Cannabis / Hennep

Cannabis is a leafy annual, with some varieties attaining heights of more than 3 m. The stalk may grow 7.6 to 10 cm thick, is square and hollow, and has ridges running along its length. Each leaf has 5 to 11 soft-textured leaflets, 18 to 25 cm long, radiating from the top of the stalk. The leaflets are narrow and lance-shaped with regular sawblade-like dentation. The plant is dioecious, having male or female flowers on different plants. The female plants have heavy foliage, while the male plants are more sparse. The resin mixture is found in the glandular hairs of the leaflets and floral bracts and is called hashish. Cannabis is cultivated worldwide for fiber, seed oil, and hashish. 1 , 2


The use of cannabis dates back more than 4,000 years in central Asia. It has been used for the treatment of catarrh, leprosy, fever, dandruff, hemorrhoids, obesity, asthma, urinary tract infections, loss of appetite, inflammatory conditions, and cough. It has also been used as a source of fiber for ropes and clothing. The plant's sedative effects were recognized by the ancient Chinese, but the widespread use of the plant for its psychoactive effects began in the past century. 3 , 4

Cannabis as marijuana is a schedule 1 controlled substance in the United States, with synthetic cannabinoids registered for specific indications as Marinol (THC as dronabinol), indicated as an antiemetic for chemotherapy-induced nausea and vomiting and the treatment of AIDS-related wasting syndrome, and Cesamet (nabilone), used as an antiemetic in cancer patients. The orobuccal spray Sativex is approved for multiple sclerosis spasticity in Canada and use was recently approved in the United Kingdom. 5 , 6 , 7


More than 420 different compounds have been isolated from cannabis and reported in chemical literature. The most commonly described compounds are the cannabinoids (THC, cannabidiol, cannabiniol, and 60 other related compounds). In addition, marijuana contains alkaloids, steroidal compounds, and mixtures of volatile components. 5 , 6 , 8 Synthetic cannabinoids include nabilone, ajulemic acid, HU-210, and WIN 55,212-2, some of which are nonpsychotropic agonists of cannabinoid receptors. 9 , 10

The concentration of THC varies in different parts of the plant, being higher in the bracts, flowers, and leaves and lower in the stems, seeds, and roots. THC concentration varies from insignificant amounts in hemp varieties to 3% to 6% in smoked marijuana and more than 6% in the resinous, compressed paste obtained from the dried flowers. Different cultivation methods and varieties contribute to variations in potency. 5 , 11

Analysis of cannabis includes methods such as gas chromatography, high-performance liquid chromatography, random amplification of polymorphic DNA, and thin layer chromatography. These methods are useful in sample differentiation, forensic analysis, and other applications. 12 , 13 , 14 , 15 Radioimmunoassay of hair for marijuana presence in the body has also been performed. 16

Marijuana Uses and Pharmacology

Both exogenous and endogenous cannabinoids act on 2 receptors: CB1 receptors are found primarily in the CNS but also in lung, reproductive, and vascular endothelial tissue; CB2 receptors are found mainly in peripheral and immune-related tissue, but also in retinal and microglia cells. 5 , 8 , 17 Due to the illegality of marijuana possession and use in many jurisdictions, data from clinical trials is limited and much of the relevant documentation is based on retrospective data or case studies. 18

Appetite stimulant

Dronabinol is indicated for use as an appetite stimulant in HIV patients, although limited data exist. Self-reported increases in appetite (data obtained from surveys) have not been demonstrated in prospective, blind, and randomized clinical trials, with no improvements in quality of life measures found and no weight gain over placebo. 10 , 19

Cancer/chemotherapy-induced nausea and vomiting

Animal data

Cannabinoids, including THC, have been studied in rodents for their potential in inhibiting tumor growth via the induction of apoptosis and inhibition of angiogenesis. 20

Clinical data

Synthetic cannabinoid analogs dronabinol and nabilone have been approved by the FDA for the treatment of recalcitrant chemotherapy-induced nausea and vomiting; however, clinical data on efficacy of THC and medicinal cannabis is equivocal and the incidence of adverse events is higher than that of standard neuroleptics. 10 , 19 , 21 , 22 , 23 Some studies suggest greater efficacy in specific age groups (ie, children) with causative chemotherapeutic agents and with different delivery methods. 10 , 21 , 22


Animal data

Studies in rats and rabbits suggest cannabinoids act via various mechanisms in the eye. Suppression of dopamine and presynaptic transmitter release from cones and bipolar retinal cells has been demonstrated, 24 as well as mydriasis due in part to action via sympathomimetic pathways. 25 Reduced intraocular pressure has also been demonstrated in rabbits possibly through cyclooxygenase pathways. 26

Doses of 25 to 50 mcg topical THC, 31 and 5 mg oromucosal THC 32 reduced the intraocular pressure in studies in patients with resistant glaucoma. Delivery site and preparations may influence ophthalmic effects. 26

