Disposition of Phytocannabinoids, Their Acidic Precursors and Their Metabolites in Biological Matrices of Healthy Individuals Treated with Vaporized Medical Cannabis

Francesco Paolo Busardò, Ana Pilar Pérez-Acevedo, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Lourdes Poyatos, Simona Pichini, Magí Farré, Francesco Paolo Busardò, Ana Pilar Pérez-Acevedo, Roberta Pacifici, Giulio Mannocchi, Massimo Gottardi, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Lourdes Poyatos, Simona Pichini, Magí Farré

Abstract

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed.

Keywords: cannabidiol; cannabidiol metabolism; cannabis; medical cannabis.

Conflict of interest statement

There are no potential conflict of interest or any financial or personal relationships with other people or organizations that could inappropriately bias conduct and findings of this study.

Figures

Figure 1
Figure 1
Chemical structures of Δ9-tetrahydrocannabinol (THC), its acidic precursor, and its metabolites.
Figure 2
Figure 2
Chemical structures of cannabidiol (CBD), its acidic precursor, and its metabolites.
Figure 3
Figure 3
Mean time-course of THC, CBD, and their acidic precursors (THCA and CBDA) concentrations (logarithmic scale) in serum and oral fluid following the administration of vaporized cannabis.
Figure 4
Figure 4
Mean time-course of THC metabolites concentrations in serum following the administration of vaporized cannabis.
Figure 5
Figure 5
Mean time-course of CBD metabolites concentrations in serum following the administration of vaporized cannabis.
Figure 6
Figure 6
The total amount of THC-GLUC, THC-COOH, THC-COOH-GLUC, and 6-α-OH-CBD, 6-β -OH-CBD, 7-OH-CBD, 7-COOH-CBD excreted in 24 h urine samples following the administration of vaporized medical cannabis.
Figure 7
Figure 7
Mean time-course of physiological and subjective mostly modified effects in healthy volunteers administered with 100 mg vaporized cannabis.

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