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.
Addiction researchers, neuroscientists studying the endocannabinoid system, and clinicians interested in novel treatment targets for substance use disorders.
Anandamide was elevated across most substance use disorder types
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Comprehensive review, but based on only 15 studies with conflicting results and methodological variability. The evidence base is still developing.
When this study was published
Published in 2025, literature through May 2024.
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.
Questions still open
- 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?
Common questions
Does chronic drug use change your body's endocannabinoid levels?
Could the endocannabinoid system be a target for addiction treatment?
Read the original research
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
Citation
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
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