DOI: 10.1016/j.jflm.2019.05.011

PMID: 31129558 [Indexed for MEDLINE]

4. Forensic Sci Int. 2019 Jul;300:e34-e37. doi: 10.1016/j.forsciint.2019.02.040.

Epub 2019 Feb 28.

A fatal case of poisoning of a 19-year-old after taking 3-MMC.

Margasińska-Olejak J(1), Celiński R(2), Fischer A(3), Stojko J(3).

Author information:

(1)Department of Toxicology and Bioanalysis, Medical University of Silesia,

41-200, Sosnowiec, Poland; Laboratorium Toksykologiczne ToxLab, ul. Kossutha 6,

40-844, Katowice, Poland. Electronic address: joanna.margasinska@gmail.com.

(2)Laboratorium Toksykologiczne ToxLab, ul. Kossutha 6, 40-844, Katowice, Poland.

(3)Department of Toxicology and Bioanalysis, Medical University of Silesia,

41-200, Sosnowiec, Poland.

The significant increase in the number of new psychoactive substances on the drug

market has recently been a serious problem. The manuscript presents a fatal case

of suicide poisoning with 3-MMC (3-methylmethcathinone). The biological material

collected during the autopsy of a 19-year-old woman, transferred to the

toxicological Laboratory in Katowice ToxLab, was subjected to a chemical and

toxicological analysis. The toxicological analysis of blood, vitreous humor and

gastric contents revealed 3-methylmetcatinone at a concentration of 800 ng/ml,

153 ng/ml and 5,5 mg, respectively. The presence of 3-MMC has also been confirmed

in physical evidence secured on site. 3-methylmethcathinone is a dangerous

psychoactive substance that caused the death of the 19-year-old.

DOI: 10.1016/j.forsciint.2019.02.040

PMID: 31056341 [Indexed for MEDLINE]

5. MMWR Morb Mortal Wkly Rep. 2019 May 3;68(17):388-395. doi:

10.15585/mmwr.mm6817a3.

Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential

- United States, 2003-2017.

Kariisa M(1), Scholl L(1), Wilson N(1), Seth P(1), Hoots B(1).

Author information:

(1)Division of Unintentional Injury Prevention, National Center for Injury

Prevention and Control, CDC.

In 2016, a total of 63,632 persons died from drug overdoses in the United States

(1). Drug overdose deaths involving cocaine, psychostimulants with abuse

potential (psychostimulants), or both substances combined increased 42.4% from

12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include

drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA),

dextroamphetamine, levoamphetamine, methylphenidate (Ritalin), and caffeine. From

2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased

52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug

overdoses in the United States in 2017; approximately two thirds of these deaths

involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death

rates involving cocaine and psychostimulants by demographic characteristics,

urbanization levels, U.S. Census region, 34 states, and the District of Columbia

(DC). CDC also examined trends in age-adjusted cocaine-involved and

psychostimulant-involved death rates from 2003 to 2017 overall, as well as with

and without co-involvement of opioids. Among all 2017 drug overdose deaths,

13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants.

Death rates increased from 2016 to 2017 for both drug categories across

demographic characteristics, urbanization levels, Census regions, and states. In

2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and

psychostimulant-involved overdoses, respectively, and the data suggest that

increases in cocaine-involved overdose deaths from 2012 to 2017 were driven

primarily by synthetic opioids. Conversely, increases in psychostimulant-involved

deaths from 2010 to 2017 occurred largely independent of opioids, with increased

co-involvement of synthetic opioids in recent years. Provisional data from 2018

indicate that deaths involving cocaine and psychostimulants are continuing to

increase.† Increases in stimulant-involved deaths are part of a growing

polysubstance landscape. Increased surveillance and evidence-based multisectoral

prevention and response strategies are needed to address deaths involving cocaine

and psychostimulants and opioids. Enhancing linkage to care, building state and

local capacity, and public health/public safety collaborations are critical

components of prevention efforts.

DOI: 10.15585/mmwr.mm6817a3

PMCID: PMC6541315

PMID: 31048676 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

6. N Engl J Med. 2019 Mar 21;380(12):1128-1138. doi: 10.1056/NEJMoa1813751.

Psychosis with Methylphenidate or Amphetamine in Patients with ADHD.

Moran LV(1), Ongur D(1), Hsu J(1), Castro VM(1), Perlis RH(1), Schneeweiss S(1).

Author information:

(1)From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of

Medicine, Brigham and Women's Hospital, Boston (L.V.M., S.S.); the Division of

Psychotic Disorders, McLean Hospital, Belmont, MA (L.V.M., D.O.); and the

Department of Health Care Policy (J.H.), Harvard Medical School (L.V.M., D.O.,

J.H., R.H.P., S.S.), the Mongan Institute Health Policy Center (J.H.) and the

Center for Quantitative Health, Department of Psychiatry (R.H.P.), Massachusetts

General Hospital, and Partners Research Computing, Partners HealthCare System

(V.M.C.) - all in Boston.

Comment in

N Engl J Med. 2019 Mar 21;380(12):1178-1180.

BACKGROUND: The prescription use of the stimulants methylphenidate and

amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD)

has been increasing. In 2007, the Food and Drug Administration mandated changes

to drug labels for stimulants on the basis of findings of new-onset psychosis.

Whether the risk of psychosis in adolescents and young adults with ADHD differs

among various stimulants has not been extensively studied.

METHODS: We used data from two commercial insurance claims databases to assess

patients 13 to 25 years of age who had received a diagnosis of ADHD and who

started taking methylphenidate or amphetamine between January 1, 2004, and

September 30, 2015. The outcome was a new diagnosis of psychosis for which an

antipsychotic medication was prescribed during the first 60 days after the date

of the onset of psychosis. To estimate hazard ratios for psychosis, we used

propensity scores to match patients who received methylphenidate with patients

who received amphetamine in each database, compared the incidence of psychosis

between the two stimulant groups, and then pooled the results across the two

databases.

RESULTS: We assessed 337,919 adolescents and young adults who received a

prescription for a stimulant for ADHD. The study population consisted of 221,846

patients with 143,286 person-years of follow up; 110,923 patients taking

methylphenidate were matched with 110,923 patients taking amphetamines. There

were 343 episodes of psychosis (with an episode defined as a new diagnosis code

for psychosis and a prescription for an antipsychotic medication) in the matched

populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the

methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard

ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).

CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving

prescription stimulants, new-onset psychosis occurred in approximately 1 in 660

patients. Amphetamine use was associated with a greater risk of psychosis than

methylphenidate. (Funded by the National Institute of Mental Health and others.).

DOI: 10.1056/NEJMoa1813751

PMCID: PMC6543546 [Available on 2019-09-21]

PMID: 30893533 [Indexed for MEDLINE]

7. Forensic Sci Int. 2019 May;298:39-47. doi: 10.1016/j.forsciint.2019.02.039. Epub

2019 Feb 28.

A retrospective analysis of data from forensic toxicology at the Academy of

Forensic Science in 2017.

Pan M(1), Wang X(2), Zhao Y(3), Liu W(2), Xiang P(4).

Author information:

(1)Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine,

Shanghai Forensic Service Platform, Shanghai, 200063, China; School of Pharmacy,

Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.

(2)Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine,

Shanghai Forensic Service Platform, Shanghai, 200063, China.

(3)School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103,

Shenyang, 110016, China.

(4)Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine,

Shanghai Forensic Service Platform, Shanghai, 200063, China. Electronic address:

xiangping2630@163.com.

Knowing the specific pattern of forensic toxicology cases in a region is vital to

help the local government establish an effective prevention and treatment system;

currently, there have been no published reports investigating various types of

forensic toxicology cases based on a large autopsy series and city size. The data

in this study were obtained from records kept at the Academy of Forensic Science

(AFS) between February 2017 and December 2017, and the cases were mainly from the

Public Security Organs People's Police in Shanghai, China. There were 299

autopsies; the leading cause of death was traffic accidents (37.1%), and the

manners of death were mainly accidental (54.8%). From a total of 9083 cases, 1992

involved traffic accidents, 6787 were drug abuse, 269 were poisonings, and 35

were drug-facilitated sexual assaults (DFSAs). We also investigated the pattern

of unnatural deaths and the alcohol-positive (with a blood alcohol concentration

(BAC) ≥0.20 mg/ml) rate among the various cases. The BAC ranged from 0.08 to

7.24 mg/ml in traffic cases, and the mean BAC of the total alcohol-positive

drivers was 1.44 mg/ml. It was found that 80.8% of the drivers involved had a

BAC ≥ 0.20 mg/ml (limit of civil offense), and 72.8% had a BAC ≥ 0.80 mg/ml

(limit of criminal offense). Among the drug abuse cases, there were 4073 cases

(60.0%) that were positive for at least one euphoriant; the most frequently

abused drug group was amphetamine-type stimulants (ATS). Poisonings by natural

toxins (such as scopolamine and tetrodotoxin) account for a significant portion

of accidental deaths. Pesticide poisoning was also constituted a large portion,

and organophosphorus were the cause of the majority of those cases. Suicide by

pesticide showed the highest frequency in the present study. Among the 35 DFSA

cases, dexmedetomidine was frequently detected in our study, which has rarely

been reported previously in DFSA cases.

DOI: 10.1016/j.forsciint.2019.02.039

PMID: 30878464 [Indexed for MEDLINE]

8. JAMA Netw Open. 2018 Oct 5;1(6):e183758. doi: 10.1001/jamanetworkopen.2018.3758.

Evaluation of Amphetamine-Related Hospitalizations and Associated Clinical

Outcomes and Costs in the United States.

Winkelman TNA(1)(2), Admon LK(3)(4), Jennings L(2), Shippee ND(5), Richardson

CR(4)(6), Bart G(2)(7).

Author information:

(1)Division of General Internal Medicine, Department of Medicine, Hennepin

Healthcare, Minneapolis, Minnesota.

(2)Hennepin Healthcare Research Institute, Minneapolis, Minnesota.

(3)Department of Obstetrics and Gynecology, University of Michigan Medical

School, Ann Arbor.

(4)Institute for Healthcare Policy and Innovation, University of Michigan, Ann

Arbor.

(5)Division of Health Policy and Management, School of Public Health, University

of Minnesota, Minneapolis.

(6)Department of Family Medicine, University of Michigan Medical School, Ann

Arbor.

(7)Division of Addiction Medicine, Department of Medicine, Hennepin Healthcare,

Minneapolis, Minnesota.

Importance: Despite indications of increasing amphetamine availability and

psychostimulant deaths in the United States, evidence across data sources is

mixed, and data on amphetamine-related hospitalizations are lacking.

Objective: To clarify trends in amphetamine-related hospitalizations and their

clinical outcomes and costs in the United States.

Design, Setting, and Participants: This repeated, cross-sectional study used

hospital discharge data from the Healthcare Cost and Utilization Project National

Inpatient Sample. The nationally representative sample included US adults

(n = 1 292 300) who had amphetamine-related hospitalizations between January 1,

2003, and December 31, 2015. Multivariable logistic and Poisson regression models

were used to examine in-hospital mortality and length of stay. Analysis of these

data was conducted from November 2017 to August 2018.

Exposure: Amphetamine dependence or abuse or amphetamine poisoning.

Main Outcomes and Measures: Annual hospitalizations, in-hospital mortality,

length of stay, transfer to another facility, and costs.

Results: Over the 2003 to 2015 study period, there were 1 292 300 weighted

amphetamine-related hospitalizations. Of this population, 541 199 (41.9%) were

female and 749 392 (58.1%) were male, with a mean age of 37.5 years (95% CI,

37.4-37.7 years). Amphetamine-related hospitalizations, compared with other

hospitalizations, were associated with age younger than 65 years (98.0% vs 58.0%;

P < .001), male sex (60.3% [95% CI, 59.7%-60.8%] vs 41.1% [95% CI, 40.9%-41.3%]),

Medicaid coverage (51.2% [95% CI, 49.8%-52.7%] vs 17.8% [95% CI, 17.5%-18.1%]),

and residence in the western United States (58.5% [95% CI, 55.9%-61.0%] vs 18.9%

[95% CI, 18.0%-19.8%]). Amphetamine-related hospitalizations declined between

2005 and 2008, and then increased from 55 447 hospitalizations (95% CI, 44 936-65

959) in 2008 to 206 180 hospitalizations (95% CI, 95% CI, 189 188-223 172) in

2015. Amphetamine-related hospitalizations increased to a greater degree than

hospitalizations associated with other substances. Adjusted mean length of stay

(5.9 [95% CI, 5.8-6.0] vs 4.7 [95% CI, 4.7-4.8] days; P < .001), transfer to

another facility (26.0% [95% CI, 25.3%-26.8%] vs 18.5% [95% CI, 18.3%-18.6%];

P < .001), and mean in-hospital mortality (28.3 [95% CI, 26.2-30.4] vs 21.9 [95%

CI, 21.6-22.1] deaths per 1000 hospitalizations; P < .001) were higher for

amphetamine-related than other hospitalizations. Annual hospital costs related to

amphetamines increased from $436 million (95% CI, $312 million-$559 million) in

2003 to $2.17 billion (95% CI, $1.95 billion-$2.39 billion) by 2015.

Conclusions and Relevance: Given that amphetamine-related hospitalizations and

costs substantially increased between 2003 and 2015, pharmacologic and

nonpharmacologic therapies for amphetamine use disorders and a coordinated public

health response are needed to curb these rising rates.

DOI: 10.1001/jamanetworkopen.2018.3758

PMCID: PMC6324446

PMID: 30646256

9. Emergencias. 2018 Dic;30(6):405-407.

Acute street drug poisoning in the patient with human immunodeficiency virus

infection: the role of chemsex.

[Article in English, Spanish; Abstract available in Spanish from the publisher]

Perelló R(1), Aused M(1), Saubí N(2), Quirós C(1), Luis Blanco J(2),

Martínez-Rebollar M(2), Galicia M(1), Salgado E(1), Nogué S(1).

Author information:

(1)Área de Urgencias, Hospital Clínic, Barcelona, España.

(2)Servicio de Infecciones, Hospital Clínic, Barcelona, España.

OBJECTIVES: To identify the drugs usually abused in cases of acute poisoning in

human immunodeficiency virus (HIV) infected patients.

MATERIAL AND METHODS: Retrospective study of episodes of acute street drug

poisoning in HIV-infected patients in our emergency department over a period of 1

year. Chemsex was defined as the use of methamphetamines, -hydroxybutyrate (GHB),

-butyrolactone (GBL), and/or mephedrone in order to prolong sexual activity.

RESULTS: We included 101 patients, 93 (92%) of whom were men. The drug that

caused the most cases of acute poisoning was cocaine, detected in 52 patients

(51%). GHB and amphetamines were the next most frequently implicated street

drugs. The prevalence of chemsex in this series was 87%. Mortality was 2%.

Amphetamine poisoning was related to intensive care unit admission (odds ratio,

9,2 [95% CI, 1.6-52.2], P=.012).

CONCLUSION: Cocaine use was the main cause of acute poisoning in this series. The

prevalence of chemsex was high.

Publisher: Identificar la principales drogas de abuso que producen intoxicación

aguda en el paciente VIH.Estudio retrospectivo de 1 año evolución de los

episodios de intoxicación por drogas de abuso en el paciente VIH en un servicio

de urgencias. Se definió chemsex como el consumo de metanfetamina, GHB/GBL o

mefedrona para mantener relaciones sexuales prolongadas.Se incluyeron 101

pacientes, 93 (92%) eran varones. La principal droga fue la cocaína en 52 (51%)

pacientes, seguida del GHB y anfetaminas. La prevalencia de chemsex fue del 87%.

La mortalidad de la serie fue del 2%. El consumo de anfetaminas predijo ingreso

en cuidados intensivos: OR 9,2 (IC 95% 1,6-52,2); p = 0,012.La cocaína fue la

principal causa de intoxicación aguda. El chemsex tuvieron una elevada

prevalencia.

PMID: 30638344

10. Forensic Sci Int. 2019 Feb;295:54-63. doi: 10.1016/j.forsciint.2018.11.024. Epub

2018 Dec 3.

The novel psychoactive substance 3-methylmethcathinone (3-MMC or metaphedrone): A

review.

Ferreira B(1), Dias da Silva D(2), Carvalho F(1), de Lourdes Bastos M(1), Carmo

H(1).

Author information:

(1)UCIBIO/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of

Porto, Rua Jorge Viterbo Ferreira, 228, Porto, 4050-313, Portugal.

(2)UCIBIO/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of

Porto, Rua Jorge Viterbo Ferreira, 228, Porto, 4050-313, Portugal. Electronic

address: dsilva@ff.up.pt.

3-Methylmethcathinone (3-MMC or metaphedrone) is a synthetic cathinone, recently

introduced in the market of the new psychoactive substances (NPS), initially to

replace mephedrone (4-methylmethcathinone or 4-MMC), and rapidly widespread among

drug users. 3-Methylmethcathinone is legally controlled in many countries, but is

still easily available for purchase from websites, and frequently found in

recreational settings. Most toxicological data on this drug come from human case

reports of intoxications. Thus, further investigation on their pharmacological

and toxicological properties is necessary to evaluate its potential harmful

effects. The present work provides a review on the available data about 3-MMC

legal status, chemistry, patterns of use, prevalence, biological effects,

toxicokinetics, toxicity and factors affecting stimulant/toxicological effects.

DOI: 10.1016/j.forsciint.2018.11.024

PMID: 30572220 [Indexed for MEDLINE]

11. J Forensic Leg Med. 2019 Feb;61:56-64. doi: 10.1016/j.jflm.2018.11.006. Epub 2018

Nov 10.

Toxicological findings in 1000 cases of suspected drug facilitated sexual assault

in the United States.

Fiorentin TR(1), Logan BK(2).

Author information:

(1)The Center for Forensic Science Research and Education (CFSRE), 2300 Stratford

Ave, Willow Grove, PA, 19090, USA. Electronic address:

tais.fiorentin@frfoundation.org.

(2)The Center for Forensic Science Research and Education (CFSRE), 2300 Stratford

Ave, Willow Grove, PA, 19090, USA; NMS Labs, 2300 Welsh Rd, Willow Grove, PA,

19090, USA.

The purpose of this study was to identify the extent and types of drugs found in

alleged drug facilitated sexual assaults (DFSA) in 37 states and 1 territory of

the United States. In total, 1000 cases were reviewed. Between the cases that

gender was provided (613), most of the victims (91.68%) were woman, mean age of

26.8 years old. Blood and/or urine samples were tested. Twenty-one point six

percent of the cases were negative for intoxicating substances. A hundred and one

different substances were detected. Overall, ethanol was the most prevalent

substance, detected in 30.9% of the cases (309 cases), followed by cannabinoids

(THC/THCCOOH/11-OH-THC) (28.8% of cases), amphetamine/methamphetamine (16.5% of

cases), cocaine/metabolites (10.4% of cases), and clonazepam/metabolite (7.6% of

cases). The mean, median and range concentrations of ethanol in blood (n = 309)

were 98.6 mg/dL, 82.0 mg/dL and 9.2-366 mg/dL, respectively. Ethanol and

cannabinoids were the most frequent combination found. The absence of alcohol and

drugs in some cases may represent delay in collecting samples.

rights reserved.

DOI: 10.1016/j.jflm.2018.11.006

PMID: 30453150 [Indexed for MEDLINE]

12. Am J Forensic Med Pathol. 2018 Dec;39(4):364-366. doi:

10.1097/PAF.0000000000000431.

Postmortem Hyperthermia: Two Case Reports and a Review of the Literature.

Angélique F, Guillaume G, Nicolas G, Jean Sébastien R(1), Laurent M.

Author information:

(1)Institut de médecine légale de Strasbourg, Université de Strasbourg,

Strasbourg, France.

In this daily practice, the forensic pathologist is rarely confronted with

postmortem hyperthermia associated with the rapid onset of rigor mortis. We

report 2 similar cases where the rectal temperature value taken during the

on-scene investigations by the forensic pathologist was greater than 40°C (104°F)

in both cases, and rigor mortis was complete within less than 6 hours postmortem.

The first case was due to a deadly intoxication by ecstasy and the second one to

the deadly association of methadone and a possible neuroleptic malignant

syndrome. Infection-related deaths were eliminated. Thus, the association of

postmortem hyperthermia and rapid-onset rigor mortis would suggest in the first

hypothesis a toxic death, particularly 3,4-methylenedioxymethamphetamine.

However, an autopsy and toxicological analysis are necessary to confirm the cause

of death.

DOI: 10.1097/PAF.0000000000000431

PMID: 30198916 [Indexed for MEDLINE]

13. Handb Exp Pharmacol. 2018;252:3-49. doi: 10.1007/164_2018_160.

Responding to New Psychoactive Substances in the European Union: Early Warning,

Risk Assessment, and Control Measures.

Evans-Brown M(1), Sedefov R(2).

Author information:

(1)European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal.

michael.evans-brown@emcdda.europa.eu.

(2)European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal.

New psychoactive substances (NPS) are drugs that are not controlled by the United

Nations international drug control conventions of 1961 and 1971 but that may pose

similar threats to public health. Many of them are traded as "legal" replacements

to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine,

amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by

globalization, there has been a large increase in the availability and,

subsequently, harms caused by these substances over the last decade in Europe.

The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is

monitoring more than 670 NPS that have appeared on Europe's drug market in the

last 20 years, of which almost 90% have appeared in the last decade. While some

recent policy responses have been successful in reducing availability and sales

of these substances in some settings - such as "legal highs" and "research

chemicals" sold openly in the high street and online - and there are signs that

growth in the market is slowing, new challenges have emerged. This includes

monitoring a growing number of highly potent substances - including 179 synthetic

cannabinoid receptor agonists and 28 fentanils - that can pose a high risk of

life-threatening poisoning to users and can cause explosive outbreaks. This

chapter briefly traces the origins of NPS, provides an overview of the situation

in Europe, and discusses the work of the EMCDDA as part of a legal framework of

early warning, risk assessment, and control measures that allows the European

Union to rapidly detect, assess, and respond to public health and social threats

caused by these substances.

DOI: 10.1007/164_2018_160

PMID: 30194542 [Indexed for MEDLINE]

14. BMJ Case Rep. 2018 Aug 29;2018. pii: bcr-2018-224731. doi:

10.1136/bcr-2018-224731.

