Δ9-THC exposure attenuates aversive effects and reveals appetitive effects of K2/'Spice' constituent JWH-018 in mice.
William S Hyatt, William E Fantegrossi
Behavioural Pharmacology June 2014 DOI: 10.1097/fbp.0000000000000034 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | JWH-018 Δ9-tetrahydrocannabinol (Δ9-THC) |
| Measures | conditioned taste aversion, conditioned place preference |
| Topics | Cannabis |
| Key points | In mice, prior exposure to an ascending-dose regimen of Δ9-THC significantly blunted the magnitude and duration of JWH-018-induced conditioned taste aversion and reduced JWH-018-induced place aversions, with apparent rewarding effects at a low JWH-018 dose. The authors suggest that cannabinoid-naive individuals using K2/'Spice' may face increased risk of adverse reactions, while those with a history of marijuana use may be more sensitive to the reinforcing effects of high-efficacy synthetic cannabinoids. |
Abstract
The emergence of high-efficacy synthetic cannabinoids as drugs of abuse in readily available K2/'Spice' smoking blends has exposed users to much more potent and effective substances than the phytocannabinoids present in cannabis. Increasing reports of adverse reactions, including dependence and withdrawal, are appearing in the clinical literature. Here we investigated whether the effects of one such synthetic cannabinoid, 1-pentyl-3-(1-naphthoyl)indole (JWH-018), would be altered by a prior history of Δ9-tetrahydrocannabinol (Δ9-THC) exposure, in assays of conditioned taste aversion and conditioned place preference. In the conditioned taste aversion procedure, JWH-018 induced marked and persistent aversive effects in mice with no previous cannabinoid history, but the magnitude and duration of these aversive effects were significantly blunted in mice previously treated with an ascending dose regimen of Δ9-THC. Similarly, in the conditioned place preference procedure, JWH-018 induced dose-dependent aversive effects in mice with no previous drug history, but mice exposed to Δ9-THC before place conditioning showed reduced aversions at a high JWH-018 dose and apparent rewarding effects at a low dose of JWH-018. These findings suggest that a history of Δ9-THC exposure 'protects' against aversive effects and 'unmasks' appetitive effects of the high-efficacy synthetic cannabinoid JWH-018 in mice. This pattern of results implies that cannabinoid-naive individuals administering K2/'Spice' products for the first-time may be at an increased risk for adverse reactions, whereas those with a history of marijuana use may be particularly sensitive to the reinforcing effects of high-efficacy cannabinoids present in these commercial smoking blends.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Optogenetic brain‐stimulation reward: A new procedure to re‐evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter‐Cre mice Addiction Biology February 3, 2021
- Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression Frontiers in Pharmacology March 16, 2023
- Dopamine, γ-aminobutyric acid, and glutamate balance in the nucleus accumbens shell: Differential effects of cannabinoid 1 receptor agonists Δ9-Tetrahydrocannabinol, AM11101, and AM8936. Neuropharmacology June 1, 2026
- Δ(9)-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. Psychopharmacology May 2016
- Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice. Behavioural Pharmacology December 2014
Cites 5
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