AEF0117, a novel agent signalling specific inhibitor of the cannabinoid receptor 1, reduced the positive subjective effects of cannabis in patients with cannabis use disorder (CUD) in a double-blind, placebo-controlled randomised trial.
Although most people using cannabis do not have problems related to its use, between 10% and 30% of users report symptoms consistent with CUD. Most of the effects of cannabis linked to the psychoactive component tetrahydrocannabinol (THC) are mediated via interaction with the type 1 cannabinoid receptor, which has become a promising drug target.
Currently, there are no effective treatments for CUD, but AEF0117 appears to selectively inhibit a subset of intracellular effects resulting from THC binding without modifying behaviour. Moreover, AEFO117 potently inhibits the effects of THC without producing any psychoactive effects.
Writing in the journal Nature Medicine, researchers initially found that AEF0117 decreased cannabinoid self-administration and THC-related behavioural impairment, but without producing significant adverse effects. Based on these initial phase 1 findings, they tried using the drug in patients with CUD.
Effect of AEFO117 on cannabis use disorder
In a randomised, double-blind, placebo-controlled, crossover phase 2a trial, researchers randomised volunteers with CUD to two ascending-dose cohorts (0.06 mg and 1 mg), which were given every day.
The primary outcome was the effect of AEFO117 on cannabis’ positive subjective effects, which were measured using a visual analogue scale. The results showed that the drug significantly reduced the positive subjective effects of cannabis by 19% with the 0.06 mg dose but 38% for the 1 mg dose, compared to placebo (p < 0.04).
In addition, a 1 mg dose of AEFO117 also reduced cannabis self-administration (p < 0.05). It appeared to be well tolerated and did not precipitate cannabis withdrawal.
The safety of cannabis for medical uses has recently been questioned over increasing evidence that its use is associated with adverse cardiovascular effects.