SIADH and water intoxication related to ecstasy.

Salathe C(1), Blanc AL(2), Tagan D(3).

Author information:

(1)Service de Médecine Intensive Adulte, Centre Hospitalier Universitaire

Vaudois, Lausanne, Switzerland.

(2)Pharmacie Clinique, Pharmacie des Hôpitaux de l'Est Lémanique, Vevey,

Switzerland.

(3)Internal Medicine, Hopital Riviera-Chablais, Vevey, Switzerland.

Recreational drug use is a significant societal issue and remains a clinical

challenge in emergency and critical care departments. We report on a 19-year-old

woman admitted to hospital semiconscious and with severe hyponatraemia.

Urinalysis was positive for methamphetamine and supported a diagnosis of

hyponatraemia related to ecstasy use together with a syndrome of inappropriate

antidiuretic hormone secretion (SIADH). The woman was transferred to an intensive

care unit, where a hypertonic saline infusion was started. Three hours

postadmission she developed polyuria. Follow-up urinalysis at this point was

consistent with water intoxication. This case is a reminder that hyponatraemia is

a potentially fatal complication after the ingestion of

3,4-methylenedioxymethamphetamine, illustrates the sequential nature of an SIADH

and water intoxication and highlights the importance of considering the sequence

of onset of hyponatraemia, as the patient may be admitted at any stage.

© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and

permissions. Published by BMJ.

DOI: 10.1136/bcr-2018-224731

PMID: 30158258 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: None declared.

15. Handb Exp Pharmacol. 2018;252:495-541. doi: 10.1007/164_2018_110.

Fatal Poisonings Associated with New Psychoactive Substances.

Kronstrand R(1)(2), Guerrieri D(3)(4), Vikingsson S(3)(4), Wohlfarth A(3)(4),

Gréen H(3)(4).

Author information:

(1)Department of Forensic Genetics and Forensic Toxicology, National Board of

Forensic Medicine, Linköping, Sweden. robert.kronstrand@rmv.se.

(2)Division of Drug Research, Linköping University, Linköping, Sweden.

robert.kronstrand@rmv.se.

(3)Department of Forensic Genetics and Forensic Toxicology, National Board of

Forensic Medicine, Linköping, Sweden.

(4)Division of Drug Research, Linköping University, Linköping, Sweden.

This chapter describes how new psychoactive substances (NPS) have been involved

in fatal intoxications from 2010 and onwards. It summarizes the circumstances,

antemortem symptoms, and adverse effects that have led to death after ingestion

of one or more NPS and tabulates concentrations, and postmortem findings from

these intoxications.Consumption of NPS exerts health problems and unknown risks

for the users. Data on toxicity of many NPS are scarce or nonexistent and

long-term toxicity and risks are still largely unknown. In addition, purity and

composition of products containing NPS are often inconsistent or not known, which

places users at high risk as evidenced by hospital emergency admissions and

deaths.The most serious threat to drug users are the synthetic opioids that with

strong central nervous depressant effects have caused numerous accidental deaths

spread over the entire globe. The synthetic cannabinoids seem to be the most

unpredictable with no clear toxidrome and unknown or poorly understood mechanisms

of toxicity, but with adverse effects pointing toward the cardiovascular system.

The toxidromes commonly encountered after ingestion of cathinones and

phenethylamines are of sympathomimetic and hallucinogenic character, which

includes risk of developing a serotonin syndrome, excited delirium, and

life-threatening cardiovascular effects. In comparison to their conventional

"parent" drug, i.e., heroin, cannabis, and amphetamine, most NPS appear to

exhibit more severe adverse effects. The deaths attributed to NPS have

dramatically increased in the last years. In our opinion, this is because of the

shift from synthetic cannabinoids and cathinones to the even more toxic and

dangerously potent fentanyl analogues.

DOI: 10.1007/164_2018_110

PMID: 30105471 [Indexed for MEDLINE]

16. Psychiatry Res. 2018 Oct;268:189-192. doi: 10.1016/j.psychres.2018.05.033. Epub

2018 May 17.

The prevalence of substance-induced psychotic disorder in methamphetamine

misusers: A meta-analysis.

Lecomte T(1), Dumais A(2), Dugré JR(3), Potvin S(4).

Author information:

(1)Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal,

Montreal, Canada; Department of Psychology, University of Montreal, Montreal,

Canada.

(2)Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal,

Montreal, Canada; Department of Psychiatry, Faculty of Medicine, University of

Montreal, Montreal, Canada; Institut Philippe-Pinel de Montréal, Montreal,

Canada.

(3)Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal,

Montreal, Canada; Department of Psychiatry, Faculty of Medicine, University of

Montreal, Montreal, Canada.

(4)Centre de recherche de l'Institut Universitaire en Santé Mentale de Montréal,

Montreal, Canada; Department of Psychiatry, Faculty of Medicine, University of

Montreal, Montreal, Canada. Electronic address: stephane.potvin@umontreal.ca.

There is little consensus regarding the prevalence of methamphetamine-induced

psychotic disorder (MIPD). A search of the literature was performed, effect size

estimates were calculated with event rates and were aggregated with a

random-effects model. Seventeen studies were included in the meta-analysis,

resulting in a composite event rate of 36.5%. The event rate of MIPD was

significantly higher when the period of assessment was lifetime (42.7%) and when

only individuals with methamphetamine use disorders (MUD) (43.3%) were included.

The prevalence of MIPD in the reviewed studies is elevated. These results

highlight the need for detection and prevention strategies, and population

studies.

DOI: 10.1016/j.psychres.2018.05.033

PMID: 30041133 [Indexed for MEDLINE]

17. Prim Care Companion CNS Disord. 2018 Jun 21;20(3). pii: 17l02197. doi:

10.4088/PCC.17l02197.

Caffeine-Induced Psychosis in a Bodybuilder With Chronic Testosterone and

Amphetamine/Dextroamphetamine Misuse.

Gomes CAB(1)(2), Mahgoub Y(2).

Author information:

(1)calbuquerquegom@maimonidesmed.org.

(2)Department of Psychiatry, Maimonides Medical Center, Brooklyn, New York, USA.

DOI: 10.4088/PCC.17l02197

PMID: 29947481 [Indexed for MEDLINE]

18. J Anal Toxicol. 2018 Nov 1;42(9):655-660. doi: 10.1093/jat/bky039.

A Case Study Involving U-47700, Diclazepam and Flubromazepam-Application of

Retrospective Analysis of HRMS Data.

Partridge E(1)(2), Trobbiani S(1), Stockham P(1)(2), Charlwood C(1), Kostakis

C(1).

Author information:

(1)Forensic Science SA (Toxicology), Adelaide, South Australia, Australia.

(2)Flinders University of South Australia, College of Science and Engineering,

Sturt Road, Bedford Park, South Australia, Australia.

The number of new psychoactive substances (NPS) available is constantly

increasing, making it difficult for toxicology laboratories to keep screening

methods up to date. Full scan high-resolution mass spectrometry (HRMS) is a

versatile technique which allows for progressive updating of spectral databases

to increase the scope of screening. It also allows for retrospective screening of

data-specifically, reprocessing of data files using an updated spectral database

without the need for re-extraction or reanalysis.The coronial case reported here

illustrates the application of retrospective processing of HRMS data in the

detection of emerging NPS. A 28-year-old male with a history of illicit drug use

was found deceased at home. Initial routine screening of the post-mortem

peripheral blood identified only methylamphetamine, amphetamine and trace amounts

of lorazepam. A compound with an accurate mass and isotope ratio consistent with

the opioid AH-7921 was also detected in the liquid chromatography (LC)-HRMS

screen; however; the retention time and mass spectrum did not match the library.

Further investigation confirmed the compound to be U-47700, another opioid and

structural isomer of AH-7921. Several months later, after additional NPS had been

added to the in-house HRMS database, retrospective screening of the HRMS data was

performed, revealing the presence of designer benzodiazepines, diclazepam and

flubromazepam as well as the psychedelic drug 2,5-dimethoxy-4-chloroamphetamine

(DOC). Quantitative analysis gave the following results in peripheral post-mortem

blood: U-47700 (330 μg/L), diclazepam (70 μg/L), flubromazepam (10 μg/L),

methylamphetamine (290 μg/L) and amphetamine (150 μg/L) (DOC not quantitated).

These substances, along with lorazepam and etizolam, were also confirmed in the

post-mortem urine and an investigation into blood and urinary metabolites was

carried out. All analyses were performed using the same LC-quadrupole-time of

flight method. The cause of death was aspiration (of gastric content into airways

and lungs) due to mixed drug toxicity.

DOI: 10.1093/jat/bky039

PMID: 29945197 [Indexed for MEDLINE]

19. Drug Alcohol Depend. 2018 Jun 1;187:363-369. doi:

10.1016/j.drugalcdep.2018.03.023. Epub 2018 Apr 22.

Relationship between the duration of methamphetamine use and psychotic symptoms:

A two-year prospective cohort study.

Ma J(1), Li XD(2), Wang TY(1), Li SX(3), Meng SQ(3), Blow FC(4), Ilgen M(4),

Degenhardt L(5), Lappin J(5), Wu P(3), Shi J(3), Bao YP(6), Lu L(7).

Author information:

(1)National Institute on Drug Dependence and Beijing Key Laboratory of Drug

Dependence, Peking University, Beijing, 100191, China; School of Public Health,

Peking University, Beijing, 100191, China.

(2)Zhuhai Jinding Vocabulary Rehabilitation Hospital, Zhuhai, Guangdong, 519085,

China.

(3)National Institute on Drug Dependence and Beijing Key Laboratory of Drug

Dependence, Peking University, Beijing, 100191, China.

(4)Department of Psychiatry, University of Michigan Medical School, Ann Arbor,

MI, USA; Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI,

USA.

(5)National Drug and Alcohol Research Centre, University of New South Wales,

Sydney, New South Wales, Australia.

(6)National Institute on Drug Dependence and Beijing Key Laboratory of Drug

Dependence, Peking University, Beijing, 100191, China; National Drug and Alcohol

Research Centre, University of New South Wales, Sydney, New South Wales,

Australia. Electronic address: baoyp@bjmu.edu.cn.

(7)National Institute on Drug Dependence and Beijing Key Laboratory of Drug

Dependence, Peking University, Beijing, 100191, China; Institute of Mental

Health, National Clinical Research Center for Mental Disorders, Key Laboratory of

Mental Health and Peking University Sixth Hospital, Peking University, Beijing,

100191, China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern

Institute for Brain Research, Peking University, Beijing, 100191, China.

Electronic address: linlu@bjmu.edu.cn.

BACKGROUND: Psychosis is a key harm associated with methamphetamine (MA) use.

This study examined the relationship between the duration of MA use and risk of

psychotic symptoms.

METHODS: A cohort of 528 individuals with chronic MA use was followed for two

years after leaving treatment center in Guangdong, China. Psychotic symptoms were

assessed using the Positive and Negative Syndrome Scale at baseline and four

follow-up visits (6, 12, 18 and 24 months after baseline). MA use during the past

six months was investigated at each assessment. Generalized Estimating Equations

for longitudinal panel data were developed to examine the risk of MA-associated

psychotic symptoms among individuals with different durations of MA use. 340 MA

users who completed at least one follow-up were included in the analysis.

RESULTS: During 6-month intervals, participants who reported MA use showed a

two-fold increase in the risk of psychotic symptoms compared to those with no MA

use (odds ratio [OR] = 2.15, 95% confidence interval [CI] = 1.33-3.49). A

dose-response effect was found between the duration of MA use and the risk of

psychotic symptoms (continued 12-month MA use vs. no use: OR = 2.84, 95%

CI = 1.39-5.77; continued 18-month MA use vs. no use: OR = 9.93, 95%

CI = 3.58-27.57). There was no assessment for 24-month intervals due to a small

sample size of the continuous use group.

CONCLUSIONS: Longer periods of MA use predicted a higher risk of experiencing

psychotic symptoms. Early prevention of MA use could help reduce the risk of

psychosis in MA users.

DOI: 10.1016/j.drugalcdep.2018.03.023

PMID: 29715654 [Indexed for MEDLINE]

20. Psychiatry Res. 2018 Jul;265:19-24. doi: 10.1016/j.psychres.2018.04.015. Epub

2018 Apr 5.

The relationship between illicit amphetamine use and psychiatric symptom profiles

in schizophrenia and affective psychoses.

Voce A(1), McKetin R(2), Burns R(3), Castle D(4), Calabria B(5).

Author information:

(1)Centre for Research on Ageing, Health and Wellbeing, Australian National

University, Building 54, Mills Road, Acton, ACT 2601, Australia. Electronic

address: alexandra.voce@anu.edu.au.

(2)National Drug Research Institute, Curtin University, 10 Selby Street, Shenton

Park, Perth, WA 6845, Australia; National Drug and Alcohol Research Centre,

University of New South Wales, 22-32 King Street, Randwick, NSW 2031, Australia.

(3)Centre for Research on Ageing, Health and Wellbeing, Australian National

University, Building 54, Mills Road, Acton, ACT 2601, Australia.

(4)St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia;

Department of Psychiatry, University of Melbourne, Grattan St, Melbourne, VIC

3010, Australia.

(5)National Centre for Epidemiology and Population Health, Australian National

University, Building 62, Mills Road, Acton, ACT 2601, Australia; National Drug

and Alcohol Research Centre, University of New South Wales, 22-32 King Street,

Randwick, NSW 2031, Australia.

This study examines whether illicit amphetamine use is associated with

differences in the prevalence of specific psychiatric symptoms in a community

sample of individuals diagnosed with schizophrenia or affective psychotic

disorders. Data was drawn from the Australian Survey of High Impact Psychosis.

The Diagnostic Interview for Psychosis was used to measure substance use and

psychiatric symptoms. Participants had used amphetamine within their lifetime and

had an ICD-10 diagnosis of schizophrenia (n = 347) or an affective psychotic

disorder (n = 289). The past year prevalence of psychiatric symptoms was compared

among those who had used amphetamine in the past year (past-year use, 32%) with

those who had not (former use, 68%). Univariate logistic regression analysis

indicated that past-year users with schizophrenia had a significantly higher past

year prevalence of hallucinations, persecutory delusions, racing thoughts,

dysphoria, and anhedonia relative to former amphetamine users with schizophrenia.

There were no significant differences in symptoms between past-year and former

users with affective psychotic disorders. The relationship between amphetamine

use and specific psychiatric symptoms varies across different psychotic

disorders. Amphetamine use may hinder prognosis by exacerbating symptoms of

schizophrenia through dopaminergic dysfunctions or depressive vulnerabilities,

however, this needs to be confirmed by prospective longitudinal research.

DOI: 10.1016/j.psychres.2018.04.015

PMID: 29680513 [Indexed for MEDLINE]

21. J Clin Nurs. 2018 Jul;27(13-14):2569-2582. doi: 10.1111/jocn.14493. Epub 2018 May

28.

Rates and features of methamphetamine-related presentations to emergency

departments: An integrative literature review.

Jones R(1), Woods C(1), Usher K(1).

Author information:

(1)School of Health, University of New England, Armidale, NSW, Australia.

AIMS AND OBJECTIVES: To review the clinical impact methamphetamine has on

emergency departments by assessing the available research on the rates and

features of methamphetamine-related presentations.

BACKGROUND: Globally, methamphetamine availability, distribution and use have

rapidly increased. As a result, the number of methamphetamine-related

presentations to emergency departments has also increased. In this context, it is

timely to review the rate and features of methamphetamine-related presentations

to understand the impact of methamphetamine on emergency departments and

facilitate the allocation of services, staff and resources.

DESIGN: An integrative literature review.

METHODS: This study presents an integrated literature review, following the

systematic review process as outlined in the PRISMA flow chart. Several databases

were searched using a combination of search terms. Articles were measured against

inclusion and exclusion criteria, and the final ten articles were subjected to

quality appraisal and outcomes reported.

RESULTS: Methamphetamine accounted for 2.3% or less of all emergency departments

presentations. The majority of methamphetamine users presenting to emergency

departments were males, with a mean age 31-37. Methamphetamine-related

presentations to emergency departments were more likely to present with trauma,

psychosis, and be placed on 24-hr psychiatric hold. Methamphetamine-related

presentations were more likely to present with agitation, aggression and

homicidal behaviour and present to emergency departments out of hours and

accompanied by police compared with other emergency departments substance-related

presentations.

CONCLUSIONS: Several important themes were highlighted in this review that has an

impact on emergency departments services, resources and staff. Understanding the

rate and patterns of methamphetamine-related presentations can help to provide

evidence for policy development and staff education in emergency departments.

RELEVANCE TO CLINICAL PRACTICE: Methamphetamine-related presenters are more

aggressive and agitated and more likely to be brought in by police. There is a

need for policy development and staff training around these issues and further

research in this area using stronger study designs.

DOI: 10.1111/jocn.14493

PMID: 29679414 [Indexed for MEDLINE]

22. Australas Psychiatry. 2018 Aug;26(4):417-421. doi: 10.1177/1039856218762307. Epub

2018 Mar 13.

Ice in the Outback: the epidemiology of amphetamine-type stimulant-related

hospital admissions and presentations to the emergency department in Hedland,

Western Australia.

Monahan C(1), Coleman M(2).

Author information:

(1)Medical Student, Faculty of Medicine, University of Western Australia,

Nedlands, WA, Australia.

(2)Consultant Psychiatrist, Great Southern Mental Health Service, Albany, WA,

and; Senior Clinical Lecturer, The Rural Clinical School of Western Australia,

University of Western Australia, Nedlands, WA, Australia.

OBJECTIVES: Despite research showing higher use of amphetamine-type stimulants

(ATS) in rural areas, limited research has examined the epidemiology of

ATS-related presentations and admissions to remote regional centres. To determine

the epidemiology of ATS-related (a) Emergency Department (ED) presentations and

(b) inpatient admissions over a five-year period at the Hedland Health Campus

(HHC) in remote Western Australia.

METHODS: A retrospective review of medical records was conducted. Demographic

data including gender, age and indigenous status were captured.

RESULTS: Four hundred and eighty-two ATS-related hospital presentations were

identified during the study period. The most common reason for ED presentation

was mental and behavioural problems. Of those presenting, 66% were male and 69%

identified as Aboriginal. ATS-related ED presentations increased seven-fold over

the study period. Ninety-nine ATS-related inpatient admissions were identified

during the study period. Psychotic disorder was the most common reason for

admission. Males made up 75% of admissions and 53% identified as Aboriginal.

CONCLUSIONS: This study showed a disproportionally high burden of ATS-related

harm among Aboriginal people. The number of ATS-related ED presentations and

inpatient admissions increased significantly over the study period.

DOI: 10.1177/1039856218762307

PMID: 29533079 [Indexed for MEDLINE]

23. Emerg (Tehran). 2018;6(1):e1. Epub 2018 Jan 10.

Predictive Factors of Mortality in Acute Amphetamine Type Stimulants Poisoning; a

Review of 226 Cases.

Rahimi M(1), Lookzadeh S(1), Sadeghi R(2), Soltaninejad K(3), Shadnia S(1),

Pajoumand A(1), Hassanian-Moghaddam H(1), Zamani N(1), Latifi-Pour M(1).

Author information:

(1)Toxicology Research Center, Excellence Center of Clinical Toxicology,

Department of Clinical Toxicology, Loghman Hakim Hospital, School of Medicine,

Shahid Beheshti University of Medical Sciences, Tehran, Iran.

(2)Cardiology Department, Loghman Hakim Hospital, School of Medicine, Shahid

Beheshti University of Medical Sciences, Tehran, Iran.

(3)Department of Forensic Toxicology, Legal Medicine Research Center, Legal

Medicine Organization, Tehran, Iran.

Introduction: Amphetamine type stimulants (ATS) such as amphetamine and

methamphetamine (MA) are one of the most important causes of poisoning in the

world. In this study we aimed to define the predictive factors of mortality in

acute ATS poisoning patients.

Methods: This is a retrospective cross-sectional study on all cases with acute

ATS poisoning who were referred to a referral center for poisoning, Tehran, Iran,

from April 2011 to March 2014. Using patients' medical records, demographic data,

route of exposure, type and amount of ATS, the cause of poisoning, clinical

presentations, and electrocardiogram (ECG) and laboratory findings, as well as

patient's outcomes were collected and analyzed regarding the independent

predictive factors of mortality.

Results: 226 cases with the mean age of 32.9 ± 10.9 years were studied (77%

male). MA was the most abused ATS (97.4%) and the most frequent route of exposure

was oral (55.3%). The mortality rate was 5.4%. There was a significant

association between agitation (p = 0.002), seizure (p = 0.001), loss of

consciousness (p < 0.001), creatine phosphokinase level (p = 0.002), serum pH (p

= 0.002), serum HCO3 (p = 0.02), and PCO2 (p = 0.01) with mortality. However,

serum HCO3 [OR=1.27 (95% CI: 1.07-1.50); p value=0.005], PCO2 [OR=0.89 (95% CI:

0.84-0.96); p value=0.002], and loss of consciousness [OR=0.019 (95% CI:

0.003-0.106); p value=0.000] were the only independent predictive factors of

mortality.

Conclusion: PCO2 ≥ 51 mmHg, serum bicarbonate ≤ 22.6 mEq/L, and loss of

consciousness on admission could be considered as prognostic factors of mortality

in acute ATS poisoning cases presenting to emergency department.

PMCID: PMC5827041

PMID: 29503826

Conflict of interest statement: The authors declare that there is no conflict of

interests regarding the publication of this paper.

24. BMC Complement Altern Med. 2018 Feb 23;18(1):76. doi: 10.1186/s12906-018-2094-z.

Protective and restorative effects of the traditional Chinese medicine Jitai

tablet against methamphetamine-induced dopaminergic neurotoxicity.

Xu S(1), Tu S(1), Gao J(1), Liu J(1), Guo Z(1), Zhang J(2), Liu X(3), Liang J(4),

Huang Y(5), Han M(6).

Author information:

(1)Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of

Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Haidian district,

Beijing, China.

(2)Chinese PLA General Hospital, Beijing, China.

(3)Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai,

China.

(4)Department of Molecular and Cellular Pharmacology, Peking University School of

Pharmaceutical Sciences, Beijing, 100191, China. liangjh@bjmu.edu.cn.

