Cannabinoid Clinical Trials: Cannabis Effects on Alcohol Urge

Clinical Takeaway

People who use alcohol heavily and cannabis regularly show different responses to cannabis depending on their working memory capacity, meaning the brain’s ability to hold and process information temporarily. In this controlled trial, working memory capacity predicted how much cannabis affected the urge to drink alcohol, suggesting that cognitive factors shape cannabis-alcohol interactions. This finding helps explain why cannabis appears to increase alcohol cravings in some individuals but reduce them in others.

#15 Working memory capacity predicts cannabis-induced effects on alcohol urge.

Citation: Gunn Rachel L et al.. Working memory capacity predicts cannabis-induced effects on alcohol urge.. Addictive behaviors. 2026. PMID: 41275744.

Study type: Journal Article, Randomized Controlled Trial  |  Topic area: Geriatrics  |  CED Score: 11

Design: 5 Journal: 0 N: 2 Recency: 3 Pop: 2 Human: 1 Risk: -2

Why This Matters
Working memory capacity may serve as a clinically useful predictor for determining which patients will experience reduced versus increased alcohol urges following cannabis use, potentially explaining the heterogeneous effects observed in prior research. This finding has implications for personalized medicine approaches in substance use treatment, as it suggests that cognitive screening could help identify patients for whom cannabis might be contraindicated due to risk of increased alcohol craving. Understanding these individual differences in cannabis-alcohol interactions is essential for clinical decision-making regarding cannabis use in patients with concurrent alcohol use disorders.

Quality Gate Alerts:

  • Preclinical only

Abstract: BACKGROUND: Cannabis has shown mixed results in its association with alcohol urge, which may be explained by individual differences. One such factor, working memory capacity (WMC) is associated with drug-related cue reactivity and implicated in alcohol use and problems. In the current study, we examined whether WMC moderates the acute effect of cannabis on alcohol urge in a randomized placebo-controlled crossover trial. METHODS: Participants aged 21 to 44 (N = 125, 32 % female) reporting heavy alcohol use and cannabis use ≥ twice weekly completed a laboratory protocol across three days where they smoked a placebo, 3.1 % delta-9 tetrahydrocannabinol (THC), and 7.2 % THC cannabis cigarette. Participants were asked to rate their alcohol urge pre and post smoking. Prior to the experimental sessions, participants completed WMC measures including the n-back and the complex span tasks, operation span (OS) and symmetry span (SS). RESULTS: Those with higher WMC, as assessed via the SS task, reported significantly lower alcohol urge after smoking the 7.2 %, but not the 3.1 %, THC dose, relative to placebo. Performance on the OS task was not associated with alcohol urge. Lower WMC as determined via n-back scores was associated with higher alcohol urge overall, but n-back scores did not moderate the impact of cannabis on alcohol urge. CONCLUSION: Findings suggest individuals with higher but not lower working memory experience lower alcohol urge under acute effects of cannabis. Although cannabis is increasingly perceived as a substitute for alcohol, individuals with lower working memory may be less likely to experience such benefits when attempting to reduce their drinking.

Clinical Perspective

🧠 This crossover trial suggests that working memory capacity may be a meaningful individual difference factor predicting whether cannabis reduces or increases alcohol urge, which could help explain the mixed findings in prior literature on cannabis and alcohol cravings. The study’s strength lies in its randomized placebo-controlled design and reasonable sample size, though the relatively narrow age range (21-44) and participant selection criteria limit generalizability to broader populations, and the mechanisms linking working memory to cannabinoid effects remain incompletely understood. Additionally, acute laboratory-induced urge may not fully translate to real-world relapse risk or sustained drinking behavior in naturalistic settings. From a clinical standpoint, these findings suggest that cannabis use as a potential intervention for alcohol use disorder should not be considered a one-size-fits-all approach, and screening for baseline cognitive factors like working memory might eventually help identify which patients could theoretically benefit versus those at risk for paradoxical increases in alcohol craving.

Full Article  |  PubMed