Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol.
Robert E Vann, Thomas F Gamage, Jonathan A Warner, Ericka M Marshall, Nathan L Taylor, Billy R Martin, Jenny L Wiley
Drug and Alcohol Dependence April 1, 2008 DOI: 10.1016/j.drugalcdep.2007.11.017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Long-Evans rats and ICR mice |
| Interventions | Cannabidiol (CBD) Delta(9)-tetrahydrocannabinol (THC) |
| Dose | 10 mg/kg THC; CBD:THC dose ratios of 1:1 and 1:10 |
| Measures | two-lever THC discrimination procedure, conditioned place preference/aversion (CPP/A) model |
| Topics | Cannabis CBD |
| Key points | CBD did not alter THC's discriminative stimulus effects at any CBD:THC ratio tested in rats, but at 1:1 and 1:10 ratios it reversed conditioned place aversion produced by 10 mg/kg THC in mice. The authors suggest CBD may reduce THC's aversive effects at therapeutic ratios while THC-like subjective effects may persist. |
Abstract
Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Delta(9)-tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids (e.g., cannabidiol (CBD)) has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC's abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC's discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
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- Evaluation of the Modulatory Effects of Minor Cannabinoids and Terpenes on Delta-9-Tetrahydrocannabinol Discrimination in Rats. Cannabis and Cannabinoid Research September 2023
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Cites 6
- Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug Brazilian Journal of Medical and Biological Research April 1, 2006
- Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology June 2006
- Adenosine A2A receptors are involved in physical dependence and place conditioning induced by THC. European Journal of Neuroscience October 2004
- Effects of smoked marijuana in healthy and HIV + marijuana smokers. The Journal of Clinical Pharmacology November 2002
- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999
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