Researchers are about to enroll the first patient in a pilot study of potential weight loss with nabilone — a manufactured cannabinoid similar to the active component of the marijuana (cannabis) plant.
Although cannabis is associated with the “munchies,” paradoxically, “people who use cannabis regularly actually have lower body mass index (BMI), lower risk of obesity, and a lower risk of diabetes than people who don’t use cannabis,” said Justin Matheson, PhD, University of Toronto, Ontario, Canada, in an article in U of T News.
“There’s been quite a bit of evidence that targeting the cannabinoid system is effective for weight loss,” Matheson, a postdoctoral research fellow at the Centre for Addiction and Mental Health, elaborated in an interview with Medscape Medical News.
“Unfortunately, the drugs that have been tried before, cannabinoid receptor antagonists,” such as rimonabant, “have really serious psychiatric adverse effects,” he noted.
However, nabilone, which is approved to treat nausea, has an acceptable safety profile, and animal studies suggest it may be effective for weight loss in patients with obesity.
Therefore, the researchers, led by Bernard Le Foll, PhD, chair of addiction psychiatry in the Temerty Faculty of Medicine, University of Toronto, designed a first-in-man feasibility and safety study to test this hypothesis.
“We’re hoping to see [weight-loss] effects without those serious psychiatric adverse effects,” said Matheson.
First-in-Man Study of Nabilone for Weight Loss in Obesity
Delta-9-tetrahydrocannabinol (Δ9-THC), better known as THC, is the primary psychoactive compound found in the marijuana plant and is one of many cannabinoids.
Le Foll was part of a research group that published a study showing that Δ9-THC reduced weight gain in mice with diet-induced obesity but not in lean mice.
The current feasibility study will investigate the potential weight-loss effect of nabilone, a synthetic cannabinoid similar to naturally occurring Δ9-THC, in people with obesity.
Sold under the brand name Cesamet in the United States, nabilone is approved by the US Food and Drug Administration to treat nausea and vomiting induced by cancer chemotherapy. Nabilone has different brand names in Canada, where it is also available as a generic drug.
In clinical trials, the most common adverse effects of nabilone were drowsiness, vertigo, dry mouth, and euphoria.
Researchers plan to enroll 60 men and women aged 25-45 with a BMI > 30 kg/m2 who have not used cannabis in the past.
Patients will be randomized to receive placebo, low-dose nabilone (titrated to 2 mg daily), or high-dose nabilone (titrated to 6 mg daily) for 12 weeks.
Nabilone will be generic 0.5-mg capsules dosed twice daily.
The primary outcomes are safety (adverse and serious adverse events) and feasibility (study dropouts).
Secondary outcomes include weight-loss effectiveness (changes in body weight and abdominal fat).
Other secondary outcomes include:
Changes in the gut microbiome (based on analysis of stool samples at baseline and week 12).
Blood levels of metabolic markers such as glucose, insulin, cholesterol, leptin, and ghrelin (at baseline and weeks 5, 9, and 12).
The brain’s neural activity in response to pictures of food versus control pictures (seen with functional MRI).
The researchers expect to have study findings in 2 years.
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