Clinical data

Clinical trials are generally lacking or of very small sample size. An early study achieved reductions in intraocular pressure at 1 hour after 2 g of marijuana was smoked via a water pipe, 27 with case reports suggesting similar findings. 28 , 29 An open-label study conducted by ophthalmologists found an initial reduction in intraocular pressure in 9 subjects with glaucoma unresponsive to standard therapy. However, the effect was not sustained at the end of the 9-month study and all participants elected to discontinue the therapy. Oral THC up to a maximum of 20 mg 4 times a day was used. 30 In another small study (N = 8), a single topical application of THC was effective in reducing the intraocular pressure after 30 minutes to a maximum effect at 60 minutes. 31 A randomized, double-blind, crossover study (N = 6) evaluating oromucosal delivery of THC and cannabidiol found THC to have some effect, but not cannabidiol. Intraocular pressure returned to baseline at 4 hours. 32

Multiple sclerosis

Animal data

Studies from in vitro and animal experiments support the effectiveness of cannabinoids in multiple sclerosis, including the reduction of oligodendrocyte and neuronal cell death, influence on inflammation and microglial migration, and enhancement of remyelination. 33 , 34 Experimentally, it has been demonstrated that antagonism of CB1 receptors (but not CB2 receptors) inhibits spasticity, but can sometimes transiently worsen it. 8

Clinical data

A number of small studies on marijuana use in multiple sclerosis have been published, as well as a large (N = 667) multicenter trial conducted in the United Kingdom. 33 , 35 , 36 , 37 , 38 Despite availability of clinical data from these trials, a definitive role for the use of cannabis extracts or its analogs in multiple sclerosis is still lacking. This is due in part to difficulty in obtaining objective clinical measures of reductions in spasticity, as most trials use self-reporting as the primary outcome measure. 8 , 33 , 34 The multicenter Cannabinoids in Multiple Sclerosis (CAMS) study found no effect on the primary outcome of muscle spasticity at 15 weeks; however, at 12 months a small improvement was found over baseline. 37 , 38 , 39 Improvements in self-reported outcomes of pain, spasticity, and spasms, and quality of sleep were recorded. No functional improvement in tremor was found in a short-term trial. 40

Improvements in urge incontinence were demonstrated in the CAMS study and other open-label trials. 8 , 33 , 41 Decreased incontinence episode rate was observed in both treatment arms of the study as well as in the placebo arm, but improvement was greater with cannabinoids compared with placebo. 41

A large, multicenter trial used initial doses of 5 mg oral THC daily, self-titrated up to 25 mg THC daily for up to 52 weeks. 38


Surveys reveal widespread usage of cannabis to manage pain among patients with HIV, multiple sclerosis, rheumatoid arthritis, and cancer. 42 , 43 , 44 THC has been shown to affect brain-derived neurotrophic factor involved in the health of neurons and modulate neuroplasticity, which may be relevant in processes underlying learning and memory. 45

Animal data

Results from experiments conducted in animals provide support for a therapeutic role in the management of pain. 46 , 47 Experiments are focusing on finding cannabinoid derivatives devoid of psychoactive properties, such as ajulemic acid. 9

Clinical data

Clinical trials investigating the efficacy of cannabis and derivatives have been conducted on acute postoperative pain, induced pain in volunteers, and chronic pain, including neuropathic pain and pain due to cancer. 48 Studies evaluating efficacy in postoperative pain have produced mixed results, with some reporting no difference compared with placebo (single dose of 5 mg of THC) and others showing a dose-dependent effect. 48 , 49 , 50 In volunteers, no effect on experimental pain (eg, pressure, heat, cold, electrical) was found with a single dose of 20 mg THC. 51 Similarly, no effect on the pain threshold was found in one study, while a modest analgesic effect was found in another. 52 , 53

In systematic reviews of clinical trials in chronic and neuropathic pain, including multiple sclerosis, HIV, and diabetic neuropathies, low to moderate decreases in pain have been demonstrated, with estimates of relative efficacy for THC compared with codeine for pain as 10 mg THC to 60 mg codeine. 8 , 48 , 54 , 55 The value of these results is moderated by a simultaneous increase in adverse events, with number-needed-for-harm estimates between 5 and 8 on visual analog scales for cognitive and motor function adverse events. 55 Clinical trials conducted after these reviews produced mixed results, with some, 56 , 57 but not all, 58 , 59 demonstrating greater pain reduction with THC than with placebo.

Estimates of relative efficacy for THC compared with codeine for pain are 10 mg THC to 60 mg codeine 48 THC is distributed rapidly throughout the body, especially to tissues with high lipid content. Approximately 80% to 90% of an IV dose of THC is excreted in urine and the remainder is excreted in feces via the bile. 70


Limited studies have evaluated the efficacy of cannabinoids in sleep disorders, 60 , 61 , 62 anxiety, 63 , 64 dyskinesia, 65 and Tourette syndrome 66 , 67 with mixed results.


