Effect of two oral formulations of cannabidiol on responses to emotional stimuli in healthy human volunteers: pharmaceutical vehicle matters

Abstract

Objective: To compare plasma concentrations of cannabidiol (CBD) following oral administration of two formulations of the drug (powder and dissolved in oil), and to evaluate the effects of these distinct formulations on responses to emotional stimuli in healthy human volunteers. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, 45 healthy male volunteers were randomly assigned to three groups of 15 subjects that received either 150 mg of CBD powder; 150 mg of CBD dissolved in corn oil; or placebo. Blood samples were collected at different times after administration, and a facial emotion recognition task was completed after 150 min. Results: There were no significant differences across groups in the subjective and physiological measures, nor in the facial emotion recognition task. However, groups that received the drug showed statistically significant differences in baseline measures of plasma CBD, with a significantly greater difference in favor of the oil formulation. Conclusion: When administered as a single 150-mg dose, neither formulation of oral CBD altered responses to emotional stimuli in healthy subjects. The oil-based CBD formulation resulted in more rapid achievement of peak plasma level, with an approximate fourfold increase in oral bioavailability.

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence

“…Crippa et al 39 examined the effects of 150 mg oral CBD in two formulations; one as a powder and the other as CBD dissolved in corn oil. CBD did not affect anxiety, sedation, cognitive impairment, or discomfort scales.…”

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

“…In humans, nine studies reported anxiety outcomes (Bergamaschi et al, 2011b; Crippa et al, 2004, 2011, 2021; Fusar-Poli et al, 2009, 2010; Linares et al, 2019; Zuardi et al, 1993, 2017) and 14 studies reported PK outcomes but no anxiety outcomes (Atsmon et al, 2018; Crockett et al 2020; Grimm et al, 2018; Hosseini et al, 2020; Knaub et al, 2019; Martín-Santos et al, 2012; Patrician et al, 2019; Perkins et al, 2020; Schoedel et al, 2018; Taylor et al, 2018, 2019; Tayo et al, 2020; Verrico et al, 2020; Williams et al, 2021). In three studies, both types of outcomes were reported (Crippa et al, 2021; Fusar-Poli et al, 2009, 2010).…”

“…In humans, nine studies reported anxiety outcomes (Bergamaschi et al, 2011b;Crippa et al, 2004Crippa et al, , 2011Crippa et al, , 2021Fusar-Poli et al, 2009Linares et al, 2019;Zuardi et al, 1993Zuardi et al, , 2017 and 14 studies reported PK outcomes but no anxiety outcomes AEA: anandamide; CBD: cannabidiol; CB1R: cannabinoid type 1 receptor; THC: Δ9-tetrahydrocannabinol. (Atsmon et al, 2018;Crockett et al 2020;Grimm et al, 2018;Hosseini et al, 2020;Knaub et al, 2019;Martín-Santos et al, 2012;Patrician et al, 2019;Perkins et al, 2020;Schoedel et al, 2018;Taylor et al, 2018Taylor et al, , 2019Tayo et al, 2020;Verrico et al, 2020;Williams et al, 2021).…”

“…(Atsmon et al, 2018;Crockett et al 2020;Grimm et al, 2018;Hosseini et al, 2020;Knaub et al, 2019;Martín-Santos et al, 2012;Patrician et al, 2019;Perkins et al, 2020;Schoedel et al, 2018;Taylor et al, 2018Taylor et al, , 2019Tayo et al, 2020;Verrico et al, 2020;Williams et al, 2021). In three studies, both types of outcomes were reported (Crippa et al, 2021;Fusar-Poli et al, 2009.…”

“…Most human studies used healthy volunteers and described restrictions concerning the use of recreational drugs. However, concomitant medication use and drugs-of-abuse tests were not reported in several papers (Bergamaschi et al, 2011b;Crippa et al, 2004Crippa et al, , 2011Crippa et al, , 2021Crockett et al, 2020;Hosseini et al, 2020;Izgelov et al, 2020a;Knaub et al, 2019;Linares et al, 2019;Patrician et al, 2019;Schoedel et al, 2018;Taylor et al, 2018Taylor et al, , 2019Tayo et al, 2020;Williams et al, 2021;Zuardi et al, 1993). Information about bioanalytical methods validation in studies with PK data varied from no description (e.g.…”