(5)PET Center, Department of Radiology and Biomedical Imaging, Yale University

School of Medicine, New Haven, USA. henry.huang@yale.edu.

(6)Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of

Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Haidian district,

Beijing, China. hanmei@bnu.edu.cn.

BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability

that affects the monoamine neurotransmitter systems, particularly the dopamine

system. Currently there are no effective medications for the treatment of METH

abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a

commercial traditional Chinese medicinal preparation, has been shown to modulate

the dopaminergic function both in heroin addicts and in morphine-dependent rats.

The purpose of this study was to investigate, in a rodent model, whether JTT can

protect against METH-induced neurotoxicity, and/or restore METH-damaged

dopaminergic function.

METHODS: Immunohistochemical staining and/or autoradiography staining were used

to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to

examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and

TH levels in the striatum. Using a stereotyped behavior rating scale, we

evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization.

RESULTS: Repeated METH administration induced obvious stereotyped behavior and

neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly

attenuated METH-induced stereotyped responses, and interdicted METH-induced

changes in the levels of DAT, D2R and TH expression. Treatment with JTT after

METH administration restored DAT, D2R and TH expression to normal levels.

CONCLUSIONS: Our results indicated that JTT protects against METH-induced

neurotoxicity and restores the dopaminergic function, and thus might be a

potential treatment for the dopaminergic deficits associated with METH abuse.

DOI: 10.1186/s12906-018-2094-z

PMCID: PMC6389157

PMID: 29475448 [Indexed for MEDLINE]

25. Suicide Life Threat Behav. 2019 Feb;49(1):328-337. doi: 10.1111/sltb.12442. Epub

2018 Feb 14.

Completed Suicide Among Methamphetamine Users: A National Study.

Darke S(1), Kaye S(1)(2), Duflou J(1)(3), Lappin J(1)(4).

Author information:

(1)National Drug & Alcohol Research Centre, University of New South Wales,

Sydney, NSW, Australia.

(2)Justice Health and Forensic Mental Health Network, NSW Health, Sydney, NSW,

Australia.

(3)Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

(4)School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.

All Australian cases of methamphetamine-related suicide (2009-2015) retrieved

from the National Coronial Information System were examined to determine crude

mortality rates, characteristics and circumstances of death, and blood

toxicology. There were 300 cases, 18.2% of all methamphetamine-related deaths,

and 1.6% of all completed suicides. The mean age was 33.1 years, and 77.0% were

male. The crude mortality rate was 1.9 per 106 , with males having a

significantly higher rate than females (2.9 vs. 0.9 per 106 ). A quarter were

known to have previous suicide attempts, and a history of psychosis was noted in

12.3%. In 40.7% of cases, witnesses described the decedent as having been

agitated and/or aggressive immediately prior to the incident. The vast majority

(85.3%), and of both sexes (males 87.0%, females 79.7%), used violent methods.

Hanging (70.3%) was overwhelmingly the most frequent method among both males

(70.1%) and females (71.0%). Prescription medications were frequently present:

hypnosedatives (23.6%), antidepressants (19.5%), and antipsychotics (8.4%).

Self-poisoning cases were significantly more likely to have antidepressants (odds

ratio: 4.2) and opioids (4.9) present, but less likely to have cannabis (0.3).

Methamphetamine-related suicide makes a large contribution to

methamphetamine-related death and represents a substantial clinical and public

health problem.

DOI: 10.1111/sltb.12442

PMID: 29444345 [Indexed for MEDLINE]

26. Med Klin Intensivmed Notfmed. 2018 Feb 5. doi: 10.1007/s00063-018-0405-2. [Epub

ahead of print]

[Bonzai, lead and bath salt-poisoning with new and old drugs : Synthetic

amphetamines, cathinones, cannabinoids and opioids-an overview].

[Article in German]

Strube J(1), Schaper A(2).

Author information:

(1)Giftinformationszentrum-Nord, Universitätsmedizin Göttingen,

Robert-Koch-Straße 40, 37075, Göttingen, Deutschland. jstrube@giz-nord.de.

(2)Giftinformationszentrum-Nord, Universitätsmedizin Göttingen,

Robert-Koch-Straße 40, 37075, Göttingen, Deutschland.

BACKGROUND: There has been an increase in the number of serious poisonings and

deaths after the use of new psychoactive substances (NPS). These are usually

bought online: sometimes legally, often illegally or "in the grey area".

OBJECTIVES: Characteristics of different NPS. Legal status concerning the New

Psychoactive Substances Act (NpSG). Risk assessment of several substance groups,

possible complications of acute poisonings, therapeutic recommendations.

MATERIALS AND METHODS: Literature search and evaluation of own case data.

Discussion of official statistics, literature and expert recommendations.

RESULTS: There has been an increase in the number of poisonings with NPS and

associated deaths: in Germany in 2016 there were 98 deaths compared to 39 deaths

in 2015. Serious acute poisonings require intensive care therapy. Therapy is

usually symptomatic. Referring to the drugs discussed in this article an antidote

is only available for the synthetic opioid: naloxone.

CONCLUSIONS: With the NpSG being in force since the end of 2016, the number of

severe intoxications with NPS will probably (not immediately) decrease. It

remains to be seen if the increasing number of fatalities will decrease again.

Consultation with a poison centre is recommended in cases of suspected

intoxication with NPS. Diagnosis and therapy can then be discussed. Toxicological

screening may be false negative because many synthetic drugs are not detected in

standard analysis. The NPS often require a special analysis.

DOI: 10.1007/s00063-018-0405-2

PMID: 29404633

27. Pediatr Ann. 2017 Dec 1;46(12):e443-e448. doi: 10.3928/19382359-20171121-01.

Pediatric Poisoning by Ingestion: Developmental Overview and Synopsis of National

Trends.

Lee VR, Connolly M, Calello DP.

The American Association of Poison Control Centers' National Poison Data

Surveillance System provides real-time toxico-surveillance and epidemiologic

trends, and pediatric ingestions comprise most of those reports. The sequences in

social and physical developmental milestones from young childhood to adolescence

reveal the vulnerability of these age groups to a wide variety of potential

poisonous ingestions. Most pediatric ingestions are exploratory. Some common

agents associated with pediatric fatalities include disc batteries, laundry

detergent "pods," opioid analgesics, acetaminophen, benzodiazepines, and

amphetamines. The pediatric provider can be a valuable resource at all points

throughout a child's life, offering anticipatory guidance to caregivers targeting

developmental changes associated with poisonous ingestions. [Pediatr Ann.

2017;46(12):e443-e448.].

DOI: 10.3928/19382359-20171121-01

PMID: 29227519 [Indexed for MEDLINE]

28. Pediatr Emerg Care. 2017 Nov;33(11):e124-e125. doi: 10.1097/PEC.0000000000001301.

A Stinging Suspicion Something Was Just Not Right: Methamphetamine Toxicity in

Infant Mimics Scorpion Envenomation.

Pariury HE(1), Steiniger AM, Lowe MC.

Author information:

(1)From the Department of Pediatrics, University of Arizona, Tucson, AZ.

The sting from Centuroides sculpturatus, commonly known as the bark scorpion, is

a serious medical problem and can be potentially fatal to young children.

Centuroides sculpturatus envenomation can cause a wide spectrum of symptoms,

often including autonomic dysfunction, cranial nerve abnormalities, and somatic

motor abnormalities. We discuss a 6-month-old male infant who presented with

signs and symptoms consistent with bark scorpion envenomation, later found to be

secondary to methamphetamine toxicity. Emergency pediatricians should be aware of

the strong similarities between scorpion envenomation and methamphetamine

toxicity in pediatric patients residing in or having visited the southwestern

region of the United States. Methamphetamine toxicity should be considered in

their differential diagnosis.

DOI: 10.1097/PEC.0000000000001301

PMID: 29095780 [Indexed for MEDLINE]

29. Handb Clin Neurol. 2017;145:181-192. doi: 10.1016/B978-0-12-802395-2.00014-6.

Neurotoxicology and drug-related disorders.

Weis S(1), Büttner A(2).

Author information:

(1)Division of Neuropathology, Department of Pathology and Neuropathology, Kepler

University Hospital and School of Medicine, Johannes Kepler University, Linz,

Austria. Electronic address: serge.weis@gespag.at.

(2)Department of Forensic Medicine, University of Rostock, Rostock, Germany.

Neuropsychiatric disorders caused by toxic substances pose a great diagnostic

challenge due to the large variety of changes caused in the central and

peripheral nervous system. The pathogenetic mechanisms at work are multifaceted

and partly not solved. In human drug abusers (cannabis, opiates, cocaine,

amphetamines, methamphetamine and "designer drugs"), a broad spectrum of central

nervous system alterations are observed including infarction, intracerebral and

subarachnoidal hemorrhage, hypoxic-ischemic leukoencephalopathy, infections,

neuronal loss, specific astroglial and microglial reaction patterns, and vascular

changes, including the endothelial cell as well as the basal lamina.

DOI: 10.1016/B978-0-12-802395-2.00014-6

PMID: 28987169 [Indexed for MEDLINE]

30. Med Klin Intensivmed Notfmed. 2017 Sep;112(6):557-575. doi:

10.1007/s00063-017-0323-8. Epub 2017 Aug 21.

[Intoxication with psychotropic drugs].

[Article in German]

Bellmann R(1), Joannidis M(2).

Author information:

(1)Gemeinsame Einrichtung für Internistische Notfall- und Intensivmedizin,

Universitätsklinik für Innere Medizin I, Medizinische Universität Innsbruck,

Anichstraße 35, 6020, Innsbruck, Österreich.

(2)Gemeinsame Einrichtung für Internistische Notfall- und Intensivmedizin,

Universitätsklinik für Innere Medizin I, Medizinische Universität Innsbruck,

Anichstraße 35, 6020, Innsbruck, Österreich. michael.joannidis@i-med.ac.at.

Comment in

Med Klin Intensivmed Notfmed. 2018 Mar;113(2):157.

Med Klin Intensivmed Notfmed. 2018 Mar;113(2):158.

Psychotropic drugs are medications that are indicated for treatment of

psychiatric disorders. Attempted suicide is the major reason for intoxication but

inadvertent overdosing may also occur. Other psychotropic agents are taken

because of their stimulating and hallucinogenic effects and many have a high

addictive potential. Poisoning is usually due to accidental overdosing. For

treatment of benzodiazepine and opioid intoxication, flumazenil and naloxone,

respectively, are used as specific antagonists. For intoxication by tricyclic

antidepressants, sodium bicarbonate is the treatment of choice. It can also be

administered for poisoning caused by selective serotonin re-uptake inhibitors and

neuroleptics, in cases of cardiotoxicity. Torsades de pointes can be terminated

with defibrillation and intravenous magnesium. Symptomatic treatment is performed

for intoxications caused by analeptics or hallucinogens. Beta blockers must be

avoided in cocaine and amphetamine poisoning.

DOI: 10.1007/s00063-017-0323-8

PMID: 28828702 [Indexed for MEDLINE]

31. Scand J Public Health. 2017 Dec;45(8):773-781. doi: 10.1177/1403494817707634.

Epub 2017 Aug 21.

The prognosis following amphetamine poisoning.

Horwitz H(1), Dalhoff KP(1), Klemp M(2)(3), Horwitz A(4), Andersen JT(1), Jürgens

G(1)(5).

Author information:

(1)1 The Department of Clinical Pharmacology, Bispebjerg and Frederiksberg

Hospital, University of Copenhagen, Denmark.

(2)2 Department of Economics and Population Studies & Training Center, Brown

University, USA.

(3)3 Department of Economics, University of Copenhagen, Denmark.

(4)4 Department of Neuroscience and Pharmacology, University of Copenhagen,

Denmark.

(5)5 Clinical Pharmacology Unit, Zealand University Hospital, Denmark.

AIMS: This study investigated the long-term mortality following poisoning by

amphetamine or substituted amphetamines. Furthermore, we examined the social

problems and somatic and psychiatric co-morbidity related to amphetamine

poisoning, and their impact on the long-term survival.

METHODS: We identified amphetamine poisoned patients from the Danish Poison

Information Centre database and correlated their personal identification numbers

with seven Danish national registries related to different social and health

aspects. For each case, we sampled 100 age and gender matched controls from the

background population.

RESULTS: From August 2006 to December 2013 we identified 1444 patients (70%

males) who experienced amphetamine poisoning; 52% of the cases were classified as

mixed poisonings and the average age at first contact was 24.8 years (SD 8.6).

The prevalence of psychiatric disorders, HIV, viral hepatitis, and previous

prison incarceration was approximately 10 times higher than among healthy

controls. After seven years 11% were deceased as opposed to 0.6% in the control

group, and 64% of the patients died from unnatural causes. Male gender (HR 2.29,

95% CI (1.07-4.90)), age (HR 1.06, 95% CI (1.03-1.09)), opioid dependence (HR

2.88, 95% CI (1.42-5.85)), schizophrenia (HR 3.09,95% CI (1.63-5.86)), affective

disorders (HR 2.65, 95% CI (1.44-4.90)) and HIV (HR 5.45, 95% CI (1.19-24.90))

were associated with a high mortality. Furthermore, a significant proportion of

these patients experienced social and health related deterioration in the years

following poisoning.

CONCLUSIONS: Amphetamine poisoning is associated with a poor long-term prognosis

and is complicated by additional social and health related issues.

DOI: 10.1177/1403494817707634

PMID: 28825523 [Indexed for MEDLINE]

32. Am J Emerg Med. 2017 Sep;35(9):1385.e3-1385.e6. doi: 10.1016/j.ajem.2017.06.040.

Epub 2017 Jun 27.

Isolated non-cardiogenic pulmonary edema - A rare complication of MDMA toxicity.

Haaland A(1), Warman E(2), Pushkar I(3), Likourezos A(4), Friedman MS(5).

Author information:

(1)Department of Emergency Medicine, Maimonides Medical Center, 4802 Tenth

Avenue, Brooklyn, New York 11219, USA. Electronic address:

ahaaland@maimonidesmed.org.

(2)SUNY Downstate College of Medicine, 450 Clarkson Avenue, Brooklyn, NY 11203,

USA.

(3)Department of Emergency Medicine, Maimonides Medical Center, 965 48th Street,

Brooklyn, NY 11219, USA. Electronic address: ipushkar@maimonidesmed.org.

(4)Department of Emergency Medicine, Maimonides Medical Center, 965 48th Street,

Brooklyn, NY 11219, USA. Electronic address: alikourezos@maimonidesmed.org.

(5)Department of Emergency Medicine, Maimonides Medical Center, 4802 Tenth

Avenue, Brooklyn, New York 11219, USA. Electronic address:

MattFriedman@maimonidesmed.org.

This is a case of a 19-year-old male who presented to the medical tent at an

outdoor electronic dance music festival (EDMF) due to an altered mental state in

the setting of acute 3,4-methylenedioxymethamphetamine (MDMA) intoxication. He

was noted to be in severe respiratory distress, required endotracheal intubation

in the field and subsequently developed Acute Respiratory Distress Syndrome

(ARDS) without other acute organ dysfunction. He was hospitalized for 5days

requiring endotracheal intubation and mechanical ventilation. By presenting this

case, we will explore and discuss the cardiopulmonary effects of MDMA

intoxication that can lead to a rare, deleterious complication of MDMA

intoxication other than previously reported adverse outcomes.

DOI: 10.1016/j.ajem.2017.06.040

PMID: 28733094 [Indexed for MEDLINE]

33. Acta Med Iran. 2017 May;55(5):344-347.

Fatal Small Intestinal Ischemia Due to Methamphetamine Intoxication: Report of a

Case With Autopsy Results.

Attaran H(1).

Author information:

(1)Legal Medicine Research Center, Legal Medicine Organization, Mashhad, Iran.

Methamphetamine is one of the most common abused drugs, so its various effects on

different body organs should be familiar to all physicians. Regarding its

gastrointestinal sequels, there are few reports of ischemic colitis induced by

its vasoconstrictive effects. This is the first report of isolated small

intestinal infarction resulting in death following methamphetamine toxicity. A

40-year-old woman with a past history of medical treatment for obesity referred

to hospital with severe chest and back pain, perspiration, nausea, agitation,

high blood pressure, bradycardia and subsequent lethargy and vasomotor

instability. Cardiac evaluations were normal, and a toxicologic urinalysis

revealed methamphetamine. Later, abdominal pain predominated, and ultrasonography

revealed signs of bowel infarction. She did not consent to surgery and succumbed

afterward. At autopsy gangrene and perforation of distal ileum were found. The

cause of death was determined as intestinal gangrene following methamphetamine

toxicity. Methamphetamine has anorectic effects and so is used in some "diet

pills"; Consumers may not even know they are using methamphetamine. Hence in

cases of either known MA abuse or those using unknown weight reduction drugs

presenting with gastrointestinal complaints or abdominal pain, intestinal

ischemia should be kept in mind and if plausible, intervened promptly.

PMID: 28724276 [Indexed for MEDLINE]

34. Am J Ther. 2017 Sep/Oct;24(5):e639-e640. doi: 10.1097/MJT.0000000000000618.

Phenibut (β-Phenyl-γ-Aminobutyric Acid) Psychosis.

Li W(1), Madhira B.

Author information:

(1)Department of Internal Medicine, SUNY Upstate Medical University, Syracuse,

NY.

DOI: 10.1097/MJT.0000000000000618

PMID: 28723730 [Indexed for MEDLINE]

35. Sultan Qaboos Univ Med J. 2017 May;17(2):e213-e217. doi:

10.18295/squmj.2016.17.02.013. Epub 2017 Jun 20.

Discrimination Between Drug Abuse and Medical Therapy: Case report of a

tranylcypromine overdose-related fatality.

Akhgari M(1), Jokar F(1), Etemadi-Aleagha A(2), Ghasemi A(2).

Author information:

(1)Department of Forensic Toxicology, Legal Medicine Research Center, Legal

Medicine Organization, Tehran, Iran.

(2)Department of Anaesthesiology & Critical Care, Tehran University of Medical

Sciences, Tehran, Iran.

Tranylcypromine is an effective antidepressant from the class of monoamine

oxidase inhibitors and is structurally related to amphetamine. However, reports

differ regarding the potential metabolism of tranylcypromine to amphetamine and

methamphetamine within the human body. We report a 25-year-old woman with severe

depression who died due to a fatal tranylcypromine overdose in 2016. She had been

prescribed tranylcypromine one day previously and had no history of previous

suicide attempts or substance abuse. The body was transferred to a forensic

medicine department in Tehran, Iran for the autopsy. A urine sample was positive

for tranylcypromine, amphetamine and methamphetamine using gas

chromatography/mass spectrometry after derivatisation with heptafluorobutyric

acid. As amphetamines were present in the urine sample, it was assumed that the

tranylcypromine had been converted to amphetamines metabolically. As such, it is

possible that the legitimate use of certain prescription drugs may complicate the

interpretation of test results for illegal drugs.

DOI: 10.18295/squmj.2016.17.02.013

PMCID: PMC5488824

PMID: 28690895 [Indexed for MEDLINE]

36. J Pharmacol Exp Ther. 2017 Sep;362(3):474-488. doi: 10.1124/jpet.116.238501. Epub

2017 Jun 19.

Molecular, Behavioral, and Physiological Consequences of Methamphetamine

Neurotoxicity: Implications for Treatment.

Moszczynska A(1), Callan SP(2).

Author information:

(1)Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy

and Health Sciences, Wayne State University, Detroit, Michigan amosz@wayne.edu.

(2)Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy

and Health Sciences, Wayne State University, Detroit, Michigan.

Understanding the relationship between the molecular mechanisms underlying

neurotoxicity of high-dose methamphetamine (METH) and related clinical

manifestations is imperative for providing more effective treatments for human

METH users. This article provides an overview of clinical manifestations of METH

neurotoxicity to the central nervous system and neurobiology underlying the

consequences of administration of neurotoxic METH doses, and discusses

implications of METH neurotoxicity for treatment of human abusers of the drug.

Therapeutics.

DOI: 10.1124/jpet.116.238501

PMID: 28630283 [Indexed for MEDLINE]

37. Toxicol Lett. 2017 Aug 5;277:84-91. doi: 10.1016/j.toxlet.2017.05.030. Epub 2017

Jun 1.

Intoxication by gamma hydroxybutyrate and related analogues: Clinical

characteristics and comparison between pure intoxication and that combined with

other substances of abuse.

Miró Ò(1), Galicia M(2), Dargan P(3), Dines AM(4), Giraudon I(5), Heyerdahl F(6),

Hovda KE(6), Yates C(7), Wood DM(3), Liakoni E(8), Liechti M(9), Jürgens G(10),

Pedersen CB(11), O'Connor N(12), Markey G(12), Moughty A(13), Lee C(13),

O'Donohoe P(13), Sein Anand J(14), Puiguriguer J(15), Homar C(15), Eyer F(16),

Vallersnes OM(17), Persett PS(18), Chevillard L(19), Mégarbane B(19), Paasma

R(20), Waring WS(21), Põld K(22), Rabe C(23), Kabata PM(24).

Author information:

(1)Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona,

Barcelona, Catalonia, Spain.

(2)Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona,

Barcelona, Catalonia, Spain. Electronic address: mgalicia@clinic.cat.

(3)Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's

Health Partners, London, UK; Clinical Toxicology, Faculty of Life Sciences and

Medicine, King's College London, London, UK.

(4)Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's

Health Partners, London, UK.

(5)European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon,

Portugal.

(6)The National CBRNe Centre of Medicine, Department of Acute Medicine, Medical

Division, Oslo University Hospital, Oslo, Norway.

(7)Emergency Department and Clinical Toxicology Unit, Hospital Universitari Son

Espases, Mallorca, Spain.

(8)Clinical Pharmacology and Toxicology, Department of General Internal Medicine,

Inselspital, Bern University Hospital, University of Bern, Switzerland; Division

of Clinical Pharmacology and Toxicology, Basel University Hospital and University

of Basel, Switzerland.

(9)Division of Clinical Pharmacology and Toxicology, Basel University Hospital

and University of Basel, Switzerland.

(10)Zealand University Hospital Roskilde Clinical Pharmacology Unit Roskilde,

Denmark.

(11)Department of Anaesthesia University Hospital of Zealand, Køge, Denmark.

(12)Department of Emergency Medicine, Our Lady of Lourdes Hospital, Drogheda,

County Louth, Republic of Ireland.

