Systematic review examines benefits and adverse effects of cannabinoid therapy

1. Cannabinoid therapy shows modest efficacy in reducing chronic pain, spasticity, and nausea and vomiting symptoms in patients.

2. Cannabinoid therapy is associated with numerous short-term adverse effects; long-term adverse effects have not yet been assessed in large trials.

Evidence Rating Level: 2 (Good)       

Study Rundown: Medical cannabinoids are cannabinoid-derived substances that are used to alleviate medical symptoms, usually in chronically-ill patients. This systematic review sought to evaluate the evidence for the benefits and adverse effects of medical cannabinoids. Results showed that there is statistically non-significant evidence that cannabinoids may be beneficial in chronic pain and spasticity. The evidence for cannabinoid efficacy for other symptoms, such as nausea/vomiting, low appetite, and psychiatric disorders was less clear, with few studies available for data analysis.

Strengths of this study included the rigorous evaluation of potential studies performed by the authors when choosing which studies to incorporate in the systematic review. Seventy-nine RCTs were included and they evaluated the data for a variety of cannabinoid therapy indications. However, there were many weaknesses associated with this study. Primarily, there was significant heterogeneity among the RCTs included and majority had high-risk of internal bias. Furthermore, the majority of the studies lacked the power to detect a statistical significance in efficacy and for many of the medical indications included in this systematic review, there were just too few studies to extract any valuable information from the conclusions. Nevertheless, studies assessing the efficacy of cannabinoids in a variety of symptoms are still in its infancy and more knowledge will be gained as we continue to conduct larger trials focusing on cannabinoid therapy in medical practice.

Click to read the study, published today in JAMA

Click to read an accompanying editorial, published today in JAMA

Relevant Reading: The medicinal use of cannabis and cannabinoids – an international cross-sectional study on administration forms.

In-Depth [systematic review]: This systematic review looked at 79 randomized controlled trials and uncontrolled trials (with >25 participants) that evaluated the efficacy and adverse effects of medical cannabinoid use. Appropriate medical indications for cannabinoid use in these studies included nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity from paraplegia or multiple sclerosis, increased intraocular pressure in glaucoma, Tourette’s syndrome, and depression, anxiety, and sleep disorders.

For nausea and vomiting, three trials showed greater resolution of symptoms from cannabinoids as compared with placebo (OR 3.82, 95%CI 1.55-9.42). The comparison between cannabinoids and active controls showed a greater benefit from the former, but did not reach clinical significance. For appetite stimulation in HIV/AIDS infection, cannabinoids were more effective than placebo but one trial comparing them to megastrol acetate showed greater benefit from the latter. For chronic pain, reduction of pain was on average, 30% greater with cannabinoids vs. placebo (OR 1.41, 95%CI 0.99-2.00). For spasticity, some of the studies showed improvement with cannabinoids but the data did not reach statistical significance. Too few studies were available to assess the efficacy of cannabinoids in depression, anxiety, psychosis, sleep disorders, glaucoma, and Tourette’s. A total of 29 out of 3714 participants (0.7%) experienced adverse effects of cannabinoids. Significant adverse effects included GI disorders, psychiatric and nervous system disorders, vertigo/dizziness, dry mouth, nausea/vomiting, diarrhea, fatigue, somnolence, drowsiness, confusion, euphoria, and hallucinations.

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