Cannabidiol shows no immediate effect on brain or behavior in young people with alcohol use disorder, study finds

A new placebo-controlled study has found that a single dose of cannabidiol does not appear to change brain chemistry, reduce alcohol cravings, or influence drinking behavior in youth with alcohol use disorder. Published in Neuropsychopharmacology, the study provides evidence that acute cannabidiol administration, at least in isolation, may not have measurable therapeutic effects in this population. Although cannabidiol is widely marketed as a natural remedy for substance use problems, this research suggests its impact in youth may be more limited than hoped—at least in the short term.

Youth alcohol use continues to be a significant public health concern. Nearly one in seven adolescents meets the criteria for alcohol use disorder by age 18. Although psychotherapy remains the primary method of treatment, these interventions often show only modest benefits. Because there are few approved medications for young people with alcohol use disorder, researchers are actively exploring new pharmacological options that might be safer, more appealing, or better tailored to this age group.

Cannabidiol, a non-intoxicating compound found in cannabis, has attracted attention as a possible treatment due to its safety profile and potential to reduce alcohol-related behaviors in animal studies. Preclinical research suggests that cannabidiol can reduce alcohol consumption, prevent relapse, and protect the brain from alcohol-induced damage. Because it lacks the euphoric properties of THC and is generally well-tolerated, cannabidiol has been proposed as a promising candidate for young people with substance use issues, especially those who are skeptical of conventional pharmaceuticals.

Cannabidiol interacts with multiple brain systems that are linked to addiction, including the cannabinoid, glutamate, GABA, dopamine, and serotonin systems. Animal models suggest it may influence brain circuits involved in craving, decision-making, and impulse control. However, very few studies have evaluated these effects in humans, particularly in adolescents and young adults. The new study was designed to rigorously test whether cannabidiol could produce measurable short-term changes in brain function or alcohol-related behavior in young people diagnosed with alcohol use disorder.

“A lot of people don’t know this, but alcohol use disorder often begins during adolescence and young adulthood. Unfortunately, there are not many effective treatments for this age group and no approved medications that might help to improve the effectiveness of existing psychosocial treatments,” said study author Anna E. Kirkland of the Medical University of South Carolina.

“We wanted to see if CBD might be a potential medication to help youth struggling with alcohol use right now and maybe even help to prevent a lifetime problem with alcohol. CBD is very safe and tolerable, plus it has some solid work in animals indicating it might reduce alcohol use, so we thought it would be really interesting and useful to see if there was any indication that CBD could help reduce alcohol use in young people.”

The researchers recruited 36 young adults between the ages of 17 and 22, all of whom met diagnostic criteria for alcohol use disorder. Participants were not seeking treatment, and many were actively using alcohol during the study. Nearly 70 percent of the sample was female, and most participants identified as white. Participants were screened for other mental health conditions and underwent a full medical evaluation before being cleared for the study.

In a double-blind, placebo-controlled, crossover design, participants attended two lab sessions spaced at least 18 days apart. In one session, they received a 600 mg oral dose of cannabidiol. In the other, they received a placebo solution. The order was randomized, and neither the participants nor the researchers knew which session involved cannabidiol. The cannabidiol used in the study was an approved pharmaceutical-grade solution, and all participants consumed a high-fat snack beforehand to increase the compound’s absorption.

Two to three hours after ingestion, participants underwent a series of tests to assess the short-term impact of cannabidiol on brain function and behavior. These included brain scans to measure levels of the neurotransmitters glutamate and GABA in the anterior cingulate cortex, a region involved in impulse control and emotion regulation. Functional MRI scans were used to track brain activity while participants viewed alcohol-related images.

Participants also completed an olfactory cue-reactivity task, where they smelled their preferred alcoholic beverage and rated their craving. Physiological responses such as heart rate variability and skin conductance were recorded during this task. Finally, participants reported their alcohol use over the following week to see if cannabidiol influenced subsequent drinking behavior.

The results showed no significant effects of cannabidiol on any of the key outcomes measured. Neuroimaging data indicated that cannabidiol did not change glutamate or GABA levels in the anterior cingulate cortex compared to placebo. There were also no differences in whole-brain activity or in specific reward-related regions, such as the amygdala or nucleus accumbens, when participants were exposed to alcohol cues.

During the olfactory cue task, participants reported higher craving after smelling alcohol compared to non-alcoholic beverages, which suggests the task was effective in eliciting a response. However, cannabidiol did not reduce self-reported craving levels compared to placebo. There were also no differences in physiological responses such as heart rate variability or skin conductance during exposure to alcohol cues.

“We were surprised that the olfactory/smell task (where individuals smelled their favorite alcohol in comparison to apple juice or water) did not result in any changes in heart rate or skin conductance,” Kirkland told PsyPost. “We were excited to try this as a new human laboratory task to look at the effects of alcohol without taste, since a large portion of our participants are under the legal drinking age. It seems like smell might not be an important part of alcohol use in this age range.”

The researchers also analyzed participants’ drinking behavior over the week following each session. They found no evidence that cannabidiol reduced the number of drinks consumed or the number of drinking days. The only significant predictor of alcohol use during that week was the participant’s baseline drinking level, not whether they had received cannabidiol or placebo.

“Importantly, we just gave a single dose of CBD to see if it affected things that we know are related to alcohol use (like craving),” Kirkland said. “While we did not observe any significant findings in our study, we do not think this is the end of the CBD story for alcohol use disorder. It will be important to test other things, like higher doses, longer term use instead of just one dose, or other ways that CBD might help young people, such as reducing anxiety. Science is always a work in progress!”

The absence of significant effects may reflect several factors, including the short-term nature of the intervention. Many previous studies showing benefits of cannabidiol have used higher doses, longer treatment periods, or adult populations with more established substance use problems. For example, some studies in adults with alcohol use disorder have reported changes in craving and brain activity after several days of cannabidiol administration or after combining it with more intense alcohol-related cues.

It is also possible that the brain systems of younger individuals may be less sensitive to cannabidiol’s effects, or that the cues used in the study were not strong enough to provoke meaningful brain or physiological responses. The researchers noted that taste cues, rather than smells or images, tend to produce more robust reactions, but such methods were not appropriate given that many participants were under the legal drinking age.

Additionally, there were no adverse events reported across any of the sessions, supporting the general safety of a single 600 mg dose of cannabidiol in this population.

While this study did not find evidence of short-term effects, it lays the groundwork for future trials that may examine chronic dosing, different formulations, or combinations with other therapies. The researchers emphasize that longer studies with larger and more diverse samples may be needed to fully evaluate the potential of cannabidiol as a treatment for youth with alcohol use disorder.

“Our study was focused on the potential acute effects of CBD, which means participants only received a single dose of CBD,” Kirkland noted. “It seems likely that CBD may need to be taken for longer periods of time in order to see mechanistic level results like we were interested in.”

“We are so proud of this study! We used very strict methods and tried our best to do the very best science possible. Our team was fantastic, and we could not have done this study without the generous volunteers who participated.”

The study, “The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial,” was authored by Anna E. Kirkland, Brittney D. Browning, Lindsay R. Meredith, Elizabeth Robertson, Cori Herring, Rachel L. Tomko, Kevin M. Gray, and Lindsay M. Squeglia.