(13)Emergency Department Mater Misericordiae University Hospital, Dublin 7,

Republic of Ireland.

(14)Department of Clinical Toxicology Medical University of Gdansk, Gdansk,

Poland; Pomeranian Centre of Toxicology, Gdansk, Poland.

(15)Clinical Toxicology Unit Emergency Department, Hospital Son Espases, Palma de

Mallorca, Balearic Island, Spain.

(16)Department of Clinical Toxicology, Klinikum rechts der Isar, Technical

University of Munich, Munich, Germany.

(17)Department of General Practice, University of Oslo, Oslo, Norway; Oslo

Accident and Emergency Outpatient Clinic, City of Oslo Health Agency, Oslo,

Norway.

(18)Department of Acute Medicine, Medical Division, Oslo University Hospital,

Oslo, Norway.

(19)Department of Medical and Toxicological Critical Care, Lariboisière Hospital,

INSERM UMRS-1144, Paris-Diderot University, Paris, France.

(20)Foundation Pärnu Hospital, Pärnu, Estonia.

(21)Acute Medical Unit York Teaching Hospitals NHS Foundation Trust York, UK.

(22)Emergency Medicine Department North-Estonia Medical Centre Tallinn, Estonia.

(23)Department of Clinical Toxicology, Klinikum rechts der Isar, Technical

University of Munich, Germany.

(24)Pomeranian Centre of Toxicology, Gdansk, Poland; Medical University Gdansk,

Department of Clinical Toxicology, Gdansk, Poland.

OBJECTIVE: To study the profile of European gamma-hydroxybutyrate (GHB) and

gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical

manifestations produced by intoxication by GHB/GBL alone and in combination with

other substances of abuse.

METHOD: We prospectively collected data on all the patients attended in the

Emergency Departments (ED) of the centres participating in the Euro-DEN network

over 12 months (October 2013 to September 2014) with a primary presenting

complaint of drug intoxication (excluding ethanol alone) and registered the

epidemiological and clinical data and outcomes.

RESULTS: We included 710 cases (83% males, mean age 31 years), representing 12.6%

of the total cases attended for drug intoxication. Of these, 73.5% arrived at the

ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in

combination with other substances of abuse, the most frequent additional agents

being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis

(8%). Among 15 clinical features pre-defined in the project database, the 3 most

frequently identified were altered behaviour (39%), reduced consciousness (34%)

and anxiety (14%). The severity ranged from mild cases requiring no treatment

(308 cases, 43.4%) to severe cases requiring admission to intensive care (103

cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were

reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL

with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and

cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment

(59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED

stay >12h, p<0.01).

CONCLUSIONS: The profile of the typical GHB/GBL-intoxicated European is a young

male, requiring care for altered behaviour and reduced level of consciousness,

mainly during the weekend. The clinical features are more severe when GHB is

consumed in combination with other substances of abuse.

DOI: 10.1016/j.toxlet.2017.05.030

PMID: 28579487 [Indexed for MEDLINE]

38. Int J Legal Med. 2018 Jan;132(1):173-179. doi: 10.1007/s00414-017-1601-y. Epub

2017 May 13.

Postmortem diagnosis of hyponatremia: case report and literature review.

Vanhaebost J(1), Palmiere C(2), Scarpelli MP(3), Bou Abdallah F(4), Capron

A(5)(6), Schmit G(1).

Author information:

(1)Service d'Anatomie Pathologique et Médecine Légale, Cliniques Universitaires

Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

(2)CURML, University Center of Legal Medicine, Chemin de la Vulliette 4, 1000,

25, Lausanne, Switzerland. cristian.palmiere@chuv.ch.

(3)CURML, University Center of Legal Medicine, Chemin de la Vulliette 4, 1000,

25, Lausanne, Switzerland.

(4)University Paris-Descartes, Laboratory of Medical Ethics and Forensic

Medicine, Paris, France.

(5)Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels,

Belgium.

(6)Louvain Center for Toxicology and Applied Pharmacology, Université Catholique

de Louvain, UCL, Brussels, Belgium.

Hyponatremia is defined as a plasma sodium concentration less than 135 or

130 mEq/L (or mmol/L) and may be responsible for life threatening symptoms that

can be observed in a variety of medical conditions. Cases of fatal hyponatremia

have been reported in both clinical and forensic literature in situations of

water intoxication due to psychogenic polydipsia, amphetamine derivative drug

intake, high-endurance exercise, iatrogenic causes, and exceptional cases of

child abuse by forced water intoxication. Vitreous sodium levels have been

determined to be relatively stable during the early postmortem period and similar

to levels found in normal serum of living subjects. Nevertheless, there are

relatively few cases of fatal hyponatremia described in literature that underwent

exhaustive postmortem biochemical investigations. A case of fatal water

intoxication in a psychiatric patient who underwent medicolegal investigations,

including postmortem biochemistry, was chosen as a starting point to a literature

review of deaths by hyponatremia that may be encountered in the forensic setting.

DOI: 10.1007/s00414-017-1601-y

PMID: 28503702 [Indexed for MEDLINE]

39. Med Sci Law. 2017 Apr;57(2):91-94. doi: 10.1177/0025802417699343. Epub 2017 Mar

12.

Intravenous administration of cannabis and lethal anaphylaxis.

Gilbert JD(1), Grabowski M(1), Byard RW(1)(2).

Author information:

(1)1 Forensic Science SA, Australia.

(2)2 School of Medicine, The University of Adelaide, Australia.

Cannabis allergy appears to be increasing. A 33-year-old woman is reported who

collapsed and died shortly after injecting herself with a cannabis solution

prepared by pouring boiling water onto plant material. There were no significant

findings at autopsy, except for a single recent venepuncture wound in the left

cubital fossa. Toxicological examination of the blood revealed low levels of

methylamphetamine and amphetamine with tetrahydrocannabinol (Δ9-THC) and

11-nor-9-carboxy-Δ9-THC, and no opiates. The syringe used by the decedent

contained Δ9-THC. Serum tryptase levels were markedly elevated (>200 µg/L;

N < 12 µg/L). This finding coupled with the sudden collapse after injecting an

aqueous extract of cannabis indicated a likely anaphylactic or anaphylactoid

reaction to the extract. Cannabis allergy may occur following handling,

inhalation, swallowing or injecting Cannabis sativa plants or their products. The

possibility of an allergic reaction should therefore be considered at autopsy in

deaths where there has been recent contact with cannabis.

DOI: 10.1177/0025802417699343

PMID: 28438101 [Indexed for MEDLINE]

40. Fordham Law Rev. 2017 Apr;85(5):2417-49.

Mens Rea and Methamphetamine: High Time for a Modern Doctrine Acknowledging the

Neuroscience of Addiction.

Cusick M.

In American criminal law, actus non facit reum, nisi mens sit rea, "an act does

not make one guilty, without a guilty mind." Both actus reus and mens rea are

required to justify criminal liability. The Model Penal Code's (MPC) section on

culpability has been especially influential on mens rea analysis. An issue of

increasing importance in this realm arises when an offensive act is committed

while the actor is under the influence of drugs. Several legal doctrines address

the effect of intoxication on mental state, including the MPC, limiting or

eliminating its relevance to the mens rea analysis. Yet these doctrines do not

differentiate between intoxication and addiction. Neuroscience research reveals

that drug addiction results in catastrophic damage to the brain resulting in

cognitive and behavioral deficits. Methamphetamine addiction is of particular

interest to criminal law because it causes extensive neural destruction and is

associated with impulsive behavior, violent crime, and psychosis. Furthermore,

research has revealed important distinctions between the effects of acute

intoxication and addiction. These findings have implications for the broader

doctrine of mens rea and, specifically, the intoxication doctrines. This Note

argues for the adoption of an addiction doctrine that acknowledges the effect of

addiction on mens rea that is distinct from doctrines of intoxication.

PMID: 28379674 [Indexed for MEDLINE]

41. Pharmacol Res. 2017 Jun;120:60-67. doi: 10.1016/j.phrs.2017.03.009. Epub 2017 Mar

14.

Methamphetamine: Effects on the brain, gut and immune system.

Prakash MD(1), Tangalakis K(1), Antonipillai J(1), Stojanovska L(1), Nurgali

K(1), Apostolopoulos V(2).

Author information:

(1)Immunology in Chronic Diseases Program, Centre for Chronic Disease, College of

Health and Biomedicine, Victoria University, Melbourne, Australia.

(2)Immunology in Chronic Diseases Program, Centre for Chronic Disease, College of

Health and Biomedicine, Victoria University, Melbourne, Australia. Electronic

address: Vasso.Apostolopoulos@vu.edu.au.

Methamphetamine (METH) is a powerful central nervous system stimulant which

elevates mood, alertness, energy levels and concentration in the short-term.

However, chronic use and/or at higher doses METH use often results in psychosis,

depression, delusions and violent behavior. METH was formerly used to treat

conditions such as obesity and attention deficit hyperactivity disorder, but now

is primarily used recreationally. Its addictive nature has led to METH abuse

becoming a global problem. At a cellular level, METH exerts a myriad of effects

on the central and peripheral nervous systems, immune system and the

gastrointestinal system. Here we present how these effects might be linked and

their potential contribution to the pathogenesis of neuropsychiatric disorders.

In the long term, this pathway could be targeted therapeutically to protect

people from the ill effects of METH use. This model of METH use may also provide

insight into how gut, nervous and immune systems might break down in other

conditions that may also benefit from therapeutic intervention.

DOI: 10.1016/j.phrs.2017.03.009

PMID: 28302577 [Indexed for MEDLINE]

42. Emerg (Tehran). 2017;5(1):e47. Epub 2017 Jan 14.

Recurrent Syncope following Substance Abuse; a Case Report.

Salehi F(1), Hassanzadeh Taheri MM(2), Riasi H(3), Mehrpour O(4).

Author information:

(1)Department of Pediatric, Birjand University of Medical Sciences, Birjand,

Iran.

(2)Department of Anatomical Sciences, Faculty of Medicine, Birjand University of

Medical Sciences, Birjand, Iran.

(3)Neurology Department, Birjand University of Medical sciences, Birjand, Iran.

(4)Atherosclerosis and Coronary Artery Research Center, Birjand University of

Medical Sciences, Birjand, Iran.; Medical Toxicology and Drug Abuse Research

Center, Birjand University of Medical Sciences, Birjand, Iran.

Drug abuse is considered as the most common poisoning in the world. Stimulants

agent especially amphetamines and methamphetamines are among important abused

substances. Different types of neurologic, psychiatric, respiratory,

gastrointestinal, and cardiogenic complications have been reported to be related

to methamphetamine consumption. Some of these substances could cause dysrhythmias

which is the most prevalent etiology of cardiogenic syncope. Ecstasy, as one of

the most commonly abused drugs, is known as a cause of cardiac dysrhythmias. Here

we report a young boy who was admitted into the emergency department following

three syncope attacks. All cardiac and neurologic assessments were normal; and

finally ecstasy abuse was detected as the main etiology of syncopes.

PMCID: PMC5325918

PMID: 28286854

Conflict of interest statement: The authors declare that there is no conflict of

interest.

43. Psychiatry Res. 2017 May;251:349-354. doi: 10.1016/j.psychres.2017.02.028. Epub

2017 Feb 13.

Differences in the symptom profile of methamphetamine-related psychosis and

primary psychotic disorders.

McKetin R(1), Baker AL(2), Dawe S(3), Voce A(4), Lubman DI(5).

Author information:

(1)National Drug Research Institute, Faculty of Health Sciences, Curtin

University, Perth, Australia; Centre for Research on Ageing, Health and

Well-being, the Australian National University, Canberra, Australia; National

Drug and Alcohol Research Centre, University of New South Wales, Sydney,

Australia. Electronic address: rebecca.mcketin@curtin.edu.au.

(2)School of Medicine and Public Health, University of Newcastle, Callaghan,

Australia.

(3)School of Applied Psychology, Menzies Health Institute Queensland, Griffith

University, Brisbane, Australia.

(4)Centre for Research on Ageing, Health and Well-being, the Australian National

University, Canberra, Australia.

(5)Turning Point, Eastern Health and Monash University, Melbourne, Australia.

We examined the lifetime experience of hallucinations and delusions associated

with transient methamphetamine-related psychosis (MAP), persistent MAP and

primary psychosis among a cohort of dependent methamphetamine users. Participants

were classified as having (a) no current psychotic symptoms, (n=110); (b)

psychotic symptoms only when using methamphetamine (transient MAP, n=85); (c)

psychotic symptoms both when using methamphetamine and when abstaining from

methamphetamine (persistent MAP, n=37), or (d) meeting DSM-IV criteria for

lifetime schizophrenia or mania (primary psychosis, n=52). Current psychotic

symptoms were classified as a score of 4 or more on any of the Brief Psychiatric

Rating Scale items of suspiciousness, hallucinations or unusual thought content

in the past month. Lifetime psychotic diagnoses and symptoms were assessed using

the Composite International Diagnostic Interview. Transient MAP was associated

with persecutory delusions and tactile hallucinations (compared to the no symptom

group). Persistent MAP was additionally associated with delusions of reference,

thought interference and complex auditory, visual, olfactory and tactile

hallucinations, while primary psychosis was also associated with delusions of

thought projection, erotomania and passivity. The presence of non-persecutory

delusions and hallucinations across various modalities is a marker for persistent

MAP or primary psychosis in people who use methamphetamine.

DOI: 10.1016/j.psychres.2017.02.028

PMID: 28282630 [Indexed for MEDLINE]

44. Subst Abuse Treat Prev Policy. 2017 Feb 22;12(1):2. doi:

10.1186/s13011-017-0088-3.

Evaluation of blood lead level in methamphetamine users in Tehran.

Mostafazadeh B(1), Shadnia S(2), Tavakkoli MA(3), Khoddami Vishteh HR(4).

Author information:

(1)Department of Forensic Medicine, School of Medicine, Shahid Beheshti

University of Medical Sciences, Loghman Hakim Hospital, Makhsoos St, South

Karegar Ave, Tehran, Iran. mstzbmd@sbmu.ac.ir.

(2)Department of Clinical Toxicology, School of Medicine, Shahid Beheshti

University of Medical Sciences, Tehran, Iran.

(3)Department of Forensic Medicine, School of Medicine, Shahid Beheshti

University of Medical Sciences, Loghman Hakim Hospital, Makhsoos St, South

Karegar Ave, Tehran, Iran.

(4)Shahid Beheshti University of Medical Sciences, Tehran, Iran.

BACKGROUND: Given the increasing number of lead poisoning in opioids users and

since no study has been conducted so far to review lead poisoning in

methamphetamine (crystal) users, this study aimed to investigate blood lead level

in methamphetamine addicts.

METHODS: This study was conducted on 20 patients with methamphetamine poisoning

and their blood lead level was measured. The subjects were selected from among

patients with a history of continuous use of methamphetamine, without a history

of using opiates in the past 6 months confirmed by a negative urine tests, and

without a history of heavy metal poisoning.

RESULTS: Of all, 18 patients were male and the mean age was 32 ± 10 years; 17

patients were abusing the drug via inhalation and three persons via oral

administration. The mean blood lead level was 2.3 ± 1.1 μg/dL and poisoning was

not observed in any of the cases. Blood lead level was not associated with age,

sex, dosage, and route of administration.

CONCLUSION: Although blood lead level was not at poisoning level in people who

only used methamphetamine in Iran, due to the simultaneous use of other

substances and because of non-specific symptoms, lead poisoning must be suspected

in all cases of substances poisoning.

DOI: 10.1186/s13011-017-0088-3

PMCID: PMC5320762

PMID: 28222753 [Indexed for MEDLINE]

45. Anasthesiol Intensivmed Notfallmed Schmerzther. 2017 Feb;52(2):145-151. doi:

10.1055/s-0042-118022. Epub 2017 Feb 21.

Ecstasy-Intoxikation mit disseminierter intravasaler Gerinnung und

Multiorganversagen.

[Article in German]

Jochum M, Oeding J, Lackner D, Lienhart H.

This case presents the clinical treatment of a patient with severe MDMA

intoxication. The history of stimulating psychotropic substances is presented as

well as the modes of action of current party drugs. Data from the Austrian Drug

Report indicate a tendency away from "hard drugs" towards the consumption of

cannabis and amphetamine derivates. The lethal outcome in our case demonstrates

the risk potential of these substances and underlines the necessity of aggressive

resuscitation efforts.

Georg Thieme Verlag KG Stuttgart · New York.

DOI: 10.1055/s-0042-118022

PMID: 28222475 [Indexed for MEDLINE]

46. Daru. 2017 Feb 17;25(1):5. doi: 10.1186/s40199-017-0170-4.

Histopathological study of cardiac lesions in methamphetamine poisoning-related

deaths.

Akhgari M(1), Mobaraki H(2), Etemadi-Aleagha A(3).

Author information:

(1)Department of Forensic Toxicology, Legal Medicine Research Center, Legal

Medicine Organization, Old Ghom Road, 500 meters after Beheste Zahra, 1816153141,

Tehran, Iran. akhgari1349@yahoo.com.

(2)Department of Forensic Pathology, Legal Medicine Research Center, Legal

Medicine Organization, Tehran, Iran.

(3)Tehran University of Medical Sciences (TUMS), Amir Alam Hospital, Tehran,

Iran.

BACKGROUND: Methamphetamine abuse is a worldwide health concern. Methamphetamine

causes health hazards in many vital organs. It can cause damage to cardiac tissue

via catecholamines release. Methamphetamine related deaths are becoming one of

the most important problems in Iran. The purpose of the present study was to

determine cardiac pathology in methamphetamine poisoning-related deaths.

METHODS: The study included 100 cases of methamphetamine poisoning-related deaths

and 100 cases as control group. Toxicology analysis of liver, gastric content,

bile, urine, blood and vitreous humor were conducted to detect drugs, poisons and

alcohols using thin layer chromatography, gas chromatography/mass spectrometry,

and high performance liquid chromatography. Positive toxicology analysis results

except for amphetamine and methamphetamine were excluded from the study in order

to omit interfering factors. The most striking features of cardiac damage were

observed by light microscopy.

RESULTS: Methamphetamine and amphetamine were detected in either urine or gastric

content samples. In all of the cases methamphetamine toxicity was determined to

be a direct cause of death by forensic medicine practitioner. Cardiovascular

pathology was noted in 68% of studied cases. The most common histopathologic

features were myocardial fiber hypertrophy, mild, moderate to severe

atherosclerosis and focal degeneration/necrosis.

CONCLUSION: The results of the present study indicate that cardiotoxicity is one

of the major contributing factors in methamphetamine poisoning related deaths.

Overall, the current study highlights the fact that cardiotoxic effects of

methamphetamine can explain increasing reports of heart failure and consequently

death in young abusers.

TRIAL REGISTRATION: Not applicable. Histopathological study of cardiac lesions in

methamphetamine poisoning-related deaths.

DOI: 10.1186/s40199-017-0170-4

PMCID: PMC5316196

PMID: 28212679 [Indexed for MEDLINE]

47. Early Interv Psychiatry. 2018 Oct;12(5):928-934. doi: 10.1111/eip.12404. Epub

2016 Dec 19.

Twelve-month course and outcome of methamphetamine-induced psychosis compared

with first episode primary psychotic disorders.

Hajebi A(1), Amini H(2)(3), Kashani L(2)(3), Sharifi V(2)(3).

Author information:

(1)Research Center for Addiction & Risky Behavior (ReCARB), Department of

Psychiatry, Iran University of Medical Sciences, Tehran, Iran.

(2)Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical

Sciences, Tehran, Iran.

(3)Psychiatry and Psychology Research Center, Tehran University of Medical

Sciences, Tehran, Iran.

BACKGROUND: To assess the clinical course and outcome of patients with

methamphetamine-induced psychosis in comparison with patients with primary

psychotic disorders.

METHODS: This prospective study was conducted on patients with

methamphetamine-induced psychosis, and 2 groups of primary psychotic disorders:

affective psychosis and non-affective psychosis admitted to 2 psychiatric

hospitals in Tehran, Iran, with a first episode of a psychotic illness. A total

of 165 subjects (55 in each group) were selected using convenience sampling. They

were assessed at the time of admission, discharge and 6 and 12 months after

discharge using the Positive and Negative Syndrome Scale, the Young Mania Rating

Scale and the Global Assessment of Functioning Scale. The frequency of

readmissions and suicide attempts were also assessed.

RESULTS: Significant differences were found in the trend of changes of symptoms

and functioning among the 3 groups. At all-time points, the severity of negative

psychotic symptoms and dysfunction in the non-affective psychosis group were

greater than those in affective or methamphetamine-induced psychosis groups, with

latter 2 having similar profiles. However, the course of positive symptoms in

methamphetamine-induced psychosis was more similar to non-affective psychosis.

Number of suicide attempts and readmissions were non-significantly higher in

methamphetamine-induced psychosis than in the other groups.

CONCLUSION: Methamphetamine-induced psychosis does not have a satisfactory course

and in some cases symptoms may remain even after many months of follow-up. Rate

of certain outcomes such as re-hospitalization is also considerably high. It is a

challenge for the health-care system that requires evidence-based interventions.

DOI: 10.1111/eip.12404

PMID: 27991722 [Indexed for MEDLINE]

48. Therapie. 2017 Jun;72(3):367-372. doi: 10.1016/j.therap.2016.10.002. Epub 2016

Nov 24.

[Acute psychiatric symptoms during methylphenidate intravenous injections: A case

report].

[Article in French]

Vérité F(1), Micallef J(2).

Author information:

(1)EPSM de la Sarthe, unité d'accueil et d'orientation, 20, avenue du

19-Mars-1962, 72700 Allonnes, France. Electronic address:

f.verite@epsm-sarthe.fr.

(2)Service de pharmacologie, CEIP-addictovigilance PACA Corse, INT, institut des

neurosciences Timone, Aix-Marseille université, CNRS, CHU Timone, AP-HM, 13385

Marseille, France.

We report the case of a 32-year-old man who developed acute psychiatric disorders

after repeated intravenous injections of methylphenidate. The behavioural

disorders with extreme psychomotor restlessness and delirious syndrome have

resolved within 24hours. The available data highlight the fact that the

prescriptions of methylphenidate, an amphetamine-like substance, are constantly

increasing in Europe and Northern America. The potential of abuse and addiction

to this drug, which is growingly misused, is now clearly established. The medical

professionals should be cautious and attentive to the risk of misuse of this

drug.

DOI: 10.1016/j.therap.2016.10.002

PMID: 27988038 [Indexed for MEDLINE]

49. J Pediatr. 2017 Mar;182:385-388.e3. doi: 10.1016/j.jpeds.2016.11.038. Epub 2016

Dec 13.

A Case Report of Reversible Takotsubo Cardiomyopathy after

Amphetamine/Dextroamphetamine Ingestion in a 15-Year-Old Adolescent Girl.

Toce MS(1), Farias M(2), Bruccoleri R(3), Brown DW(2), Burns MM(4).

Author information:

(1)Harvard Medical Toxicology Program, Boston Children's Hospital, Boston, MA.

Electronic address: michael.toce@childrens.harvard.edu.

(2)Department of Medicine, Division of Cardiology, Boston Children's Hospital,

Boston, MA.

(3)Harvard Medical Toxicology Program, Boston Children's Hospital, Boston, MA.

(4)Harvard Medical Toxicology Program, Boston Children's Hospital, Boston, MA;

Department of Medicine, Division of Emergency Medicine, Boston Children's

Hospital, Boston, MA.

Stimulant medications are used in the treatment of attention deficit

hyperactivity disorder and serious cardiac complications can occur when these

medications are abused. We present a 15-year-old adolescent girl who was found to

have a Takotsubo cardiomyopathy after acute amphetamine/dextroamphetamine

ingestion.

DOI: 10.1016/j.jpeds.2016.11.038

PMID: 27979580 [Indexed for MEDLINE]

50. Psychopathology. 2016;49(6):429-435. doi: 10.1159/000452476. Epub 2016 Dec 8.

First-Rank Symptoms in Methamphetamine Psychosis and Schizophrenia.

Shelly J(1), Uhlmann A, Sinclair H, Howells FM, Sibeko G, Wilson D, Stein DJ,

Temmingh H.

Author information:

(1)Department of Psychiatry and Mental Health, Faculty of Health Sciences,

University of Cape Town, Cape Town, South Africa.

BACKGROUND: Methamphetamine psychosis (MAP) symptomatology has been described as

indistinguishable from that of schizophrenia (SZ), yet research comparing these

two disorders on specific psychotic symptoms such as schneiderian first-rank

symptoms (FRS) is lacking. We aimed to determine and compare the occurrence and

associations of FRS in patients diagnosed with MAP and with SZ.

SAMPLING AND METHOD: Data from SCID-I interviews performed on patients with

either a diagnosis of SZ or MAP were compared. We calculated the prevalence of

different FRS between MAP and SZ patients and used logistic regression to assess

the association between FRS and diagnosis.

RESULTS: 102 patients were included in the study (MAP = 33, SZ = 69). Thought

broadcasting occurred significantly more often in SZ (42%) than in MAP (24.2%)

patients (adjusted OR = 3.02; 95% CI: 1.12-8.15; p = 0.028), while auditory

hallucinations (voices conversing) were significantly higher in MAP (48.5%) than

in SZ (20.3%) patients (adjusted OR = 0.27; 95% CI: 0.10-0.66; p = 0.004).

However, there was no significant difference in the occurrence of one or more FRS

in MAP and SZ, with most FRS showing overlap.

CONCLUSIONS: We found that first-rank auditory hallucinations were more prevalent

in MAP, whereas first-rank delusions of thought broadcasting were more prevalent

in SZ. However, there was a substantial overlap in MAP and SZ for most FRS. This

is consistent with the finding that FRS may have limited diagnostic specificity

and that there is significant overlap in the symptoms of MAP and SZ. Future

research into the neurobiology of delusions and hallucinations needs to take FRS

into account.

DOI: 10.1159/000452476

PMID: 27926911 [Indexed for MEDLINE]

51. Curr Neuropharmacol. 2017;15(5):738-749. doi: 10.2174/1570159X14666161130130718.

Neurotoxicity Induced by Mephedrone: An up-to-date Review.

Pantano F(1), Tittarelli R(1), Mannocchi G(1), Pacifici R(2), di Luca A(2),

Busardò FP(3), Marinelli E(1).

Author information:

(1)Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological,

Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome. Italy.

(2)Drug Abuse and Doping Unit, Department of Therapeutic Research and Medicines

Evaluation, Istituto Superiore di Sanità, Rome. Italy.

(3)Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological,

Forensic and Orthopedic Sciences, Sapienza University, Viale Regina Elena 336,

00161 Rome, Italy. Italy.

BACKGROUND: Mephedrone is a β-ketoamphetamine belonging to the family of

synthetic cathinones, an emerging class of designer drugs known for their

hallucinogenic and psychostimulant properties as well as for their abuse

potential.

OBJECTIVE: The aim of this review was to examine the emerging scientific

literature on the possible mephedrone-induced neurotoxicity, yet not well defined

due to the limited number of experimental studies, mainly carried on animal

models.

MATERIALS AND METHODS: Relevant scientific articles were identified from

international literature databases (Medline, Scopus, etc.) using the keywords:

"Mephedrone", "4-MMC," "neurotoxicity," "neuropharmacology", "patents",

"monoamine transporters" and "neurochemical effects".

RESULTS: Of the 498 sources initially found, only 36 papers were suitable for the

review. Neurotoxic effect of mephedrone on 5-hydroxytryptamine (5-HT) and

dopamine (DA) systems remains controversial. Although some studies in animal

models reported no damage to DA nerve endings in the striatum and no significant

changes in brain monoamine levels, some others suggested a rapid reduction in

5-HT and DA transporter function. Persistent serotonergic deficits were observed

after binge like treatment in a warm environment and in both serotonergic and

dopaminergic nerve endings at high ambient temperature. Oxidative stress

cytotoxicity and an increase in frontal cortex lipid peroxidation were also

reported. In vitro cytotoxic properties were also observed, suggesting that

mephedrone may act as a reductant agent and can also determine changes in

mitochondrial respiration. However, due to the differences in the design of the

experiments, including temperature and animal model used, the results are

difficult to compare.

CONCLUSIONS: Further studies on toxicology and pharmacology of mephedrone are

therefore necessary to establish an appropriate treatment for substance abuse and

eventual consequences for public health.

epub@benthamscience.org.

DOI: 10.2174/1570159X14666161130130718

PMCID: PMC5771050

PMID: 27908258 [Indexed for MEDLINE]

52. Prim Care Companion CNS Disord. 2016 Nov 3;18(6). doi: 10.4088/PCC.16m02002.

Clinical Course of Methamphetamine-Induced Psychotic Disorder in a 3-Month

Follow-Up.

Javadian S(1), Shabani A(2), Shariat SV(3)(2).

Author information:

(1)Department of Psychiatry, Iran University of Medical Sciences, Tehran, Iran.

(2)Mental Health Research Center, Tehran Institute of Psychiatry-School of

Behavioral Sciences and Mental Health, Iran University of Medical Sciences,

Tehran, Iran.

(3)Seyed Vahid Shariat, Mental Health Research Center, Tehran Institute of

Psychiatry-School of Behavioral Sciences and Mental Health, Mansouri Lane,

Niayesh Street, Sattarkhan Ave, Tehran, Iran. shariat.v@iums.ac.ir.

Objective: To assess the clinical course of patients with methamphetamine-induced

psychotic disorder (MIPD) and any possible predictors of the clinical course in a

3-month follow-up.

Methods: This prospective cohort study included 50 patients (7 female, 43 male)

with MIPD and was performed from September 2014 to October 2015. Patients were

assessed during hospitalization and in a follow-up visit 3 months later.

Diagnoses were made using interviews based on the Structured Clinical Interview

for DSM-IV Axis I Disorders. Positive, negative, manic, and depressive symptoms

were the main outcome measures that were assessed using the Scale for the

Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms,

Young Mania Rating Scale, and Hamilton Depression Rating Scale, respectively.

Paired t test and regression analysis were used to analyze the data.

Results: Forty-six patients (92%) were reassessed at follow-up. More than half of

the patients relapsed to methamphetamine use, did not adhere to treatment, and

were functionally impaired. Positive, negative, and manic symptoms, but not

depressive symptoms, improved in abstinent patients (P < .001, P = .001, P <

.001, and P = .395, respectively). The best predictor of depressive and negative

symptoms at follow-up was the patients' respective baseline scores; but positive

and manic symptoms were best predicted by reuse of methamphetamine during

follow-up.

Conclusions: Various symptom categories do not always change in the same

direction during the course of the disorder, especially depressive symptoms that

do not improve with abstinence but aggravate with frequency of methamphetamine

use. Negative symptoms at baseline also seem to have a possible role in

prediction of methamphetamine reuse in patients with MIPD. Physicians should be

advised to independently address all of the symptom categories of their patients

with MIPD at each follow-up visit.

DOI: 10.4088/PCC.16m02002

PMID: 27907276 [Indexed for MEDLINE]

53. Curr Top Behav Neurosci. 2017;32:209-230. doi: 10.1007/7854_2016_21.

Neurotoxicology of Synthetic Cathinone Analogs.

Angoa-Pérez M(1)(2), Anneken JH(3)(4), Kuhn DM(3)(4).

Author information:

(1)Research & Development Service, John D. Dingell VA Medical Center, Detroit,

MI, 48201, USA. maperez@med.wayne.edu.

(2)Department of Psychiatry and Behavioral Neurosciences, Wayne State University

School of Medicine, Detroit, MI, 48201, USA. maperez@med.wayne.edu.

(3)Research & Development Service, John D. Dingell VA Medical Center, Detroit,

MI, 48201, USA.

(4)Department of Psychiatry and Behavioral Neurosciences, Wayne State University

School of Medicine, Detroit, MI, 48201, USA.

The present review briefly explores the neurotoxic properties of methcathinone,

mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic

cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of

the commonly abused amphetamines and display pharmacological effects resembling

cocaine and amphetamines, but despite their commonalities in chemical structures,

synthetic cathinones possess distinct neuropharmacological profiles and produce

unique effects. Among the similarities of synthetic cathinones with their

non-keto analogs are their targeting of monoamine systems, the release of

neurotransmitters, and their stimulant properties. Most of the literature on

synthetic cathinones has focused on describing their properties as

psychostimulants, their behavioral effects on locomotion, memory, and potential

for abuse, whereas descriptions of their neurotoxic properties are not abundant.

The biochemical gauges of neurotoxicity induced by non-keto analogs are well

studied in humans and experimental animals and include their ability to induce

neuroinflammation, oxidative stress, excitotoxicity, temperature alterations as

well as dysregulation of neurotransmitter systems and induce changes in monoamine

transporters and receptors. These neurotoxicity gauges will serve as parameters

to discuss the effects of the four previously mentioned synthetic cathinones

alone or in combination with either another cathinone or with some of their

non-keto analogs. Bath salts are not a defined combination of drugs and may

consist of one synthetic cathinone compound or combinations of more cathinones.

Furthermore, this review also presents some of the mechanisms that are thought to

underlie this toxicity. A better understanding of the cellular and molecular

mechanisms involved in the synthetic cathinones-induced neurotoxicity should

contribute to generate modern therapeutic approaches to prevent or attenuate the

adverse consequences of use of these drugs in humans.

DOI: 10.1007/7854_2016_21

PMCID: PMC6100737

PMID: 27753008 [Indexed for MEDLINE]

54. J Psychiatr Pract. 2016 Sep;22(5):405-9. doi: 10.1097/PRA.0000000000000179.

Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of

Psychopharmacologic Issues.

Zhu Y(1), Kolawole T, Jimenez XF.

Author information:

(1)ZHU: Cleveland Clinic Lerner College of Medicine, Cleveland, OH KOLAWOLE and

JIMENEZ: Center for Behavioral Health, Cleveland Clinic, Cleveland, OH.

Bupropion is an atypical antidepressant that is structurally similar to

amphetamines. Its primary toxic effects include seizure, sinus tachycardia,

hypertension, and agitation; however, at higher amounts of ingestion, paradoxical

cardiac effects are seen. We report the case of a 21-year-old woman who ingested

13.5 g of bupropion, a dose higher than any other previously reported. The

patient presented with seizure, sinus tachycardia with prolonged QTc and QRS

intervals, dilated pupils, and agitation. Four days after overdose, the patient's

sinus tachycardia and prolonged QTc and QRS intervals resolved with symptomatic

management, but she soon developed sinus bradycardia, hypotension, and mild

transaminitis. With continued conservative management and close monitoring, her

sinus bradycardia resolved 8 days after the overdose. The transaminitis resolved

12 days after the overdose. Our findings are consistent with previously reported

toxic effects associated with common overdose amounts of bupropion. In addition,

we have observed transient cardiotoxicity manifesting as sinus bradycardia

associated with massive bupropion overdose. These findings are less frequently

reported and must be considered when managing patients with massive bupropion

overdose. We review the psychopharmacologic implications of this and comment on

previous literature.

DOI: 10.1097/PRA.0000000000000179

PMID: 27648505 [Indexed for MEDLINE]

55. Curr Top Behav Neurosci. 2017;32:1-18. doi: 10.1007/7854_2016_34.

The Growing Problem of New Psychoactive Substances (NPS).

Madras BK(1)(2).

Author information:

(1)Harvard Medical School, Department of Psychiatry, Boston, MA, USA.

bmadras@partners.org.

(2)Division of Alcohol and Drug Abuse, McLean Hospital, Oaks Building, Room 342,

115 Mill Street, Belmont, MA, 02478, USA. bmadras@partners.org.

The term "new psychoactive substances" (NPS) can be defined as individual drugs

in pure form or in complex preparations that are not scheduled under the Single

Convention on Narcotic Drugs (1961) or the Convention on Psychotropic Substances

(1971). NPS may be categorized by chemical structure, by psychoactive properties,

by biological targets, or by source (plant, synthetic, or combined). The

emergence of hundreds of NPS in the past decade is challenging for public health

and drug policies globally. The novelty of NPS, their ambiguous legal status,

ability to evade toxicological tests, swift adaptation to legal restrictions,

global Internet marketing, and scant public knowledge of their adverse effects

are among the key drivers of this twenty-first century phenomenon.

Multi-disciplinary research in areas of biology, epidemiology, prevention, and

web analytics are needed to develop effective responses in a domain capable of

overwhelming current international conventions and national drug control

policies. Ultimately, research-guided prevention education will fortify societies

against this tidal wave.

DOI: 10.1007/7854_2016_34

PMID: 27571747 [Indexed for MEDLINE]

56. BMC Psychiatry. 2016 Aug 18;16:293. doi: 10.1186/s12888-016-1002-7.

Psychosis associated with acute recreational drug toxicity: a European case

series.

Vallersnes OM(1)(2), Dines AM(3), Wood DM(3)(4), Yates C(5), Heyerdahl F(6),

Hovda KE(6), Giraudon I(7); Euro-DEN Research Group, Dargan PI(3)(4).

Collaborators: Anand J, Blake A, Chevillard L, Eyer F, Galicia M, Homar C,

Jürgens G, Liakoni E, Liechti ME, Markey G, Mégarbane B, Miro O, Moughty A,

O'Connor N, Paasma R, Pedersen C, Pöld K, Puiguriguer J, Sedefov R, Stenzel J,

Waldman W, Waring W.

Author information:

(1)Department of General Practice, University of Oslo, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

(2)Oslo Accident and Emergency Outpatient Clinic, City of Oslo Health Agency,

Oslo, Norway. o.m.vallersnes@medisin.uio.no.

(3)Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's

Health Partners, London, UK.

(4)Clinical Toxicology, Faculty of Life Sciences and Medicine, King's College

London, London, UK.

(5)Emergency Department and Clinical Toxicology Unit, Hospital Universitari Son

Espases, Mallorca, Spain.

(6)The Norwegian CBRNe Centre of Medicine, Oslo University Hospital, Oslo,

Norway.

(7)European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon,

Portugal.

Erratum in

BMC Psychiatry. 2016 Nov 16;16(1):405.

BACKGROUND: Psychosis can be associated with acute recreational drug and novel

psychoactive substance (NPS) toxicity. However, there is limited data available

on how common this is and which drugs are most frequently implicated. We describe

a European case series of psychosis associated with acute recreational drug

toxicity, and estimate the frequency of psychosis for different recreational

drugs.

METHODS: The European Drug Emergencies Network (Euro-DEN) collects data on

presentations to Emergency Departments (EDs) with acute recreational drug and NPS

toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through

September 2014 was retrospectively searched, and cases with psychosis were

included. The proportion of cases with psychosis per drug was calculated in the

searched Euro-DEN dataset.

RESULTS: Psychosis was present in 348 (6.3 %) of 5529 cases. The median

(interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114

(32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were

cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1

%). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in

those ED presentations involving tryptamines (4/7; 57.1 %),

methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %),

lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8

%), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine

(87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %),

methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3

%). Amphetamine was the most frequent drug associated with psychosis when only

one agent was reported, with psychosis occurring in 32.4 % of these

presentations.

CONCLUSION: The frequency of psychosis in acute recreational drug toxicity varies

considerably between drugs, but is a major problem in amphetamine poisoning. In

rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network

contributes to measuring the scale of drug-related harms in Europe beyond other

more established indicators.

DOI: 10.1186/s12888-016-1002-7

PMCID: PMC4990880

PMID: 27538886 [Indexed for MEDLINE]

57. J Crit Care. 2016 Oct;35:29-32. doi: 10.1016/j.jcrc.2016.04.022. Epub 2016 Apr

30.

Opioid overdose leading to intensive care unit admission: Epidemiology and

outcomes.

Pfister GJ(1), Burkes RM(1), Guinn B(2), Steele J(1), Kelley RR(2), Wiemken

TL(2), Saad M(1), Ramirez J(2), Cavallazzi R(1).

Author information:

(1)Division of Pulmonary, Critical Care and Sleep Medicine, University of

Louisville, Louisville, KY.

(2)Division of Infectious Diseases, University of Louisville, Louisville, KY.

Comment in

J Crit Care. 2017 Feb;37:259-260.

PURPOSE: There is a scarcity of studies assessing the patient population admitted

to the intensive care unit (ICU) with opioid overdose. We sought to characterize

the epidemiologic features and outcomes of this patient population.

MATERIALS AND METHODS: This is a retrospective cohort study of adult patients

admitted to the ICU at University of Louisville Hospital for opioid overdose. We

reviewed each patient's hospital record for demographic data, comorbidities,

opioid used, coingestions, and outcomes.

RESULTS: We included 178 adult patients, of which 107 (60%) were females. The

median age was 41 years (interquartile range [IQR], 23). Oxycodone and

hydrocodone were the 2 most commonly abused opioids. Benzodiazepines were the

most common drug coingested, followed by amphetamines. Tobacco smoking, chronic

pain, and alcoholism were the most frequent comorbidities identified. Mental

disorders were also common. Most patients required invasive mechanical

ventilation (84.8%). Median ICU length of stay was 3 days. Eighteen patients

(10.1%) died in the hospital, whereas 6 patients (3.4%) were discharged to a

nursing home. Patients who had any coingestion were significantly more likely to

undergo invasive mechanical ventilation (91% vs 77%; P=.014) and had longer ICU

length of stay (3 [IQR, 2] vs 2 [IQR, 1.8] days; P=.024).

CONCLUSION: Opioid overdose is a common cause of ICU admission and affects a

relatively young population. Most have respiratory failure requiring mechanical

ventilation. It is associated with a relatively high inhospital mortality.

Coingestions appear to have an impact on outcomes.

DOI: 10.1016/j.jcrc.2016.04.022

PMID: 27481733 [Indexed for MEDLINE]

58. Clin Neuropharmacol. 2016 Sep-Oct;39(5):272-5. doi: 10.1097/WNF.0000000000000166.

A Case of Disulfiram-Induced Psychosis in a Previously Asymptomatic Patient

Maintained on Mixed Amphetamine Salts: A Review of the Literature and Possible

Pathophysiological Explanations.

Spiegel DR(1), McCroskey A, Puaa K, Meeker G, Hartman L, Hudson J, Hung YC.

Author information:

(1)Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical

School, Norfolk, VA.

Although perhaps better known as an irreversible aldehyde dehydrogenase inhibitor

causing increased acetaldehyde levels after concomitant intake of ethanol,

disulfiram or one of its metabolites (diethyldithiocarbamate) also inhibit

dopamine β-hydroxylase, an enzyme that converts dopamine to norepinephrine. This

mechanism has been advanced as a possible explanation for the development of

psychosis, during disulfiram treatment, either in monotherapy or in combination

therapy, when interaction-emergent psychosis could be causal. We present a young

woman who was taking mixed amphetamine salts for treatment of

attention-deficit/hyperactivity disorder and developed a short-lived psychosis

after introduction of disulfiram. The psychotic symptoms resolved after

discontinuation of both medications, without the use of antipsychotic drugs. We

proceed with a review of the literature of disulfiram-induced psychosis and

discuss pathophysiological theories that possibly were involved in our patient's

phenomenology.

DOI: 10.1097/WNF.0000000000000166

PMID: 27466724 [Indexed for MEDLINE]

59. Clin Toxicol (Phila). 2017 Jan;55(1):51-54. doi: 10.1080/15563650.2016.1209764.

Epub 2016 Jul 22.

Near death from a novel synthetic opioid labeled U-47700: emergence of a new

opioid class.

Schneir A(1)(2), Metushi IG(3), Sloane C(2), Benaron DJ(2), Fitzgerald RL(3).

Author information:

(1)a Division of Medical Toxicology , University of California, San Diego Health

System , San Diego , CA , USA.

(2)b Department of Emergency Medicine , University of California, San Diego

Health System , San Diego , CA , USA.

(3)c Department of Pathology, Center for Advanced Laboratory Medicine ,

University of California, San Diego Health System , San Diego , CA , USA.

Comment in

Clin Toxicol (Phila). 2017 Jan;55(1):73.

BACKGROUND: In the last decade there has been a worldwide surge in the

recreational abuse of novel psychoactive substances, particularly amphetamine

derivatives and synthetic cannabinoids. Synthetic opioids such as AH-7921, MT-45,

and U-47700, with structures distinct from those ever used therapeutically or

described recreationally, have also recently emerged.

