2017
DOI: 10.1016/j.euroneuro.2017.10.037
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Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC

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Cited by 192 publications
(180 citation statements)
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“…Third, females had higher blood levels of the major active metabolite, 11-OH-THC, relative to males (Tseng et al 2004; Wiley and Burston 2014). Fourth, inhibition of THC metabolism by CBD observed in the present study has been reported previously in rats (Britch et al 2017; Klein et al 2011; Hložek et al 2017), mice (Varvel et al 2006), and humans (Nadulski et al 2005). The present results therefore suggest that these four findings are reliable.…”
Section: Discussionsupporting
confidence: 88%
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“…Third, females had higher blood levels of the major active metabolite, 11-OH-THC, relative to males (Tseng et al 2004; Wiley and Burston 2014). Fourth, inhibition of THC metabolism by CBD observed in the present study has been reported previously in rats (Britch et al 2017; Klein et al 2011; Hložek et al 2017), mice (Varvel et al 2006), and humans (Nadulski et al 2005). The present results therefore suggest that these four findings are reliable.…”
Section: Discussionsupporting
confidence: 88%
“…One possible mechanism underlying this drug interaction is inhibition of THC metabolism by CBD: consistently higher blood levels of THC during the chronic THC treatment period would result in greater CB 1 receptor down-regulation and/or desensitization, two known mechanisms of cannabinoid tolerance in rats (Sim-Selley 2003; Burston et al 2010) and in humans (Villares 2007). Although CBD significantly increased blood levels of THC only in female rats, this sex difference was likely due to the single time point assessed after completion of THC dose-effect curve determination, since CBD has been shown previously to increase blood and brain levels of THC in male rats, at 0.5–1 h post-injection (Klein et al 2011; Hložek et al 2017). In the present study, repeated CBD treatment also increased blood levels of CBN, an active metabolite, in chronic THC-treated rats of both sexes.…”
Section: Discussionmentioning
confidence: 96%
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“…In this study, AUC 0– ∞ and C max following oral administration of CBD oil were similar to the results of previously published studies [26, 27, 30, 36]. The present results demonstrated that the novel CBD-NE formulation improved the bioavailability of CBD (AUC 0– ∞ /dose) by approximately 65%, although this change was not significant.…”
Section: Discussionsupporting
confidence: 81%
“…Thus, studying the effects of THC in the presence of other phytocannabinoids is important for modeling cannabis use. Current animal models typically use the intravenous route for drug delivery; even though, the most common route of recreational cannabis use is inhalation [13], and the pharmacokinetics of cannabinoids vary considerably depending on administration route [14][15][16]. For example, intravenous THC administration produces adverse effects in humans, likely related to high dosing and faster infusion rates [17].…”
Section: Introductionmentioning
confidence: 99%