Effects of Δ9-tetrahydrocannabinol, (R)-methanandamide, SR 141716, and d-amphetamine before and during daily Δ9-tetrahydrocannabinol dosing

Richard J. Lamb, Torbjörn U.C. Järbe, Alexandros Makriyannis, Sonyan Lin, Andreas Goutopoulos

Research output: Contribution to journalArticle

21 Scopus citations


We examined the effects of Δ9-tetrahydrocannabinol (Δ9-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide, AM 356), SR 141716, and d-amphetamine on fixed-ratio (FR) responding maintained by food in rats before and during daily dosing with Δ9-THC. Rats responded under a FR 10 schedule of food reinforcement. Cumulative dose-response curves for the various drugs were determined before and during daily Δ9-THC administration. All four drugs dose-dependently decreased responding both before and during daily dosing with Δ9-THC (18 mg/kg/day). The dose-response curves for both Δ9-THC and (R)-methanandamide were shifted to the right with daily dosing with Δ9-THC, indicating tolerance to the effects of Δ9-THC and cross-tolerance to the effects of (R)-methanandamide. The doses of d-amphetamine examined produced similar effects both before and during daily dosing with Δ9-THC. The effects of SR 141716 were not consistently altered by daily Δ9-THC administration. These results indicate that tolerance develops to the effects of Δ9-THC, when Δ9-THC is administered repeatedly. These results also indicate that cross-tolerance to (R)-methanandamide develops with repeated Δ9-THC administration. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2
Publication statusPublished - Jun 16 2000



  • (R)-Methanandamide
  • Amphetamine
  • Anandamide
  • Cross-tolerance
  • Dependence
  • Operant behavior
  • Rat
  • SR 141716
  • Tolerance
  • Δ9-Tetrahydrocannabinol

ASJC Scopus subject areas

  • Pharmacology

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