CASE DETAILS: We report a patient who suffered respiratory failure and depressed

level of consciousness after recreationally using a novel synthetic opioid

labeled U-47700. A single dose of naloxone administered by paramedics completely

reversed his opioid poisoning. Comprehensive laboratory analysis confirmed the

presence of a novel synthetic opioid and excluded other drugs. The drug used

appeared to have caused a false positive benzodiazepine result on the initial

urine drugs of abuse panel.

CONCLUSION: The case we describe of toxicity from the synthetic opioid labeled

U-47700 highlights the emerging trend of novel synthetic opioid abuse.

DOI: 10.1080/15563650.2016.1209764

PMID: 27448790 [Indexed for MEDLINE]

60. J Anal Toxicol. 2016 Sep;40(7):553-60. doi: 10.1093/jat/bkw061. Epub 2016 Jul 11.

Reporting Two Fatalities Associated with the Use of 4-Methylethcathinone (4-MEC)

and a Review of the Literature.

Smith PR(1), Cole R(1), Hamilton S(2), West K(3), Morley SR(1), Maskell PD(4).

Author information:

(1)Forensic Toxicology Unit, Department of Chemical Pathology and Metabolic

Medicine, University Hospitals of Leicester, Leicester Royal Infirmary Leicester,

LE1 5WW, UK.

(2)East Midlands Forensic Pathology Unit, University of Leicester, Robert

Kilpatrick Building, Leicester LE2 7LX, UK.

(3)Department of Histopathology, University Hospitals of Leicester, Leicester

Royal Infirmary, Leicester LE1 5WW, UK.

(4)Department of Chemical and Forensic Sciences, School of Applied Sciences,

University of Huddersfield, Huddersfield HD1 3DH, UK p.d.maskell@hud.ac.uk.

We report two fatalities that are related to the cathinone

4-methylethcathinone (4-MEC) and review the current knowledge of 4-MEC.

Qualitative and quantitative analysis of 4-MEC was performed by validated high

performance liquid chromatography-tandem mass spectrometry methods. In the first

case a 22-year-old male died in hospital following collapse and seizures after

using 4-MEC. Toxicological analysis of postmortem femoral blood revealed the

presence of 4-MEC (0.167 mg/L), ethanol (27 mg/100 mL) and paracetamol (5 mg/L).

Death was attributed solely to 4-MEC toxicity. The second case involved a

54-year-old man found with a taped plastic bag over his head. Toxicological

analysis of postmortem femoral blood revealed the presence of 4-MEC (1.73 mg/L)

along with ethanol (229 mg/100 mL), propranolol (0.036 mg/L), venlafaxine (0.284

mg/L) and its metabolite O-desmethylvenlafaxine (0.205 mg/L), and diazepam

(<0.005 mg/L) and its metabolite nordiazepam (0.033 mg/L). Death was attributed

primarily to asphyxiation. These cases and a review of the current knowledge of

4-MEC pharmacology/toxicology adds to the body of case material for 4-MEC and

will assist with interpretation in postmortem toxicology cases in which 4-MEC is

detected.

Permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/jat/bkw061

PMID: 27405367 [Indexed for MEDLINE]

61. J Anal Toxicol. 2016 Sep;40(7):546-52. doi: 10.1093/jat/bkw058. Epub 2016 Jul 11.

Fatal Combination with 3-Methylmethcathinone (3-MMC) and Gamma-Hydroxybutyric

Acid (GHB).

Jamey C(1), Kintz P(2), Martrille L(3), Raul JS(2).

Author information:

(1)Laboratoire de Toxicologie, Institut de Médecine légale, 11 rue Humann, 67000

Strasbourg, France c.jam@laposte.net.

(2)Laboratoire de Toxicologie, Institut de Médecine légale, 11 rue Humann, 67000

Strasbourg, France.

(3)Institut de Médecine Légale, Rue du Morvan, 54511 Vandoeuvre-les-Nancy,

France.

We reported the case of 69-year-old man who was discovered dead at a friend's

home. 3-Methylmethcathinone (3-MMC) and poppers (alkyl nitrites) were found at

the scene by the police. Autopsy specimens including peripheral and cardiac

blood, urine, gastric content, bile and hair were sent to our laboratory to

document a possible death involving abuse of drugs. Routine toxicological

analysis was performed with gas chromatography with flame ionization detection

(GC-FID), high performance liquid chromatography-diode array detection

(HPLC-DAD), headspace gas chromatography-mass spectrometry (HS-GC-MS), gas

chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass

spectrometry (LC-MS)-MS. After liquid-liquid extraction at alkaline pH, 3-MMC was

identified with GC-MS (to allow the discrimination with 4-MMC) and quantified

with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-MS with

the two following transitions: m/z 178.1 > 160 and 178.1 > 144.9.

Gamma-hydroxybutyric acid (GHB) was analyzed by GC-MS for fluids and GC-MS-MS for

hair. Toxicological analysis in peripheral blood revealed the presence of 3-MMC

(0.33 mg/L), pseudoephedrine (0.03 mg/L) and GHB (576 mg/L). These molecules have

also been found in other post-mortem fluids. Furthermore, testing for "poppers"

by HS-GC-MS was negative. Hair analysis, without segmentation, demonstrated the

presence of 3-MMC (206.7 ng/mg), pseudoephedrine (0.16 ng/mg) and GHB (96.3

ng/mg) and suggested a repeated consumption of these substances. However, one

cannot exclude contamination by sweat during the agony period. Toxicological

post-mortem results suggest a fatal combination of 3-MMC and GHB. Despite his

age, the decedent was known to abuse drugs.

Permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/jat/bkw058

PMID: 27405362 [Indexed for MEDLINE]

62. Forensic Sci Int. 2016 Sep;266:e27-e31. doi: 10.1016/j.forsciint.2016.06.030.

Epub 2016 Jun 28.

A fatal case of paramethoxyamphetamine poisoning and its detection in hair.

Jang M(1), Yang W(2), Jeong S(2), Park S(2), Kim J(2).

Author information:

(1)National Forensic Service, 139 Jiyang-ro, Yangcheon-Gu, Seoul 158-707,

Republic of Korea. Electronic address: jmh1229@korea.kr.

(2)National Forensic Service, 139 Jiyang-ro, Yangcheon-Gu, Seoul 158-707,

Republic of Korea.

Paramethoxyamphetamine (PMA) is a phenethylamine derivative that is structurally

related to 3,4-methylenedioxymethamphetamine (MDMA), but has higher toxicity than

MDMA. Here, we report a fatal intoxication case involving PMA. A 36-year-old man

was found dead in a hotel room. Toxicological analysis revealed that PMA

concentrations were 0.57 and 0.59mg/L in peripheral and heart blood,

respectively. Ketamine and diazepam were also detected in his blood. Based on

toxicological results and autopsy findings, the cause of death was determined to

be acute fatal intoxication with PMA. Hair analysis using gas chromatography/mass

spectrometry was performed and PMA was detected at a concentration of 20.1ng/mg

after methanol extraction for 20h. This is the first report of the determination

of PMA concentration in the hair from a drug abuser.

DOI: 10.1016/j.forsciint.2016.06.030

PMID: 27396905 [Indexed for MEDLINE]

63. Psychosomatics. 2016 Sep-Oct;57(5):534-9. doi: 10.1016/j.psym.2016.05.002. Epub

2016 May 10.

Complexities of Diagnosing Neuroleptic Malignant Syndrome in a Patient with Burn

Injury: Could Stimulant Abuse be a Risk Factor?

Laughon SL(1), Sowa NA(2), Gala GJ(3).

Author information:

(1)University of North Carolina School of Medicine, Chapel Hill, NC. Electronic

address: sarah_laughon@med.unc.edu.

(2)University of North Carolina Hospitals, Chapel Hill, NC.

(3)University of North Carolina School of Medicine, Chapel Hill, NC.

DOI: 10.1016/j.psym.2016.05.002

PMID: 27374755 [Indexed for MEDLINE]

64. Arch Pediatr. 2016 Aug;23(8):820-2. doi: 10.1016/j.arcped.2016.05.010. Epub 2016

Jun 23.

[Accidental amphetamine poisoning in an 11-month-old boy].

[Article in French]

Fogel S(1), Lesage F(2), Cheron G(3).

Author information:

(1)Service des urgences pédiatriques, hôpital Necker Enfants Malades, 149, rue de

Sèvres, 75015 Paris, France. Electronic address: stephanie.fogel@nck.aphp.fr.

(2)Service de réanimation polyvalente pédiatrique, hôpital Necker Enfants

Malades, 149, rue de Sèvres, 75015 Paris, France.

(3)Service des urgences pédiatriques, hôpital Necker Enfants Malades, 149, rue de

Sèvres, 75015 Paris, France; Université Paris Descartes, Paris, France.

INTRODUCTION: In France, the use of illicit drugs is increasing and therefore

accidental poisoning may occur in infants and children. We report on a case of

ecstasy poisoning in an infant who presented with atypical neurological symptoms.

CASE REPORT: An 11-month-old infant suddenly developed agitation with eye rolling

and unreactive bilateral mydriasis. All neurologic causes were excluded. The

search for toxicants revealed an intoxication with an amphetamine and MDMA.

Progression was favorable in 24h.

CONCLUSION: Although rare, pediatric intoxications by ecstasy have become more

common in recent years, due to its consumption within households, exposing young

children and infants to accidental ingestion of a tablet of ecstasy.

DOI: 10.1016/j.arcped.2016.05.010

PMID: 27345557 [Indexed for MEDLINE]

65. Am J Drug Alcohol Abuse. 2016 Sep;42(5):520-529. Epub 2016 Jun 9.

Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics

and autopsy findings.

Ezaki J(1), Ro A(1), Hasegawa M(1), Kibayashi K(1).

Author information:

(1)a Department of Legal Medicine, School of Medicine , Tokyo Women's Medical

University , Tokyo , Japan.

BACKGROUND: Sixty-one autopsy cases involving cathinones and/or cannabinoids

(synthetic cathinones/cannabinoids) use have been reported. However, little is

known about the demographics and autopsy findings in fatal synthetic

cathinones/cannabinoids users.

OBJECTIVES: To elucidate demographic and autopsy findings (i.e. major organ

pathology and causes of death) in synthetic cathinones/cannabinoids cases.

METHODS: We reviewed forensic autopsy reports in Department of Legal Medicine of

Tokyo Women's Medical University (Tokyo, Japan) between 2011 and 2015 (a total of

359). We compared demographic and autopsy findings between synthetic

cathinones/cannabinoids and methamphetamine cases (as control subjects).

RESULTS: There were 12 synthetic cathinones/cannabinoids cases and 10

methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly

younger than methamphetamine users (p < 0.01), and there were no cases that used

both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication

and cardiac ischemia were the two most prominent causes of death in both

synthetic cathinones/cannabinoids users and methamphetamine users. Excited

delirium syndrome and pulmonary aspiration were found only in synthetic

cathinones/cannabinoids cases.

CONCLUSIONS: The populations of synthetic cathinones/cannabinoids and

methamphetamine users who died of an overdose are different in Japan. Acute

intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration,

and drowning are the major autopsy findings in synthetic

cathinones/cannabinoids-related death. Clinicians shuld be aware of these

potentially fatal complications in the medical management of synthetic

cathinones/cannabinoids users.

DOI: 10.3109/00952990.2016.1172594

PMID: 27283516 [Indexed for MEDLINE]

66. Iran Red Crescent Med J. 2016 Apr 9;18(4):e35483. doi: 10.5812/ircmj.35483.

eCollection 2016 Apr.

Survey on Hypothermia and Hyperthermia in Poisoned Patients in a Unique Referral

Hospital, Tehran, Iran.

Mozafari N(1), Talaie H(2), Shoaei SD(3), Hashemian M(4), Mahdavinejad A(2).

Author information:

(1)Plastic Surgery Department, 15 Khordad Hospital, Shahid Beheshti University of

Medical Sciences, Tehran, IR Iran.

(2)Toxicological Research Center, Department of Clinical Toxicology,

Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran,

IR Iran.

(3)Clinical Research and Development Center, Imam Hossein Hospital, Shahid

Beheshti University of Medical Sciences, Tehran, IR Iran.

(4)Department of Anesthesiology and Pain Medicine, Bahonar Hospital, Kerman

University of Medical Sciences, Kerman, IR Iran.

BACKGROUND: Body temperature is a critical criterion of health. Drugs and a

variety of poisons can affect body temperature in poisoned patients, causing

hyperthermia and hyperpyrexia.

OBJECTIVES: Our previous study's findings in patients poisoned with

organophosphate led us to the goal of this study: obtaining the initial tympanic

temperature in patients poisoned by a variety of toxins.

MATERIALS AND METHODS: A cross-sectional study reviewed the records of poisoned

patients who were admitted to the toxicological intensive care unit (TICU) at

Loghman Hakim hospital poison center (LHHPC) from February 2014 to February 2015.

The data collected included gender, age, type of poisoning, the season during

which poisoning occurred, vital signs, initial tympanic temperature (first four

hours), presence of seizures, white blood cell (WBC) count, creatinine

phosphokinase (CPK), length of stay and patient outcome. We determined the mean

(SD) for normally distributed continuous variables, the median and interquartile

range for non-normally distributed continuous variables, and the absolute and

relative frequency (%) for categorical variables. All were determined using SPSS

version 16.

RESULTS: Data were collected from 310 eligible patients. The mean patient age was

32.65 (with a standard deviation of 14.40). Of the patients in the study, 183

(59%) were male. Intentional poisoning in an attempted suicide was documented in

253 (81.6%) patients. The most prevalent poisoning agent was aluminum phosphate

(18.70%), followed by methadone (10%) and opium (10%). Seventy percent of the

patients (n = 217) were diagnosed and classified with fever or hyperthermia. A

temperature ≥ 40°C was detected in just three cases. The highest mean temperature

was found in patients poisoned with amphetamine, organophosphate and tramadol.

Patients with alcohol and phenobarbital poisoning were included in the sample,

but these patients were not diagnosed with hypothermia. WBC ≥ 10,000 cells/mL and

CPK ≥ 975 IU/L were recorded in 57.7% and 13.2% of subjects, respectively.

CONCLUSIONS: Body temperature changes in human poisonings are a matter in need of

special attention. A literature review did not reveal any controversy over

hypothermia, but poisoning cases exhibit a variety of patterns of fever and

hyperthermia. If there are no limits to the diagnosis of fever and hyperthermia,

all cases with a poor prognosis which fail to respond to treatment could be

categorized as drug-induced hyperthermia. Therefore, a different approach is

needed for poisoning cases.

DOI: 10.5812/ircmj.35483

PMCID: PMC4893414

PMID: 27275403

67. Ugeskr Laeger. 2016 May 16;178(20). pii: V02160124.

[Hepatitis after chewing of khat leaves].

[Article in Danish]

Teisen E, Vainer B, Ytting H(1).

Author information:

(1)henriette.ytting@regionh.dk.

Chewing of leaves from the Catha edulis (khat) plant has amphetamine-like,

stimulating effects and is used in rituals among East African men. In recent

years, a possible liver-toxic effect has been observed in Somali immigrants in

Western countries and has in severe cases led to death or liver transplantation.

It is discussed whether the liver insufficiency represents a severe ethnic

variant of autoimmune hepatitis, or a khat-induced hepatitis with autoimmune

features. We describe six patients with Somalian background and possibly

khat-induced toxic hepatitis.

PMID: 27189105 [Indexed for MEDLINE]

68. Curr Opin Psychiatry. 2016 Jul;29(4):236-41. doi: 10.1097/YCO.0000000000000254.

Psychosis induced by amphetamines.

Bramness JG(1), Rognli EB.

Author information:

(1)aNorwegian Centre for Addiction Research (SERAF), University of Oslo bDivision

of Mental Health and Addiction, Oslo University Hospital, Oslo cNorwegian

National Advisory Unit on Concurrent Substance Abuse and Mental Health Disorders,

Brumunddal, Norway.

PURPOSE OF REVIEW: The study reviews publications on the use of methamphetamine

and amphetamine in relation to psychotic symptoms, substance-induced psychosis,

and primary psychosis published between July 2014 and December 2015. The

databases MEDLINE, Embase, and PsycINFO were searched using the terms

'amphetamine psychosis' and 'methamphetamine psychosis' for the time period 1

July 2014 to 31 December 2015.

RECENT FINDINGS: There were 37 studies published on the subject during this time

period. Risk factors for psychotic symptoms, substance-induced psychosis, and

primary psychosis included patterns of drug use, but results also pointed to the

importance of nondrug-related vulnerability. Cognitive impairment is associated

with both amphetamine use and psychosis, and the impairment among those with

amphetamine-induced psychosis resembles that of schizophrenia. At the neuronal

level, GABAergic mechanisms may offer some understanding about the association

between stimulant use and psychosis. Several different types of antipsychotic

medication are effective for treating agitation and psychosis, but drugs with

high DRD2 blockade should be used with caution. Some novel treatments are

described, but are not sufficiently repeated to be recommended.

SUMMARY: During the past 18 months, studies have been published that cover risk

factors, neuronal mechanisms, and treatment. These recent results do not differ

from previous understandings, but the role of cognition and GABAergic dysfunction

should be further investigated, and knowledge about resilience factors is still

scarce. Also, a clearer evidence base for medical treatment of psychosis with

concurrent amphetamine use is warranted. VIDEO ABSTRACT.

DOI: 10.1097/YCO.0000000000000254

PMID: 27175554 [Indexed for MEDLINE]

69. Psychiatry Res. 2016 Jun 30;240:431-434. doi: 10.1016/j.psychres.2016.04.053.

Epub 2016 Apr 21.

Demographic and mental history-related data predicted occurrence of psychosis in

metamphetamine users.

Farnia V(1), Shakeri J(1), Tatari F(1), Juibari TA(1), Bajoghli H(2), Golshani

S(1), Hookari S(1), Holsboer-Trachsler E(3), Brand S(4).

Author information:

(1)Substance Abuse Prevention Research Center, Psychiatry Department, Kermanshah

University of Medical Sciences, Kermanshah, Iran.

(2)Iranian National Center for Addiction Studies (INCAS), Tehran University of

Medical Sciences, Tehran, Iran.

(3)Psychiatric Clinics of the University of Basel, Center for Affective, Stress

and Sleep Disorders, Basel, Switzerland.

(4)Psychiatric Clinics of the University of Basel, Center for Affective, Stress

and Sleep Disorders, Basel, Switzerland; Department of Sport, Exercise and

Health, Sport Science Section, Faculty of Medicine, University of Basel, Basel,

Switzerland. Electronic address: serge.brand@upkbs.ch.

Methamphetamine use is increasing worldwide, and the occurrence of psychosis

further complicates treatment. This holds also true for Iran. The aim of the

present study was to investigate possible predictors of metamphetamine-induced

psychosis. 237 methamphetamine users (70.9% with psychosis; mean age: M=33.41

years) took part in the study. A psychiatric interview was performed covering

socio-demographic and illness-related information. Male gender, low education,

unemployment, being single, a history of mental disorders, and a higher number of

previous hospitalizations predicted the occurrence of psychosis, while age and

duration of metamphetamine use were excluded from the equation. Socio-demographic

and mental illness-related dimension seemed suitable to predict occurrence of

psychosis among metamphetamine abusers.

DOI: 10.1016/j.psychres.2016.04.053

PMID: 27172885 [Indexed for MEDLINE]

70. Leg Med (Tokyo). 2016 May;20:23-6. doi: 10.1016/j.legalmed.2016.03.007. Epub 2016

Mar 14.

Drug-related deaths with evidences of body packing: Two case reports and

medico-legal issues.

Cappelletti S(1), Aromatario M(2), Bottoni E(2), Fiore PA(2), Straccamore M(2),

Umani Ronchi F(2), De Mari GM(2), Ciallella C(2).

Author information:

(1)Legal Medicine Section - SAIMLAL Department, SAPIENZA University of Rome,

Viale Regina Elena, 336, 00161 Roma, Italy. Electronic address:

simone.cappelletti@uniroma1.it.

(2)Legal Medicine Section - SAIMLAL Department, SAPIENZA University of Rome,

Viale Regina Elena, 336, 00161 Roma, Italy.

Body packing is a general term used to indicate the internal transportation of

drug packages, mainly cocaine, heroin, amphetamines, and methamphetamine, within

the gastrointestinal tract. We described two cases of accidental drug

intoxication, observed over the last year period, with evidence of intracorporeal

drug concealment. The first case concerned a body packer transporting 69 drug

packages of heroin adulterated with piracetam. The second body packer transported

16 drug packages of cocaine adulterated with levamisole. For both cases, forensic

examination and toxicological analysis of drug packages and biological samples

were carried out. Authors also wants to highlight the main medico-legal issues

that commonly arise in cases of suspected or ascertained body packers.

DOI: 10.1016/j.legalmed.2016.03.007

PMID: 27161917 [Indexed for MEDLINE]

71. Ann Emerg Med. 2017 Jan;69(1):79-82. doi: 10.1016/j.annemergmed.2016.03.042. Epub

2016 May 4.

Acute Toxicity Associated With the Recreational Use of the Novel Psychoactive

Benzofuran N-methyl-5-(2 aminopropyl)benzofuran.

Hofer KE(1), Faber K(2), Müller DM(3), Hauffe T(4), Wenger U(4), Kupferschmidt

H(2), Rauber-Lüthy C(2).

Author information:

(1)National Poisons Centre, Tox Info Suisse, Associated Institute of the

University of Zurich, Zurich, Switzerland. Electronic address:

katharina.hofer@toxinfo.ch.

(2)National Poisons Centre, Tox Info Suisse, Associated Institute of the

University of Zurich, Zurich, Switzerland.

(3)Institute for Clinical Chemistry, University Hospital Zurich, Zurich,

Switzerland.

(4)Division of Medical Intensive Care Unit, University Hospital Zurich, Zurich,

Switzerland.

