• CAM-summaries
  • Alternative medical systems
  • Biologically-based practices
    • Boswellia
    • Cannabinoids
      • What are Cannabinoids?
      • How well do Cannabinoids work?
      • Are Cannabinoids safe?
      • Cannabinoids conclusions
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    • Galavit
    • Laetrile
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    • Ukrain
    • Black cohosh
  • Diet & nutrition
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  • Manipulative & body-based practices
  • Mind-body medicine
• CAM systematic reviews
• CAM and the law
• Prevalence of CAM use

Are Cannabinoids safe?

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 elderly (ref 14).

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 dizziness (ref 24). 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 paranoia (ref 17).

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 reported (ref 28). 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 abruptly (ref 28).

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 (ref 29).

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 drugs (ref 30). 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.

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.

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

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 motility (ref 31). Therefore, pregnant and breast-feeding women, and women and men who wish to have children must not use cannabinoid products.

References

14. Bruera,E. and Castro,M. (2003): Cannabinoids in supportive care: are they necessary? Support Care Cancer, 11:133-134.
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.

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.

28. Radbruch,L. and Nauck,F. (2004): Cannabinoide in der Behandlung von Übelkeit und Erbrechen. Schmerz, 18:306-310.

30. 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.

31. 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.