How chronic substance use changes the body's own cannabis-like chemicals
Chronic use of alcohol, cannabis, cocaine, and opioids generally increases levels of anandamide, one of the body's endocannabinoids, though results are often conflicting across studies.
Quick Facts
What This Study Found
Across substance use disorders, anandamide (AEA) concentrations were usually elevated, while 2-AG was measured less often and showed mixed results. Cannabis use disorder specifically increased both AEA and 2-AG.
Key Numbers
15 studies reviewed: 3 in alcohol use disorder, 3 in cannabis use disorder, 4 in cocaine use disorder, 1 in opioid use disorder, 4 across multiple SUDs. AEA was usually increased across most substance types.
How They Did This
Comprehensive review of 15 studies assessing endocannabinoid ligand concentrations in people diagnosed with substance use disorders, searching EBSCO, PubMed, and Google Scholar through May 2024.
Why This Research Matters
The endocannabinoid system is being explored as a treatment target for addiction. Understanding how chronic substance use disrupts this system provides the scientific basis for developing new therapies.
The Bigger Picture
If chronic substance use consistently disrupts endocannabinoid signaling, therapies that restore normal endocannabinoid function could potentially address addiction across multiple substances rather than requiring substance-specific treatments.
What This Study Doesn't Tell Us
Only 15 studies available, many with small samples and varying methodology. Peripheral blood levels may not reflect brain endocannabinoid levels. Treatment status and abstinence duration varied across studies.
Questions This Raises
- ?Do elevated AEA levels in substance use disorders drive continued use, or are they a compensatory response?
- ?Would normalizing endocannabinoid levels reduce craving or relapse?
Trust & Context
- Key Stat:
- Anandamide was elevated across most substance use disorder types
- Evidence Grade:
- Comprehensive review, but based on only 15 studies with conflicting results and methodological variability. The evidence base is still developing.
- Study Age:
- Published in 2025, literature through May 2024.
- Original Title:
- Changes in peripheral endocannabinoid levels in substance use disorders: a review of clinical evidence.
- Published In:
- The American journal of drug and alcohol abuse, 51(2), 152-164 (2025)
- Authors:
- Elliott, Georgia O, Petrie, Gavin N(6), Kroll, Sara L(2), Roche, Daniel J O, Mayo, Leah M
- Database ID:
- RTHC-06399
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
Does chronic drug use change your body's endocannabinoid levels?
Generally yes. This review found that anandamide, one of the body's own cannabis-like chemicals, was usually elevated in people with alcohol, cannabis, cocaine, and opioid use disorders.
Could the endocannabinoid system be a target for addiction treatment?
The consistent finding of disrupted endocannabinoid levels across multiple substance types supports this possibility, but the evidence base is still small and results are sometimes conflicting.
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Cite This Study
https://rethinkthc.com/research/RTHC-06399APA
Elliott, Georgia O; Petrie, Gavin N; Kroll, Sara L; Roche, Daniel J O; Mayo, Leah M. (2025). Changes in peripheral endocannabinoid levels in substance use disorders: a review of clinical evidence.. The American journal of drug and alcohol abuse, 51(2), 152-164. https://doi.org/10.1080/00952990.2025.2456499
MLA
Elliott, Georgia O, et al. "Changes in peripheral endocannabinoid levels in substance use disorders: a review of clinical evidence.." The American journal of drug and alcohol abuse, 2025. https://doi.org/10.1080/00952990.2025.2456499
RethinkTHC
RethinkTHC Research Database. "Changes in peripheral endocannabinoid levels in substance us..." RTHC-06399. Retrieved from https://rethinkthc.com/research/elliott-2025-changes-in-peripheral-endocannabinoid
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.