N-methyl-5-(2 aminopropyl)benzofuran (5-MAPB) is a novel psychoactive benzofuran,

created by N-methylation of 5-(2-aminopropyl)benzofuran (5-APB), which shares

structural features with methylenedioxymethamphetamine (MDMA). To our knowledge,

no case of 5-MAPB-related toxicity has been published in the scientific

literature. We report a case of oral 5-MAPB exposure confirmed by liquid

chromatography-tandem mass spectrometry in a 24-year-old previously healthy white

man. Observed symptoms and signs such as paleness, cold and clammy skin,

hypertension, elevated high-sensitive troponin T level, tachycardia, ECG change,

diaphoresis, mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus,

agitation, disorientation, hallucinations, convulsions, reduced level of

consciousness, and creatine kinase level elevation (305 IU/L) were compatible

with undesired effects related to 5-APB or MDMA exposure. Signs and symptoms

resolved substantially within 14 hours with aggressive symptomatic treatment,

including sedation with benzodiazepines, external cooling, analgesia and sedation

with fentanyl-propofol, and treatment with urapidil, an α-receptor-blocking

agent. 5-MAPB showed first-order elimination kinetics with a half-life of 6.5

hours, comparable to the half-life of MDMA. According to the chemical structure,

this case report, and users' Web reports, 5-MAPB appears to have an acute

toxicity profile similar to that of 5-APB and MDMA, with marked vasoconstrictor

effect.

DOI: 10.1016/j.annemergmed.2016.03.042

PMID: 27156124 [Indexed for MEDLINE]

72. J Forensic Sci. 2016 May;61(3):735-42. doi: 10.1111/1556-4029.12999. Epub 2016

Mar 30.

Manners of Death in Drug-Related Fatalities in Florida.

Lee D(1), Delcher C(2), Maldonado-Molina MM(2), Thogmartin JR(3), Goldberger

BA(1).

Author information:

(1)UF Health Pathology Laboratories, Department of Pathology, Immunology and

Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL.

(2)Department of Health Outcomes and Policy, Institute for Child Health Policy,

University of Florida College of Medicine, Gainesville, FL.

(3)District Six Medical Examiner's Office, Largo, FL.

To understand the mortality patterns among drug users and potential risk factors,

we evaluated drug-related deaths reported to the Florida Medical Examiners

Commission from 2001 to 2013, by substances, demographics, and manner of death.

The annual drug-related fatalities increased by 57% from 2001 to 2013 (total n =

100,882); 51.8% were accidental, 7.9% homicide, 18.6% natural, and 19.6% suicide.

The different manners of death exhibited distinct demographic profiles and drug

composition. The gender gap was more prominent in homicide. Age ≥55 years was

more closely associated with natural death and suicide. Age <35 years and central

nervous system (CNS) stimulants including amphetamines and cocaine showed higher

relative risks for accidental death and homicide, whereas CNS depressants

including benzodiazepines, carisoprodol, opioids, and zolpidem were more strongly

associated with accidental death and/or suicide. The findings aid in identifying

populations more vulnerable to drug-related deaths, developing targeted

interventions and thereby improving efficiency of preventive efforts.

DOI: 10.1111/1556-4029.12999

PMID: 27122413 [Indexed for MEDLINE]

73. Pediatr Emerg Care. 2017 Sep;33(9):e55-e57. doi: 10.1097/PEC.0000000000000788.

Methylphenidate Overdose Causing Secondary Polydipsia and Severe Hyponatremia in

an 8-Year-Old Boy.

Patel V(1), Krishna AS, Lefevre C, Kaagaza M, Wittkamp M.

Author information:

(1)From the *Department of Pediatrics, University of Kentucky School of Medicine;

†Department of Pediatrics, Division of Pediatric Critical Care, University of

Kentucky School of Medicine; ‡University of Kentucky School of Medicine,

Lexington, KY.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is an increasingly

common diagnosis of childhood that manifests with symptoms that affect cognitive,

academic, behavioral, emotional, and social functioning. There are a multitude of

pharmaceutical therapies to choose from when managing this condition, and though

many studies on the safety and efficacy of these medications have been published,

adverse effects still occur.

CASE: This case discusses a previously healthy 8-year-old boy who had been

prescribed 20-mg lisdexamfetamine dimesylate for ADHD however mistakenly took his

brother's 36-mg methylphenidate extended-release tablets, resulting in

hyperhidrosis, excessive thirst, polydipsia, and combative behavior that began

within 3 hours of ingestion. He was evaluated at a community hospital emergency

department and given lorazepam due to agitation and combativeness before

discharge. However, he returned with hypothermia, hyponatremia, and status

epilepticus resulting in intubation. Patient was transferred to our facility

where a computer tomography of his head was negative and hyponatremia was

corrected with 3% NaCl saline solution. A lumbar puncture was performed due to

temperature instability before starting broad-spectrum antibiotics. Cerebrospinal

fluid findings were normal, and he was extubated at 18 hours postingestion.

Patient was discharged home after 3 days with no residual symptoms.

DISCUSSION/CONCLUSIONS: Though both lisdexamfetamine dimesylate and

methylphenidate are widely used among pediatricians today for treatment of ADHD,

reports of life-threatening water intoxication as a result of overdose is rare.

Studies have reported that severe 3,4-methylenedioxymethamphtamine toxicity in

adults is associated with syndrome of inappropriate diuretic hormone (SIADH)

secretion, hyponatremia, and seizures, along with serotonin-induced transient

elevation in antidiuretic hormone. Adult schizophrenics who receive

psychostimulants have also been shown to develop polydipsia with hyponatremia.

Although the use of psychostimulants in adult schizophrenic patients has been

studied, literature on toxicity and effects in the pediatric psychiatric

population is scarce. We would suggest that this patient's polydipsia and

hyponatremia are most likely a result of his ingestion of a toxic dose of a

long-acting agent known to cause secondary psychosis.

DOI: 10.1097/PEC.0000000000000788

PMCID: PMC5592986

PMID: 27115479 [Indexed for MEDLINE]

74. Psychiatry Res. 2016 Apr 30;238:166-171. doi: 10.1016/j.psychres.2016.02.038.

Epub 2016 Feb 18.

Correlates of transient versus persistent psychotic symptoms among dependent

methamphetamine users.

McKetin R(1), Gardner J(2), Baker AL(3), Dawe S(4), Ali R(5), Voce A(2), Leach

LS(2), Lubman DI(6).

Author information:

(1)National Drug Research Institute, Faculty of Health Sciences, Curtin

University, Perth, Australia; Centre for Research on Ageing, Health and

Well-being, the Australian National University, Canberra, Australia; National

Drug and Alcohol Research Centre, University of New South Wales, Sydney,

Australia. Electronic address: rebecca.mcketin@curtin.edu.au.

(2)Centre for Research on Ageing, Health and Well-being, the Australian National

University, Canberra, Australia.

(3)Priority Research Centre for Translational Neuroscience and Mental Health,

University of Newcastle, Callaghan, Australia.

(4)School of Applied Psychology, Menzies Health Institute Queensland, Griffith

University, Brisbane, Australia.

(5)University of Adelaide, Adelaide, Australia.

(6)Turning Point, Eastern Health and Monash University, Melbourne, Australia.

This study examined correlates of transient versus persistent psychotic symptoms

among people dependent on methamphetamine. A longitudinal prospective cohort

study of dependent methamphetamine users who did not meet DSM-IV criteria for

lifetime schizophrenia or mania. Four non-contiguous one-month observation

periods were used to identify participants who had a) no psychotic symptoms,

(n=110); (b) psychotic symptoms only when using methamphetamine (transient

psychotic symptoms, n=85); and, (c) psychotic symptoms both when using

methamphetamine and when abstaining from methamphetamine (persistent psychotic

symptoms, n=37). Psychotic symptoms were defined as a score of 4 or greater on

any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations

or unusual thought content. Relative no psychotic symptoms, both transient and

persistent psychotic symptoms were associated with childhood conduct disorder and

comorbid anxiety disorders. Earlier onset methamphetamine use and being male were

more specifically related to transient psychotic symptoms, while a family history

of a primary psychotic disorder and comorbid major depression were specifically

related to persistent psychotic symptoms. We conclude that there are overlapping

but also distinct clinical correlates of transient versus persistent psychotic

symptoms, suggesting potentially heterogeneous etiological pathways underpinning

the psychotic phenomena seen amongst people who use methamphetamine.

DOI: 10.1016/j.psychres.2016.02.038

PMID: 27086229 [Indexed for MEDLINE]

75. Neurosci Lett. 2016 May 27;622:37-44. doi: 10.1016/j.neulet.2016.04.019. Epub

2016 Apr 11.

Association study of GABA system genes polymorphisms with amphetamine-induced

psychotic disorder in a Han Chinese population.

Zhang K(1), Zhao Y(2), Wang Q(2), Jiang H(2), Du J(2), Yu S(3), Zhao M(4).

Author information:

(1)Shanghai Mental Health Center, Shanghai Jiao Tong University School of

Medicine, 200030, Shanghai, China; Wuxi Mental Health Center, Nanjing Medical

University, 214151, Wuxi, China.

(2)Shanghai Mental Health Center, Shanghai Jiao Tong University School of

Medicine, 200030, Shanghai, China.

(3)Shanghai Mental Health Center, Shanghai Jiao Tong University School of

Medicine, 200030, Shanghai, China. Electronic address: yushuny@yahoo.com.

(4)Shanghai Mental Health Center, Shanghai Jiao Tong University School of

Medicine, 200030, Shanghai, China. Electronic address: drminzhao@gmail.com.

GABA system genes have been implicated in neurotrophy and neurogenesis, which

play pivotal roles in an individual's variation in vulnerability to amphetamine

addiction or amphetamine-induced psychosis (AIP). We hypothesized that common

genetic variants in the GABA system genes may be associated with

amphetamine-induced psychotic disorder. In our study, thirty-six single

nucleotide polymorphisms (SNPs) within the GABA system genes were genotyped in

400 amphetamine-induced psychotic disorder patients and 400 amphetamine use

disorders patients (AUP) (not including those categorized as psychosis) in the

Han Chinese population. In this study, 51.88% of the Han Chinese amphetamine-type

substance use disorder patients met the criteria of amphetamine-induced psychotic

disorder, and 79.5% amphetamine-induced psychotic disorder patients had auditory

hallucinations, while 46.5% had delusions of reference. The allele frequency of

rs1129647 showed nominal association with AIP in the Han Chinese population

(P=0.03). Compared with AUP group patients, T allele frequency of AIP group

patients was significantly increased. The adjustment for age and gender factors

in the AIP and AUP patients was executed using unconditional logistic regression

under five inheritance models. The genotype frequency of rs1129647 showed nominal

association with AIP in the log-additive model (P=0.04). The genotype frequency

of rs2290733 showed nominal association with AIP in the recessive model (P=0.04).

Compared with female AIP patients, male patients were more likely to have the CC

genotype of rs17545383 (P=0.04). Moreover, we determined that more male patients

carried the T allele of rs2290733 in the AIP group (P=0.004). Unfortunately, the

significant differences did not survive Benjamini-Hochberg false discovery rate

correction (adjusted P>0.05). No association between the SNPs of the GABA system

genes and amphetamine-induced psychotic disorder risk was identified. No

haplotype of the GABA system genes affected amphetamine-induced psychotic

disorder risk. This report describes the first association study between the GABA

system genes and amphetamine-induced psychotic disorder in the Han Chinese

population. Our data may provide a reference for future research.

DOI: 10.1016/j.neulet.2016.04.019

PMID: 27080428 [Indexed for MEDLINE]

76. Psychopathology. 2016;49(2):108-15. doi: 10.1159/000445065. Epub 2016 Apr 13.

Differences in Clinical Features of Methamphetamine Users with Persistent

Psychosis and Patients with Schizophrenia.

Wang LJ(1), Lin SK, Chen YC, Huang MC, Chen TT, Ree SC, Chen CK.

Author information:

(1)Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial

Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.

BACKGROUND: Methamphetamine exerts neurotoxic effects and elicits psychotic

symptoms. This study attempted to compare clinical differences between

methamphetamine users with persistent psychosis (MAP) and patients with

schizophrenia. In addition, we examined the discrimination validity by using

symptom clusters to differentiate between MAP and schizophrenia.

METHODS: We enrolled 53 MAP patients and 53 patients with schizophrenia. The

psychopathology of participants was assessed using the Chinese version of the

Diagnostic Interview for Genetic Studies and the 18-item Brief Psychiatric Rating

Scale. Logistic regression was used to examine the predicted probability scores

of different symptom combinations on discriminating between MAP and

schizophrenia. The receiver operating characteristic (ROC) analyses and area

under the curve (AUC) were further applied to examine the discrimination validity

of the predicted probability scores on differentiating between MAP and

schizophrenia.

RESULTS: We found that MAP and schizophrenia demonstrated similar patterns of

delusions. Compared to patients with schizophrenia, MAP experienced significantly

higher proportions of visual hallucinations and of somatic or tactile

hallucinations. However, MAP exhibited significantly lower severity in conceptual

disorganization, mannerism/posturing, blunted affect, emotional withdrawal, and

motor retardation compared to patients with schizophrenia. The ROC analysis

showed that a predicted probability score combining the aforementioned 7 items of

symptoms could significantly differentiate between MAP and schizophrenia (AUC =

0.77).

CONCLUSION: Findings in the current study suggest that nuanced differences might

exist in the clinical presentation of secondary psychosis (MAP) and primary

psychosis (schizophrenia). Combining the symptoms as a whole may help with

differential diagnosis for MAP and schizophrenia.

DOI: 10.1159/000445065

PMID: 27071042 [Indexed for MEDLINE]

77. Int J Law Psychiatry. 2016 Jul-Aug;47:68-73. doi: 10.1016/j.ijlp.2016.02.037.

Epub 2016 Mar 25.

Drug driven psychoses and legal responsibility or insanity in six Western Pacific

nations.

Mellsop G(1), Choi WK(2), Every-Palmer S(3), Green B(4), Heffernan E(4), Kachaeva

M(5), Shiina A(6), Wang X(7).

Author information:

(1)University of Auckland, New Zealand. Electronic address:

graham.mellsop@waikatodhb.health.nz.

(2)Castle Peak Hospital, Hong Kong.

(3)Central Regional Forensic Services, Wellington, New Zealand.

(4)Queensland Forensic Mental Health Services, Australia.

(5)Serbsky National Research Centre for Social & Forensic Psychiatry, Moscow,

Russian Federation.

(6)Chiba University Hospital, Japan.

(7)Mental health Institute of the second Xiangya Hospital, Central South

University, China.

Prompted by four questions, forensic mental health clinicians from Russia, China,

Japan, Hong Kong, Australia and New Zealand provided information on both the

legislative basis and current practice concerning the relationship between legal

insanity, intoxication and drug induced psychosis in their six Pacific Rim

Countries which account for nearly 20% of the world's population. Details of the

survey for each contributing nation are provided. While there are significant

variations in practice that have been shaped by regional legal, clinical and

cultural influences there is considerable similarity in the legislation

underpinning how these issues are considered. Consequently there remain similar

challenges for each nation. In none of the legislative bases was the issue of

drug induced psychosis specifically addressed. The authors conclude that evolving

pharmaco-neuropsychiatric knowledge, societal values and patterns of substance

misuse require nations to consider developments in scientific and clinical

knowledge to support their interpretations of the relationship between altered

mental states as a result of substance use and the legal construct of insanity.

DOI: 10.1016/j.ijlp.2016.02.037

PMID: 27021135 [Indexed for MEDLINE]

78. Biol Psychiatry. 2016 Apr 1;79(7):526-38. doi: 10.1016/j.biopsych.2016.01.011.

Epub 2016 Feb 2.

Human Laboratory Studies on Cannabinoids and Psychosis.

Sherif M(1), Radhakrishnan R(1), D'Souza DC(1), Ranganathan M(2).

Author information:

(1)Schizophrenia and Neuropharmacology Research Group, VA Connecticut Healthcare

System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental

Health Center, New Haven, Connecticut; Department of Psychiatry, Yale University

School of Medicine, New Haven, Connecticut.

(2)Schizophrenia and Neuropharmacology Research Group, VA Connecticut Healthcare

System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental

Health Center, New Haven, Connecticut; Department of Psychiatry, Yale University

School of Medicine, New Haven, Connecticut. Electronic address:

mohini.ranganathan@yale.edu.

Some of the most compelling evidence supporting an association between

cannabinoid agonists and psychosis comes from controlled laboratory studies in

humans. Randomized, double-blind, placebo-controlled, crossover laboratory

studies demonstrate that cannabinoid agonists, including phytocannabinoids and

synthetic cannabinoids, produce a wide range of positive, negative, and cognitive

symptoms and psychophysiologic deficits in healthy human subjects that resemble

the phenomenology of schizophrenia. These effects are time locked to drug

administration, are dose related, and are transient and rarely necessitate

intervention. The magnitude of effects is similar to the effects of ketamine but

qualitatively distinct from other psychotomimetic drugs, including ketamine,

amphetamine, and salvinorin A. Cannabinoid agonists have also been shown to

transiently exacerbate symptoms in individuals with schizophrenia in laboratory

studies. Patients with schizophrenia are more vulnerable than healthy control

subjects to the acute behavioral and cognitive effects of cannabinoid agonists

and experience transient exacerbation of symptoms despite treatment with

antipsychotic medications. Furthermore, laboratory studies have failed to

demonstrate any "beneficial" effects of cannabinoid agonists in individuals with

schizophrenia-challenging the cannabis self-medication hypothesis. Emerging

evidence suggests that polymorphisms of several genes related to dopamine

metabolism (e.g., COMT, DAT1, and AKT1) may moderate the effects of cannabinoid

agonists in laboratory studies. Cannabinoid agonists induce dopamine release,

although the magnitude of release does not appear to be commensurate to the

magnitude and spectrum of their acute psychotomimetic effects. Interactions

between the endocannabinoid, gamma-aminobutyric acid, and glutamate systems and

their individual and interactive effects on neural oscillations provide a

plausible mechanism underlying the psychotomimetic effects of cannabinoids.

DOI: 10.1016/j.biopsych.2016.01.011

PMID: 26970363 [Indexed for MEDLINE]

79. Psychosomatics. 2016 May-Jun;57(3):325-9. doi: 10.1016/j.psym.2015.12.011. Epub

2015 Dec 31.

Methamphetamine Intoxication Encephalopathy Associated With Hyperammonemia.

Lama M(1), Shannon S(2), Davin Q(2).

Author information:

(1)Department of Psychiatry, University of New Mexico, Albuquerque, NM.

Electronic address: LMuhammad@salud.unm.edu.

(2)Department of Psychiatry, University of New Mexico, Albuquerque, NM.

DOI: 10.1016/j.psym.2015.12.011

PMID: 26961794 [Indexed for MEDLINE]

80. Eur J Paediatr Neurol. 2016 May;20(3):418-20. doi: 10.1016/j.ejpn.2016.02.010.

Epub 2016 Feb 21.

A pseudoencephalitis presentation of a pediatric non-intentional intoxication.

Bréhin C(1), Cessans C(1), Monchaud C(2), Lavit M(3), Majorel C(4), Claudet I(5).

Author information:

(1)Pediatric Emergency Unit, Children Hospital, CHU Toulouse, France.

(2)Laboratory of Toxicology, Dupuytren Hospital, CHU Limoges, France.

(3)Laboratory of Toxicology, Purpan Hospital, CHU Toulouse, France.

(4)Pediatric Neurology Unit, Children Hospital, CHU Toulouse, France.

(5)Pediatric Emergency Unit, Children Hospital, CHU Toulouse, France. Electronic

address: claudet.i@chu-toulouse.fr.

We report a case of a pseudo encephalitis presentation of pediatric intoxication

- Case report - a 7 year-old girl was admitted to our pediatric emergency unit

after she developed sudden agitation, visual and tactile hallucinations. She was

febrile (38.3 °C). She had not experienced any recent head trauma, infection or

toxic ingestion; she did not take any medication for ADD. Her physical exam

revealed tachycardia, normal pupils, reflexes and normal plantar responses.

Laboratory investigations (complete blood count, basic metabolic panel, plasma

lactate level, ammonia level) produced normal results. Lumbar puncture and

computed tomography of the brain were normal. A serum and urine drug screening

(benzodiazepines, barbiturates, cocaine, cannabis, amphetamines, methadone,

ethanol) was negative. An electroencephalogram, performed during an episode of

hallucinations, was compatible with benzodiazepine intoxication. A larger toxic

detection by liquid chromatography/diode array detector (LC-DAD) detected

promethazine and its metabolites. Symptoms lasted 20 h and she finally said she

drank syrup from an over-the-counter cough suppressant medication. Comments -

Anticholinergic syndrome is not well recognized or evoked in children presenting

hallucinations. Promethazine is still present in several over-the-counter

medications, alone or in combination with acetaminophen, carbocisteine or

opiates.CONCLUSION: Medications containing promethazine should not be prescribed

in children. Such intoxication can mimic encephalitis.

DOI: 10.1016/j.ejpn.2016.02.010

PMID: 26947545 [Indexed for MEDLINE]

81. Drug Alcohol Depend. 2016 Apr 1;161:104-9. doi: 10.1016/j.drugalcdep.2016.01.018.

Epub 2016 Jan 30.

The profile of psychiatric symptoms exacerbated by methamphetamine use.

McKetin R(1), Dawe S(2), Burns RA(3), Hides L(4), Kavanagh DJ(4), Teesson M(5),

McD Young R(4), Voce A(3), Saunders JB(6).

Author information:

(1)National Drug Research Institute, Faculty of Health Sciences, Curtin

University, Perth, Australia; National Drug and Alcohol Research Centre,

University of New South Wales, Sydney, Australia; Centre for Research on Ageing,

Health and Wellbeing, Research School of Population Health, Australian National

University, Canberra, Australia. Electronic address:

rebecca.mcketin@curtin.edu.au.

(2)School of Applied Psychology and Menzies Health Institute Queensland,

Griffith University, Brisbane, Queensland, Australia.

(3)Centre for Research on Ageing, Health and Wellbeing, Research School of

Population Health, Australian National University, Canberra, Australia.

(4)Centre for Youth Substance Abuse Research, School of Psychology and

Counselling, and Institute of Health & Biomedical Innovation, Queensland

University of Technology (QUT), Brisbane, Queensland, Australia.

(5)National Drug and Alcohol Research Centre, University of New South Wales,

Sydney, Australia.

(6)Centre for Youth Substance Abuse Research, University of Queensland, Brisbane,

Queensland, Australia; Disciplines of Psychiatry and Addiction Medicine, Faculty

of Medicine, University of Sydney, New South Wales, Australia.

