Researchers from National Institute on Alcohol Abuse and Alcoholism in the US found that the new drug increases sensitivity to the hormone leptin, a natural appetite suppressant found in the body.
The study was published in the journal Cell Metabolism.
"By sensitising the body to naturally occurring leptin, the new drug could not only promote weight loss, but also help maintain it," senior study author George Kunos from the institute said in a statement.
"This finding bodes well for the development of a new class of compounds for the treatment of obesity and its metabolic consequences," Kunos added.
Although leptin is an appetite suppressant, leptin supplements alone have not been effective at reducing body weight in humans.
It's thought that this is because of desensitisation to the hormone. Leptin is still there, but our bodies can no longer respond to it.
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While it is not entirely clear how this desensitisation occurs, cannabinoid receptors, which mediate the feelings of hunger produced by marijuana and naturally occurring cannabinoids in the body, are thought to be involved.
So blocking these receptors, rather than providing excess leptin, could be more effective at long-term weight loss.
In the new study, Kunos tested a new compound, JD5037, that targets cannabinoid receptor type 1 (CB1R) without penetrating the brain.
JD5037 suppressed the appetite of obese mice, caused weight loss, and even improved metabolic health, in part by resensitising mice to the appetite-suppressing hormone leptin.
Importantly, the mice did not show signs of anxiety or other behavioural side effects.