Two waves of sampling were done on groups regarding the frequency of their marijuana usage.

The study results show that those with substance abuse disorders and anxiety disorders have a 70.5% and 21.8% chance, respectively, to use marijuana more than once a month.

Although this study indicates there is a strong correlation between mental illness and substance abuse it has some flaws.

The article itself stated that they over sampled in specific communities such as the black and Hispanic community.

Additionally, there is no control group—e.g., a collection of individuals with no disorders—to compare to. This makes it difficult to see the significance of the results of this study.

THC can cause anxiety in some users of cannabis during intoxication.

CBD has anxiolytic, anxiety reducing, properties which suggests that cannabis with CBD and THC could produce less anxiety than cannabis with just THC.

Study included 26 healthy recreational cannabis users. 

Used THC-dominant cannabis, CBD-dominant cannabis, THC/CBD cannabis, and placebo cannabis.

Anxiety levels were assessed with the State-Trait Anxiety Inventory (STAI).

State levels of anxiety were objectively assessed with a computer-based emotional Stroop task.

THC and THC/CBD cannabis increased self-rated anxiety in comparison to the placebo. THC produced higher anxiety reports than THC/CBD. 

Occurs between April 22 and May 11, 2020.

1,008 participants ages 18-35 recruited through social media. 

They self-reported loneliness using 5-point Likert scales.

49% of respondents reported loneliness scores above 50.

80% reported significant depressive symptoms.

61% reported moderate to severe anxiety.

30% reported harmful levels of drinking.

38% reported severe drug use.

Substance use behaviors were evaluated using the Alcohol Use Disorder Identification Test (AUDIT) and the Drug Abuse Screening Test (DAST-10).

Anxiety and Depression assessed using the Generalized Anxiety Disorder (GAD-7) Questionnaire and the Center for Epidemiologic Studies Depression scale (CES-D-10)

Canadian military personnel (all male) with PTSD received a double-blind treatment with 0.5mg NAB (nabilone) or placebo (PBO)--titrated to a max of 3.0mg.

Nabilone is a drug in the cannabinoid family.

The subjects were from ages 18-65 and were referred to a military trauma clinic with a diagnosis of PTSD as per DSM-IV-TR.

Criteria required was a traumatic event which had occurred 2 years prior to the screening for the study.

Frequent nightmares and difficulty sleeping were also requirements.

Subjects were allowed to continue taking their medications and attend psychotherapy.

They were checked weekly for vital signs, changes in nightmares, and a systematic recording of adverse events in responses to a general inquiry.

Sample included 10 Caucasian males, mean age of 43.6 years plus or minus 8.2 with a median of 44.

The group who received NAB reported an increase in score of the General Well Being Questionnaire. It increased from 28.4 plus or minus 21.6 to 49.3 plus or minus 21.6. The placebo group reported a score of 29.0 plus or minus 20.8 before the study and 23.0 plus or minus 17.2 after the study.

Marijuana motives:

• Relations with use

• Problems

• And alcohol motives

• Study has sample of 141 (78 female) young adults with a mean age of 20.17 years.

• Reports of coping, enhancement, social, and expansion motives show a significant likelihood of marijuana use in the past 30 days.

• Anxiety sensitivity was related to coping motives for marijuana use.

• Anxiety sensitivity is defined as a relatively stable individual difference factor reflecting the fear of arousal-related sensations.

• These sensations are believed to have harmful personal consequences.

• Subjects recruited through newspapers posted in and outside of university settings.

• 96% of the sample was Caucasian.

• 2/3 of sample smoked marijuana on a weekly basis.

• Marijuana use is related to a variety of negative outcomes such as physical health problems, disorders, and psychological symptoms.

Endocannabinoid (EC) system is widely distributed throughout the brain. It is involved in mood and related disorders. 

Exogenous cannabinoids can affect these receptors.

CBD is a non-psychotropic component of Cannabis. 

Cells were grown as monolayers in minimum essential medium. 

