The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients : Pilot Study
Gil Bar-Sela, Daniela Zalman, Valerya Semenysty and Eyal Ballan
Integrative Cancer Therapies, 2019, Volume 18, 1–8
Background : Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients.
Methods : The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline.
Results : Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated.
Conclusions : Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.
Keywords : cancer, cachexia, anorexia, cannabis capsules, appetite loss
Cachexia is defined as a “multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.”1 Cachexia may be masked by excess weight, obesity, edema,2 or tumor mass.3 Anorexia is a subjective term describing reduction or loss of appetite. Although it is commonly known that patients coping with cancer and cancer treatments experience loss of appetite, the exact prevalence of anorexia is unknown. In one study on advanced cancer patients, more than half the patients experienced anorexia.4 A North Central Cancer Treatment Group study of 1115 patients with colorectal and lung cancer found that cancer patients with anorexia had lower survival rates and experienced more toxicity from chemotherapy than similarly matched patients who maintained their appetite.5 Cachexia primarily caused by anorexia or reduced intake has been defined as cancer-related cachexia and anorexia syndrome (CACS). CACS, unlike cachexia, includes weight loss caused by muscle wasting, as well as lipolysis and decreased intake.
Cannabis has long been suggested to stimulate appetite, decrease nausea and vomiting, and improve quality of life (QoL) in cancer patients.6-8 However, the few studies on these effects yielded mixed and inconclusive findings.9-11 In addition, some studies included various methodological limitations that limit the ability to draw any firm clinical conclusions (eg, small sample,12 unknown cannabis products,
different ways of intake).
Several formulations of cannabis with different pharmacokinetic and pharmacodynamics are available in the market. Pulmonary assimilation of inhaled THC (tetrahydrocannabinol) causes a maximum plasma concentration within minutes; psychotropic effects start within seconds to a few minutes, reach a maximum after 15 to 30 minutes, and taper off within 2 to 3 hours. Following oral ingestion, absorption is slow and erratic, resulting in maximal plasma concentrations usually after 60 to 120 minutes. In several studies, maximal plasma concentrations were observed as late as 4 hours, and even 6 hours in some cases.13 Several subjects showed more than 1 plasma peak. In case of oral administration, psychotropic effects set in with a delay of 30 to 90 minutes, reach their maximum after 2 to 3 hours,
and last for about 4 to 12 hours, depending on dose and specific effect.13 Another common route of administration is sublingual. Pure cannabinoids are extracted from the raw plant, dissolved in different oils, and administered with a dropper. The therapeutic window of sublingual oil administration is 2 to 4 hours with a rapid onset due to quick absorption through the oral cavity.
The most common oral administration of cannabinoids is through eating edibles, mainly cookies, chocolate bars, and lozenges. Since absorption is attenuated when cannabinoids are ingested orally,14 edibles usually contain high dosages of cannabinoids (50-300 mg). The high dosage may cause undesirable side effects, mainly dizziness, anxiety, and dissociation. These side effects may cause patients to withdraw from the therapeutic process. The oral administration route has the longest therapeutic window (4-8 hours)14 and lacks the undesirable effects of smoking. The unmet
need for an oral formulation with higher bioavailability and a lower peak of psychoactive effect led us to use a new oral capsule standardized with a longer therapeutic window and lower C max .13,14 In Israel, cannabis pills are given under the regulations of the Ministry of Health to advanced cancer patients with various symptoms to improve their QoL.15,16
Given the potential effect of cannabis use on CACS and the mixed findings regarding this subject, the current study aimed to evaluate the influence of cannabis pills on CACS in advanced cancer patients. Secondary objectives were to evaluate the safety and toxicity of the cannabis treatment and to observe changes in appetite and in TNF-α (tumor necrosis factor-α) levels. To test the hypothesis that cannabis pills can improve body weight by more than 10%, the number needed to treat was calculated according to true response probability of less than 5%. This calculation with the same primary end point that achieved 3% true response on dronabinol and 11% on megestrol was based on the results of a phase III study.9
Based on a significance level of .05 (α) and a power of 0.90, the sample size for the pilot study should be 21 patients. If only 1 patient achieves the primary end-point, the study will be terminated.17