An experimental drug combining nabilone and gabapentin reduced the severity and bothersomeness of cannabis withdrawal symptoms in a small randomized, placebo-controlled trial involving adults with moderate-to-severe cannabis use disorder. The results offer an early signal of potential benefit, but with only 14 participants, a short study period and financial ties to the drug’s developer, much larger trials will be needed to determine whether PP-01 actually works as a treatment.
Quitting cannabis after frequent, long-term use does not typically produce the kind of potentially fatal withdrawal associated with some other substances, such as cocaine or opioids. Cannabis also does not cause fatal overdoses. Still, quitting the plant isn’t always easy.
There is a clinically recognized cannabis withdrawal syndrome. It can emerge after stopping or reducing heavy, prolonged use and can include irritability, anxiety, sleep disturbances, loss of appetite, restlessness or depressed mood, along with physical symptoms such as abdominal pain, sweating, tremors or headaches. It typically begins within the first 24 to 48 hours, peaks during the first week, and can last for one to two weeks.
That doesn’t mean everyone who uses cannabis will develop dependence, either. But there is such a thing as cannabis use disorder, a diagnosis that describes patterns of use that cause significant distress or impairment in everyday life. Withdrawal can be one of its manifestations and, for some people, can become a barrier to quitting or contribute to relapse.
That’s exactly what PP-01—an experimental drug recently evaluated in a small study published in The American Journal on Addictions—is designed to address.
Two Known Drugs, One New Combination
PP-01 combines nabilone, a synthetic cannabinoid, with gabapentin, a medication currently used for neurological indications. In the trial, the formulation contained 6 mg of nabilone and 600 mg of gabapentin. The hypothesis is that the two substances work through different mechanisms, potentially relieving several components of withdrawal at the same time.
The study was a randomized, double-blind, placebo-controlled Phase 1b/2a trial with a crossover design. It included just 14 adults with moderate or severe cannabis use disorder who consumed at least one gram of cannabis daily or on a near-daily basis and had previously experienced withdrawal when trying to quit marijuana. They were not seeking treatment.
The average age was 31.2 years, with participants ranging from 23 to 44 years old. 57% were women, 71% were Black, and 29% were White. On average, they reported using around 3.5 grams of cannabis per day before entering the study. Two participants didn’t receive treatment during the second period of the study.
During two study periods separated by 14 days, participants received PP-01 and placebo while remaining abstinent under supervision.
Did It Work?
The results are promising, but still very preliminary.
When participants received PP-01, they reported less severe withdrawal symptoms and said those symptoms were less bothersome than when they received placebo. Differences began to emerge within hours of the first dose. Improvements were also observed in cannabis-related hunger, or the “munchies,” and in sleep quality.
The drug was well tolerated during the trial, and no serious adverse events were reported. The side effects observed were mild and primarily included feeling “high,” relaxed, and fatigued.
That, however, is still a long way from proving that PP-01 is an effective treatment for cannabis withdrawal.
The study included only 14 people, lasted just a few days and was conducted at a single center. Its goal was to provide preliminary evidence of safety and potential efficacy, not to definitively determine whether the drug works in the general population. The researchers themselves note that the findings will need to be replicated in considerably larger trials.
There is also an important detail to consider when interpreting the results: the trial was sponsored by PleoPharma, the company developing PP-01. Three of the authors are company employees and hold stock or stock options, while other researchers served as consultants to the company.
For now, it is also worth noting that there is no FDA-approved medication specifically for treating cannabis use disorder or cannabis withdrawal syndrome. PP-01 aims to fill that gap, but it will still need to demonstrate in much larger studies that the signals observed in these 14 participants hold up.
Cover photo created with AI
