Nicotinic alpha 7 receptors as a new target for treatment of cannabis abuse

J Neurosci. 2007 May 23;27(21):5615-20. doi: 10.1523/JNEUROSCI.0027-07.2007.


Increasing use of cannabis makes the search for medications to reduce cannabis abuse extremely important. Here, we show that homomeric alpha7 nicotinic receptors are novel molecular entities that could be targeted in the development of new drugs for the treatment of cannabis dependence. In rats, systemic administration of the selective alpha7 nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA), but not the selective heteromeric non-alpha7 nicotinic acetylcholine receptor antagonist dihydrobetaerythroidine, (1) antagonized the discriminative effects of delta-9-tetrahydrocannabinol (THC), the main active ingredient in cannabis, (2) reduced intravenous self-administration of the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone, mesylate salt], and (3) decreased THC-induced dopamine elevations in the shell of the nucleus accumbens. Altogether, our results indicate that blockade of alpha7 nicotinic receptors reverses abuse-related behavioral and neurochemical effects of cannabinoids. Importantly, MLA reversed the effects of cannabinoids at doses that did not produce depressant or toxic effects, further pointing to alpha7 nicotinic antagonists as potentially useful agents in the treatment of cannabis abuse in humans.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines / administration & dosage
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Drug Delivery Systems / methods*
  • Male
  • Marijuana Abuse / drug therapy*
  • Marijuana Abuse / physiopathology
  • Morpholines / administration & dosage
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Naphthalenes / administration & dosage
  • Nicotinic Antagonists / pharmacology*
  • Nicotinic Antagonists / therapeutic use
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / metabolism*
  • Receptors, Nicotinic / physiology
  • Self Administration
  • alpha7 Nicotinic Acetylcholine Receptor


  • Benzoxazines
  • Chrna7 protein, human
  • Chrna7 protein, rat
  • Morpholines
  • Naphthalenes
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone