Products containing JWH-018 (naphthalen-1-yl-(1-pentylindol-3-yl) methanone) and JWH-073 (naphthalen-1-yl-(1-butylindol-3-yl) methanone) are emerging drugs of abuse. Here, the behavioral effects of JWH-018 and JWH-073 were examined in one behavioral assay selective for cannabinoid agonism, rhesus monkeys (n=4) discriminating Δ9-tetrahydrocannabinol (Δ9-THC; 0.1 mg/kg i.v.) and another assay sensitive to cannabinoid withdrawal, i.e., monkeys (n=3) discriminating the cannabinoid antagonist rimonabant (1 mg/kg i.v.) during chronic Δ9-THC (1 mg/kg/12 h s.c.) treatment. Δ9-THC, JWH-018, and JWH-073 increased drug-lever responding in monkeys discriminating Δ9-THC; the ED50 values were 0.044, 0.013, and 0.058 mg/kg, respectively and the duration of action was 4, 2, and 1 h, respectively. Rimonabant (0.32-3.2 mg/kg) produced surmountable antagonism of Δ9-THC, JWH-018, and JWH-073. Schild analyses and single-dose apparent affinity estimates yielded apparent pA2/pKB values of 6.65, 6.68, and 6.79 in the presence of Δ9-THC, JWH-018, and JWH-073, respectively. In Δ9-THC treated monkeys discriminating rimonabant, the training drug increased responding on the rimonabant lever; the ED50 value of rimonabant was 0.20 mg/kg. Δ9-THC (1-10 mg/kg), JWH-018 (0.32-3.2 mg/kg), and JWH-073 (3.2-32 mg/kg) dose-dependently attenuated the rimonabant discriminative stimulus (i.e., withdrawal). These results suggest that Δ9-THC, JWH-018, JWH-073 act through the same receptors to produce Δ9-THC like subjective effects and to attenuate Δ9-THC withdrawal. The relatively short duration of action of JWH-018 and JWH-073 might lead to more frequent use which could strengthen habitual use by increasing the frequency of stimulus-outcome pairings. This coupled with the possible greater efficacy of JWH-018 at CB1 receptors could be associated with greater dependence liability than Δ9-THC.
- Received September 6, 2011.
- Revision received September 29, 2011.
- Accepted September 29, 2011.
- The American Society for Pharmacology and Experimental Therapeutics