Benefits
Fasting blood sugar and pancreatic beta-cell function
In a 13-week placebo-controlled trial, adults with type 2 diabetes taking a low oral dose had lower fasting blood sugar than placebo and a better score for pancreatic beta-cell function. This was a small pilot, the main cholesterol endpoint did not change, and the result has not been repeated in larger trials.
Adiponectin and other metabolic blood markers
In the same 13-week trial, the low oral dose raised adiponectin, a fat-tissue hormone tied to insulin action, and shifted apolipoprotein A compared with placebo. These were secondary measurements in a small study, several other blood markers did not change, and the findings need confirming.
Insulin sensitivity in animal (mouse) studies
In two mouse models of obesity, oral THCV improved glucose tolerance and raised insulin sensitivity, and it restored insulin signaling in insulin-resistant liver and muscle cells. These are laboratory and animal findings and have not been shown as clinical outcomes in people.
Appetite and food intake in animal studies
In lean mice, oral THCV reduced food intake and body weight, the opposite of THC. In obese mice and in the human diabetes trial, THCV did not significantly change appetite or body weight, so any effect on appetite in people has not been demonstrated.
Brain responses to food cues in imaging studies
In two small brain-imaging studies in healthy volunteers, a single oral dose changed activity and connectivity in brain regions that handle food reward, aversion and self-control, without changing how people felt. These are exploratory brain measurements, not evidence of weight loss or appetite change.
Mechanism of action
A THC relative that acts on cannabinoid receptors
THCV is the propyl analog of THC. In laboratory and animal work it blocks the CB1 cannabinoid receptor at low doses, which can curb appetite, but at higher doses it can switch to acting like THC at the same receptor, which is why it can become intoxicating. It also partly activates the CB2 receptor.
Effects on glucose handling and energy use
In animal and cell studies, THCV improved how the body cleared glucose, increased insulin sensitivity, restored insulin signaling in liver and muscle cells and caused a brief rise in energy expenditure. These mechanisms come from preclinical work and one small human trial that measured blood sugar.
Appetite and reward pathways in the brain
Unlike the withdrawn weight-loss drug rimonabant, which blocked CB1 as an inverse agonist and caused mood problems, THCV blocks CB1 in a neutral way. Brain-imaging studies in volunteers found it altered responses in food-reward and self-control circuits, a profile researchers have linked to possible appetite effects.
Clinical trials
Randomized, double-blind, placebo-controlled parallel-group pilot trial of cannabidiol and THCV, alone and combined, for 13 weeks; one author worked for the drug's maker (Jadoon et al. 2016, Diabetes Care)
62 adults with non-insulin-treated type 2 diabetes across five treatment arms, with THCV given at 5 mg twice daily.
The primary endpoint, HDL cholesterol, did not change. Compared with placebo, THCV lowered fasting plasma glucose and improved a pancreatic beta-cell function score, and raised adiponectin and apolipoprotein A. Appetite, body weight, insulin sensitivity and the combination treatments showed no significant change. THCV was well tolerated.
Dose-ranging animal study of oral THCV in diet-induced and genetically obese mice, with supporting experiments in insulin-resistant liver and muscle cells; funded in part by the compound's maker (Wargent et al. 2013, Nutr Diabetes)
Diet-induced obese and ob/ob mice, plus cultured hepatocytes and myotubes.
THCV did not significantly change food intake or body weight but improved glucose tolerance, increased insulin sensitivity, produced an early transient rise in energy expenditure and restored insulin signaling in insulin-resistant cells. Animal and cell evidence only.
Controlled animal feeding study comparing the CB1 antagonist AM251 and plant-derived THCV in fasted and free-feeding mice (Riedel et al. 2009, Br J Pharmacol)
Fasted and non-fasted mice.
Pure THCV reduced food intake and body weight at doses as low as 3 mg/kg, acting like a CB1 antagonist, with no rebound the next day. A THCV-rich cannabis extract did not suppress intake, probably because of residual THC. Animal evidence only; the doses were far higher per unit of body weight than people use.
Placebo-controlled, double-blind crossover pilot trial giving 10 mg oral THCV daily for five days followed by intravenous THC on day five (Englund et al. 2016, J Psychopharmacol)
10 healthy male cannabis users.
THCV at 10 mg a day was well tolerated and subjectively indistinguishable from placebo. It appeared to blunt some THC effects, such as a THC-induced rise in heart rate and delayed-recall impairment, while increasing memory intrusions. A very small pilot that did not measure appetite or blood sugar.
Within-subject, double-blind study using functional MRI to measure brain responses to rewarding and aversive food stimuli after a single 10 mg oral THCV dose or placebo (Tudge et al. 2014, Int J Neuropsychopharmacol)
20 healthy volunteers.
Subjective ratings of the foods did not differ between THCV and placebo. THCV increased brain responses to chocolate (reward) and to unpleasant food images and tastes (aversion) in several regions. The authors called this a profile of possible interest for obesity; it is not a measure of appetite or weight.
Randomized, within-subject, double-blind study of a single 10 mg oral THCV dose or placebo using resting-state functional MRI (Rzepa et al. 2015, Int J Neuropsychopharmacol)
20 healthy volunteers.
THCV produced no change in subjective experience but reduced connectivity in the default mode network and increased connectivity in cognitive-control regions. The authors suggested this pattern could be relevant to obesity. An exploratory brain-imaging result, not a clinical outcome.