For many years, anecdotal evidence has suggested that acute exposure to cannabis can increase appetite. Epidemiological studies have also shown that active cannabis users tend to consume more energy and nutrients than non-users. Controlled laboratory studies with healthy individuals have demonstrated that both inhalation and oral ingestion of Δ9-THC-containing capsules are positively correlated with an increase in food consumption, caloric intake, and body weight. The high concentration of CB1 receptors in brain regions associated with food intake and satiety provides further support for the link between cannabis use and appetite regulation. Moreover, growing evidence indicates that the endocannabinoid system (ECS) plays a role in not only modulating appetite, food intake, and palatability, but also in energy and glucose metabolism. In clinical situations where weight gain is beneficial, such as HIV-associated muscle wasting and weight loss, cannabis’s ability to stimulate appetite and food intake has been utilized.

A randomized, open-label, multi-center study examined the safety and pharmacokinetics of dronabinol and megestrol acetate (an orexigenic) alone or in combination. The high-dose megestrol acetate treatment alone (750 mg/day) resulted in a significant increase in mean weight over 12 weeks of treatment in patients diagnosed with HIV-associated wasting syndrome, while dronabinol alone (2.5 mg b.i.d, 5 mg total Δ9-THC/day) or the combination of low-dose megestrol acetate (250 mg/day) and dronabinol (2.5 mg b.i.d, 5 mg total Δ9-THC/day) did not produce a significant clinical effect. However, the lack of effect with dronabinol could be due to the low dosage. A clinical study that utilized higher doses of dronabinol or smoked cannabis found that acute administration of high doses of dronabinol (four to eight times the standard dose) and smoked cannabis (three puffs at 40 sec intervals) increased caloric intake in HIV-positive cannabis smokers with significant muscle mass loss. Another inpatient study used even higher doses of dronabinol and smoked cannabis, which produced comparable increases in food intake and body weight as well as improvements in mood and sleep. It appears that the increase in body weight in this patient population may result from an increase in body fat rather than lean muscle mass.

A double-blind, cross-over, placebo-controlled pilot sub-study examining the effects of cannabis use on appetite hormones in HIV-infected adult men with HIV sensory neuropathy on combination anti-retroviral therapy (ART) found that smoked cannabis was associated with significant increases in plasma levels of ghrelin and leptin and decreases in plasma levels of peptide YY, compared to placebo. Higher THC levels were associated with greater increases in ghrelin, showing a dose-response relationship, whereas higher THC levels were associated with smaller increases in leptin; no dose-response was observed for peptide YY.

Finally, a systematic review and meta-analysis of 28 randomized controlled trials (N = 2 454 participants) of various cannabinoids, including dronabinol, smoked cannabis, and CBD, showed that dronabinol was associated with an increase in weight, as well as increased appetite, greater percentage of body fat, reduced nausea, and improved functional status in patients with HIV/AIDS, compared to placebo.

Reference information: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html#a4.1