Circulating endocannabinoid levels rise with exercise and stress, follow a circadian rhythm tied to sleep, and are disrupted in chronic pain and PTSD.
Anyone curious about why the body has a cannabinoid system in the first place, and what it does when you're not using cannabis.
What the researchers found
Endocannabinoids aren't just in the brain. They circulate in the bloodstream, and their levels shift in response to specific physiological states. This review mapped those patterns across multiple domains.
Energy balance was the most consistent finding: endocannabinoid signaling tracked with increased energy consumption and storage, supporting the system's role in appetite and metabolism. Physical exercise mobilized endocannabinoids — a finding that contributes to the "runner's high" hypothesis and may explain some of exercise's analgesic and mood-elevating effects.
2-AG, one of the two main endocannabinoids, followed a strong circadian rhythm that became dysregulated when sleep was disrupted. Circulating levels also shifted with inflammation, chronic pain, and stress. In PTSD specifically, endocannabinoid concentrations were altered in ways that suggested the system's stress-recovery function was impaired.
Why it matters
This review connects cannabis science to broader biology. The endocannabinoid system isn't just relevant when someone uses cannabis — it's active in exercise, sleep, eating, stress recovery, and pain processing every day. Understanding these baseline patterns helps explain why cannabis affects so many different things: it's acting on a system that already touches nearly every major physiological process.
The exercise connection is particularly interesting. If runner's high partly comes from endocannabinoids, then exercise and cannabis may be acting on overlapping pathways — which could matter for both addiction treatment and mental health.
The numbers in context
• 2-AG levels follow a significant circadian rhythm, disrupted by sleep loss
• Exercise increases circulating endocannabinoid levels
• Endocannabinoid concentrations altered in PTSD, chronic pain, and inflammation
• Endocannabinoid signaling consistently associated with increased energy intake and storage
How the study worked
Comprehensive review of human studies measuring circulating endocannabinoid concentrations (primarily 2-AG and anandamide) in relation to physiological states and clinical conditions. Published in Neuropsychopharmacology. Covers energy balance, exercise, sleep, stress, pain, and psychiatric conditions.
Who was studied
Review of various studies on endocannabinoids in humans and animals.
What this study cannot tell us
Circulating endocannabinoid levels may not reflect brain levels or tissue-specific signaling. Many factors influence blood concentrations simultaneously, making it difficult to isolate individual contributions. The review synthesizes human observational data, which cannot establish causation. Methods for measuring endocannabinoids vary across studies.
How to read the evidence
Comprehensive review of human observational studies. Strong pattern identification but based on correlational data that cannot prove causation.
When this study was published
Published in 2018. Endocannabinoid measurement methods and understanding have continued to improve.
The bigger picture
The paper's core insight is that measuring blood endocannabinoid levels can tell researchers something about how the system is functioning — but so many things influence those levels that they can't serve as a standalone biomarker. This complexity is actually the point: the endocannabinoid system is a crossroads where exercise, sleep, stress, pain, and metabolism all converge. Cannabis acts on that crossroads.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Could endocannabinoid blood levels be used to guide personalized cannabis dosing?
- Does regular exercise reduce the drive to use cannabis by naturally activating the same system?
- How do circulating endocannabinoid disruptions in PTSD relate to self-medication with cannabis?
Common questions
Does exercise produce cannabinoids?
What happens to endocannabinoids when you don't sleep?
Read the original research
Circulating endocannabinoids: from whence do they come and where are they going?
Neuropsychopharmacology, 43(1), 155-172
Neuropsychopharmacology is a well-respected journal focusing on the effects of drugs on the brain and behavior.
Citation
Hillard, Cecilia J.. (2018). Circulating endocannabinoids: from whence do they come and where are they going?. Neuropsychopharmacology, 43(1), 155-172. https://doi.org/10.1038/npp.2017.130
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