____________________________________________________ Medical Marijuana and Other Cannabinoids
vomiting. The drugs of the NK1 receptor antagonist class are more effective with delayed as well as acute vomiting, although they are much less effective in reducing nausea. Nausea is the most distressing symptom experienced by chemotherapy patients because it is a continuous sensation, and as many as 20% of patients with cancer discontinue chemotherapy because current standard agents fail to control nausea [105; 208]. A vast body of anecdotal evidence from the past 150 years as well as preclinical and clinical trial results strongly indicate a valuable role for cannabis in controlling nausea and vomit- ing caused by cytotoxic drug administration or secondary to another primary medical condition [105]. Most studies showing cannabinoid efficacy have used oral synthetics. The synthetic THC analogue nabilone and the synthetic THC dronabinol received initial regulatory approval for chemotherapy-induced nausea and vomiting based on improved outcomes over standard antiemetics used in the 1980s [105]. An older study of Δ 8-THC, a close but less psychoactive relative of Δ 9-THC, in pediatric patients with chemotherapy-induced nausea and vomiting found effective suppression of nausea and vomiting with negligible side effects [101]. More recently, an RCT with adults experiencing chemotherapy-induced nausea and vomiting found dronabinol comparable to the 5-HT3 antagonist ondansetron and superior to placebo [105; 209]. An additional rationale for cannabis use in chemotherapy- induced nausea and vomiting involves the principle of opti- mizing treatment by combining agents that inhibit multiple neurotransmitter pathways that mediate nausea and vomiting reflexes. Cannabinoids have known activity in many of these systems and can effectively compensate for the deficiencies of 5-HT3 antagonists and NK1 receptor inhibitors in preventing nausea and delayed and breakthrough chemotherapy-induced vomiting. Because cannabidiol does not induce psychotropic effects, its potential role as an antiemetic for patients undergo- ing chemotherapy is being investigated [210]. An RCT with patients with gynecologic cancer found that a cannabinoid extract (THC:CBD 1:1) was an appropriate adjuvant to reduce chemotherapy-induced nausea and vomiting in patients receiv- ing high-emetogenic chemotherapy [211]. The potential role of smoked cannabis in rapidly alleviating breakthrough nausea and vomiting is especially promising given the findings of strong patient preference for smoked can- nabis over oral therapies in a number of comparative clinical trials [3]. A study comparing 748 patients with cancer who smoked cannabis before and after chemotherapy with 345 patients using dronabinol found a reduction in nausea and vomiting of 70% to 100% with cannabis compared with 76% to 88% with dronabinol [212]. Oral cannabinoids may be less effective than sublingual or inhaled cannabis in chemotherapy- induced nausea and vomiting, and most patients prefer smoked marijuana over oral synthetic cannabinoids [213]. Several reasons account for this preference:
• The advantages and ease of self-titration with smoked cannabis • Difficulty in swallowing pills when experiencing emesis • Rapid speed of onset compared with oral delivery • The combined therapeutic effects of additional can- nabinoids in smoked cannabis A meta-analysis of cannabinoid efficacy in chemotherapy- induced nausea and vomiting found superior antiemetic efficacy of dronabinol, nabilone, levonantradol (not approved for use in the United States), and smoked cannabis compared with conventional drugs and placebo [214]. Smoked cannabis has also been shown to improve non- chemotherapy medication adherence in which nausea and vomiting are common side effects. In a study of 258 patients receiving antiretroviral therapy for HIV infection, the subgroup of patients experiencing moderate-to-severe nausea who used marijuana were significantly more adherent to their regimen than non-marijuana users (75% vs. 48%). Alcohol use, the use of other illicit drugs, and marijuana use in those without nausea were associated with lower adherence [215]. HEPATITIS C THERAPY Until 2014, interferon/ribavirin combination therapy was the sole treatment for hepatitis C virus infection, and it remains widely used. However, patient intolerability of side effects has been a substantial barrier to treatment success. Most patients experience significant side effects that can include debilitating fatigue, headaches, nausea, anorexia, clinical depression, and insomnia. Patients usually require adjunctive pharmacotherapy for side-effect management, but relief is often incomplete, lead- ing to dose reduction or termination. Illicit cannabis is used by some patients to lessen side effects. A prospective study compared 71 patients with hepatitis C receiving interferon/ribavirin who either used cannabis (31%) or did not use cannabis (69%) for side effect relief [216]. Sev- eral statistically significant differences were found between the cannabis-and non-cannabis using patients. Five percent of cannabis users vs. 33% of non-users discontinued therapy. Compared with 18% of non-users, 54% of cannabis users had a sustained virologic response, with post-treatment virologic relapse rates of 14% in cannabis users vs. 61% in non-users. Finally, 86% of cannabis users were treatment-adherent, while 59% of non-users adhered to treatment. Occasional and regular cannabis users did not differ in adherence or sustained viro- logic response. The authors conclude that moderate cannabis use may offer significant benefit to some patients enduring the frequently debilitating medication regimen for hepatitis C and that an additional biologic benefit beyond adherence promotion cannot be ruled out [216].
139
EliteLearning.com/Dental
Powered by FlippingBook