A systematic review found that exercise, diet, massage, acupuncture, and several medication classes all appear to upregulate the endocannabinoid system.
Read this if you want to learn how to naturally support your body's endocannabinoid system.
322 studies reviewed: exercise, diet, medications, and complementary therapies all modulate the endocannabinoid system
What the researchers found
The review identified multiple categories of clinical interventions that enhance the endocannabinoid system. Pharmaceutical approaches included analgesics (acetaminophen, NSAIDs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants.
Complementary and alternative medicine approaches that upregulated the system included massage and manipulation, acupuncture, dietary supplements, and herbal medicines.
Lifestyle factors also modulated the endocannabinoid system: diet, weight control, exercise, and psychoactive substance use (alcohol, tobacco, coffee, and cannabis). The authors connect these findings to the concept of "endocannabinoid deficiency syndrome," which has been proposed as a factor in migraine, fibromyalgia, irritable bowel syndrome, and certain psychological disorders.
Why it matters
The endocannabinoid system is involved in pain, mood, sleep, appetite, and immune function. Understanding how to naturally support this system could offer therapeutic approaches for conditions where endocannabinoid tone may be deficient, potentially reducing reliance on external cannabinoids.
The numbers in context
184 in vitro studies, 102 animal studies, and 36 human studies were included. The review identified upregulation mechanisms across cannabinoid receptors CB1 and CB2, ligand synthesis (anandamide and 2-AG), and degradation enzyme inhibition.
How the study worked
The researchers searched PubMed for clinical trials, observational studies, and preclinical research on interventions that enhance the endocannabinoid system. Data synthesis was qualitative. After applying exclusion criteria, they included 184 in vitro studies, 102 in vivo animal studies, and 36 human studies.
What this study cannot tell us
Most of the evidence came from preclinical studies (in vitro and animal). Only 36 human studies were included, many with small sample sizes. The clinical significance of measured endocannabinoid changes is often unclear. Qualitative synthesis means effect sizes across studies were not formally compared.
How to read the evidence
This is a systematic review, but most included studies were preclinical. The human evidence base remains limited.
When this study was published
Published in 2014. Research on endocannabinoid system modulation has continued, though clinical applications remain largely investigational.
The bigger picture
This review connects diverse fields of research, from exercise science to pharmacology to complementary medicine, through the common thread of endocannabinoid system modulation. The finding that everyday activities like exercise and common medications like acetaminophen interact with this system underscores how central it is to human physiology.
Questions still open
- Is endocannabinoid deficiency syndrome a valid clinical entity? Could measuring endocannabinoid levels help guide treatment decisions? Would combinations of lifestyle interventions produce synergistic effects on endocannabinoid tone?
Common questions
What is endocannabinoid deficiency syndrome?
How does exercise affect the endocannabinoid system?
Read the original research
Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.
PloS one, 9(3), e89566
Citation
McPartland, John M; Guy, Geoffrey W; Di Marzo, Vincenzo. (2014). Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.. PloS one, 9(3), e89566. https://doi.org/10.1371/journal.pone.0089566
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