The affinity of CBD for human VR1 receptors was assessed by means of displacement assays carried out with membranes from HEK-hVR1 cells, and the high affinity VR1 ligand.

CBD increased the calcium levels and acted as full agonists in comparison to capsaicin.

In conclusion, CBD produces anti-inflammatory effects.

Generalized Social Anxiety Disorder (SAD) is a common anxiety condition.

Cannabidiol (CBD) is a major non-psychotomimetic compound of cannabis sativa plant.

CBD has shown anxiolytic effects in both humans and animals.

24 Subjects with generalized SAD and 12 healthy control (HC) subjects were selected for this study.

They were given 600mg of CBD or placebo.

Factors like heart rate and arterial blood pressure were taken throughout the study.

SAD patients had a significantly higher anxiety level and greater cognitive impairment, discomfort, and alertness in comparison to HC subjects.

The treatment of SAD patients with CBD significantly reduced anxiety, cognitive impairment, and discomfort in their speech performance.

A sample which included 387 current or past-CBD users answered a 20-question survey online.

The survey utilized social media and email databases to send to CBD users.

The sample consisted of 61.2% females.

The top 4 reasons for CBD usage was perceived anxiety, sleep problems, stress, and general health and wellbeing.

Certain differences could be found between sexes and age when it came to the reasons an individual used CBD.

Through self-reported data, 42.6% of individuals use or take CBD in order to manage self-perceived anxiety.

42.5% of subjects used CBD to help with sleep and/or reduce insomnia

Additionally 37.5% of respondents use CBD in order to reduce self-perceived stress

Most people in the study were using CBD daily.

99.2% of subjects reported reduced stress levels with CBD.

86.5% of individuals reported that they felt less anxiety.

10 Right-handed men with SAD--generalized anxiety disorder were selected for this study from a group of 2320 university students.

SAD diagnosis is confirmed for these subjects through the SCID and the DSM-IV.

The mean age of the subjects was 24.2 years.

The subjects received gelatin capsules packed with 400mg of CBD dissolved in corn oil.

The placebo group received the same pill with just corn oil. 

There is an increased blood flow in the right posterior cingulate gyrus of SAD subjects during cannabidiol condition relative to the placebo condition as shown on a coronal section.

This study shows that acute administration of CBD can reduce subjective anxiety in patients that are clinically diagnosed with an anxiety disorder.

Adult male Wistar rats (WR) and SHR (five-month-old) from a colony were housed in controlled temperature (22-23°C) and lightning (12/12h light/dark cycle). 

Groups of 5 animals were kept in cages with access to food and water.

CBD was given to the rats through injection.

Acute treatment of CBD did not reverse the deficit in social interaction.

However, an acute dose of CBD (1mg/kg) increased passive and total social interaction in WRs.

Male CD rats used.

Adolescent rats are 28 days old.

Adult rats are 64-66 days old.

Elevated plus maze is used in this experiment to determine anxiety level of rats.

Percentage of time in open arms: [seconds in open arms/ (seconds in open arms + seconds in closed arms)] x 100

Light-dark task performed in Hamilton-Kinder activity monitors.

3 factors included for these sessions- total distance traveled (cm) in both light and dark sides, time spent in the light half of the chamber (s), and emergence from the dark (emergence interval).

The rats were conditioned to have a taste aversion. This was done with water and a 0.2% saccharin solution.

There was also a conditioned place aversion through receiving injections in a specific chamber.

The rats were injected with THC which was dissolved in 10% ethanol:emulphor (1:1) and 90% normal saline.

Injections were done intraperitoneally.

Control rats received  10% ethanol:emulphor (1:1) and 90% normal saline.

THC was anxiogenic in both adult and adolescent rats according to the elevated plus maze.

In the first five minutes of the light-dark task, THC was anxiogenic in adolescents, but not in adults. 

• This was likely due to a floor effect in the adults

THC is less anxiogenic, less aversive, and less locomotor reducing in adolescent rats than in adult rats.

37 healthy females who are occasional cannabis users used for this study.