Hempseed oil has shown no benefit with regard to changes in the lipid profile, plasma glucose, or insulin. 68 , 69


Information regarding safety and efficacy of medicinal marijuana in pregnancy and lactation is lacking. Avoid use. In retrospective studies, marijuana use has had a modest effect on fetal growth. Some mild developmental abnormalities have been associated with maternal use of the drug during pregnancy, but were not sustained in the long term (at 3 years of age), and no apparent differences in IQ were noted. Data, however, are inconsistent. 71 , 72 , 73 THC crosses the placental barrier and is excreted in breast milk. 72 Lower baseline plasma prolactin levels have been demonstrated with frequent cannabis use. 74


None well documented. Potentiation of analgesic medicines can be expected. 75 A study conducted in rats found that cannabis inhibited the CYP-450 pathway. 47

Adverse Reactions

Medical marijuana or its analogs are regarded as having a relatively positive safety profile, but supportive studies are limited. 6 High doses are rarely fatal; however, a narrow dosing index exists between desired medicinal benefit and undesirable adverse reactions. Study dropouts are commonly recorded, due mainly to the impairment of cognitive ability (eg, attention, working memory) and GI disturbances. 6 , 76 , 77 Nonserious adverse events due to medicinal cannabinoid use were found to be 1.86 times higher than those seen with placebo in a systematic review of clinical studies. 77 White lesions in the mouth similar to chemical burns have been reported with the use of oromucosal cannabinoids. 78 Increases in plasma cortisol due to administered THC have been demonstrated, 74 and increases in heart rate and both transient hypotension and increased systolic blood pressure have also been recorded. 2 An increased risk of cardiovascular events, such as acute myocardial infarction, has been suggested. 71

No serious adverse events were reported in a 12-month study of cannabis use in multiple sclerosis patients. 38 A systematic review of studies using medicinal cannabinoids, but not nabilone, found no difference in serious adverse events and no difference in death versus placebo. 77 A study evaluating the use of oral Cannador in postoperative pain was terminated due to a vasovagal event in 1 patient. 50


No consensus exists on the risk of lung cancer from smoked medical marijuana, despite a plausible biological rationale and epidemiological data. The risks of medical marijuana should be considered in the context of applications in intractable diseases. 71 , 79 Likewise, the potential for addiction and risk of inducing mental illness is debated. 80 A systematic review found an increased risk of psychotic outcomes with the use of cannabis (odds ratio 1.41; 95% CI 1.20 to 1.65). 81

A systematic review of long-term toxicity due to nonmedical (recreational) cannabis use found increased risks for psychotic, respiratory, and cardiovascular events, as well as for cancers of the lung, head and neck, brain, cervix, prostate, and testis. 73 Heavy cannabis use is also associated with bone loss. 73


1. Cannabis sativa . USDA, NRCS. 2007. The PLANTS Database ( , May, 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.

2. Cohen PJ. Medical marijuana: the conflict between scientific evidence and political ideology. Part one of two. J Pain Palliat Care Pharmacother . 2009;23(1):4-25.

3. Duke JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1985: 9697.

4. Fehr K, et al. Cannabis and Health Hazards . Toronto, Canada: Addiction Research Foundation; 1983.

5. Seamon MJ. The legal status of medical marijuana. Ann Pharmacother . 2006;40(12):2211-2215.

6. Wilkins MR; Working Party on Cannabis and Cannabis -based Medicines. Cannabis and Cannabis -based medicines: potential benefits and risks to health. Clin Med . 2006;6(1):16-18.

7. Cannabis -based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. Drugs R D . 2003;4(5):306-309.

8. Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurol . 2003;2(5):291-298.

9. Burstein SH, Karst M, Schneider U, Zurier RB. Ajulemic acid: A novel cannabinoid produces analgesia without a “high.” Life Sci . 2004;75(12):1513-1522.

10. Di Marzo V, Petrocellis LD. Plant, synthetic, and endogenous cannabinoids in medicine. Ann Rev Med . 2006;57:553-574.

11. Cohen PJ. Medical marijuana: the conflict between scientific evidence and political ideology. Part two of two. J Pain Palliative Care Pharmacother . 2009;23(2):120-140.

12. Lerckher G, Bocci F, Frega N, Bortolomeazzi R. Cannabinoid acids analysis. Farmaco . 1992;47(3):367-378.

13. Debruyne D, Albessard F, Bigot MC, Moulin M. Comparison of three advanced chromatographic techniques for cannabis identification. Bull Narc . 1994;46(2):109-121.

14. Petri G, Nyiredy S, Veszki P, Oroszlán P, Turiák G. Gas chromatographic analysis of cannabinoids on tandem columns [in Hungarian]. Acta Pharm Hung . 1995;65(3):63-67.

15. Gillan R, Cole MD, Linacre A, Thorpe JW, Watson ND. Comparison of Cannabis sativa by random amplification of polymorphic DNA (RAPD) and HPLC of cannabinoids: a preliminary study. Sci Just . 1995;35(3):169-177.

16. Hindin R, McCusker J, Vickers-Lahti M, Bigelow C, Garfield F, Lewis B. Radioimmunoassay of hair for determination of cocaine, heroin, and marijuana exposure: comparison with self-report. Int J Addict . 1994;29(6):771-789.

17. Bari M, Battista N, Fezza F, Gasperi V, Maccarrone M. New insights into endocannabinoid degradation and its therapeutic potential. Mini Rev Med Chem . 2006;6(3):257-268.

18. American Medical Association. Use of cannabis for medicinal purposes. Report 3 of the Council on Science and Public Health (I-09). Available at: . Accessed April 17, 2010.

