Joy Lian

Marijuana is addictive, but what happens when people who smoke cannabis want to quit? A new Yale study has found a drug that can help with marijuana withdrawal.

A team of researchers tested the chemical on a group of 70 participants, who all reported smoking at least three marijuana joints per day on average. The participants were first hospitalized for five days without marijuana to induce withdrawal. After four weeks, those who were not given the placebo reported better sleep, less cannabis use and a reduction in withdrawal symptoms overall. At a time when marijuana legalization is on the legislative horizon for many states, the study is good news for people who may want to quit in the future. If approved by the FDA, the drug will be the first to treat cannabis use disorder. The study was published in The Lancet Psychiatry on Dec. 6.

“I would not say it’s a miracle drug as a scientist. Before we get too sold on this drug, we first need to replicate [the findings]. But I’m cautiously optimistic,” said first author and Yale psychiatry professor Deepak D’Souza.

Much like how opioids target the brain’s receptors for dopamine, cannabis attaches to receptors for naturally-occurring chemicals called cannabinoids, encouraging the body to stop producing them. When someone stops smoking, it takes time for the body to start producing cannabinoids at normal levels again, leading to symptoms of withdrawal, including irritability, anger, depression, sleep difficulty and loss of appetite.

According to D’Souza, the drug — called a fatty acid amide hydrolase inhibitor — works by preventing enzymes from breaking down cannabinoids in the first place. By ensuring receptors in the brain never go without the chemical, withdrawal symptoms are less severe and, in turn, relapse is less likely.

“In a nutshell,” he said, “the drug reduced withdrawal, reduced use, restored stage 3 sleep and did so without having any significant adverse effects.”

Researchers used state-of-the-art methods of data collection in order to make sure the study produced accurate results. In addition to constantly monitoring the test subjects at the Connecticut Mental Health Center for just under a week, D’Souza’s team issued iPhones to the subjects and video-called them every day while they took either the placebo or the drug at home. The researchers also used blood tests and urine samples to measure how often they took the drug, and in some cases, how often they relapsed.

According to D’Souza, his team also used sophisticated brain-wave technology to analyze the subjects’ sleep patterns. Before their in-patient stay at the Connecticut Mental Health Center, they were invited to spend a few nights sleeping in a research facility to become more familiar with the environment. After the four-week trial was over, subjects slept under surveillance once more to observe to what extent their sleep improved.

“We found that in the group that received the placebo, there was a reduction in stage 3 sleep, which is necessary for feeling rested. It was significantly attenuated by treatment with the inhibitor,” he said.

According to D’Souza, this drug is not the first to be tested on humans with cannabis use disorder. In a French study published in 2016, a subject died after nine days of taking a similar drug. Other subjects in the 2016 study reported memory loss and permanent brain injury.

However, study co-author and associate research scientist at the School of Medicine Jose Cortes-Briones said that these side effects resulted because the chemical used in the previous study — a different fatty acid amide hydrolase inhibitor — targeted unintended areas of the brain in addition to the cannabinoid receptors.

“The drug was just not specific enough. That’s what caused the toxicity and the side effects, not the action on the FAAH,” he said.

Given the fact that this trial had no serious side effects, D’Souza’s team is now working on replicating the study at Columbia University, Johns Hopkins and the Medical University of South Carolina. If those trials report back similar results, this drug could find its way into the hands of marijuana smokers nationwide.

THC, the molecule responsible for marijuana’s psychological effects, was first isolated in 1964 by scientists in Israel.

Matt Kristoffersen | matthew.kristoffersen@yale.edu