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Young Adult Cannabis Use and Circulating Endocannabinoid Concentrations on Cognitive Performance.

Alexander L. Wallace, Rachel E. Baca, Gianna Andrade, Cecilia J. Hillard, Joseph P Happer, Natasha E Wade, Kelly E Courtney, Margie Hernandez Mejia, Joanna Jacobus

Frontiers in adolescent medicine 2025 DOI: 10.3389/fradm.2025.1538448 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cross-sectional study Peer reviewed
Sample size 87
Population Young adults aged 18-20 (63% female) who use cannabis
Measures Rey Auditory Verbal Learning Task (RAVLT)
Topics Cannabis
Key findings Heavy cannabis use was associated with worse verbal memory. Among heavy users, higher 2-AG concentrations correlated with better verbal learning and memory, while higher AEA concentrations correlated with worse verbal learning. Men with heavy use and high 2-AG showed better verbal learning than men with lower 2-AG. The authors propose circulating endocannabinoid profiles may serve as a biomarker for cannabis-related cognitive deficits.

Abstract

The endocannabinoid (eCB) system is a regulatory mechanism that helps to maintain homeostasis in the brain. Cannabis use and circulating eCB disruptions have been linked with altered memory; however, this work has largely been done in animal models with minimal investigation into these relationships by sex. We aim to investigate how circulating eCB concentrations in cannabis using young adults are associated verbal memory. We hypothesize that greater amounts of self-reported cannabis use and lower eCB circulating concentrations will be associated with worse learning and memory. Sex as a potential moderator was explored. Eighty-seven participants between the ages of 18-20 (63% female) completed measures on past 30-day cannabis use, verbal learning and memory (Rey Auditory Verbal Learning Task; RAVLT), and a blood draw. Serum sample analysis from blood draws assessed concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA). Linear regressions examining cannabis group status based on past 30 day cannabis use (no use, light use (<8 use days), and heavy cannabis use (≥8 use days)), eCB concentrations, and their interaction on RAVLT learning and memory scores. Three-way sex by cannabis status by eCB concentrations interactions were also explored. Heavy cannabis use was associated with worse verbal memory performance. Significant interactions between 2-AG and heavy cannabis use were observed, revealing that individuals with elevated 2-AG concentrations and heavy cannabis use showed better performance on verbal learning and memory tasks. In contrast, heavy cannabis use with higher AEA concentrations performed worse on verbal learning tasks. There was a significant three-way interaction with sex, cannabis use group, and 2-AG concentrations on verbal learning where men with heavy cannabis use and high 2-AG concentrations had better verbal learning compared to men with lower 2-AG concentrations. Distinct patterns emerged between 2-AG and AEA concentrations and memory performance among individuals with heavy cannabis. Higher 2-AG concentrations and lower AEA concentrations correlated with improved memory performance in the heavy cannabis use group, suggesting that circulating eCB profiles may serve as a biomarker for cannabis-related cognitive deficits. More work is needed to disentangle the complex relationships between circulating eCB concentrations, cannabis use, and neurocognitive functioning.

Comparable studies

Other cross-sectional and survey studies on cannabis, most cited first.

Study Year Design Participants
Cannabis use before age 15 and subsequent executive functioning 104 chronic cannabis users (49 early-onset before age 15, 55 late-onset after age 15)... 2011 Observational cross-sectional study n = 148
Patterns of simultaneous polysubstance use in drug using university students Drug-using university students 2006 Cross-sectional survey n = 149
Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey Online survey respondents 2020 Cross-sectional survey
User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study Users of hallucinogenic drugs who completed a web-based questionnaire 2010 Cross-sectional survey n = 600
Illicit Use of LSD or Psilocybin, but not MDMA or Nonpsychedelic Drugs, is Associated with Mystical Experiences in a Dose-Dependent Manner Adults recruited from the MAPS website and newsletter, most reporting use of various... 2012 Cross-sectional survey n = 337

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