Effect of two oral formulations of cannabidiol on responses to emotional stimuli in healthy human volunteers : pharmaceutical vehicle matters, Jose´A. Crippa et al., 2021

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

Jose´A. Crippa, Luiz C. Pereira Junior, Livia C. Pereira, Patricia M. Zimmermann, Liberato Brum Junior, Leticia M. Rechia, Isabella Dias, Jaime E. Hallak, Alline C. Campos, Francisco S. Guimaraes, Regina H. Queiroz, Antonio W. Zuardi

Brazilian Journal of Psychiatry, 2021, 1-6.

Doi : 10.1590/1516-4446-2020-1684


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.

Keywords : Cannabidiol; CBD; drug interactions; pharmacokinetics



Cannabidiol (CBD) is one of the main components of Cannabis sativa. It does not cause the typical effects of cannabis in humans, and has therapeutic potential for many clinical conditions.1 One of the greatest challenges of oral CBD administration is that this cannabinoid undergoes intense first-pass metabolism, as it is mostly metabolized by human liver microsomes (HLMs), the so-called CYP450 complex, and presents low solubility in aqueous solutions.2,3 Several studies in humans have shown beneficial effects of CBD in the treatment of different neuropsychiatric disorders, using oral administration of the drug dissolved in oil4,5 or in powder form.6,7 However, evidence on the plasma concentrations of CBD following oral administration with different vehicles is still scarce.8-10 Knowledge of the exact impact of standardized, oil-based formulations on CBD pharmacokinetics is essential to predicting dosage requirements; assessing changes in dosage; estimating rates of elimination and rate of absorption; characterizing intra- and inter-subject variability; understanding concentration-effect relationships; and establishing safety margins, efficacy parameters, and the therapeutic window. In turn, understanding the pharmacokinetics of CBD is critical to comprehending the time to onset, intensity, and duration of its pharmacodynamic effects, thus maximizing therapeutic effects and minimizing adverse effects.

Therefore, given the increasing interest in the therapeutic uses of CBD, the primary objective of the present study is to compare plasma concentrations of CBD following oral administration of two formulations of the drug, in powder form and dissolved in oil, while controlling for possible acute side effects, in order to determine the most suitable form of CBD administration. Moreover, there is evidence that certain medications (especially anxiolytics) affect the processing of external social cues, which could result in biases in the attention to and interpretation of social threat.11 Tasks based on the recognition of facial emotions have, therefore, been widely used to assess biases in the evaluation of social judgment (positive or negative evaluations by others), including the effect of cannabinoid agents.12 Thus, we also evaluated the effects of these two formulations of CBD on responses to emotional stimuli in healthy human volunteers.


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