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QUESTION: In patients with chemotherapy-induced sickness, what are the antiemetic efficacy and adverse effects of cannabinoids?
Full publications of studies were identified by searching Medline (from 1966), EMBASE/Excerpta Medica (from 1982), and the Cochrane Library (2000, Issue 3) with the terms cannabinoids, cannabis, nabilone, tetrahydrocannabinol (THC), THC, marihuana, marijuana, levonantradol, dronabinol, randomized, and human. Bibliographies of relevant studies were checked.
Studies were selected if they were randomised controlled trials (RCTs) comparing the antiemetic efficacy of cannabis with any other antiemetic agent or placebo in patients having chemotherapy.
Data were extracted on study quality, patients, interventions and regimens, and outcomes.
30 RCTs (1366 patients) published between 1975 and 1997 met the selection criteria. The mean number of patients per study was 46 (range 8 to 139 patients). 16 studies examined oral nabilone, 13 examined oral dronabinol, and 1 examined intramuscular levonantradol. The active control groups were administered prochlorperazine (12 studies), metoclopramide (4 studies), chlorpromazine (2 studies), thiethylperazine (1 study), haloperidol (1 study), domperidone (2 study), and alizapride (1 study). Cannabinoids were more effective than other active treatment drugs for completely relieving nausea and vomiting in the first 24 hours of chemotherapy (table). Cannabinoids also increased both potentially beneficial and harmful additional effects (table).
In patients having chemotherapy, cannabinoids control nausea and vomiting better than selected conventional antiemetics but are associated with increased side effects.
Studies done in the previous few years have suggested that cannabinoids may be effective in certain populations for alleviating nausea and symptoms of anorexia, although their clinical indications have been unclear because of the high incidence of psychotropic side effects and the lack of sound trials comparing cannabinoids with standard treatment.1,2 Despite the lack of clear evidence on safety and efficacy, a survey done in 1994 showed that most physicians in the UK wished to have cannabinoids available by prescription.3 In this setting, Campbell et al and Tramér et al completed their respective systematic reviews, which examined the efficacy of cannabinoids in the treatment of pain and chemotherapy-induced nausea and vomiting.
Cannabinoids in pain management provide analgesic effects similar to those of codeine. Cannabinoids commonly cause psychotropic side effects, but whether these effects are more common than with codeine is uncertain. At present, insufficient evidence exists to support the widespread use of cannabinoids over currently available analgesic treatments for pain management. However, the effects of inhaled cannabinoids were not assessed in this analysis.
The findings regarding chemotherapy-induced nausea and vomiting were somewhat more intriguing: cannabinoids were shown to be slightly superior to such conventional antiemetics as prochlorperazine or metoclopramide. Although psychotropic side effects remained common, some of these effects, including euphoria and sedation, may have been perceived as beneficial. Many patients reported having a preference for cannabinoids, but whether this preference was because of beneficial side effects was not evaluated.
What is to be gained from these 2 reviews? The review by Campbell et al assessing the efficacy of cannabinoids in the treatment of pain puts to rest the question of whether these oral or intramuscular agents are useful in that setting. Clearly, the review of published trials shows that unless more potent and less toxic cannabinoid derivatives are developed and studied, these agents are unlikely to have any important role as therapeutic options in pain management.
The results of the review by Tramér et al assessing the efficacy of cannabinoids in the treatment of nausea and vomiting are less clear. One can certainly argue that any relevance of the “slightly superior” outcomes of treatment with cannabinoids over conventional antiemetics may be offset by the concerns about the psychotropic side effects that routinely accompany the use of these agents. However, as pointed out in Belknap's commentary4 on the Voth study,1 no clinical trials were reported comparing cannabinoids to 5-hydroxytryptamine-3 receptor antagonists, which have become the standard of care in the prevention of chemotherapy-induced nausea and vomiting. Until such trials are done, the use of cannabinoids for this indication remains uncertain.
Of greater importance is the observation that patients often expressed a preference for the cannabinoids over other antiemetics for future chemotherapy despite the related psychotropic effects. This observation cannot be ignored. One can only speculate whether patient preference was a result of the beneficial side effects, such as euphoria, or another unknown effect. Irrespective of the reason, patient preference should be included as a valid outcome in the design of future studies that evaluate the efficacy of cannabinoids in the treatment of chemotherapy-induced nausea and vomiting.
Sources of funding: Swiss National Science Foundation and Royal College of Nursing Institute.
For correspondence: Dr M R Tramèr, Division d'Anesthésiologie, Département Anesthésiologie, Pharmacologie Clinique et Soins Intensif de Chirurgie, Hôpitaux Universitaries, CH-1211 Geneva 14, Switzerland..