Inducing the Munchies: THC for Cancer Cachexia

By Russell H. Greenfield, MD, Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill; Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson

Synopsis: A short trial of a synthetic cannabinoid for people with advanced cancer was shown to improve caloric intake, appetite, and sensory perceptions around food, as well as quality of life.

Source: Brisbois TD, de Kock IH, Watanabe SM, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: Results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 2011 Feb 22; doi:10.1093/anonc/mdq727.

People with advanced cancer frequently report loss of interest in food, an altered taste of their favorite dishes, and diminished appetite. The authors of this randomized, double-blind, placebo-controlled 22-day Phase 2 pilot study sought to determine whether a synthetic form of marijuana (delta-9-tetrahydrocannabinol, or THC) could improve taste and smell (chemosensory) perception, appetite, caloric intake, and quality of life (QOL) for patients with advanced cancers who had associated chemosensory alterations and poor appetite.

Subjects were adults with advanced cancer (defined as locally recurrent, locally advanced, or metastatic) of any site except brain who had a score on a Taste and Smell Survey indicative of a significant chemosensory alteration (> 2 out of 16), decreased caloric and protein intake, and poor QOL. They were recruited from two Canadian oncology clinics and randomized to receive either THC (2.5 mg, Marinol®; Solvay Pharma Inc.; n = 24) or placebo oral capsules (n = 22) twice daily for 18 days. Patients started on THC 2.5 mg or placebo once daily for the first 3 days and the dose was increased to THC 2.5 mg or placebo twice daily on the fourth day. Participants had the option to increase their drug dose to a maximum of 20 mg/day.

Subjects completed assessments at baseline and after 18 days of treatment. All assessments used patient-reported outcomes to capture and describe changes experienced by the patients. The Taste and Smell Survey was used to identify and quantify chemosensory alterations "since study treatment." The 100 mm Satiety Labeled Intensity Magnitude (SLIM) scale was completed 10-15 minutes before each meal for 1-day pretreatment and following 18 days of treatment for an assessment of appetite. The Macronutrient Preference Checklist (MPC) was completed with the SLIM to assess macronutrient preferences. SLIM and MPC premeal scores were averaged for an overall day score. A 3-day dietary record was used to estimate total calories and macronutrient intake. QOL was assessed with the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, and the 11-point Edmonton Symptom Assessment System was used to assess nausea. Interviews were also conducted to determine patients' treatment-related changes in food preferences and chemosensory alterations.

Twenty-one of the initial 46 participants completed the trial. Patient characteristics and dropout rates were similar for THC and placebo groups. In the THC group, 8 patients followed the dosing protocol (i.e., 2.5 mg bid) and 3 patients increased to 2.5 mg tid by taking an additional 2.5 mg before supper. In the placebo group, 7 patients followed the dosing protocol and 3 patients increased their dose to 3 capsules/day.

Compared with placebo, THC-treated patients reported improved (P = 0.026) and enhanced (P < 0.001) chemosensory perception and that food "tasted better" (P = 0.04). The majority of THC-treated patients reported an increased overall appreciation of food compared with patients receiving placebo (30%). In addition, 73% of THC-treated patients indicated a renewed ability to discriminate tastes, flavors, and food odors. In contrast, 80% of patients in the placebo group reported their taste and smell function to be the "same as before" (60%) or "worse" (20%) compared with baseline. Premeal appetite (P = 0.05) and proportion of calories consumed as protein increased compared with placebo (P = 0.008). In contrast, the majority of patients receiving placebo had either decreased appetite (50%) or showed no change (20%). FAACT global QOL scores improved similarly for both THC and placebo groups, but THC-treated patients reported improved quality of sleep (P = 0.025) and relaxation (P = 0.045). Nausea scores were unaffected by THC treatment (P = 0.532), and total caloric intake was improved in both THC and placebo groups. Relative to baseline, 73% of THC-treated patients increased their caloric intake (range 100-775 kcal/day) compared with 50% of patients in the placebo group (100-965 kcal/day). THC was well tolerated.

The authors concluded that THC may be helpful to people with advanced cancer and chemosensory alterations by improving and enhancing chemosensory perception, altered macronutrient preference, appeal of savory foods, appetite, relaxation, and quality of sleep.

Commentary

Discussions that center on medical marijuana quickly become emotional. So do discussions of people with advanced cancer, who frequently no longer enjoy the taste of food and so take in too few calories.

THC appears to increases appetite in animals and healthy people, and in those with acquired immunodeficiency syndrome (AIDS), likely via stimulation of endocannabinoid receptors located in reward-related areas of the brain. The researchers chose to focus on self-report of chemosensory perception as the most relevant predictor of food preference and enjoyment instead of objective clinical measures (i.e., millimolar concentration thresholds for detection of individual tastants and odorants) because they view taste and smell alterations as more than quantifiable physiological changes — they see them as potentially impacting a person's ability to enjoy food. Their words: "clinical measures of chemosensation cannot capture dimensions such as flavor, food enjoyment, or impact on patient's food-intake behavior."

The dropout rate was significant, especially in such a small study, but the authors address this by stating that investigations in those with advanced cancer must necessarily account for the possibility of increasing morbidity and even death. They go on to note that the dropout rate was not significantly different from that seen with other studies of people in this state of health.

The researchers declare their purpose was to establish a starting point from which new research could take hold. With there being no yet accepted treatment for the chemosensory changes experienced by those with advanced stages of cancer and cancer cachexia, from a purely medical perspective one has to wonder why this line of research is controversial when there exists promise to help relieve suffering. A review published in 2007 noted that the combination of opioids and cannabinoids could produce opioid-sparing effects, thereby extending the duration of analgesia and reducing the risk of dependency.1 It also described studies where cannabinoids were successfully used to treat pain, enhance sleep, reduce muscle spasm, and improve appetite in a variety of palliative care situations.

Studies such as the current trial help balance science and emotion, and forward the healing art. Here's hoping it contributes toward compassionate palliative care winning out over politics and fear-mongering.

Reference

1. McCarberg BH. Cannabinoids: Their role in pain and palliation. J Pain Palliat Care Pharmacother 2007;21:19-28.