BACKGROUND: Methamphetamine use can produce symptoms almost indistinguishable

from schizophrenia. Distinguishing between the two conditions has been hampered

by the lack of a validated symptom profile for methamphetamine-induced

psychiatric symptoms. We use data from a longitudinal cohort study to examine the

profile of psychiatric symptoms that are acutely exacerbated by methamphetamine

use.

METHODS: 164 methamphetamine users, who did not meet DSM-IV criteria for a

lifetime primary psychotic disorder, were followed monthly for one year to assess

the relationship between days of methamphetamine use and symptom severity on the

24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with

methamphetamine use was quantified using random coefficient models. The

dimensions of symptom exacerbation were examined using principal axis factoring

and a latent profile analysis.

RESULTS: Symptoms exacerbated by methamphetamine loaded on three factors:

positive psychotic symptoms (suspiciousness, unusual thought content,

hallucinations, bizarre behavior); affective symptoms (depression, suicidality,

guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms

(tension, excitement, distractibility, motor hyperactivity). Methamphetamine use

did not significantly increase negative symptoms. Vulnerability to positive

psychotic and affective symptom exacerbation was shared by 28% of participants,

and this vulnerability aligned with a past year DSM-IV diagnosis of

substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056).

CONCLUSION: Methamphetamine use produced a symptom profile comprised of positive

psychotic and affective symptoms, which aligned with a diagnosis of

substance-induced psychosis, with no evidence of a negative syndrome.

DOI: 10.1016/j.drugalcdep.2016.01.018

PMID: 26874915 [Indexed for MEDLINE]

82. AIDS Behav. 2016 Oct;20(10):2372-2386. doi: 10.1007/s10461-016-1303-3.

Patterns of Drug Use and Drug-related Hospital Admissions in HIV-Positive and

-Negative Gay and Bisexual Men.

Moore CL(1), Gidding HF(2), Jin F(3), Mao L(4), Petoumenos K(3), Zablotska IB(3),

Poynten IM(3), Prestage G(3)(5), Law MG(3), Grulich AE(3), Amin J(3).

Author information:

(1)The Kirby Institute, University of New South Wales, Wallace Wurth Building,

Sydney, NSW, 2052, Australia. cmoore@kirby.unsw.edu.au.

(2)School of Public Health and Community Medicine, University of New South Wales,

Sydney, Australia.

(3)The Kirby Institute, University of New South Wales, Wallace Wurth Building,

Sydney, NSW, 2052, Australia.

(4)Centre for Social Research in Health, University of New South Wales, Sydney,

Australia.

(5)Australian Research Centre in Sex, Health and Society, La Trobe University,

Melbourne, Australia.

We aimed to compare rates of illicit drug-related hospitalisations in

HIV-negative (HIV-ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and

bisexual men (GBM) with rates seen in the general male population and to examine

the association between self-reported illicit drug use and drug-related

hospitalisation. Participants were asked how often they used a range of illicit

drugs in the previous 6 months at annual interviews. Drug-related hospital

admissions were defined as hospital admissions for mental or behavioural

disorders due to illicit drug use (ICD 10: F11-16, F18, F19), drug poisoning

(T40-T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related

hospitalisations were 4.8 times higher in the HIV-ve cohort [SIR 4.75 (95 % CI

3.30-6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92-5.88)]

compared with the general population. Periods of weekly drug use [IRR 1.86

(1.01-3.46)], poly-drug use [IRR 2.17 (1.07-4.38)] and cannabis use [low use-IRR

1.95 (1.01-3.77), high use-IRR 2.58 (1.29-5.16)] were associated with

drug-related hospitalisation in both cohorts, as was being a consistently high

meth/amphetamine user throughout follow-up [IRR 3.24 (1.07-9.83)] and being an

inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94

(1.61-9.66), IRR 4.43(1.04-18.76), respectively]. Other risk factors for

drug-related hospitalisation indicated the likelihood of comorbid drug and mental

health issues in GBM hospitalised for drug use.

DOI: 10.1007/s10461-016-1303-3

PMCID: PMC4970975

PMID: 26837635 [Indexed for MEDLINE]

83. Prog Brain Res. 2016;223:295-310. doi: 10.1016/bs.pbr.2015.07.010. Epub 2015 Oct

16.

Clinical neuroscience of amphetamine-type stimulants: From basic science to

treatment development.

Courtney KE(1), Ray LA(2).

Author information:

(1)Department of Psychology, University of California, Los Angeles, CA, USA.

(2)Department of Psychology, University of California, Los Angeles, CA, USA.

Electronic address: lararay@psych.ucla.edu.

Abuse of amphetamine-type stimulants (ATS) poses a significant public health

concern with known neurotoxic and neurocognitive effects to the user. In this

chapter, we seek to integrate the latest research on ATS, particularly

methamphetamine, by covering areas of pharmacology, neurocognitive effects, and

the treatment of ATS use disorders with the goal of advancing the clinical

neuroscience of ATS and highlighting avenues for future research.

DOI: 10.1016/bs.pbr.2015.07.010

PMID: 26806782 [Indexed for MEDLINE]

84. Prog Brain Res. 2016;223:19-41. doi: 10.1016/bs.pbr.2015.07.004. Epub 2015 Oct 1.

Drug-induced neurotoxicity in addiction medicine: From prevention to harm

reduction.

Mohammad Ahmadi Soleimani S(1), Ekhtiari H(2), Cadet JL(3).

Author information:

(1)Neurocognitive Laboratory, Iranian National Center for Addiction Studies

(INCAS), Tehran University of Medical Sciences, Tehran, Iran; Department of

Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran,

Iran.

(2)Neurocognitive Laboratory, Iranian National Center for Addiction Studies

(INCAS), Tehran University of Medical Sciences, Tehran, Iran; Translational

Neuroscience Program, Institute for Cognitive Science Studies (ICSS), Tehran,

Iran; Research Center for Molecular and Cellular Imaging (RCMCI), Tehran

University of Medical Sciences, Tehran, Iran.

(3)Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research

Program, National Institutes of Health, Baltimore, MD, USA. Electronic address:

jcadet@intra.nida.nih.gov.

Neurotoxicity is considered as a major cause of neurodegenerative disorders. Most

drugs of abuse have nonnegligible neurotoxic effects many of which are primarily

mediated by several dopaminergic and glutamatergic neurotransmitter systems.

Although many researchers have investigated the medical and cognitive

consequences of drug abuse, the neurotoxicity induced by these drugs still

requires comprehensive attention. The science of neurotoxicity promises to

improve preventive and therapeutic strategies for brain disorders such as

Alzheimer disease and Parkinson's disease. However, its clinical applications for

addiction medicine remain to be defined adequately. This chapter reviews the most

commonly discussed mechanisms underlying neurotoxicity induced by common drugs of

abuse including amphetamines, cocaine, opiates, and alcohol. In addition, the

known factors that trigger and/or predispose to drug-induced neurotoxicity are

discussed. These factors include drug-related, individual-related, and

environmental insults. Moreover, we introduce some of the potential

pharmacological antineurotoxic interventions deduced from experimental animal

studies. These interventions involve various targets such as dopaminergic system,

mitochondria, cell death signaling, and NMDA receptors, among others. We conclude

the chapter with a discussion of addicted patients who might benefit from such

interventions.

DOI: 10.1016/bs.pbr.2015.07.004

PMID: 26806769 [Indexed for MEDLINE]

85. Przegl Lek. 2016;73(8):596-8.

[Morphine (obtained from poppy seeds) and dextrometorfan poisoning– a case

report].

[Article in Polish]

Kwiecień-Obara E, Szponar J, Krajewska A, Witkowska A, Radoniewicz A, Szponar M.

Morphine is one of the many, and pharmacologically most important, opium poppy

alkaloid (Papaver somniferum). A poppy plant consists of a lot of alkaloids. Most

of them are morphine, codeine, narcotine, papaverine, thebaine, narceine and

narcotoline. Most of the alkaloid is in the poppy milk - opium..It is a dried and

properly processed juice with precut immature poppy-heads. It induces euphoria,

somnolence, has an analgesic effect. In the study was presented a 24-yearold

patient who was admitted to the Department of Toxicology and Cardiology because

of suspicion of poisoning with unknown drugs. In retrospect, it turned out that

he was poisoned brew with 5 kg of poppy and dextromethorphan. In the past, he

drank alcohol heavily, used legal highs, amphetamine, methamphetamine, opiates,

diazepam, cannabinoids. At the time of admission to the department, his general

condition was severe, he was unconscious, with periodic breathing disorders,

pinpoint pupils. In the laboratory: opiates>2000 ng/ml, other toxicological tests

were negative. On the subsequent days of his stay he remained in a generally very

severe condition; he was unconscious. Some electrolyte disorders were observed,

as well as characteristics of developing rhabdomyolysis. With the applied

intensive medical therapy, a gradual improvement of his general condition was

achieved. Due to quadriplegia on the 30th day of the hospitalization, the patient

was transferred to the Department of Neurology for further treatment.

PMID: 29677437 [Indexed for MEDLINE]

86. Pediatrics. 2015 Dec;136(6):e1625-8. doi: 10.1542/peds.2014-3333. Epub 2015 Nov

Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug

Screens in Children.

Kaplan J(1), Shah P(2), Faley B(1), Siegel ME(3).

Author information:

(1)Department of Pharmacy, Hackensack University Medical Center, Hackensack, New

Jersey, and Ernest Mario School of Pharmacy, Rutgers University, New Brunswick,

New Jersey;

(2)Department of Pharmacy, Hackensack University Medical Center, Hackensack, New

Jersey, and Ernest Mario School of Pharmacy, Rutgers University, New Brunswick,

New Jersey; poojashah@hackensackumc.org.

(3)Department of Pediatrics, Hackensack University Medical Center, Hackensack,

New Jersey.

Urine drug screens (UDSs) are used to identify the presence of certain

medications. One limitation of UDSs is the potential for false-positive results

caused by cross-reactivity with other substances. Amphetamines have an extensive

list of cross-reacting medications. The literature contains reports of

false-positive amphetamine UDSs with multiple antidepressants and antipsychotics.

We present 2 cases of presumed false-positive UDSs for amphetamines after

ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested

15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode

of vomiting containing no identifiable tablets. She remained sluggish with

periods of irritability and was admitted for observation. UDS on 2 consecutive

days came back positive for amphetamines. Case 2 was of a 20-month-old girl who

was brought into the hospital after accidental ingestion of an unknown quantity

of her father's medications which included aripiprazole. UDS on the first day of

admission came back positive only for amphetamines. Confirmatory testing with gas

chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also

performed for both patients on presentation to detect amphetamines and were

subsequently negative. Both patients returned to baseline and were discharged

from the hospital. To our knowledge, these cases represent the first reports of

false-positive amphetamine urine drug tests with aripiprazole. In both cases,

aripiprazole was the drug with the highest likelihood of causing the positive

amphetamine screen. The implications of these false-positives include the

possibility of unnecessary treatment and monitoring of patients.

DOI: 10.1542/peds.2014-3333

PMID: 26527556 [Indexed for MEDLINE]

87. Clin Toxicol (Phila). 2015 Nov;53(9):893-900. doi: 10.3109/15563650.2015.1088157.

Acute recreational drug and new psychoactive substance toxicity in Europe: 12

months data collection from the European Drug Emergencies Network (Euro-DEN).

Dines AM(1), Wood DM(1)(2), Yates C(3), Heyerdahl F(4), Hovda KE(4), Giraudon

I(5), Sedefov R(5), Dargan PI(1)(2); Euro-DEN Research Group.

Collaborators: Archer JR, Pedersen CB, Chevillard L, Donnelly A, Eyer F, Galicia

M, Homar C, Jürgens G, Kabata P, Kitching G, Liakoni E, Liechti ME, Markey G,

Mégarbane B, Miro O, Moughty A, O' Connor N, Paasma R, Persett PS, Põld K,

Puiguriguer J, Stenzel J, Vallersnes OM, Waldman W, Waring WS.

Author information:

(1)a Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's

Health Partners , London , UK.

(2)b Faculty of Life Sciences and Medicine, King's College London , London , UK.

(3)c Emergency Department and Clinical Toxicology Unit , Hospital Universitari

Son Espases , Mallorca , Spain.

(4)d The National CBRNe Centre of Medicine, Department of Acute Medicine ,

Medical Division, Oslo University Hospital , Norway.

(5)e European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) , Lisbon ,

Portugal.

Erratum in

Clin Toxicol (Phila). 2015 Nov;53(9):930. Liechti, M E [added]; Markey, Gerard

[added]; Mégarbane, Bruno [added]; Miro, Oscar [added]; Moughty, Adrian [added].

CONTEXT: Despite the potential for recreational drugs and new psychoactive

substances (NPSs) to cause significant morbidity and mortality, there is limited

collection of systematic data on acute drug/NPS toxicity in Europe.

OBJECTIVE: To report data on acute drug/NPS toxicity collected by a network of

sentinel centres across Europe with a specialist clinical and research interest

in the acute toxicity of recreational drugs and NPS to address this knowledge

gap.

METHODS: Sixteen sentinel centres in 10 European countries (Denmark, Estonia,

France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK)

collected data on all acute drug toxicity presentations to their Emergency Rooms

(ERs) for 12 months (October 2013-September 2014); information on the drug(s)

involved in the presentations was on the basis of patient self-reporting.

RESULTS: Data were collected on a total of 5529 presentations involving 8709

drugs (median (interquartile range [IQR]): 1 (1-2) drugs per presentation), a

median of 0.3% of all ER attendances. Classical recreational drugs were most

common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The 'top

five' drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904),

GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by

ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age

was 31 (24-39) years and 75.4% were male. Although serious clinical features were

not seen in most presentations and 56.9% were medically discharged from the ER

(median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in

10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27

fatalities with opioids implicated in 13.

CONCLUSION: The Euro-DEN dataset provides a unique insight into the drugs

involved in and clinical pattern of toxicity/outcome of acute recreational drug

toxicity presentations to hospitals around Europe. This is complimentary to other

indicators of drug-related harm and helps to build a fuller picture of the public

health implications of drug use in Europe.

DOI: 10.3109/15563650.2015.1088157

PMID: 26503789 [Indexed for MEDLINE]

88. Prog Neurobiol. 2017 Aug;155:149-170. doi: 10.1016/j.pneurobio.2015.09.011. Epub

2015 Oct 9.

Amphetamine-related drugs neurotoxicity in humans and in experimental animals:

Main mechanisms.

Moratalla R(1), Khairnar A(2), Simola N(3), Granado N(4), García-Montes JR(4),

Porceddu PF(3), Tizabi Y(5), Costa G(3), Morelli M(6).

Author information:

(1)Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC,

Madrid, Spain; CIBERNED, ISCIII, Madrid, Spain. Electronic address:

moratalla@cajal.csic.es.

(2)Applied Neuroscience Research Group, CEITEC - Central European Institute of

Technology, Masaryk University, Brno, Czech Republic.

(3)Department of Biomedical Sciences, Section of Neuropsychopharmacology,

University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.

(4)Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC,

Madrid, Spain; CIBERNED, ISCIII, Madrid, Spain.

(5)Department of Pharmacology, Howard University College of Medicine, Washington,

DC, USA.

(6)Department of Biomedical Sciences, Section of Neuropsychopharmacology,

University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy; Centre of

Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari,

Italy; National Research Council (CNR), Institute of Neuroscience, Cagliari,

Italy.

Amphetamine-related drugs, such as 3,4-methylenedioxymethamphetamine (MDMA) and

methamphetamine (METH), are popular recreational psychostimulants. Several

preclinical studies have demonstrated that, besides having the potential for

abuse, amphetamine-related drugs may also elicit neurotoxic and neuroinflammatory

effects. The neurotoxic potentials of MDMA and METH to dopaminergic and

serotonergic neurons have been clearly demonstrated in both rodents and non-human

primates. This review summarizes the species-specific cellular and molecular

mechanisms involved in MDMA and METH-mediated neurotoxic and neuroinflammatory

effects, along with the most important behavioral changes elicited by these

substances in experimental animals and humans. Emphasis is placed on the

neuropsychological and neurological consequences associated with the neuronal

damage. Moreover, we point out the gap in our knowledge and the need for

developing appropriate therapeutic strategies to manage the neurological problems

associated with amphetamine-related drug abuse.

DOI: 10.1016/j.pneurobio.2015.09.011

PMID: 26455459 [Indexed for MEDLINE]

89. Dan Med J. 2015 Oct;62(10):A5147.

Fatal poisoning among patients with drug addiction.

Simonsen KW(1), Christoffersen DJ, Banner J, Linnet K, Andersen LV.

Author information:

(1)kirsten.wiese@sund.ku.dk.

INTRODUCTION: Fatal poisonings among drug addicts in Denmark in 2012 were

examined. Cause of death, abuse pattern and geographic differences are discussed

and data are compared with previous studies.

METHODS: All fatal poisonings examined at the three institutes of forensic

medicine in Denmark in 2012 were included in the study.

RESULTS: A total of 188 fatal intoxications were recorded. The median age

increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%).

Methadone (59%) was the main intoxicant. The decrease in the frequency of

heroin/morphine deaths since 1997 (71%) continued, declining to 44% in 2002, 33%

in 2007 and finally to 27% in 2012. Few deaths from central stimulants

(amphetamine and cocaine) occurred. Multiple drug use was common and consisted

mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol.

Heroin/morphine use was most frequent on Funen and in South Jutland. Cocaine was

most frequently detected in East Denmark, while amphetamine was more frequent in

West Denmark.

CONCLUSIONS: The number of fatal poisonings among drug addicts has stabilised

around 200. The increase in methadone deaths continued and, as in 2007, methadone

was the main intoxicant. The increase in methadone deaths seems to be associated

with use of methadone in substitution treatment. Nevertheless, methadone

treatment also seems to save lives, as indicated by the increasing median age.

Use of antidepressants and antipsychotics increased to a high level compared with

2007, indicating that a considerable number of drug addicts also have psychiatric

illness.

FUNDING: none.

TRIAL REGISTRATION: not relevant.

PMID: 26441394 [Indexed for MEDLINE]

90. Arch Kriminol. 2015 Jan-Feb;235(1-2):53-61.

[Death after the intake of amphetamine/ecstasy: two case reports].

[Article in German]

Wöllner K, Stockhausen S, Mußhoff F, Madea B.

Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA,

Ecstasy) have become recreational drugs in German discotheques because of their

euphoric and mood-brightening effects. However, their consumption involves

considerable risks, which may even be lethal under certain circumstances. A

19-year-old man was taken to a university hospital for suspected intoxication

with a narcotic drug, where he died the next day. As cause of death "fulminant

liver failure" was diagnosed. In blood from the femoral vein, MDMA was found in a

concentration of 4.27 mg/l. Histological examination showed acute necrosis of the

liver and parenchymatous bleeding. The second case is that of a 39-year-old man

who collapsed at his workplace and died in hospital shortly afterwards. In his

rucksack, a small bag with 1.6 g of amphetamine was found. Analysis of blood from

the femoral vein showed an amphetamine concentration of 1.08 mg/l.

PMID: 26419092 [Indexed for MEDLINE]

91. Nihon Rinsho. 2015 Sep;73(9):1481-6.

[Methamphetamine, cannabis].

[Article in Japanese]

Naruse N.

The persons with marijuana abuse tend to be increasing in Japan, although illegal

drugs use in lifetime is remarkably lower than other advanced countries, Europe

and USA. In addition, there have been many methamphetamine users in Japan. As use

of methamphetamine induces psychotic states, we recognize them as one of the key

illegal drugs for clinical psychiatrists. Regarding to diagnosis of

methamphetamine psychosis, there is a large difference between Japanese

psychiatrists and other advanced countries' ones. The former considers that they

have persistent symptoms. In contrast, the latter embraces it as the model of

acute toxicosis. The Japanese government has been based on a full commitment to

the crackdown on drug problems. However, they will execute the new law in 2016,

in which some persons charged with violating the methamphetamine control law will

be adapted to partially probation on drug charges. Then, we have to improve our

therapeutic and recovery supports to charged illegal drug users as rapidly as

possible.

PMID: 26394507 [Indexed for MEDLINE]

92. Am J Addict. 2015 Oct;24(7):586-9. doi: 10.1111/ajad.12274. Epub 2015 Sep 1.

Amphetamine-induced psychosis: Transition to schizophrenia and mortality in a

small prospective sample.

Medhus S(1)(2), Rognli EB(1)(3)(4), Gossop M(1)(5), Holm B(2), Mørland J(6),

Bramness JG(1).

Author information:

(1)Norwegian Centre for Addiction Research (SERAF), University of Oslo, Norway.

(2)Lovisenberg Diakonale Hospital, Oslo, Norway.

(3)Oslo University Hospital, Norway.

(4)Norwegian National Advisory Unit on Concurrent Substance Abuse and Mental

Health Disorders, Norway.

(5)Kings College London, National Addiction Centre, London, UK.

(6)Norwegian Institute of Public Health, Oslo, Norway.

BACKGROUND AND OBJECTIVES: We investigated transition from amphetamine-induced

psychosis (AIP) to schizophrenia.

METHODS: A sample of 28 individuals was identified while hospitalized for AIP. We

reviewed their hospital records after six years.

RESULTS: During follow-up, seven individuals (25%) died and nine (32%) had moved

from the area. Of the remaining 12, four individuals (25%) were diagnosed with

schizophrenia. These individuals were, at baseline, characterized by fewer

hallucinatory symptoms and more homelessness.

CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Hospitalization for AIP was a relatively

specific risk factor for schizophrenia and the mortality rate in AIP was high.

DOI: 10.1111/ajad.12274

PMID: 26332037 [Indexed for MEDLINE]

93. Am J Med. 2016 Jan;129(1):e3-4. doi: 10.1016/j.amjmed.2015.08.006. Epub 2015 Aug

21.

Methamphetamine Cardiotoxicity: Unique Presentation with Multiple Bi-Ventricular

Thrombi.

Janardhanan R(1), Kannan A(2).

Author information:

(1)Sarver Heart Center, Division of Cardiology, Department of Medicine,

University of Arizona, Tucson. Electronic address: raj@shc.arizona.edu.

(2)Sarver Heart Center, Division of Cardiology, Department of Medicine,

University of Arizona, Tucson.

DOI: 10.1016/j.amjmed.2015.08.006

PMID: 26302144 [Indexed for MEDLINE]

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