They were between the ages of 18-35.

They received THC (7.5 or 15mg) or placebo. Conditions were double blind. THC consumed orally.

Interestingly, sessions were scheduled during the follicular phase of the subjects' menstrual cycle.

Subjects had to participate in drug abstinence for this study.

They also filled out baseline mood and subjective drug questionnaires.

Skin areas were cleaned with an alcohol prep pad for electrocardiogram (ECG) electrode placement.

The ECG and thoracic impedance signals were processed using a Mindware Heart Rate Variability Analysis Software--the data was also analyzed using this software.

The findings of this study suggest that parasympathetic autonomic responses to higher doses of THC are related to cannabis-specific subjective intoxication effects--not anxiety.

In rats, estrogen increases cannabinoid receptor binding site density which is why the cycle for the participants was regulated.

• However, there is little evidence of this being true in naturally cycling women.

• Further studies may be done to investigate the influence of the phase of the menstrual cycle in responses to oral THC.

Study was done on wild type male mice.

Glu-CB1-KO and GABA-CB1-KO male and female mice were also used.

The animals were not single-housed in worry that it would increase anxiety levels.

2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol (CP-55,940, Sigma Aldrich, Munich, Germany) was used for this study.

• It is a high-affinity synthetic CB1/CB2-receptor agonist.

N,N′-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS-39783, Tocris, Wiesbaden, Germany) was also used.

Two doses were chosen: low (1 μg/kg)  and high (50 μg/kg).

An EPM and HB apparatus was performed.

CP-55,940 or vehicle was injected intraperitoneally.

GS-39783 and vehicle were administered orally.

Results of study show that CB1 receptor activation on GABAergic neurons is necessary for developing the anxiogenic-like behavior after a high dose of cannabinoids.

Fmr1 knockout mice were used for this experiment. 

Cannabidiol dissolved with 100% ethanol and diluted with 0.9% sodium chloride.

Final ratio of 1:1:18.

An open field test, elevated plus maze, continuous spontaneous alternation in the Y-maze, passive avoidance, social preference test was performed. 

Two-way analysis of variance was performed to investigate main effects of 'genotype' and 'CBD dose' and possible interactions.

Fmr1 KO mice were more explorative than WT mice.

In the EPM test. 20 mg/kg CBD decreased the anxiety response of all mice tested.

CBD treatment did not affect cognitive performance of animals in the spontaneous alternation task and the passive avoidance task.

Males were used because they tend to have more severe symptoms.

Studies done on male BALB/c mice weighing 18-24g.

A light/dark box test and open-field test was performed.

The light/dark box test was used as a model of anxiety. 

THC, nabilone, HU-210, and CP 55,940 show anxiogenic.

Cannabinoids modulate the release of certain transmitters which are implicated in the control of anxiety.

There is still debate on whether cannabinoids reduce or increase anxiety.

Male Wistar rats, 250-300g, were used for this study.

They were housed in groups of five.

Animals were injected with SR 141716A (0.4 ml-3 mg/kg body weight) or Tween-saline vehicle (equal volume).

After 15 minutes, both animals were injected with CP 55,940. 

Animals were tested 30 minutes after the second injection.

The holeboard and elevated plus-maze test.

The brains were dissected after the animals performed the EPM.

The results suggest that acute administration of C 55,940 independently alters exploratory behavior and motor activity in the rat.

• It also leads to anxiety-like responses.

CP 55,940 reduces anxiety-related indices in a dose-dependent manner and increased the rats' natural aversion to the open arms.

Male ICR mice used for this study.

They weighed 24-29g at the start of the study.

THC and SR141716 were dissolved in ethanol. 

They were also mixed with cremophor EL by vortex.

Finally, they were diluted with saline to form a vehicle mixture of ethanol/cremophor/saline with a 1:1:18 ratio.

Mice were tested for anxiety-like behaviors with an EPM.

There was a significant decrease in open arm entries and open arm time was observed in mice treated with THC at a dose of 3.0 mg/kg.

