Single dose kinetics of deuterium labelled Δ1-tetrahydrocannabinol in heavy and light cannabis users

Abstract

Deuterium labelled Δ¹‐tetrahydrocannabinol was administered intravenously (5.0 mg) and by smoking (10.0 mg) to five heavy and four light marihuana users. All subjects smoked an estimated amount of 8.6–9.9 mg Δ¹‐tetrahydrocannabinol. The plasma levels of Δ¹‐tetrahydrocannabinol were followed for 48 hours and in two subjects for 72 hours after administration. The systemic availability after inhalation calculated from the area under curve values was in the range of 27±10% for the heavy users and 14±1% for the light users. There was little difference between the groups with regard to the amount of smoked Δ¹‐tetrahydrocannabinol or plasma levels and area under curve values obtained after i.v. administration. Thus, it seems likely that the statistically significant difference in systemic availability of smoked Δ¹‐tetrahydrocannabinol was due to a more efficient smoking by the heavy users. It is also indicated that heavy users prefer slightly higher Δ¹‐tetrahydrocannabinol plasma levels than light users. Based on the area under curve values after i.v. administration, a plasma clearance of 760–1190 ml min⁻¹ was calculated. The elimination half‐life of Δ¹‐tetrahydrocannabinol is more than 20 hours. The present results do not suggest that tolerance or sensitivity to Δ¹‐tetrahydrocannabinol in heavy users is readily achieved.