Written by Natalie Magaya-Kalbermatten and the CAM-Cancer Consortium.
Updated January 19, 2016

Medical cannabis and cannabinoids

Is it safe ?

Adverse events

A number of adverse events have been observed after the intake of medical cannabis and cannabinoids. Some may be welcome, such as mood enhancement or sedation.

Commonly reported adverse effects on the central nervous system comprise alteration of mood (euphoria as well as dysphoria), depression, anxiety and paranoia, sensation of depersonalisation, hallucinations, memory impairment, blurred vision and dizziness.1 Cardiovascular adverse effects are hypotension and tachycardia. In addition, patients frequently complain of dry mouth.

A systematic review investigated the adverse events of cannabis-based medicines in 23 randomised controlled trials.36 The cannabis-based preparations examined were nabiximols, oral whole-plant extracts and isolated delta-9-tetrahydrocannabinol (THC). The rate of non-serious adverse events was higher among participants assigned to the cannabis-based medicine groups than to the control, but not for serious adverse events. The most commonly reported adverse event in the active groups was dizziness (15.5%).

Patients who intake cannabis-based medicines over the long term may develop tolerance, not only for the psychoactive but also for the cardiovascular side-effects. Long-term intake of cannabis-based medicines should therefore not be stopped abruptly.1  The overall risk for physical and psychic dependency seems to be low in comparison with opioids, tobacco, alcohol and benzodiazepines.1

Cannabinoids can change DNA synthesis and cell reproduction in vitro, but there is no evidence of mutagenic effects or of long-term carcinogenicity of orally administered cannabinoids.37

Interactions

Pharmacokinetic interactions from medical cannabis and cannabinoids may occur because of interference with metabolism at the cytochrome P450 subsystem in the liver (Cyt P450 3A4), and may theoretically lead to delayed elimination of, for example, fentanyl. Interactions are also possible with known inhibitors (ritanovir, estradiol etc.) or inductors of Cyt P450 3A4 (rifampicin, phenytoin, carbamazepin, St John’s wort).11

There is evidence that cannabinoids interact pharmacodynamically with levodopa and similar anti-Parkinson drugs.38 Currently, the use of anti-Parkinson drugs is a contraindication for cannabis-based medicines.

Little is known so far about possible interactions with other centrally active drugs, especially psychiatric medication or with herbal products.

Contraindications

Epidemiologic data have shown an association between heavy adolescent use of smoked cannabis with the development of psychotic disorders.39 Even though no causality between use of cannabis and psychotic disorders has been shown, a history or family history of psychotic disorders is generally seen as contraindication for the use of cannabis-based medicines.

The placental barrier is crossed by THC, and also accumulates in breast milk. Controversy exists regarding findings for the effects of cannabinoids on male reproduction, although there is some evidence that cannabinoids decreases sperm count and motility.40 Therefore, pregnant and breast-feeding women, and women and men who wish to have children, must not use cannabinoid products.

Some medical cannabis or cannabinoid preparations contain additives, e.g. sesame oil, which are contraindicated in people who may be allergic to these substances.41

Warnings/precautions

The use of cannabis-based medicines might impair the ability to drive a car, especially during any phases during which a dosage is being increased.

Citation

Natalie Magaya-Kalbermatten, CAM-Cancer Consortium. Cannabis and cannabinoids [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Cannabis-and-cannabinoids. January 19, 2016.

Document history

Fully revised and updated by Natalie Magaya-Kalbermatten in December 2015.

Last updated in November 2011 by Gabriele Dennert.
Fully updated and revised in November 2009 by Gabriele Dennert.
Summary first published in November 2005, authored by Gabriele Dennert.

