A 2014 systematic review found that oral cannabinoids were of unknown efficacy in treating nonchorea-related symptoms of Huntington’s disease, Tourette syndrome, cervical dystonia, and epilepsy.9 The 2015 systematic review and meta-analysis cited earlier, however, suggests that there is low-quality evidence that cannabinoids improve symptoms associated with sleep disorders and Tourette symptoms.5
Cancer-related symptoms
In 1985, the FDA approved dronabinol for the treatment of chemotherapy-induced nausea and vomiting (CINV) not controlled by other medications. Nabilone followed, receiving FDA approval in 1992.11
Serotonin receptor antagonists (5-HT3 receptor antagonists) were also introduced in the early 1990s. In 2001, a systematic review of 30 RCTs with a total of 1366 patients looked at how cannabinoids—including oral dronabinol, oral nabilone, and intramuscular levonantradol, a synthetic drug that does not have FDA approval—compared with placebo or other antiemetics.12
The researchers found the FDA-approved cannabinoids to be more effective than prochlorperazine, metoclopramide, chlorpromazine, and other antiemetics for most patients. (The included studies did not compare cannabinoids with 5-HT3 agents.) That was not the case, however, for patients receiving either very low or very highly emetogenic chemotherapy.
In crossover studies, participants reported that they preferred cannabinoids for future CINV control. Although they cited the “high,” sedation, and euphoria as potential beneficial effects, those taking cannabinoids were also more likely than patients receiving other antiemetics to withdraw from studies due to adverse effects, including dizziness, dysphoria, depression, hallucinations, and paranoia. The authors concluded that cannabinoids might be useful as mood-enhancing adjuvants for controlling CINV, but that short-term adverse effects were likely to limit their widespread use.12
Recommended antiemetic regimens for patients with highly emetogenic regimens or those whose chemotherapy comes with a high risk of delayed CINV include the serotonin antagonist dexamethasone, with or without aprepitant or fosaprepitant. Because of the availability of safer and more effective agents, the National Comprehensive Cancer Network (NCCN) does not consider cannabinoids first-line treatment for the prevention of CINV. Instead, they are reserved for breakthrough symptoms or refractory nausea and vomiting.11
In fact, NCCN practice guidelines do not recommend medical marijuana for the management of CINV because of both medical and legal concerns. Even in states in which medical marijuana is legal, the organization states, its use is controversial.11
Combatting anorexia and cachexia. An estimated 50% of cancer patients develop anorexia and cachexia. The systemic inflammation and loss of protein, energy, and lean body mass is associated not only with a poor response to chemotherapy and decreased survival rates, but also with a lower quality of life. While therapies to alleviate these symptoms typically focus on palliation and reduction of distress rather than on prolonging life, some agents, such as megestrol and medroxyprogesterone, are reported to improve survival rates as well as quality of life.22
Cannabinoids have also been used to increase appetite and food intake and facilitate weight gain in cancer patients. The exact mechanism by which this effect occurs is not known; in fact, questions about the extent of the effect itself remain.
Two RCTs failed to show benefits in this regard compared with megestrol or placebo. One study of 469 patients with advanced cancer compared dronabinol, administered alone or in combination with megestrol, with megestrol alone. Using a Functional Assessment of Anorexia/Cachexia Therapy Questionnaire to assess quality of life, the researchers found that megestrol provided better palliation of anorexia than dronabinol alone and that the combination of dronabinol and megestrol showed no advantage over megestrol alone.13
The second study was a multicenter Phase III double-blind RCT comparing cannabis extract (CE), THC, and placebo in 289 cancer patients. The researchers found no differences in appetite, quality of life, or toxicity among those in the 3 arms of the study. A data review board subsequently recommended that study recruitment be stopped because of the absence of significant differences.23
HIV and AIDS-related morbidity and mortality
Evidence of the efficacy and safety of cannabinoid use among adult patients with HIV or acquired immune deficiency syndrome (AIDS) is lacking, according to a 2013 Cochrane review.24 The review looked at RCTs that compared any marijuana intervention in this patient population to either placebo or a known treatment, such as megestrol or medroxyprogesterone.Worth noting, however, is that the review included studies that were of short duration, involved small numbers of patients, and focused on short-term measures of efficacy.
Long-term studies indicating that cannabinoids have a sustained effect on AIDS-related morbidity and mortality in patients being treated with antiretroviral therapy have yet to be conducted.24 The systematic review and meta-analysis published in 2015, however, did find evidence suggesting that cannabinoids were associated with weight gain in patients with HIV.5 Dronabinol has had FDA approval for treatment of weight loss associated with AIDS-related anorexia since 1992.