A New Drug Could Treat Marijuana Addiction, Study Finds

Experimental drug selectively inhibits cannabinoid receptors in the brain

The study, published last month in Nature Medicine, trialed the effects of the experimental drug AEF0117, a signaling-specific inhibitor(SSI) of the cannabinoid receptor 1 and the first of a new pharmacological class, in humans.^[1]

Cannabis produces its reinforcing effects when the psychoactive molecule tetrahydrocannabinol (THC) stimulates type 1 cannabinoid (CB1) receptors in the brain, with effects on pleasure, thought, motivation, and pain. Researchers theorized that blocking the activation of these receptors would blunt the rewarding effects of cannabis, making users less likely to consume it.

However, the CB1 antagonists previously considered as treatment completely inhibited the receptors, impairing endocannabinoid function in the brain, with intolerable adverse effects, and produced withdrawal in heavy cannabis users.

AEF0117, developed by the French biotech firm Aelis Farma, just selectively inhibits CB1 receptors, blocking only the cellular signals involved in cannabis use disorder.^[2]

"That way you’re able to block the euphoric effects of cannabis without causing these adverse side effects,” Dr. Scott Hadland, an addiction specialist at Mass General Hospital who wasn’t involved in the study, explained to NBC News.^[3]

Compound reduced the feel-good effects of cannabis by 39%

The phase 2a proof-of-concept trial follows the successful testing of the AEF0117 compound in mice and non-human primates. In the earlier trials, the use of the AEF0117 compound reduced cannabinoid self-administration in animals and their THC-related behavioral impairment without producing adverse effects.

In this next stage of testing, 29 adult men and women diagnosed with cannabis use disorder were recruited. The subjects were, on average, smoking around 3 grams of cannabis a day, six days per week.

Related blog: How long does THC stay in your system?

They were assigned to receive either a low (0.06mg) or high (1mg) of AEF0117 or a placebo. They were given the pill at 9 a.m. on five consecutive days and 3.5 hours later, smoked a controlled amount of cannabis.

They were then asked how they felt, rating statements including “I feel a good effect” and “I feel high.” The study found that the higher dose reduced the subjective positive effects of cannabis by a significant 38%, while the lower dose reduced it by 19%.^[1]

Participants given the higher dose also used less cannabis

Later that day, participants were also given the opportunity to purchase additional puffs of cannabis, using money from their study stipend. Those who received the higher dose of AEF0117 used a significantly lower amount of cannabis.

These reductions were achieved without producing cannabis withdrawal, even for heavily dependent users.^[2] Cannabis withdrawal can be unpleasant and discourage quitting, with symptoms including insomnia, decreased appetite, anxiety, and shakiness.^[4]

Meg Haney, lead author of the study, professor of neurobiology in the Department of Psychiatry at Columbia University, and director of the Cannabis Research Laboratory, said the results of the study were “highly encouraging.”^[3]

“We have tested over a dozen potential treatment medications in our Cannabis Research Laboratory, and this is the first to decrease both the positive mood effects of cannabis and the decision to use cannabis by daily smokers,” she said.^[2]

The trial was small, and the results will need to be confirmed by larger studies. But Haney said work is well underway on a phase 2b trial, with 300 participants being enrolled across the country and results expected as early as next year.^[3]

Drug could help the 30% of marijuana users who are dependent

Cannabis use disorder, also known as marijuana use disorder or marijuana addiction, is the inability to stop using the common psychoactive drug, despite adverse health and social effects. Signs of marijuana use disorder include cravings for cannabis, giving up important activities to use cannabis, using it in high-risk situations such as while driving, increased tolerance, and trying and failing to quit.^[5]

The Centers for Disease Control (CDC) estimates that three in ten marijuana users could be diagnosed with cannabis use disorder, with those who start using the substance during their adolescence at greatest risk for dependence.^[5] The Substance Abuse and Mental Health Services Administration (SAMHSA) estimates that 14 million Americans had cannabis use disorder in 2020.^[6]

However, the growing acceptance of the drug and its legalization for recreational use in many states has obscured the risk of addiction, researchers said.

“There’s no honest discussion of it,” Haney said. “I think the public is largely unaware of the risks to cannabis use, and it’s just talked about in very glowing terms.”^[3]

Currently, no drugs have been approved by the Food and Drug Administration (FDA) for the treatment of cannabis use disorder, despite its growing prevalence.

“Our care has really been hampered by a lack of medications that are effective for treatment,” Hadland said. “This is different from other substances like opioids, nicotine and alcohol, where we have effective medications.”^[3]

He was encouraged by the successful testing of AEF0117 but warned that patients have to be motivated to quit.

“We have to remember that this is a medication that, because it’s blocking the rewarding effects of cannabis, patients will have to actually want to take it,” he said.