Δ9-THC training dose as a determinant for (R)-methanandamide generalization in rats

T. U.C. Järbe, R. J. Lamb, A. Makriyannis, S. Lin, A. Goutopoulos

Research output: Contribution to journalArticle

51 Scopus citations

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 Δ9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg Δ9-tetrahydrocannabinol (Δ9-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% Δ9THC responses in the two lower Δ9- THC training dose conditions. However, only around 60% Δ9-THC responses occurred in the 5.6 mg/kg Δ9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer Δ9- THC-appropriate responses in this group. Morphine did not substitute for Δ9-THC. In conclusion, the data with Δ9THC 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.

Original languageEnglish (US)
Pages (from-to)519-522
Number of pages4
JournalPsychopharmacology
Volume140
Issue number4
DOIs
StatePublished - Jan 1 1998

Keywords

  • (R)-methanandamide
  • Anandamides
  • Cannabinoids
  • Drug discrimination
  • Efficacy
  • Rat
  • Δ-THC

ASJC Scopus subject areas

  • Pharmacology

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    Järbe, T. U. C., Lamb, R. J., Makriyannis, A., Lin, S., & Goutopoulos, A. (1998). Δ9-THC training dose as a determinant for (R)-methanandamide generalization in rats. Psychopharmacology, 140(4), 519-522. https://doi.org/10.1007/s002130050797