Nicotinic facilitation of delta9-tetrahydrocannabinol discrimination involves endogenous anandamide.
Marcello Solinas, Maria Scherma, Gianluigi Tanda, Carrie E Wertheim, Walter Fratta, Steven R Goldberg
Journal of Pharmacology and Experimental Therapeutics June 2007 DOI: 10.1124/jpet.106.116830 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats trained to discriminate THC from vehicle |
| Interventions | THC Nicotine Pilocarpine Mecamylamine Scopolamine Rimonabant URB-597 |
| Dose | THC 3 mg/kg i.p. (training), THC 0.3-1 mg/kg (test), nicotine 0.1-0.56 mg/kg s.c., pilocarpine 0.3-3 mg/kg i.p., mecamylamine 1-5.6 mg/kg i.p., scopolamine 0.01-0.1 mg/kg i.p., rimonabant 1 mg/kg i.p., URB-597 0.3 mg/kg i.p. |
| Topics | Cannabis |
| Key findings | Nicotine and pilocarpine potentiate THC discrimination, but only nicotine's effect involves anandamide, as rimonabant blocks nicotine- but not pilocarpine-induced potentiation, and URB-597 enables nicotine to produce THC-like effects. |
Abstract
Systemic administration of the main active ingredient in cannabis, Delta9-tetrahydrocannabinol (THC), alters extracellular levels of acetylcholine in several brain areas, suggesting an involvement of the cholinergic system in the psychotropic effects of cannabis. Here, we investigated whether drugs acting at either nicotinic or muscarinic receptors can modulate the discriminative effects of THC. In rats that had learned to discriminate effects of 3 mg/kg i.p. injections of THC from injections of vehicle, the nicotinic agonist nicotine (0.1-0.56 mg/kg subcutaneous) and the muscarinic agonist pilocarpine (0.3-3 mg/kg i.p.) did not produce THC-like effects, but they both potentiated the discriminative effects of low doses of THC (0.3-1 mg/kg). Neither the nicotinic antagonist mecamylamine (1-5.6 mg/kg i.p.) nor the muscarinic antagonist scopolamine (0.01-0.1 mg/kg i.p.) altered the discriminative effects of THC, but they blocked the potentiation of discriminative effects of THC by nicotine and pilocarpine, respectively. The cannabinoid CB(1) antagonist rimonabant (1 mg/kg i.p.) reversed nicotine- but not pilocarpine-induced potentiation of THC discrimination, suggesting that nicotine potentiation is, at least in part, mediated by release of endogenous cannabinoids in the brain. In addition, when metabolic degradation of the endogenous cannabinoid anandamide was blocked by the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoylbiphenil-3-yl-ester (URB-597; 0.3 mg/kg i.p.) nicotine, but not pilocarpine, produced significant THC-like discriminative effects that were antagonized by rimonabant. Our results suggest that nicotinic and muscarinic cholinergic receptors modulate the discriminative effects of THC by fundamentally different mechanisms. Nicotinic, but not muscarinic, modulation of THC discrimination involves elevations in endogenous levels of anandamide.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
- Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice. Neuropharmacology June 2015
- The endogenous cannabinoid anandamide shares discriminative stimulus effects with ∆(9)-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice. European Journal of Pharmacology April 10, 2011
- Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D(2)-induced formation of anandamide. Psychopharmacology April 2010
- Behavioral pharmacology of cannabinoids with a focus on preclinical models for studying reinforcing and dependence-producing properties. Current Drug Abuse Reviews November 2008
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Cites 6
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- The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase but not by inhibition of anandamide transport. Journal of Pharmacology and Experimental Therapeutics April 2007
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- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999
and 1 more in the library