Many states have legalized marijuana for medical use, including the condition of cancer.13 The legal limit of the amount allowed for a patient to possess varies by state. Technically marijuana contains more than 60 pharmacologically active cannabinoids, with the primary active cannabinoids being THC and cannabidiol. The therapeutic effect depends on the concentration of THC in addition to the THC-to-cannabidiol ratio. Various strains of marijuana are engineered to have different concentrations and ratios to achieve desired pharmacologic effects. Medical marijuana may be purchased from dispensaries in various dosage forms as well, and is most commonly dispensed in the form used to smoke as “cigarettes” or with a water pipe.14 It may also be inhaled through a vaporizer, eaten in food, or applied topically as a lotion.
It is important to note that adverse effects on the cardiovascular, respiratory, and central nervous system have been associated with marijuana use. Marijuana smoke has been reported to contain more carcinogens than cigarette smoke, and may lead to head and neck cancer, lung cancer, as well as bronchitis.9 The development of atrial fibrillation, myocardial infarction, stroke, drowsiness, dizziness, nightmares, difficulty sleeping, acute toxic psychosis, anxiety, and depression among many other adverse effects has been associated with marijuana use.9,14 Another concern in cancer patients is the reported immunosuppressive properties of marijuana.
Few studies have evaluated medical marijuana alone or in combination to treat nausea and vomiting related to chemotherapy. The published studies that have been conducted have mixed results. One study of 15 patients receiving adjuvant high-dose methotrexate for sarcoma were randomized to three paired trials of placebo-THC or THC-placebo with the patients serving as their own control.15THC was administered as capsules and cigarettes or matching placebos. Fourteen of the 15 patients reported a reduction in nausea and vomiting when using THC. Another study conducted by the same group in eight patients receiving adjuvant doxorubicin and cyclophosphamide for sarcoma were randomized to THC-placebo or placebo-THC in paired trials to serve as their own control.16 THC was administered as oral capsules and cigarettes compared to matching placebos. Although the investigators used the same trial design and THC regimen, a beneficial effect of THC was not seen in this patient population. The lack of benefit in this trial is thought to potentially be from lower THC concentrations achieved in this group of patients and presence of anticipatory nausea and vomiting in half of the patients.
The largest account of patients receiving marijuana for CINV was published by Musty and Rossi in 2001.17 This group compiled a report of state-run clinical trials that had been conducted evaluatingCannabis sativa (smoked marijuana and/or delta-9-tetrahydrocannabinol capsules) efficacy in reducing CINV. Six trials were included in the analysis comprising 748 patients who smoked marijuana prior to and/or after chemotherapy and 345 patients who used oral THC capsules. For the patients who smoked marijuana, 70%–100% experienced relief from nausea and vomiting, and 76%–88% of those who ingested the oral THC capsules experienced relief. Short-term side effects reported included sedation, a “high”, and smoke intolerance. More studies are needed in this area to evaluate the efficacy and safety as additional states approve medical marijuana and more patients gain access to this management option.
Dronabinol is utilized for breakthrough CINV based upon available evidence already discussed and recommendations by major oncology guidelines. Dronabinol is currently being investigated in a few studies for additional roles in the management of CINV. A completed, not published study has investigated the use of dronabinol versus standard ondansetron antiemetic therapy in the prevention of delayed CINV or retching after moderate-to-high emetogenic chemotherapy.18 Patients were randomized to ondansetron, dronabinol, combination therapy, or placebo. The study outcome was to measure response of nausea and vomiting/retching, intensity, and use of rescue medication. An additional study completed, but yet to be published, has investigated palonosetron and dexamethasone with or without dronabinol in the prevention of CINV with moderately emetogenic chemotherapy.19 Patients were assessed for protection against the development of vomiting, nausea, and use of rescue therapy. In an ongoing study of patients with primary glioma receiving chemotherapy, dronabinol is being administered to assess its tolerability, toxicity, and impact on QoL.20 Assessment of emesis will be completed by patients filling out a daily appetite and nausea/vomiting log as well as a QoL functional living index emesis scale.
With medical marijuana remaining a schedule I substance on a federal level, no studies are registered with clnicaltrials.gov to investigate its role in the management of CINV. Anecdotally patients report benefit, but more research is needed to identify the most appropriate dose, dosage form, drug–drug interactions, and safety concerns with its use before a role for medical marijuana can be elucidated in the management of CINV.