JWH-018 and JWH-073: Δ⁹-tetrahydrocannabinol-like discriminative stimulus effects in monkeys.
Brett C Ginsburg, David R Schulze, Lenka Hruba, Lance R Mcmahon
Journal of Pharmacology and Experimental Therapeutics January 2012 DOI: 10.1124/jpet.111.187757 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Behavioral pharmacology study using drug discrimination in rhesus monkeys Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Rhesus monkeys (n = 4 discriminating Δ⁹-THC; n = 3 discriminating rimonabant during chronic Δ⁹-THC treatment) |
| Interventions | JWH-018 JWH-073 rimonabant |
| Dose | Δ⁹-THC 0.1 mg/kg i.v. (discrimination training), 1 mg/kg s.c. 12 h (chronic treatment), 1-10 mg/kg (withdrawal attenuation); JWH-018 0.32-3.2 mg/kg (withdrawal attenuation); JWH-073 3.2-32 mg/kg (withdrawal attenuation); rimonabant 1 mg/kg i.v. (discrimination training), 0.32-3.2 mg/kg (antagonism) |
| Measures | drug-lever responding, ED₅₀ values, Schild analyses, apparent pA₂/pK(B) values |
| Topics | Cannabis |
| Key points | JWH-018 and JWH-073 substituted for Δ⁹-THC in monkeys discriminating Δ⁹-THC, with ED₅₀ values of 0.013 and 0.058 mg/kg versus 0.044 mg/kg for Δ⁹-THC, and had shorter durations of action (2 and 1 h versus 4 h). All three drugs attenuated rimonabant discrimination during chronic Δ⁹-THC, and rimonabant antagonized them with similar apparent affinity values. The authors suggest these synthetic cannabinoids act through the same receptors as Δ⁹-THC and that their shorter duration and JWH-018's possible greater efficacy may confer greater dependence liability. |
Abstract
Products containing naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) and naphthalen-1-yl-(1-butylindol-3-yl) methanone (JWH-073) 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 s.c. 12 h) 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/pK(B) 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, and JWH-073 act through the same receptors to produce Δ⁹-THC-like subjective effects and 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 cannabinoid 1 receptors could be associated with greater dependence liability than Δ⁹-THC.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 16
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH‐018: a phase 1, placebo‐controlled, pilot study British Journal of Pharmacology November 22, 2017
- Novel Drugs of Abuse: A Snapshot of an Evolving Marketplace. Adolescent Psychiatry April 1, 2013
- Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of five novel synthetic cannabinoids in rats. Psychopharmacology March 2018
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
and 11 more in the library
Cites 8
- Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (Δ(9)-tetrahydrocannabinol) discrimination for rats. Behavioural Pharmacology September 2011
- Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS One 2011
- Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs. Journal of Pharmacology and Experimental Therapeutics July 2010
- Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Deutsches Arzteblatt international July 3, 2009
- Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol. Psychopharmacology April 2009
and 3 more in the library