Table 1.

Key aspects of the pharmacokinetics of medicinal cannabis [26].

Pharmacokinetics	Characteristics
Absorption	The main forms of administration and formulations are: -Smoke or vapor inhalation: herbal cannabis, resins, and concentrates -Oral: nabiximols, edibles, and tinctures -Oro-mucosal or sublingual: lollipops, pills, and nabiximols -Topical or rectal: herbal cannabis, resins, and concentrates Bioavailability: around 13% after oral administration due to the high first metabolism effect. There is little relationship between the plasma concentrations of tetrahydrocannabinol (THC) and its neuropsychological effects, due to the multicompartmental pharmacokinetic pattern, with a distribution phase and rapid fall in plasma concentrations, for which the concentration/time curves indicate that the peak of maximum action occurs 7 s after administration [27,28]
Distribution	Δ-9-THC: the most psychoactive component of cannabis, 95–99% bound to plasma proteins with a volume of distribution (Vd) of 2.5–3 L. It is rapidly distributed from plasma to highly vascular tissues. Only 1% of THC crosses the blood–brain barrier, after the initial phase of distribution. THC is redistributed to less vascular tissues and accumulates in adipose tissue. Only 3% of THC circulates freely in plasma [27]. Cannabidiol (CBD): Vd is 30 L/kg [28].
Metabolism	THC: Metabolized in the liver through CYP2C9 and CYP3A4, 2C19 and 1A to 11-hydroxy-tetrahydrocannabinol (11-OH-THC), the more potent metabolite found in higher concentrations in the brain than THC. Hepatic hydroxylation of Δ-9-THC generates the compound 11-hydroxy-Δ-9-THC with a prolonged psychoactive effect [28]. CBD: Cannabidiol is metabolized to 7-OH-cannabidiol, which inhibits the metabolism of Δ-9-THC towards 11-hydroxy-Δ-9-THC and attenuates its psychoactive effects, in such a way that this additional oxidation renders 11-Nor-9-carboxy-Δ-9-tetrahydrocannabinol inactive, giving it greater security [27].
Elimination	It is eliminated unchanged and as a metabolite in urine (16%) and feces with an average of t ½ of 24 h [28].

Vd: volume of distribution, L: liter, kg: kilogram.