Written by Gabriele Dennert and the CAM-Cancer Consortium.
Updated November 25, 2011

Cannabinoids

Is it safe ?

Adverse events

A number of adverse effects have been observed after intake of cannabinoids, some of which may be welcome, such as mood enhancement or sedation. However, serious dose-limitating side effects have also been frequently reported. Most adverse effects appear to be dose-related and more severe in the elderly9.

Central nervous adverse effects comprise alteration of mood (euphoria as well as dysphoria), depression, anxiety and paranoia, sensation of depersonalisation, hallucinations, drowsiness, muddled thinking, loss of coordination/ataxia, blurred vision and dizziness24. These problems are common among patients receiving cannabinoid treatment with an incidence of about 50% for dizziness, 50% for drowsiness/somnolence/sedation, 13% for dysphoria/depression, 6% for hallucinations and 5% for paranoia17.

Cardiovascular adverse effects are also regularly observed, such as hypotension (ca. 25%) and reactive or paroxysmal tachycardia. Cases of cardiac and cerebral ischemia associated with cannabis consumption have been reported35. In addition, patients frequently complain of dry mouth.

Patients with long-term intake of cannabinoids may develop tolerance as well for the psychoactive as for the cardiovascular side effects. Long-term intake of cannabinoids should therefore not be stopped abruptly35.

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 cannabinoids36.

Interactions

Pharmacokinetic interactions may occur due to 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).

There is evidence that cannabinoids pharmacodynamically interact with levodopa and similar anti-Parkinson drugs37. Whether these interactions may be harmful for patients or may help to diminish adverse effects of dopamine agonists is under investigation. Currently, use of levodopa or similar drugs is an absolute contraindication for cannabinoids.

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

Contraindications

Due to the possible induction of psychotic episode, a history of psychosis is an absolute contraindication. Relative contraindications are severe ischaemic heart disease and arteriosclerosis of the brain as the effects of cannabinoids on the cardiovascular system cannot be predicted.

THC crosses the placenta barrier and accumulates in breast milk. Findings for cannabinoid effects on male reproduction are being discussed controversially, however, there is evidence that cannabinoids decreases sperm count and motility38. Therefore, pregnant and breast-feeding women, and women and men who wish to have children must not use cannabinoid products.

Some cannabinoid preparations contain additives, e.g. sesame oil, which are contraindicated in people with allergies toward these substances39.

Warnings/precautions

The use of cannabinoids might impair the ability to drive a car and users might be unfit to drive.

Citation Gabriele Dennert, CAM-Cancer Consortium. Cannabinoids [online document]. http://www.cam-cancer.org/CAM-Summaries/Herbal-products/Cannabinoids. November 25, 2011.

