Pharmacokinetics of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (CTHC) after intravenous administration of CTHC in healthy human subjects

After cannabis consumption there is only limited knowledge about the pharmacokinetic (PK) and metabolic properties of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (CTHC), which is formed by oxidative breakdown from Delta(9)-tetrahydrocannabinol (THC). Despite widely-varying concentrations observed in smoking studies, attempts have been made to interpret consumption behavior with special regard to a cumulated or decreasing concentration of CTHC in serum. Ten healthy nonsmoking white male individuals received 5 mg CTHC intravenously over 10 min. Highest serum concentrations of CTHC were observed at the end of the infusion (336.8 +/- 61.7 mu g/l) followed by a quick decline. CTHC concentration could be quantified up to 96 h after administration, with a terminal elimination half-life of 17.6 +/- 5.5 h. Total clearance was low (91.2 +/- 24.0 ml/min), with renal clearance having only a minor contribution (0.136 +/- 0.094 ml/min). This first metabolite-based kinetic approach will allow an advanced understanding of CTHC PKs data obtained in previous studies with THC.