This Breakthrough Drug Might Finally Treat an Elusive Cannabis Disorder

An entirely new class of drugs appears to cater to the needs of those experiencing cannabis use disorder.

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People demonstrate for the legalization of cannabis in Bogota, Colombia on May 6, 2023. (Photo by: C...
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In the 1936 film Reefer Madness (1936), smoking marijuana invariably leads to debauchery, loose morals, and murder. Suffice it to say this film’s take on weed borders on hysterical.

While this cautionary tale spectacularly overblows cannabis’ dangers, weed isn’t risk-free. In a fraction of users, it can lead to disordered use, known as cannabis use disorder (CUD). Currently, CUD lacks effective pharmacological treatments, but an entirely new class of drugs appears to cater to the needs of those experiencing the disorder.

A new paper published in the journal Nature Medicine outlines the results of three clinical trials using the first drug of this novel class.

A class of its own

A new pharmacological class of drugs has demonstrated success in decreasing cannabis use in those with CUD. This group is called signal-specific inhibitors of the cannabinoid receptor type 1 (CB1), and the inaugural drug goes by AEF0117. Developed by Aelis Farma, this compound helps reduce cannabis use by blocking the specific molecular pathways associated with a high rather than blocking all molecules from binding to the receptor. This block decreases a user’s inclination to smoke without causing side effects.

“It directly targets the direct effects of cannabis,” Margaret Haney, a psychiatric neurobiology professor at Columbia University who led clinical trials, tells Inverse. “That's really unique.”

The CB1 receptor is like a lock in our brain that only matches certain keys. Tetrahydrocannabinol (THC), the psychoactive compound in marijuana, is one such key. It can bind to this receptor and unlock those blissed-out feelings. However, CB1 is also an ideal lock for endogenous cannabinoids, which are cannabinoids that our brains produce naturally.

So far, the only drugs available to aid in CUD are known as agonists, which basically cover the keyhole to CB1, so nothing can bind to it, not even endogenous cannabinoids. As a result, we suffer side effects such as drowsiness or brain fog. This signal-specific inhibitor does just that — it inhibits specific signals, in this case, the signals from THC that induce a high. Pier Vincenzo Piazza, a physician as well as Aelis Farma’s CEO, says he and his team were surprised at how well their drug worked at only blocking cannabis’s high-inducing effects.

In their phase 2 clinical trial, 29 volunteers with CUD took one dose of this new drug a day for two weeks. They were given the opportunity to smoke if they wanted, but as the trial went on, they opted not to smoke. The drug was dampening the good feelings of the high and made smoking less desirable.

The reality of cannabis addiction

As with other substances or behaviors, cannabis can be addictive. Haney says that most people wouldn’t consider cannabis to be addictive compared to substances like alcohol, opioids, or cocaine. Rather, CUD comes from how cannabis affects other aspects of the user’s life. Experts characterize this behavior as consistent continued use in spite of resulting problems in someone’s personal and private life. A key sign is if someone wants to use less or quit but can’t.

Cannabis use disorder (CUD) affects an estimated 10 percent of the world’s 193 million cannabis users. CUD still lacks a robust pharmacological treatment. While methadone, for example, commonly treats those addicted to heroin and opioids, no such drug exists for those who can’t control their cannabis intake.

What’s more, the researchers clarify that the goal of treatment isn’t necessarily abstinence. It’s for the user to decide if they want to cut cannabis out entirely or just cut back on how much or how frequently they use it.

What’s next

The drug still has a ways to go before it reaches consumers. However, Piazza is hopeful that it will be available in about five years. He’s optimistic about its safety profile, saying that between its effectiveness and lack of side effects, this drug is quite promising.

“It sounds very Disneyland, but it’s true,” he tells Inverse.

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