Endocannabinoid

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An endocannabinoid (endogenous cannabinoid) is a neurotransmitter created in the brain which binds to cannabinoid receptors. The two types of receptors are CB1 receptors expressed primarily in the brain, and CB2 receptors involved with the immune system.

The Endocannabinoids

  1. Anandamide[1]
  2. 2-Arachidonoylglycerol (2-AG)[2]
  3. 2-arachidonyl glyceryl ether[3]
  4. N-arachidonoyl-dopamine (NADA)[4]
  5. Virodhamine[5]

Role in appetite

For more information, see: Endocannabinoid system in appetite regulation.

Smoking cannabis is a potent stimulator of appetite, and is sometimes prescribed for medicinal purposes to stimulate eating. The role of the endocannabinoid system in appetite regulation has been investigated through the discovery of a CB1 selective antagonist. Antagonism of the CB1 receptor has significant appetite reducing and weight reduction effects. This factor, coupled to the appetite enhancing affects of anandamide and THC and because the CB1 receptor and endocannabinoids are expressed in brain regions associated with appetite regulation, provided the impetus for the drive in research centered around how the EC system is implicated in appetite regulation.

Studies involving rodents confirmed the role of the EC system and the CB1 receptor in appetite regulation; Mice lacking the CB1 receptor reduce their food intake, even after fasting, and lose weight compared to wild type mice and when wild type mice receive a dose of the CB1 antagonist Rimonabant, food intake is also decreased. These results imply that the CB1 receptor is responsible for the changes observed in food intake. This has resulted in the release of the CB1 antagonist, Rimonabant, trade name Acomplia, as an anti-obesity drug.


References

  1. Devane WA, Hanus L, Breuer A, et al (1992). "Isolation and structure of a brain constituent that binds to the cannabinoid receptor". Science 258 (5090): 1946–9. PMID 1470919.
  2. Stella N, Schweitzer P, Piomelli D (1997). "A second endogenous cannabinoid that modulates long-term potentiation". Nature 388 (6644): 773–8. PMID 9285589.
  3. Hanus L, Abu-Lafi S, Fride E, et al (2001). "2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (7): 3662–5. PMID 11259648.
  4. Marinelli S, Di Marzo V, Florenzano F, et al (2007). "N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors". Neuropsychopharmacology 32 (2): 298–308. PMID 16760924.
  5. Porter AC, Sauer JM, Knierman MD, et al (2002). "Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor". J. Pharmacol. Exp. Ther. 301 (3): 1020–4. PMID 12023533.

Rinaldi-Carmona M et al. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Letters 350:240-4 [PMID 8070571] - The identification of the first CB1 selective antagonist