Clinical effects and plasma levels of ?9-Tetrahydrocannabinol (?9-THC) in heavy and light users of cannabis

Abstract

delta 9-Tetrahydrocannabinol (delta 9-THC) was administered in a crossover design by smoking and IV injection to groups of heavy and light users of marihuana. Plasma concentrations of delta 9-THC were similar for the groups after IV injection of 5.0 mg delta 9-THC, but the AUC0-240 min showed a trend towards lower values for the heavy user group. To achieve a maximum desired "high", both groups smoked similar amounts (about 13 mg) of delta 9-THC. Heavy users tended to have higher plasma levels than light users. The systemic availability of smoked delta 9-THC was significantly higher for the heavy users (heavy users 23 +/- 16% vs 10 +/- 7% for light users). These results also indicate that heavy cannabis users smoke more efficiently than casual smokers. Both light and heavy users showed more clinical effect following IV administration than after smoking. The response of the heavy users, both with respect to effect on heart and "high", was quite comparable to that of light users. The present study does not suggest that tolerance readily develops in heavy users.

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

“…Fourth, the route of administration (intravenous) and rate of administration (2 min) in this study is not socially relevant and may have resulted in a faster delivery and higher levels of D-9-THC than what is typically achieved by recreational users. However, peak D-9-THC plasma concentrations with the 2.5 mg dose (82787.4 l ng/ dl) and 5 mg (119.27166.5 ng/dl) were within the range of levels achieved by ad libitum smoking of a standard NIDA cigarette (70-163 ng/ml) containing 1-2.5% THC (16-34 mg) (Heishman et al, 1990;Lindgren et al, 1981;Ohlsson et al, 1980a). Of note is that the D-9-THC content of cannabis has increased (ElSohly et al, 2000) probably as a result of the cloning of high yield cannabis plants and advanced cultivation techniques.…”

“…However, this seems unlikely since (1) alcohol was undetectable in blood; (2) subjects did not report behavioral effects consistent with the alcohol; and (3) in a limited number of subjects who participated in other studies, cognitive test performance on the placebo THC test day (ethanol vehicle) was not different to their performance on the placebo condition (saline) of other studies that they participated in. Finally, other studies using alcohol vehicle did not report any interactions between alcohol and D-9-THC (Agurell et al, 1986;Lindgren et al, 1981;Ohlsson et al, 1980a). The elimination half-life of D-9-THC has been reported to vary from 18 h to 4.3 days (Hunt and Jones, 1980;Johansson et al, 1989;Kelly, 1992;Sadler et al, 1984;Wall et al, 1976Wall et al, , 1983Wall and Perez-Reyes, 1981).…”

“…Two doses of D-9-THC were chosen to examine dose-response relationships and were based on previous studies with D-9-THC demonstrating feasibility and safety (Agurell et al, 1986;Volkow et al, 1991Volkow et al, , 1996. The intravenous route of administration was chosen to reduce inter and intraindividual variability in plasma D-9-THC levels with the inhaled route (Azorlosa et al, 1992) and to mimic the time course of plasma D-9-THC levels associated with the clinical 'high' (Agurell et al, 1986;Lindgren et al, 1981;Ohlsson et al, 1980a). Most studies with D-9-THC employ an oral or inhalation (smoking) route of administration.…”

Self-administration of cannabinoids by experimental animals and human marijuana smokers

“…As a result, after smoking, plasma THC concentration rapidly falls below 20 ng/ml within 30-45 minutes ( Figure 1b). A very similar profile of THC plasma levels is produced by intravenous injection of THC (e.g., Lindgren et al, 1981;Figure 1a). Also, reports of THC-produced "highs" peak at around 20 minutes and are virtually gone 3 hours after both smoking of marijuana and intravenous administration of THC in human subjects (Lindgren et al, 1981;Ohlsson et al, 1980).…”

“…This rate of absorption accounts for the rapid onset of effects from smoked marijuana. Plasma concentration of THC peaks immediately at the end of smoking (Huestis et al, 1992b) and is usually in the range of 70 to 160 ng/ml (Lindgren et al, 1981;Heishman et al, 1990;Azorlosa et al, 1992;Huestis et al, 1992a) (Figure 1b). Because THC is a highly lipophilic molecule, it leaves the blood rapidly and is deposited in the fatty tissues of the body.…”