19. Cannabis -In-Cachexia-Study-Group, Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis -In-Cachexia-Study-Group. J Clin Oncol . 2006;24(21):3394-3400.

20. Blázquez C, Carracedo A, Salazar M, et al. Down-regulation of tissue inhibitor of metalloproteinases-1 in gliomas: a new marker of cannabinoid antitumoral activity? Neuropharmacology . 2008;54(1):235-243.

21. Machado Rocha FC, Stéfano SC, De Cássia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl) . 2008;17(5):431-443.

22. Engels FK, de Jong FA, Mathijssen RH, Erkens JA, Herings RM, Verweij J. Medicinal cannabis in oncology. Eur J Cancer . 2007;43(18):2638-2644.

23. Di Carlo G, Izzo AA. Cannabinoids for gastrointestinal diseases: potential therapeutic applications. Expert Opin Investig Drugs . 2003;12(1):39-49.

24. Yazulla S. Endocannabinoids in the retina: from marijuana to neuroprotection. Prog Retin Eye Res . 2008;27(5):501-526.

25. Korczyn AD, Eshel Y. Mydriasis induced by tetrahydrocannabinol (THC) in rats. Invest Ophthalmol Vis Sci . 1982;22(3):408-410.

26. Green K, Kearse EC, McIntyre OL. Interaction between delta-9-tetrahydrocannabinol and indomethacin. Ophthalmic Res . 2001;33(4):217-220.

27. Hepler RS; Frank IR. Marihuana smoking and intraocular pressure. JAMA . 1971;217(10):1392.

28. Trittibach P, Frueh BE, Goldblum D. Bilateral angle-closure glaucoma after combined consumption of "ecstasy" and marijuana. Am J Emerg Med . 2005;23(6):813-814.

29. Zhan GL, Camras CB, Palmberg PF, Toris CB. Effects of marijuana on aqueous humor dynamics in a glaucoma patient. J Glaucoma . 2005;14(2):175-177.

30. Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc . 2002;100:215-222.

31. Porcella A, Maxia C, Gessa GL, Pani L. The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur J Neurosci . 2001;13(2):409-412.

32. Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma . 2006;15(5):349-353.

33. Teare L, Zajicek J. The use of cannabinoids in multiple sclerosis. Expert Opin Investig Drugs . 2005;14(7):859-869.

34. Baker D, Pryce G. The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Investig Drugs . 2003;12(4):561-567.

35. Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler . 2004;10(4):434-441.

36. Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler . 2004;10(4):417-424.

37. Hosking RD, Zajicek JP. Therapeutic potential of cannabis in pain medicine. Br J Anaesth . 2008;101(1):59-68.

38. Zajicek JP, Sanders HP, Wright DE, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry . 2005;76(12):1664-1669.

39. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet . 2003;362(9395):1517-1526.

40. Fox P, Bain PG, Glickman S, Carroll C, Zajicek J. The effect of cannabis on tremor in patients with multiple sclerosis. Neurology . 2004;62(7):1105-1109.

41. Freeman RM, Adekanmi O, Waterfield MR, Waterfield AE, Wright D, Zajicek J. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int Urogynecol J Pelvic Floor Dysfunct . 2006;17(6):636-641.

42. Ware MA, Doyle CR, Woods R, Lynch ME, Clark AJ. Cannabis use for chronic non-cancer pain: results of a prospective survey. Pain . 2003;102(1-2):211-216.

43. Woolridge E, Barton S, Samuel J, Osorio J, Dougherty A, Holdcroft A. Cannabis use in HIV for pain and other medical symptoms. J Pain Symptom Manage . 2005;29(4):358-367.

44. Wright S, Ware M, Guy G. The use of a cannabis-based medicine ( Sativex ) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford) . 2006;45(6):781.

45. D'Souza DC, Pittman B, Perry E, Simen A. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology (Berl) . 2009;202(4):569-578.

46. Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol . 2007;556(1-3):75-83.

47. Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B. Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved. Phytother Res . 2008;22(8):1017-1024.

48. Karst M, Wippermann S. Cannabinoids against pain. Efficacy and strategies to reduce psychoactivity: a clinical perspective. Expert Opin Investig Drugs . 2009;18(2):125-133.

49. Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain . 2003;106(1-2):169-172.

50. Holdcroft A, Maze M, Doré C, Tebbs S, Thompson S. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract ( Cannador ) for postoperative pain management. Anesthesiology . 2006;104(5):1040-1046.

51. Naef M, Curatolo M, Petersen-Felix S, Arendt-Nielsen L, Zbinden A, Brenneisen R. The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Pain . 2003;105(1-2):79-88.

52. Kraft B, Frickey NA, Kaufmann RM, et al. Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology . 2008;109(1):101-110.

53. Wallace M, Schulteis G, Atkinson JH, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology . 2007;107(5):785-796.

54. Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin . 2007;23(1):17-24.

55. Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med . 2009;10(8):1353-1368.

56. Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain . 2008;9(6):506-521.

57. Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology . 2009;34(3):672-680.

58. Centonze D, Mori F, Koch G, et al. Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis. Neurol Sci . 2009;30(6):531-534.

59. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product ( Sativex ) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care . 2010;33(1):128-130.

60. Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain . 2004;112(3):299-306.

61. Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg . 2010;110(2):604-610.

62. Russo EB, Guy GW, Robson PJ. Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex , a cannabis-based medicine. Chem Biodivers . 2007;4(8):1729-1743.

63. Bhattacharyya S, Fusar-Poli P, Borgwardt S, et al. Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. Arch Gen Psychiatry . 2009;66(4):442-451.

64. Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, de Wit H. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci . 2008;28(10):2313-2319.

65. Carroll CB, Bain PG, Teare L, et al. Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology . 2004;63(7):1245-1250.

66. Müller-Vahl KR, Schneider U, Prevedel H, et al. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry . 2003;64(4):459-465.

67. Müller-Vahl KR, Prevedel H, Theloe K, Kolbe H, Emrich HM, Schneider U. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology . 2003;28(2):384-388.

68. Kaul N, Kreml R, Austria JA, et al. A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr . 2008;27(1):51-58.

69. Schwab US, Callaway JC, Erkkilä AT, Gynther J, Uusitupa MI, Järvinen T. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors. Eur J Nutr . 2006;45(8):470-477.

70. Mason AP, McBay AJ. Cannabis: pharmacology and interpretation of effects. J Forensic Sci . 1985:30(3);615-631.

71. Hall W, Degenhardt L. Medical marijuana initiatives: are they justified? How successful are they likely to be? CNS Drugs . 2003;17(10):689-697.

72. Davies JK, Bledsoe JM. Prenatal alcohol and drug exposures in adoption. Pediatr Clin North Am . 2005;52(5):1369-1393, vii.

73. Reece AS. Chronic toxicology of cannabis. Clin Toxicol (Phila) . 2009;47(6):517-524.

74. Ranganathan M, Braley G, Pittman B, et al. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology (Berl) . 2009;203(4):737-744.

75. Lynch ME, Clark AJ. Cannabis reduces opioid dose in the treatment of chronic non-cancer pain. J Pain Symptom Manage . 2003;25(6):496-498.

76. Roser P, Juckel G, Rentzsch J, Nadulski T, Gallinat J, Stadelmann AM. Effects of acute oral Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers. Eur Neuropsychopharmacol . 2008;18(8):569-577.

77. Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ . 2008;178(13):1669-1678.

78. Scully C. Cannabis; adverse effects from an oromucosal spray. Br Dent J . 2007;203(6):E12;336-337.

79. Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med . 2006;166(13):1359-1367.

80. Degenhardt L, Hall WD. The adverse effects of cannabinoids: implications for use of medical marijuana. CMAJ . 2008;178(13):1685-1686.

81. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet . 2007;370(9584):319-328.

American Herbal Pharmacopoeia Releases Scientific Review of Cannabis for Seizures and Epilepsy

by Tyler Smith

HerbalGram. 2014; American Botanical Council

The nonprofit American Herbal Pharmacopoeia (AHP) recently issued a draft of its comprehensive review of medicinal cannabis for difficult-to-treat seizure conditions, including epilepsy. AHP’s announcement in mid-March came roughly six months after Illinois became the 20th state to legalize medical marijuana (Cannabis spp., Cannabaceae) and as proposed medicinal cannabis legislation was being debated in 15 other states.1

The document — titled “Cannabis in the Management and Treatment of Seizures and Epilepsy”2 — is an excerpt from AHP’s forthcoming Cannabis Therapeutic Compendium, which will be published later this year. The compendium contains “numerous scientific reviews [encompassing] the broad range of science regarding the therapeutic effects and safety of cannabis”3 and is the companion document to AHP’s historic cannabis quality standards monograph released in December 2013, the first document of its kind to be published in the United States for more than 70 years.4

Despite AHP’s two recent publications on cannabis, the organization is chiefly an herbal medicine education nonprofit without vested interests in any particular herb. AHP is known for producing meticulously researched herb monographs and literature reviews. Its 34th monograph — on aloe vera (Aloe vera, Xanthorrhoeaceae) leaf, leaf juice, and inner leaf juice — was released in December 2012.5

“AHP is not a cannabis advocacy organization,” explained AHP Executive Director Roy Upton (email, March 25, 2014). “Our job is simply to provide a scientific and critical review of the literature. How it is interpreted or used is up to the readers.”

AHP released its review of cannabis for seizures and epilepsy amid increased news coverage of the use of medical marijuana, particularly by children with these neurological disorders. CNN’s Chief Medical Correspondent Sanjay Gupta, MD, brought national attention to the issue in his August 2013 documentary Weed, which focused on the story of a six-year-old girl in Colorado whose intractable seizures were controlled by a cannabis extract when conventional pharmaceutical medications failed to work.6 Dr. Gupta’s follow-up documentary (see page 30 for a review by HerbalGram Managing Editor Ash Lindstrom) aired on March 11, 2014, the day before AHP released its review document, and reiterated that select cannabis extracts are effective for the management of seizures.7

“In recent months there has been considerable attention given to the potential benefit of cannabis for treating intractable seizure disorders including rare forms of epilepsy,” AHP noted in its press release.3 “For this reason, the lead author of the section, Ben Whalley, PhD, and AHP felt it important to release this section, in its near-finalized form, into the public domain for free dissemination.”

