Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta9-tetrahydrocannabinol.
Psychopharmacology April 2009 DOI: 10.1007/s00213-008-1230-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study Peer reviewed |
|---|---|
| Population | Rhesus monkeys |
| Interventions | anandamide methanandamide arachidonylcyclopropylamide (ACPA) rimonabant |
| Dose | Delta-9-THC 0.1 mg/kg i.v. (training dose); ED50 values: delta-9-THC 0.024 mg/kg, ACPA 0.14 mg/kg, methanandamide 0.28 mg/kg, anandamide 1.7 mg/kg |
| Topics | Cannabis |
| Key points | Delta-9-THC, anandamide, methanandamide, and ACPA all produced discriminative stimulus effects in rhesus monkeys that were surmountably antagonized by rimonabant with similar apparent affinity estimates (pA2 and pKB 6.24-6.83), indicating these cannabinoids act at the same receptors. Delta-9-THC was most potent (ED50 0.024 mg/kg) and longest acting (4-6 h), while anandamide was least potent (ED50 1.7 mg/kg) and all three non-THC agonists lasted under 50 minutes. |
Abstract
Anandamide and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) sometimes produce different discriminative stimulus effects and, therefore, appear to differ in their mechanism of action. In order to understand the widespread use of cannabis and the therapeutic potential of cannabinoids, mechanisms responsible for behavioral effects need to be identified. Drug discrimination was used to compare the mechanism of action of Delta(9)-THC, anandamide, and two structural analogs of anandamide in rhesus monkeys. Monkeys discriminated Delta(9)-THC (0.1 mg/kg i.v.) from vehicle. Delta(9)-THC, anandamide, methanandamide, and arachidonylcyclopropylamide (ACPA) were administered i.v. alone and in combination with at least one dose of rimonabant. Schild analysis and single-dose apparent affinity estimates were used to estimate the potency of rimonabant as an antagonist of each cannabinoid; these values were compared to examine whether the same receptors mediated discriminative stimulus effects. Delta(9)-THC, ACPA, methanandamide, and anandamide produced greater than 96% of responses on the Delta(9)-THC lever. The ED(50) values were 0.024 mg/kg for Delta(9)-THC, 0.14 mg/kg for ACPA, 0.28 mg/kg for methanandamide, and 1.7 mg/kg for anandamide. The duration of action of Delta(9)-THC was 4-6 h and longer than the duration of action ACPA, methanandamide, and anandamide (i.e., each less than 50 min). Rimonabant surmountably antagonized the discriminative stimulus effects of each agonist, and the apparent affinity estimates (pA (2) and pK (B) values) were 6.24-6.83. Rimonabant can produce surmountable antagonism of the behavioral effects of not only Delta(9)-THC but also anandamide, methanandamide, and ACPA, and the interactions appear simple, competitive, and reversible. These cannabinoid agonists act at the same receptors to produce discriminative stimulus effects.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 9
- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
- Inhibition of the endocannabinoid-regulating enzyme monoacylglycerol lipase elicits a CB1 receptor-mediated discriminative stimulus in mice. Neuropharmacology October 2017
- Just add water: cannabinoid discrimination in a water T-maze with FAAH(-/-) and FAAH(+/+) mice. Behavioural Pharmacology August 2016
- The cannabinoid agonist HU-210: pseudo-irreversible discriminative stimulus effects in rhesus monkeys. European Journal of Pharmacology March 15, 2014
and 4 more in the library
Cites 8
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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
- SR 141716A differentially attenuates the behavioral effects of delta9-THC in rhesus monkeys. Behavioural Pharmacology September 2005
- (R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide. Psychopharmacology August 2001
- Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science January 15, 1999
and 3 more in the library