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

Abstract

Deuterium labelled delta 1-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 delta 1-tetrahydrocannabinol. The plasma levels of delta 1-tetrahydrocannabinol were followed for 48 hours and in two subjects fof 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 delta 1-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 delta 1-tetrahydrocannabinol was due to a more efficient smoking by the heavy users. It is also indicated that heavy users prefer slightly higher delta 1-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 delta 1-tetrahydrocannabinol is more than 20 hours. The present results do not suggest that tolerance or sensitivity to delta 1-tetrahydrocannabinol in heavy users is readily achieved.

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

“…1), reduced the power to demonstrate statistically significant effects. Second, there may have been differences in the strength of cannabis effects available for blockade due to individual differences in smoking dynamics (Huestis et al 1992a) and THC bioavailability (Ohlsson et al 1981(Ohlsson et al , 1982. Third, differences in study design and subject experience, such as length of stay on the research unit before testing or number of prior cannabis cigarettes smoked in the study (none vs. one) may have altered subjects' responsiveness to cannabis.…”

Pharmacokinetics of Cannabinoids

“…Although there is still no consensus, it is probably safe to say that the terminal half-life of THC averages at least one week, but could be considerably longer. The half-life in plasma does not appear to be different between heavy and light users (33,34).…”

Cannabinoids: Forensic Toxicology and Therapeutics

“…However, about 18% of an inhaled  9 -THC dose is absorbed (Ohlsson et al, 1980), being an oral dose significantly less effective (Nahas, 1979). Moreover,  9 -THC bioavailability after inhalation is highly variable (Barnett et al, 1982Ohlsson et al 1980;Ohlsson et al, 1982, Pérez-Reyes et al, 1982, because it is affected, not only by the specific characteristics of the cigarette and its corresponding combustion, but also by the inhalation intensity, administration duration, among other factors. Experienced smokers inhale more efficiently than inexperienced people, being the  9 -THC bioavailability, in a marijuana cigarette with approximately 1-2% of the drug, between 16 and 40% for chronic users and between 13 and 14% for occasional users (Ohlsson et al, 1982).…”

“…Moreover,  9 -THC bioavailability after inhalation is highly variable (Barnett et al, 1982Ohlsson et al 1980;Ohlsson et al, 1982, Pérez-Reyes et al, 1982, because it is affected, not only by the specific characteristics of the cigarette and its corresponding combustion, but also by the inhalation intensity, administration duration, among other factors. Experienced smokers inhale more efficiently than inexperienced people, being the  9 -THC bioavailability, in a marijuana cigarette with approximately 1-2% of the drug, between 16 and 40% for chronic users and between 13 and 14% for occasional users (Ohlsson et al, 1982). Cannabinoids oral ingestion leads to lower plasma  9 -THC levels than by inhalation, i.e., gastrointestinal absorption represents, approximately, one third of the achieved via inhalation.…”

“…These changes could possibly explain the loss of  9 -THC activity after oral administration due to the acidic pH of the stomach (Garret et al, 1978). However, large intra-and inter-individual differences may also contribute to uncertainty in the effective dose distribution (Agurell et al 1986;Ohlsson et al, 1982).  9 -THC can be detected in plasma within seconds after inhaling the smoke of a marijuana cigarette ( a Huestis et al, 1992), with plasma peak levels reached about 7 to 8 minutes after starting smoking, with euphoria and a maximum heart acceleration at about 20 minutes after (Perez-Reyes et al, 1982).…”