Cross-substitution of Δ9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats.
Jenny L Wiley, Timothy W Lefever, Ricardo A Cortes, Julie A. Marusich
Pharmacology, Biochemistry, and Behavior September 2014 DOI: 10.1016/j.pbb.2014.05.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in animals Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Interventions | Δ(9)-tetrahydrocannabinol (Δ(9)-THC) JWH-018 JWH-073 JWH-210 JWH-320 rimonabant |
| Dose | 3 mg/kg Δ(9)-THC; 0.3 mg/kg JWH-018; 1 mg/kg rimonabant |
| Topics | Cannabis |
| Keywords | Discriminative stimulus Jwh-018 Jwh-073 Jwh-210 Synthetic cannabinoids Δ9-tetrahydrocannabinol |
| Key points | JWH-018, JWH-073, and JWH-210 fully substituted for the discriminative stimulus effects of 3 mg/kg THC in THC-trained rats, and THC substituted in rats trained to discriminate 0.3 mg/kg JWH-018. JWH-320, which lacks CB1 receptor affinity, did not substitute for THC, and 1 mg/kg rimonabant reduced JWH-018-lever responding. The authors conclude that THC and indole-derived synthetic cannabinoids have largely overlapping interoceptive effects. |
Abstract
Synthetic indole-derived cannabinoids, originally developed to probe cannabinoid CB1 and CB2 receptors, have become widely abused for their marijuana-like intoxicating properties. The present study examined the effects of indole-derived cannabinoids in rats trained to discriminate Δ(9)-tetrahydrocannabinol (Δ(9)-THC) from vehicle. In addition, the effects of Δ(9)-THC in rats trained to discriminate JWH-018 from vehicle were assessed. Adult male Sprague-Dawley rats were trained to discriminate 3mg/kg Δ(9)-THC or 0.3mg/kg JWH-018 from vehicle. JWH-018, JWH-073, and JWH-210 fully substituted in Δ(9)-THC-trained rats and Δ(9)-THC substituted in JWH-018-trained rats. In contrast, JWH-320, an indole-derived cannabinoid without affinity for CB1 receptors, failed to substitute for Δ(9)-THC. Pre-treatment with 1mg/kg rimonabant significantly reduced responding on the JWH-018-associated lever in JWH-018-trained rats. These results support the conclusion that the interoceptive effects of Δ(9)-THC and synthetic indole-derived cannabinoids show a large degree of overlap, which is predictive of their use for their marijuana-like intoxicating properties. Characterization of the extent of pharmacological differences among structural classes of cannabinoids, and determination of their mechanisms remain important goals.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Disruption of hippocampal synaptic transmission and long‐term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9‐tetrahydrocannabinol Addiction Biology January 5, 2016
- Repeated Exposure to the “Spice” Cannabinoid JWH-018 Induces Tolerance and Enhances Responsiveness to 5-HT1A Receptor Stimulation in Male Rats Frontiers in Psychiatry February 27, 2018
- A critical assessment of the abuse, dependence and associated safety risks of naturally occurring and synthetic cannabinoids. Frontiers in Psychiatry 2024
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Cites 12
- Differentiation between low- and high-efficacy CB1 receptor agonists using a drug discrimination protocol for rats. Psychopharmacology February 2014
- Cannabinoids in disguise: Δ9-tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles. Neuropharmacology December 2013
- Differential drug-drug interactions of the synthetic Cannabinoids JWH-018 and JWH-073: implications for drug abuse liability and pain therapy. Journal of Pharmacology and Experimental Therapeutics September 2013
- Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice. Drug and Alcohol Dependence December 1, 2012
- Internet highs--seizures after consumption of synthetic cannabinoids purchased online. Journal of Addiction Medicine September 2012
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