Dr. Whalley, director of research at the University of Reading’s School of Pharmacy in the United Kingdom, has published multiple papers on cannabis for the treatment of seizure disorders with a focus on the underlying brain mechanisms of these conditions.3

“Releasing this section of the monograph,” Dr. Whalley stated in AHP’s press release, “provides clinicians, patients, and their caregivers with a single document that comprehensively summarizes the scientific knowledge to date regarding cannabis and epilepsy and so fully support informed, evidence-based decision making.”3

According to the Maryland-based Epilepsy Foundation, approximately 2.3 million Americans currently live with this often-debilitating neurological condition. “There is an enormous unmet need for better treatments for children and adults with epilepsy,” wrote Orrin Devinsky, MD, a member of the Epilepsy Foundation’s National Board of Directors and director of New York University’s Comprehensive Epilepsy Center, in a commentary article accompanying a recent press release from the Epilepsy Foundation.8

“Approximately one-third of people with epilepsy continue to suffer from seizures despite the best medical, dietary, and surgical therapies,” Dr. Devinsky continued. These effects, he said, are often “compounded by the disabling physical, cognitive and behavioral side effects from high doses of multiple antiepileptic drugs.”8

The Epilepsy Foundation has publicly called on the US Drug Enforcement Agency to reclassify cannabis,8 which is currently a Schedule I controlled substance — a category for substances deemed to have a high potential for abuse and no accepted medical use in the United States. This restrictive classification, the Foundation says, significantly hampers research efforts and limits patient access to potentially beneficial medicine.

“[A]n end to seizures should not be determined by one’s zip code,” the Epilepsy Foundation stated in a press release from March 20.8 “If a patient and their healthcare professionals feel that the potential benefits of medical marijuana for uncontrolled epilepsy outweigh the risks, then families need to have that legal option now — not in five years or ten years.”7

Although the field of medical marijuana research in the United States is still in its infancy, current evidence suggests cannabis may have positive effects in seizure treatment.2 Due to the limited amount of human research, conflicting findings, and varying study quality, however, firm conclusions about the efficacy of cannabis for seizures and epilepsy should not be made at this time.

“The available literature (case studies, surveys, and pre-clinical data) on the use of cannabis and its constituents for the treatment of epilepsy and seizures in humans suggests there is a general consensus that cannabis exerts an anticonvulsant effect,” Dr. Whalley stated.2 “[W]hilst high CBD and low THC strains … appear to be effective, their long-term efficacy and safety have not yet been properly demonstrated in well-controlled clinical trials.”

Dr. Devinsky noted that highly publicized anecdotal reports of cannabis as a “miracle cure” for treatment-resistant seizures, coupled with the current lack of a scientific consensus regarding its efficacy, can put physicians in a difficult situation.

“We stand at an unusual inflection point where families are demanding access to a medication that may or may not be beneficial, and for which the side effects may be less than many medications prescribed by doctors; the medical community lacks convincing efficacy or safety data for children with epilepsy; and the Drug Enforcement Agency’s overly conservative scheduling of marijuana hamstrings research and access,” he wrote.8 “We urgently need data from randomized controlled trials where the biases of companies, doctors, patients, and parents are meticulously removed.”

AHP’s document, “Cannabis in the Management and Treatment of Seizures and Epilepsy,” can be downloaded free of charge at A printed copy of AHP’s Standards of Identity, Analysis, and Quality Control Cannabis monograph can be purchased for $44.95 on AHP’s website.


1. 15 states with pending legislation to legalize medical marijuana (as of Mar. 24, 2014). website. Available at: Accessed March 21, 2014.

2. Whalley B. Cannabis in the Management and Treatment of Seizures and Epilepsy. Scotts Valley, CA: American Herbal Pharmacopoeia; March 12, 2014. Available at: Accessed March 18, 2014.

3. AHP Releases Cannabis in the Management and Treatment of Seizures and Epilepsy: A Scientific Review [press release]. Scotts Valley, CA: American Herbal Pharmacopoeia; March 12, 2014. Available at: Accessed March 18, 2014.

4. Smith T. American Herbal Pharmacopoeia publishes historic monograph on cannabis. HerbalGram. 2013;101:24-25. Available at: Accessed March 21, 2014.

5. Smith T. AHP releases quality control standards monograph for aloe vera. HerbalEGram. 2013;10(1). Available at: Accessed March 26, 2014.

6. Gupta S. Why I changed my mind on weed. CNN Website. Available at: Accessed March 21, 2014.

7. Gupta S. Gupta: ‘I am doubling down’ on medical marijuana. CNN website. Available at: Accessed March 21, 2014.

8. Epilepsy Foundation calls for increased medical marijuana access and research [press release]. Landover, MD: Epilepsy Foundation; March 20, 2014. Available at: Accessed March 21, 2014.

What is CBD?

Cannabidiol or CBD is a non-intoxicating component of the cannabis plant with enormous therapeutic potential. Although CBD doesn’t make people feel high like THC does, it’s causing quite a buzz among scientists, health professionals, and medical marijuana patients who are using CBD-rich products to treat a wide range of conditions - chronic pain, cancer, Crohn’s, diabetes, rheumatoid arthritis, PTSD, cardiovascular disease, anxiety, antibiotic-resistant infections, multiple sclerosis, schizophrenia, and more. Academic research centers in the United States and elsewhere are currently studying the effects of CBD on these and other ailments. Scientists refer to CBD as a “promiscuous” compound because it confers therapeutic benefits in many different ways while tapping into how we function physiologically and biologically on a deep level. Extensive preclinical research and some clinical studies have shown that CBD has strong anti-oxidant, anti-inflammatory, anticonvulsant, anti-depressant, anti-psychotic, anti-tumoral, and neuroprotective qualities. Cannabidiol can change gene expression and remove beta amyloid plaque, the hallmark of Alzheimer’s, from brain cells.

Which is better CBD or THC? Cannabidiol and THC (The High Causer) are the power couple of cannabis therapeutics; they work best together. CBD and THC interact synergistically to potentiate each other’s curative qualities. CBD enhances THC’s painkilling and anticancer properties, while lessening THC’s psychoactivity. CBD can also mitigate adverse effects caused by too much THC, such as anxiety and rapid heartbeat. When both compounds are present in sufficient amounts in the same cannabis strain or product, CBD will lower the ceiling on the THC high while prolonging its duration. (“Relaxing but not intoxicating” is how one patient described CBD-rich cannabis.) CBD broadens the range of conditions treatable with cannabis, such as liver, cardiovascular and metabolic disorders, which may be less responsive to THC-dominant remedies. CBD and THC both stimulate neurogenesis, the creation of new brain cells, in adult mammals.

What’s the best way to take CBD? The most appropriate delivery system for CBD-rich cannabis is one that provides an optimal dose for a desired duration with few unwanted side effects. CBD-rich cannabis flower varietals for smoking or vaping are available in many medical marijuana dispensaries, but most CBD patients prefer non-inhalable products made with cannabis oil concentrates. Although banned by federal law, measurable doses of potent CBD-rich cannabis remedies are available in many non-smokable forms and can be utilized in various ways. The time of onset and duration of effect vary depending on the method of administration. CBD-rich cannabis oil products can be taken sublingually, orally (as edibles, lozenges, beverages, tinctures, and gel caps), or applied topically. Concentrated cannabis oil extracts can also be heated and inhaled with a vape pen. Inhalation is good for treating acute symptoms that require immediate attention; the effects can be felt within a minute or two and typically last for a couple of hours. The effects of orally administered CBD-rich cannabis oil can last for four hours or more, but the onset of effects is much slower (30-90 minutes) than inhalation.

Can CBD cure epilepsy? Marijuana has a rich history as a medicine for quelling seizures and convulsions going back thousands of years. In the mid-19th century, the U.S. Pharmacopeia listed cannabis tincture as a treatment for pediatric epilepsy, and subsequent scientific studies have documented the anticonvulsant effects of CBD, THC, and whole plant cannabis. CBD-dominant/low- THC cannabis strains and oil extracts can facilitate dramatic improvement in some children with intractable seizure disorders. Between 10-15 percent of severe childhood epileptics who are given CBD oil products experience a near complete cessation of seizures; most improve (with a decrease but not total elimination of seizures); and some children have worse seizures when they take CBD. Many parents of epileptic children have learned through trial and error that augmenting CBD-rich oil by adding some THC -- or better yet, THCA, the unheated, non-psychoactive form of THC that’s present in raw cannabis flowers and leaves -- helps with seizure control. The take-home message: Low-THC cannabis oil products don’t work for everyone. Patients of all ages need access to a wide spectrum of whole plant cannabis remedies, not just high CBD oil.

What is the right CBD:THC ratio for me? Cannabis therapeutics is personalized medicine. There is no single ratio or strain or product that’s right for everyone. Optimize your therapeutic use of cannabis by finding the proper combination of CBD and THC that works best for you. A person’s sensitivity to THC is a key factor in determining the appropriate ratio and dosage of CBD-rich medicine. Many people enjoy the cannabis high and can consume reasonable amounts of any cannabis product without feeling too high or dysphoric. Others find THC unpleasant. CBD can lessen or neutralize the intoxicating effects of THC. So a greater ratio of CBD-to- THC means less of a high. In some states with medical marijuana laws, cannabis oil concentrates and other products with varying ratios of CBD:THC are available so users can adjust or minimize psychoactive effects to suit their needs and sensitivities. Those who don’t like THC have the option of healing without the high by using a CBD-rich remedy with only a small amount of THC. But a low THC remedy, while not intoxicating, is not always the most effective treatment option. In essence, the goal is to administer consistent, measurable doses of a CBD-rich remedy that includes as much THC as a person is comfortable with.

