Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Abstract

Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Δ 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 10 mg/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.

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

“…Different animal models have confirmed the low psychotropic nature of CBD [69][70][71], suggesting that in contrast to what is normally observed for THC, CBD does not have hedonic property on its own, that is, it is not rewarding and does not induce drug-seeking behavior. Such studies have demonstrated that CBD does not promote conditioned place preference [69,70] or increase the reinforcing efficacy of brain stimulation [71], which are both definitive characteristics of addictive substances.…”

“…Findings to date suggest minimal CBD impact on apparent positive subjective effects induced by psychostimulants or THC [70,71,78]. Moreover, no animal studies have been published to date regarding CBD's effects on nicotine or alcohol.…”

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

“…Recent in vitro evidence suggests that CBD may inhibit the effects of THC through negative allosteric modulation of the CB 1 receptor, 38 whereas human neuroimaging studies indicate that THC and CBD differentially influence brain activity while performing cognitive or emotional tasks. [39][40][41] And while both additive 36 and antagonistic 18,42 associations have been reported between these agents in rodents, to date no studies have provided a direct mechanism as to how CBD moderates THC's behavioural effects.…”

“…We subsequently determined the impact of THC and CBD in isolation, as well as coadministered in ratios resembling those found in either street or medicinal cannabis. 3,5,18 Finally, we analyzed CB 1 receptor parameters ex vivo in brain regions previously implicated in effortful decision-making to determine if these were related to the behavioural effects of THC.…”

Cannabis and anxiety: a critical review of the evidence

“…Conversely, CBD, when administered with THC at therapeutically relevant ratios, ameliorate aversive effects associated with initial use of THC alone (Vann et al, 2008).…”