EPM can be used to demonstrate the anxiety-like behaviors associated with THC withdrawal precipitated by SR141716.

Male CD1 mice which weighed 22-24g were used for this study.

THC was dissolved in a solution of 5% ethanol, 5% cremophor EL and 90% distilled water. 

The CB1 receptor antagonist SR 141716A was dissolved in 10% ethanol, 10% cremophor EL, and 80% distilled water.

A light-dark box paradigm was used.

• Anxiolytic-like responses were evaluated using this test.

One-way ANOVA was used to determine the statistically effects of the data.

The results pose evidence for interactions between cannabinoid and opioid systems in control of anxiety-like responses.

The anxiolytic effects caused by THC were reversed by the selective CB1 antagonist SR 141716A. 

There is an involvement of certain opioid receptors in mediating the anxiolytic-like responses induced by low doses of THC.

123 Participants were used for this study, 73 were female.

They were all undergraduate students at the State University in Tallahassee, FL.

They were recruited through fliers posted on campus.

Within 24 hours of their scheduled study session time, they had to refrain from alcohol or illicit drugs.

Physiological reactivity was measured via skin conductance response (SCR).

Before starting the procedures, the hands of the participants were cleaned with rubbing alcohol.

Skin conductance electrodes were then placed on their hands.

There was a subjective psychophysiological reaction questionnaire (SPRQ).

• A loud noise is played and it is used to assess the degree to which a participant coped with the sound stressor after being told to relax.

• The total perceived coping score was measured on a scale of 1-4.

A baseline skin conductance was recorded for each patient for 2 minutes.

The results of this study suggest that SAD symptoms are associated with CUD symptoms.

Cannabis use Disorders (CUD)

Social Anxiety Disorder (SAD)

Cannabis is a naturally dioecious species--it has male and female individuals that show unisexual flowers. 

It is characterized by sexual dimorphism. Male plants tend to be taller, more slender, and have a shorter life cycle than female plants.

The male is XX and the female is XY.

This experiment was done on cv. Fibranova. It is dioecious and has a roughly 1:1 ratio for males and females.

The plants were sexed early on in the experiment.

They had their RNA and cDNA extracted.

After a microscopic analysis of the male and female apices, it was found that the meristem primordia could develop into an inflorescence bud in most cases.

The beginning of sexual differentiation between the male and female cv. Fibranova occurs roughly 50-60 days after seed germination.

Male Sprague-Dawley Rats used for this experiment.

They were housed two per cage with a 12 hour light and 12 hour dark cycle.

Rats received injections containing SR141716 (1.0, 3.0, or 10 mg/kg).

Other rats received vehicle.

SR141716 induced the accumulation of FOs-like immunoreactivity in several structures.

• Including the prefontal, cingulate, and piriform cortices.

• The ventral part of the lateral septum, the shell of nucleus accumbens, the dorsomedial caudate-putamen, the central amygdaloid nucleus, and the lateral subdivision of the bed nucleus of the stria terminalis. 

• The anatomical and pharmacological profile of the Fos-inducing effect of SR141716 is similar to that of atypical antipsychotic compounds.

Elevated plus maze was performed (EPM).

• The elevated plus maze is a good model of anxiety-like behavior because rodents are naturally adverse to open elevated places.

• Gerbils show this behavior as well. They prefer to stay in the closed arms rather than the open arms as seen in many other rodents.

Female Mongolian Gerbils which weigh 30-50g were used for this study.

Gerbils are housed with three per cage.

EPM was done on a Plexiglas plus-maze elevated to a height of 35 cm.

• It had two open arms and two closed arms.

• Gerbils are placed into center of maze facing an open arm.

Observer is blind to which group they are observing.

Gerbils are given known drugs with anxiolytic effects to see if this paradigm is applicable to gerbils.

The maze had to be adapted due to the "hopping-style" locomotion seen in gerbils.

In the end, the gerbil displays an anxiety-like behavioral profile similar to the rats and mice under specific conditions.