References

  1. Grotenhermen,F. (2003): Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet, 42:327-360.
  2. Guy,G.W., Whittle,B.A., Robson,P.J.(2004): The medicinal uses of cannabis and cannabinoids. Pharmaceutical Press, London.
  3. Walsh,D., Nelson,K.A., and Mahmoud,F.A. (2003): Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer, 11:137-143.
  4. Mutschler,E., Geisslinger,G. , Kroemer, H.K., Schäfer-Korting,M. (Eds.) (2001): Mutschler Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart.
  5. Cota,D., Marsicano,G., Lutz,B., Vicennati,V., Stalla,G.K., Pasquali,R., and Pagotto,U. (2003): Endogenous cannabinoid system as a modulator of food intake. Int J Obesity, 27:289-301.
  6. Martin,B.R. and Wiley,J.L. (2004): Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain. J Support Oncol, 2:305-314.
  7. Townsend,D.W., Thayer,S.A., and Brown,D.R. (2002): Cannabinoids throw up a conundrum. Br J Pharmacology, 173:575-577.
  8. Brenneisen,R. (2001): Pharmakokinetik. In: Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potential, edited by F.Grotenhermen, pp. 87-92. Hans Huber Verlag, Bern.
  9. Bruera,E. and Castro,M. (2003): Cannabinoids in supportive care: are they necessary? Support Care Cancer, 11:133-134.
  10. Robson,P.J. and Guy,G.W. (2004): Clinical studies of cannabis-based medicines. In: The medicinal uses of cannabis and cannabinoids, edited by G.W.Guy, et al, pp. 229-269. Pharmaceutical Press, London.
  11. Svendsen,K.B., Jensen,T.S., and Bach,F.W. (2004): Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ, 329:253
  12. Grotenhermen,F.(Ed.)(2001): Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potential. Hans Huber Verlag, Bern.
  13. Russo,E. (2004): History of cannabis as a medicine. In: The medicinal uses of cannabis and cannabinoids, edited by G.W.Guy, et al, pp. 1-16. Pharmaceutical Press, London.
  14. Ware,M.A., Adams,H., and Guy,G.W. (2005): The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract., 59:291-295.
  15. Gorter,R.W., Butorac,M., Cobian,E.P., and van der,S.W. (2005): Medical use of cannabis in the Netherlands. Neurology, 64:917-919.
  16. www.acmed.org [International Organization for Cannabis as Medicine] (accessed 21/10/2011)
  17. Tramer,M.R., Carroll,D., Campbell,F.A., Reynolds,D.J.M., Moore,R.A., and McQuay,H.J. (2001): Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ, 1-8.
  18. Machado Rocha,F.C., Stefano,S.C., de Cassia Haiek,R., Rosa Oliviera,L.M.Q., da Silveira,D.X. (2008): Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care, 17:431-443.
  19. Phillips, R.S., Gopaul, S., Gibson, F., Houghton, E., Craig, J.V., Light, K., Pizer, B. (2010): Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database of systematic reviews 2010, Issue 9, Art. No. CD007786. DOI: 10.1002/14651858.CD007786.pub2
  20. Plasse,T. (2001): Antiemetische Effekte. In: Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potential, edited by F.Grotenhermen, pp. 187-210. Hans Huber Verlag, Bern.
  21. Meiri,E., Jhangiani,H., Vredenburg,J.J., Barbato,L.M., Carter,F.J., Yang,H.M., Baranowski,V. (2007): Efficacy of dronabinol alone and in combination with ondansetron versus ondasetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opinion, 23:533-543.
  22. Priestman,S.G., Priestman,T.J., and Canney,P.A. (1987): A double-blind randomised cross-over comparison of nabilone and metoclopramide in the control of radiation-induced nausea. Clinical Radiology, 38:543-544.
  23. Strasser,F., Lueftner,D., Possinger,K., Ernst,G., Ruhstaller,T., Meissner,W., Ko,Y.D., Schnelle,M., Reif,M., Cerny,T. (2006): 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, 24:3394-3400.
  24. Jatoi,A., Windschitl,H.E., Loprinzi,C.L., Sloan,J.A., Dakhil,S.R., Mailliard,J.A., Pundaleeka,S., Kardinal,C.G., Fitch,T.R., Krook,J.E., Novotny,P.J., and Christensen,B. (2002): Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol, 20:567-573.
  25. Brisbois, T. D., de Kock, I. H., Watanabe, S. M., Mirhosseinie, M., Kamoureux, D. C., Chasen, M., MacDonald, N., Baracos, V. E., Wismer, W. V. (2011): Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo controlled pilot trial. Annals of Oncology; 22: 2086-2093.
  26. Regelson,W., Butler,J.R., Schulz,J., Kirk,T., Peek,L., Green,M.L., and Zalis,M.O. (1976): Tetrahydrocannabinol as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: The pharmacology of marihuana: A monograph of the National Institute of Drug Abuse, edited by M.C.Braude, et al, pp. 763-776. Raven, New York.
  27. Plasse,T.F., Gorter,R.W., Krasnow,S.H., Lane,M., Shepard,K.V., and Wadleigh,R.G. (1991): Recent clinical experience with dronabinol. Pharmacol Biochem Behav, 40:695-700.
  28. Nelson,K., Walsh,D., Deeter,P., and Sheehan,F. (1994): A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care, 10:14-18.
  29. Tazi, E., Errihani, H. (2010): Treatment of cachexia in oncology. Indian Journal of Palliative Care, 16(3): 129-137.
  30. Madeddu, C., Mantovani, G. (2009): An update on promising agents for the treatment of cancer cachexia. Current opinion in supportive & palliative care; 3(4): 258-262.
  31. Campbell,F.A., TramSr,D., Carroll,D., Reynolds,D.J.M., Moore,R.A., and McQuay,H.J. (2001): Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BMJ, 323:1-6.
  32. Johnson, J.R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E.D., Potts, R., Fallon, M.T. (2010): 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. Journal of Pain & Symptom Management 39: 167-79.
  33. GW Pharmaceuticals (2010): Phase IIb Cancer Pain Trial Data. http://www.gwpharm.com/ Phase IIb Cancer Pain Trial Data.aspx (accessed on 18/10/2011)
  34. Maida,V., Ennis,M., Irani,S. Corbo,M. Dlozhykhov,M. (2008): Adjunctive nabilone in cancer pain and symptom management: A prospective observational study using propensity scorino. Supp Oncol, 6:119-124.
  35. Radbruch,L. and Nauck,F. (2004): Cannabinoide in der Behandlung von Übelkeit und Erbrechen. Schmerz, 18:306-310.
  36. Hall,W., Christie,M., and Currow,D. (2005): Cannabinoids and cancer: causation, remediation, and palliation. Lancet Oncol, 6:35-42.
  37. Notcutt,W. (2004): Cannabis in the treatment of chronic pain. In: The medicinal uses of cannabis and cannabinoids , edited by G.W.Guy, et al, pp. 271-299. Pharmaceutical Press, London.
  38. Rossato,M., Ion,P.F., Ferigo,M., Clari,G., and Foresta,C. (2005): Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab, 90:984-991.
  39. Slatkin, N.E. (2007): Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: Beyong prevention of acute emesis. J Support Oncol, 5(suppl 3): 1-9.
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