Abstract
BackgroundCannabis contains Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) as the primary constituents responsible for pharmacological activity. However, there are numerous additional chemically-related structures to Δ9–THC and CBD that are pharmacologically active and may influence the pharmacological properties of Δ9-THC and CBD. This study chemically characterized the cannabinoid constituents in a series of cannabis chemovar extracts and investigated the potential cannabinoid entourage effect in two behavioral assays.MethodsSix chemovar extracts were compared to pure Δ9-THC, CBD and morphine for effects on the following behavioral assays in mice: hot plate and tail suspension. The battery of behavioral tests was conducted post intravenous administration of cannabis chemovar extract. Cannabinoid profiles of extracts were analyzed using high performance liquid chromatography. Cannabis extracts were administered at equal doses of Δ9-THC to investigate the role of their cannabinoid profiles in modulating the effects of Δ9-THC. Dose response curves were fit using a log[inhibitor] vs response three parameter model and differences between group means were determined using a one-way ANOVA followed by a post hoc test.ResultsCannabis chemovars tested in this study exhibited substantially different cannabinoid profiles. All chemovars produced dose-dependent immobility in the tail suspension assay and dose-dependent antinociception in the hot plate assay. The maximum antinociceptive effect and ED50 was comparable between cannabis chemovars and Δ9-THC. Two cannabis chemovars produced significantly greater immobility in the tail suspension test, with no significant differences in ED50.ConclusionsCommercially available cannabis chemovars vary widely in cannabinoid content, but when equalized for Δ9-THC content, they produce similar behavioral effects with two exceptions. These findings provide only limited support for the entourage hypothesis. Further studies are necessary to characterize the nature of these pharmacological differences between cannabis chemovars and pure Δ9-THC.
Highlights
The pharmacological activity of Δ9-tetrahydrocannabinol (Δ9-THC), the primary active ingredient of the Cannabis sativa L. (Cannabis spp. or cannabis) plant, mediates its psychoactive and allied physiological effects primarily (2020) 2:17 of the cannabinoid type 1 (CB1) receptor in vitro and displays inverse agonism at the CB2 receptor (Pertwee 2006; Borgelt et al 2013; Morales et al 2017)
In addition to Δ9-THC and CBD, the Cannabis sativa plant contains over 120 unique cannabinoids, several of which have been demonstrated to possess pharmacological activity (Morales et al 2017)
Determination of Δ9-THC, CBD and related cannabinoids in chemovars A quantitative evaluation of the principal cannabinoid constituents was conducted for all cannabis chemovars (Table 2)
Summary
The pharmacological activity of Δ9-tetrahydrocannabinol (Δ9-THC), the primary active ingredient of the Cannabis sativa L. (Cannabis spp. or cannabis) plant, mediates its psychoactive and allied physiological effects primarily (2020) 2:17 of the CB1 receptor in vitro and displays inverse agonism at the CB2 receptor (Pertwee 2006; Borgelt et al 2013; Morales et al 2017). A re-evaluation of cannabis is warranted because of the limited adverse event profile associated with its medical use It is the pleiotropic efficacy associated with cannabis plant extracts that has conveyed benefits to many diseases including pain, multiple sclerosis, inflammation, epilepsy, anorexia, glaucoma, emesis, cardiovascular disease, cancer, obesity as well as Parkinson’s and Alzheimer’s disease (Kaur et al 2016). These possible therapeutic benefits associated with the use of cannabis are claimed, they are often poorly substantiated and frequently contradictory (Belendiuk et al 2015). This study chemically characterized the cannabinoid constituents in a series of cannabis chemovar extracts and investigated the potential cannabinoid entourage effect in two behavioral assays
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