Analgesic effects anandamide

Similar to exogenous cannabinoids, anandamide has analgesic effects (Fride and Mechoulam 1993). Peripheral anandamide (10 mg/kg IM) produces antinociception in primates. However, centrally administered anandamide does not alter pain perceptive thresholds (Murillo-... 

THC acts at both spinal and supraspinal levels to produce analgesia. As with opioids (opium derivatives), cannabinoids inhibit GABAergic synaptic transmission, while opioids also inhibit post-synaptic neurones. In this way THC and opioids have synergistic analgesic effects. Endogenous cannabinoids (anandamide) produce analgesia, but anandamide is less potent than THC and synthetic cannabinoids (Vaughan and Christie 2002). 

Anandamide may reduce pain by a peripheral action, by acting on CB 1-like receptors located outside the CNS (Calignano et al. 1998). Palmitylethanolamide (PEA) is an endocannabinoid that is coreleased with anandamide and activates peripheral CB2 receptors. When the two are administered together, they show a 100-fold synergistic effect on analgesic measures. Measurements of anandamide and PEA levels in the skin show that there are sufficient amounts to create tonic activation of local cannabinoid receptors. Thus, endocannabinoids may tonically inhibit cutaneous pain. 

Racz I, Bilkei-Gorzo A, Markert A, Stamer F, Gothert M, Zimmer A (2008) Anandamide effects on 5-HT3 receptors in vivo. Eur J Pharmacol 596 98-101 Rady JJ, Fujimoto JM (2002) Nociceptin and dynorphin A(l-17) produce antianalgesia trough independent systems in mice. Life Sci 70 1085-1093 Raffa RB, Schupsky JJ, Lee DKH, Jacoby HI (1996) Characterization of endotheUn-induced nociception in mice evidence for a mechanistically distinct analgesic model. J Pharmacol Exp Ther 278 1-7... 

---