Alcohol misuse is a significant contributor to poor mental and physical health in people under age 50 worldwide. Existing interventions for alcohol misuse suffer from high attrition and relapse, prompting the search for more effective treatments.
Esketamine, a novel glutamatergic drug with dissociative, anesthetic, hallucinogenic and psychedelic properties has demonstrated antidepressant effects. A few studies suggest it may work synergistically with behavioral treatments to reduce alcohol use. Some researchers propose that esketamine facilitates greater psychological engagement with treatment in terms of motivation, commitment, and belief in the treatment process.
Gent et al. [Journal of Psychopharmacology] tested whether combining esketamine with a mindfulness training enhances treatment psychological engagement among individuals with alcohol use disorder.
The researchers randomly assigned 28 British adults (mean age = 22 years; 57% male; 93% white) with moderate to severe alcohol use disorder to a mindfulness training combined with either a single dose of esketamine or a vitamin C placebo administered on the eighth day of the intervention phase.
Participants attended the study center on day one for a baseline assessment. They were shown three brief videos introducing mindfulness and outlining its benefits for relapse prevention. They were also given a set of 14 daily mindfulness exercises, each lasting 5 to 25 minutes, to complete on their own over the following 14 days.
They returned to the study center on the eighth day of the study for a single dose of either esketamine or placebo. After dosing, participants wore an eye mask and listened to soothing music for 40 minutes. Following this, they completed a post-intervention assessment. Participants also completed a final online assessment on day 14.
The mindfulness exercises emphasized relaxation and accepting thoughts and sensations. Two of the exercises specifically addressed managing alcohol cravings through mindfulness. Assessments measured the primary outcomes of engagement with treatment and alcohol cravings and use.
The results showed a significant difference in treatment psychological engagement between esketamine and placebo groups. Engagement scores did not differ by groups during day 1-7, but after drug administration, self-reported engagement increased and remained higher for the esketamine group but not the placebo group.
There was also a significant but transient post-drug decrease in alcohol cravings on day 8 for the esketamine group, but not the placebo group. The esketamine group showed significantly more dissociative and mystical experiences after drug administration than placebo. Both groups decreased alcohol use, without a significant difference between. The groups did not differ in terms of self-reports of how many days or how many times a day they performed the mindfulness exercises.
The study shows a single dose of esketamine increased psychological engagement with a daily brief mindfulness training and transiently reduced alcohol cravings. However, it did not improve alcohol-related outcomes at the study’s 2-week endpoint.
The study’s limitations include its small sample size, the limited number of data points for assessing daily alcohol cravings, and the brevity of the mindfulness training.
Reference:
Gent, E. M., Bryan, J. W., Cleary, M. A., Clarke, T. I., Holmwood, H. D., Nassereddine, R. O., Salway, C., Depla, S., Statton, S., Krecké, J., & Morgan, C. J. (2024). Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems. Journal of Psychopharmacology, 38(6), 541–550.
Link to study
