Enhanced discriminative stimulus effects of Δ(9)-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys.
Drug and Alcohol Dependence August 1, 2016 DOI: 10.1016/j.drugalcdep.2016.05.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Rhesus monkeys |
| Interventions | Cannabidiol 8-OH-DPAT Rimonabant |
| Dose | Cannabidiol up to 17.8 mg/kg; 8-OH-DPAT up to 0.178 mg/kg; Δ9-THC 0.1 mg/kg i.v. (training dose) and 1 mg/kg/12h s.c. (daily); rimonabant 1 mg/kg i.v. |
| Topics | Addiction CBD Serotonin Cannabis |
| Keywords | 5-ht1a 8-oh-dpat Cannabinoid Drug discrimination Rhesus monkey Rimonabant |
| Key points | Cannabidiol and the 5-HT1A agonist 8-OH-DPAT did not substitute for Δ9-THC or rimonabant in rhesus monkeys, but both increased the potency of Δ9-THC's discriminative stimulus effects; 8-OH-DPAT also attenuated rimonabant's discriminative stimulus effects while cannabidiol did not. The authors conclude that cannabidiol enhances Δ9-THC's effects at doses exceeding those in Cannabis or cannabidiol-based therapeutics, and suggest 5-HT1A agonism enhances CB1 receptor-mediated effects of Δ9-THC. |
Abstract
Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ(9)-THC. The extent to which cannabidiol modifies the effects of Δ(9)-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ(9)-tetrahydrocannabinol (Δ(9)-THC; 0.1mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1mg/kg i.v.) while receiving Δ(9)-THC daily (1mg/kg/12hs.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8mg/kg) and 8-OH-DPAT (up to 0.178mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ(9)-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ(9)-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ(9)-THC.
Comparable studies
Other preclinical and animal studies on cannabis for addiction, most cited first.
Citations in the library
Cited by 4
- Evaluation of the Modulatory Effects of Minor Cannabinoids and Terpenes on Delta-9-Tetrahydrocannabinol Discrimination in Rats. Cannabis and Cannabinoid Research September 2023
- [Pharmacology of cannabidiol: Red flags, consequences and risks in humans]. The´rapie 2022
- Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology January 2018
- The renaissance in psychedelic research: What do preclinical models have to offer. Progress in Brain Research 2018
Cites 4
- JWH-018 and JWH-073: Δ⁹-tetrahydrocannabinol-like discriminative stimulus effects in monkeys. Journal of Pharmacology and Experimental Therapeutics January 2012
- A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Human psychopharmacology April 2011
- Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs. Journal of Pharmacology and Experimental Therapeutics July 2010
- Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug and Alcohol Dependence April 1, 2008