Mechanism

Anandamide and endocannabinoids

Endocannabinoid system: anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are endogenous lipids that act on CB1 (brain) and CB2 (periphery/immune) receptors. They regulate mood, memory, pain, appetite, stress response, and neuroinflammation. Target of cannabis and CBD.

Effect by goal · level of evidence

Anxiety and stress

modulates Moderate preclinical + clinical (A)

New anxiolytic target

Anandamide modulates amygdala reactivity. FAAH inhibitors (the enzyme that degrades it) increase its levels and show an anxiolytic signal in phase II RCTs. CBD indirectly enhances this pathway.

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Runner's high

modulates Moderate RCT (AA)

Basis of the runner's high

The 'runner's high' is mainly endocannabinoid (anandamide) rather than endorphin-driven: only anandamide crosses the BBB. Blocking CB1 with rimonabant eliminates the anxiolytic effect of exercise in mice.

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Chronic pain

modulates Moderate meta-analysis (AAA)

Alternative to opioids

Medical cannabis (THC + CBD) shows a modest but consistent effect in chronic neuropathic pain and in multiple sclerosis spasticity. Non-opioid target for pain.

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Immune system and neuroinflammation

modulates Moderate preclinical (A)

Immune modulator

CB2 receptors on microglia and lymphocytes modulate neuroinflammation. Target under investigation in autoimmune and neurodegenerative diseases.

Information, not medical advice. Scientific evidence reflects the quality of the studies.