Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats.
Torbjörn U C Järbe, R J Lamb, Alexandros Makriyannis, S Lin, A Goutopoulos
Psychopharmacology December 1998 DOI: 10.1007/s002130050797 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Peer reviewed |
|---|---|
| Population | Rats trained in a two-lever choice drug discrimination procedure |
| Interventions | delta9-tetrahydrocannabinol (delta9-THC) (R)-methanandamide morphine |
| Dose | 1.8, 3.0, or 5.6 mg/kg delta9-THC; 18 mg/kg (R)-methanandamide; 30 mg/kg (R)-methanandamide |
| Topics | Cannabis |
| Key points | At 18 mg/kg, (R)-methanandamide produced roughly 90% delta9-THC-appropriate responses when rats were trained with 1.8 or 3.0 mg/kg delta9-THC, but only about 60% when trained with 5.6 mg/kg; 30 mg/kg produced even fewer responses in the high-dose training group. Morphine did not substitute for delta9-THC. The authors conclude that cannabinoid agonists can differ in intrinsic activity at the receptor, act through multiple mechanisms, or both. |
Abstract
The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than delta9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg delta9-tetrahydrocannabinol (delta9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% delta9-THC responses in the two lower delta9-THC training dose conditions. However, only around 60% delta9-THC responses occurred in the 5.6 mg/kg delta9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer delta9-THC-appropriate responses in this group. Morphine did not substitute for delta9-THC. In conclusion, the data with delta9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 16
- 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
- Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats. Drug and Alcohol Dependence March 1, 2017
- Comparisons of Δ9-Tetrahydrocannabinol and Anandamide on a Battery of Cognition-Related Behavior in Nonhuman Primates. Journal of Pharmacology and Experimental Therapeutics January 29, 2016
- Cross-substitution of Δ9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats. Pharmacology, Biochemistry, and Behavior September 2014
and 11 more in the library
Cites 2
- Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoroanandamide in rhesus monkeys. Pharmacology, Biochemistry, and Behavior December 1997
- (R)-methanandamide, but not anandamide, substitutes for delta 9-THC in a drug-discrimination procedure. Experimental and Clinical Psychopharmacology August 1997