References

  1. Grotenhermen F (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet; 42:327-360.
  2. Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004.
  3. Walsh D, Nelson KA, Mahmoud FA (2003). Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer; 11:137-143.
  4. Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (Eds). Mutschler Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2001.
  5. Russo E. History of cannabis as a medicine. In: Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004; pp. 1-16.
  6. Cota D, Marsicano G, Lutz B, Vicennati V, Stalla GK, Pasquali R et al.  Endogenous cannabinoid system as a modulator of food intake. Int J Obesity 2003; 27:289-301.
  7. Martin BR, Wiley JL. Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain. J Support Oncol 2004; 2(4):305-314.
  8. Townsend DW 4th, Thayer SA, Brown DR. Cannabinoids throw up a conundrum. Br J Pharmacol 2002; 137(5):575-577.
  9. Brenneisen R. Pharmakokinetik. In: Grotenhermen F (Ed). Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potenzial. Bern: Hans Huber Verlag, 2001; pp. 87-92.
  10. Robson PJ, Guy GW. Clinical studies of cannabis-based medicines. In: Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids, London: Pharmaceutical Press, 2004; pp. 229-269.
  11. Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013; 33(2):195-209.
  12. Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 2006; 66(2):234-246.
  13. Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012; 367(1607):3364-3378.
  14. Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009; 16(2-3):97-110.
  15. Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Eur J Pharmacol 1974; 28(1):172-177.
  16. Grotenhermen F (Ed). Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potenzial. Bern: Hans Huber Verlag, 2001.
  17. Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract 2005; 59:291-295.
  18. Gorter RW, Butorac M, Cobian EP, van der Sluis W. Medical use of cannabis in the Netherlands. Neurology 2005; 64(5):917-919.
  19.  International Association for Cannabinoid Medicines website. Available at:  http://www.cannabis-med.org/ www.acmed.org. Accessed 21st October 2011.
  20. Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain 2012; 13(5):438-449.
  21. Tramer MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001; 323(7303):16-21.
  22. Machado Rocha FC, Stéfano SC, de Cássia Haiek R, Rosa Oliviera LMQ, 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.
  23. Phillips RS, Gopaul S, Gibson F, Houghton E, Craig JV, Light K et al. Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev 2010; 9: CD007786. doi: 10.1002/14651858.CD007786.pub2
  24. Meiri E, Jhangiani H, Vredenburg JJ, Barbato LM, Carter FJ, Yang HM et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 2007; 23(3):533-543.
  25. Duran M, Pérez E, Abanades S, Vidal X, Saura C, Majem M et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 2010; 70(5):656-663.
  26. Priestman SG, Priestman TJ, Canney PA. A double-blind randomised cross-over comparison of nabilone and metoclopramide in the control of radiation-induced nausea. Clinical Radiol 1987; 38(5):543-544.
  27. Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M. Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. J Support Oncol 2008; 6(3):119-124.
  28. Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002; 20(2):567-573.
  29. Cannabis-In-Cachexia-Study-Group, Strasser F, Lueftner D, Possinger K, Ernst G, Ruhstaller T et al. Comparison of orally administered cannabis extract with 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(2):3394-3400.
  30. Brisbois TD, de Kock IH, Watanabe SM, Mirhosseinie M, Kamoureux DC, Chasen M et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo controlled pilot trial. Ann Oncol 2011; 22(9):2086-2093.
  31. Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage 2010; 39(2):167-179.
  32. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12(5):489-95.
  33. Campbell FA, Tramèr MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BMJ 2001; 323(3703):13-16.
  34. Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage 2013; 46(2):207-218.
  35. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 2014; 47(1):166-73.
  36. Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ 2008; 178(13):1669-1678.
  37. Hall W, Christie M, Currow D. Cannabinoids and cancer: causation, remediation, and palliation. Lancet Oncol 2005; 6(1):35-42.
  38. Notcutt W. Cannabis in the treatment of chronic pain. In: Guy GW, Whittle BA, Robson PJ (Eds).  The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004; pp. 271-299.
  39. Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370(9584):319-328.
  40. Rossato M, Ion PF, Ferigo M, Clari G, Foresta C. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005; 90(2):984-991.
  41. Slatkin NE. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis. J Support Oncol 2007; 5(Suppl. 3): 1-9.