Psychiatry

Tackling the Treatment of Cannabis Use Disorder

    With cannabis use becoming increasingly mainstream – with 38 states, three territories, and the District of Columbia legalizing the drug for medicinal and/or recreational use – there has been a rapid increase in the number of cannabis users in the country. And with this rapid rise in usage, faculty in NewYork-Presbyterian/Columbia’s Substance Use Research Center are working to address cannabis addiction find innovative ways to treat cannabis use disorder (CUD).

    Frances Levin, MD, an addiction psychiatrist at NewYork-Presbyterian/Columbia and Chief of the Division on Substance Use Disorders at Columbia and the New York State Psychiatric Institute, works together with Margaret Haney, PhD, Co-Director of the Substance Use Research Center and Director of the Cannabis Research Laboratory at Columbia and the New York State Psychiatric Institute, to bring CUD research from the bench to the bedside. Their shared goal is to find better, more effective ways to treat CUD.

    “Having a cannabis use disorder may not produce the same dire consequences as an opiate, heroin, or methamphetamine use disorder” says Dr. Levin. “But it can certainly cause a lot of problems for some people. Quality of life is often diminished by heavy, frequent use.”

    “We're not saying that cannabis is the worst thing in the world,” Dr. Haney adds. “But nobody wants to have a substance use disorder, and [developing CUD] has to be introduced as one of the risks of daily cannabis use, and I don't think it's often discussed.”

    “Having a cannabis use disorder may not produce the same dire consequences as an opiate, heroin, or methamphetamine use disorder. But it can certainly cause a lot of problems for some people. Quality of life is often diminished by heavy, frequent use.” — Dr. Frances Levin

    A First-in-Class Drug Shows Promise for Treating CUD

    There are currently no pharmacotherapies approved for the treatment of CUD, which affects approximately 14 million Americans. According to Dr. Levin, current treatment modalities usually involve cognitive behavioral therapy (CBT), motivational interviewing, or motivational enhancement therapy with CBT. “Pharmacologic interventions are all off-label,” Dr. Levin says. “But clinicians often use a variety of medications, some that have been studied and some that haven’t, to treat the withdrawal associated with CUD.”

    Dr. Haney has been exploring CUD in her lab for decades. “This is a residential lab where we bring in daily cannabis smokers who are not seeking treatment for their cannabis use,” she explains. “They live in the lab for 5-12 days at a time and we can give them cannabis under controlled conditions. We have all the regulatory pieces in place to give them cannabis and medication and placebo and then measure their behavior around the clock. We have cameras and microphones and we’re measuring sleep, food intake, cognition, mood, everything they’re doing throughout the day. To be able to characterize the effects of cannabis, cannabis withdrawal, and then what a medication does in interaction with cannabis is incredibly unique.”

    Dr. Haney, along with Aelis Farma, recently led a Phase 2a clinical trial looking at AEF0117, a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi) developed by Aelis Farma for the potential treatment of CUD. According to the research published in June on Nature Medicine, AEF0117 works by selectively inhibiting only the cellular signals involved in CUD. This breakthrough approach differs from previous CB1 receptor antagonists that, due to their broad blockade of all CB1 receptor activity, caused significant adverse effects preventing their clinical use.

    Twenty-nine research volunteers with CUD were enrolled in this randomized, double-blind, placebo-controlled, crossover, multiple-dose-escalation study. Eligible participants were cannabis smokers of ≥ 1 grams of cannabis per day, at least 6 days per week who met the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for CUD. The participants received one of two different doses of AEF0117– 0.06mg and 1mg – in one 5-day phase and placebo and in another 5-day phase in randomized order. AEF0117 significantly reduced participants’ self-reported ratings of cannabis-related positive mood effects, the primary outcome measure, by a mean of 38% while also reducing the use of cannabis. These reductions occurred without precipitating cannabis withdrawal, even for volunteers who smoked several grams of cannabis per day.

    Image of cannabis buds

    Columbia psychiatry faculty are leading research looking at a first-in-class drug to treat cannabis use disorder.

    “We have tested over a dozen potential treatment medications in our Cannabis Research Laboratory, and we've never seen anything directly and robustly attenuate the direct effects of cannabis. This is the first [drug] to decrease both the positive mood effects of cannabis and the decision to use cannabis by daily smokers,” Dr. Haney says.

    “This is the first [drug] to decrease both the positive mood effects of cannabis and the decision to use cannabis by daily smokers.” — Dr. Meg Haney

    Based on the findings from the study, Dr. Levin is now conducting a phase 2b, two-year study which is expected to enroll 330 participants with CUD to evaluate three dose levels of AEF0117 in treating CUD. “It’s a 12-week trial looking at both if the medication achieves abstinence as well as looking at a reduction in [cannabis] use.”

    Dr. Haney is continuing research in with AEF0117 as well, looking at the effect that food has on the oral bioavailability of the AEF0117 to support the next stage of drug development.

    The NewYork-Presbyterian Approach to Cannabis and Other Substance Use Disorders

    The collaboration between Columbia’s Cannabis Research Laboratory and the Substance Use Research Center is unique. “The work in my lab is proof-of-concept looking for medications that look promising for cannabis use disorder that then move to Dr. Levin’s outpatient research clinic,” says Dr. Haney. “It’s a wonderful and unique situation we have here at Columbia – anything that looks promising in the human lab can often move straight to the research clinic testing patients, and that’s the gold standard for determining if a medication is effective.”

    Columbia’s Substance Use Research Center isn’t only focused on CUD – it’s also looking at finding interventions for other substance use disorders, including opiate, cocaine, and alcohol use disorders. “Our division does cutting-edge research into all of these disorders,” says Dr. Levin. “One of the studies that is just starting is looking at transcranial magnetic stimulation for cocaine use disorder. It has a component of neuroimaging to look at the ways in which the brain may be changed with TMS as a treatment for cocaine use disorder.”

    “We strive to train and support the next generation of clinical researchers who develop new treatment strategies for substance use disorders as well as improve the implementation of existing evidence-based interventions.” — Dr. Frances Levin

    In addition to conducting research, NewYork-Presbyterian/Columbia is dedicated to training the next generation of addiction researchers. This includes having a T32 clinical translational research fellowship in substance use disorders for over three decades. “There’s a dearth of clinical researchers and particularly clinical psychologists and physicians who are interested in careers targeting addiction,” says Dr. Levin. “We have comprehensive training for that and many of our faculty are former fellows. We strive to train and support the next generation of clinical researchers who develop new treatment strategies for substance use disorders as well as improve the implementation of existing evidence-based interventions.”

      Learn More

      Haney M, Vallée M, Fabre S, et al. Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials. Nature Medicine. 2023;29(6):1487-1499. doi: 10.1038/s41591-023-02381-w

      Clinical Trial: Effect of AEF0117 on Treatment-seeking Patients With Cannabis Use Disorder (CUD):  SPECIFIC SIGNALING INHIBITOR IN CANNABIS ADDICTION (SICA 2)

      Clinical Trial: The Effect of Food on the Oral Bioavailability of AEF0117 in Healthy Volunteers

      For more information

      image of Dr. Frances Levin
      Dr. Frances Levin
      [email protected]