Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking

Abstract

Delta-9-tetrahydrocannabinol (THC) was given intravenously, by smoking, and by mouth to 11 healthy subjects. Plasma profiles of THC after smoking and intravenous injection were similar whereas plasma levels after oral doses were low and irregular, indicating slow and erratic absorption. Based on AUC0-360 min systemic availability of THC after smoking was estimated to be 18 +/- 6%. Oral THC in a chocolate cookie provided systemic availability of 6 +/- 3%. Of the two major clinical signs of cannabis intoxication, reddened conjunctivae persisted for as long as THC levels were above 5 ng/ml, and tachycardia was a less reliable measurement of prevailing THC levels or "high." The time courses of plasma concentrations and clinical "high" were of the same order for intravenous injection and smoking, with prompt onset and steady decline over a 4-hr period. The appearance of "high" lagged behind the increase in plasma concentrations, suggesting that brain concentrations were increasing as plasma concentrations decreased. After oral THC, the onset of clinical effects was much slower and lasted longer, but effects occurred at much lower plasma concentrations than after the other two methods of administration.

Regional Cerebral Blood Flow after Marijuana Smoking

“…Perez-Reyes and associates (1982) reported peaking of THC plasma levels dur ing the 10 min of marijuana smoking and sharp re ductions thereafter, similar to our finding. Also sim ilar to previous reports, pulse rate increased significantly, as did respiratory rate (Ohlsson et al, 1980;Hollister et aI., 1981;Hollister, 1988;Mathew et aI., 1989). Blood pressure, forehead skin blood flow, and P eco2 levels showed no significant changes fol lowing the drug or placebo.…”

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

“…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).…”