Are specific CBD:THC ratios better for different conditions? Some patterns are beginning to emerge. For anxiety, depression, spasms, psychosis, and seizure disorders, many people report they do well starting with a small dose of a CBD-rich remedy with little THC. For cancer, autism, and many other diseases, some say they benefit more from a balanced ratio of CBD and THC. Extensive clinical trials conducted outside the United States have shown that a 1:1 CBD:THC ratio can be effective for neuropathic pain. Some people use cannabis products with different CBD:THC ratios at different times of the day (more CBD for sunlight hours, more THC at night). Almost any cannabis strain or product theoretically could benefit a wide range of autoimmune and inflammatory disorders because THC and other cannabis components activate the CB2 cannabinoid receptor, which regulates immune function. Note: The CBD:THC ratio in not an indication of how much CBD or THC is present in a given cannabis product or strain.

What is the optimal dosage of CBD? An effective dosage can range from as little as a few milligrams of CBD-enriched cannabis oil to a gram or more. Begin with a small dose of high CBD/low THC oil, especially if you have little or no experience with cannabis. Take a few small doses over the course of the day rather than one big dose. Use the same dose and ratio for several days. Observe the effects and if necessary adjust the ratio or amount. Don’t overdo it. Cannabis compounds have biphasic properties, which means that low and high doses of the same substance can produce opposite effects. Small doses of cannabis tend to stimulate; large doses sedate. Too much THC, while not lethal, can amplify anxiety and mood disorders. CBD has no known adverse side effects, but an excessive amount of CBD could be less effective therapeutically than a moderate dose. “Less is more” is often the case with respect to cannabis therapy.

What should one look for when choosing a CBD-rich product? Look for products with clear labels showing the quantity and ratio of CBD and THC per dose, a manufacturing date, and a batch number (for quality control). Select products with quality ingredients: No corn syrup, transfats, GMOs, artificial additives, thinning agents or preservatives. CBD-rich products should be lab tested for consistency and verified as being free of mold, bacteria, pesticides, solvent residues, and other contaminants. Best to avoid products extracted with toxic solvents like BHO, propane, hexane or other hydrocarbons. Opt for products that utilize safer extraction methods such as supercritical CO2 or food-grade ethanol.

If CBD is so good, won’t pure CBD be even better? Single-molecule CBD will inevitably become a federally approved Big Pharma medicine. Products infused with a crystalline CBD isolate, derived and extensively refined from industrial hemp, are already being marketed by unregulated internet storefronts. But single-molecule CBD is less effective therapeutically than whole plant CBD-rich oil extract. Scientific studies have established that synthetic, single-molecule CBD has a very narrow therapeutic window and requires precise, high doses for efficacy, whereas lower dose, whole-plant, CBD-rich treatment regimens are already showing efficacy for many conditions among patients in medical marijuana states. Whether synthesized in a Big Pharma lab or derived from industrial hemp, single-molecule CBD lacks critical secondary cannabinoids and other medicinal compounds found in high-resin cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits. Scientists call this the “entourage effect.” Numerous cannabis compounds have medicinal attributes, but the therapeutic impact of whole plant cannabis is greater than the sum of its parts.

Is there a difference between CBD derived from hemp and CBD derived from marijuana? If you live in a state where medical marijuana is legal and available, look for CBD products made from high-resin cannabis (rather than low resin industrial hemp) that are sold in medical marijuana dispensaries. Hemp-derived CBD-infused products of varying quality are also available via dozens of internet storefronts. Compared to whole plant CBD-rich cannabis, industrial hemp is typically low in cannabinoid content. A huge amount of hemp is required to extract a small amount of CBD, thereby raising the risk of contaminants because hemp, a bioaccumulator, draws toxins from the soil. That’s a great feature for restoring a poisoned ecosystem, but it’s not recommended for extracting medicinal oil. Heavily refined CBD paste or terpene-free CBD powder is poor starter material for formulating CBD-rich oil products. The FDA has tested dozens of so-called CBD “hemp oil” products and found that in many cases these products contained little or no CBD. CBD-infused nutraceuticals have not been approved by the FDA as food supplements; nor are these products legal in all 50 U.S. states. By and large, however, interstate CBD commerce is tolerated by federal authorities.

Is it safe to inhale hemp CBD oil fumes from a vape pen? Many cannabis- and hemp-derived CBD vape oil products include a thinning agent, which dilutes the oil that is heated and inhaled by vape pen users. Beware of vape pen oil that contains propylene glycol. When overheated, this chemical additive produces formaldehyde, a carcinogen, as a byproduct, according to a 2015 report in the New England Journal of Medicine. Why do so many vape oil products contain this thinning agent? It’s because of the dubious quality of the extracted material from which these unregulated cannabis oil products are made.

Does CBD have any adverse side effects? What about drug interactions? CBD is a very safe substance, but patients taking other medications should check with their doctor about drug interactions, which are more likely when consuming high doses of single-molecule CBD products. At sufficient dosages, CBD will temporarily deactivate cytochrome P450 enzymes, thereby altering how we metabolize a wide range of compounds, including THC. Cytochrome P450 enzymes metabolize more than 60 percent of Big Pharma meds. CBD is a more potent inhibitor of cytochrome P450 than the grapefruit compound Bergapten, so ask your doctor if grapefruit interacts with your medication. If grapefruit does, then CBD probably does, too. Patients on a CBD-rich treatment regimen should monitor changes in blood levels of prescription medications and, if need be, adjust dosage.