BACKGROUND: Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis and an active cannabinoid pharmacotherapy component. No plasma pharmacokinetic data after repeated oral THC administration are available. METHODS: Six adult male daily cannabis smokers resided on a closed clinical research unit. Oral THC capsules (20 mg) were administered every 4-8 h in escalating total daily doses (40-120 mg) for 7 days. Free and glucuronidated plasma THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) were quantified by 2-dimensional GC-MS during and after dosing. RESULTS: Free plasma THC, 11-OH-THC, and THCCOOH concentrations 19.5 h after admission (before controlled oral THC dosing) were mean 4.3 (SE 1.1), 1.3 (0.5), and 34.0 (8.4) microg/L, respectively. During oral dosing, free 11-OH-THC and THCCOOH increased steadily, whereas THC did not. Mean peak plasma free THC, 11-OH-THC, and THCCOOH concentrations were 3.8 (0.5), 3.0 (0.7), and 196.9 (39.9) mug/L, respectively, 22.5 h after the last dose. Escherichia coli beta-glucuronidase hydrolysis of 264 cannabinoid specimens yielded statistically significant increases in THC, 11-OH-THC, and THCCOOH concentrations (P < 0.001), but conjugated concentrations were underestimated owing to incomplete enzymatic hydrolysis. CONCLUSIONS: Plasma THC concentrations remained >1 mug/L for at least 1 day after daily cannabis smoking and also after cessation of multiple oral THC doses. We report for the first time free plasma THC concentrations after multiple high-dose oral THC throughout the day and night, and after Escherichia coli beta-glucuronidase hydrolysis. These data will aid in the interpretation of plasma THC concentrations after multiple oral doses.
BACKGROUND:Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis and an active cannabinoid pharmacotherapy component. No plasma pharmacokinetic data after repeated oral THC administration are available. METHODS: Six adult male daily cannabis smokers resided on a closed clinical research unit. Oral THC capsules (20 mg) were administered every 4-8 h in escalating total daily doses (40-120 mg) for 7 days. Free and glucuronidated plasma THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) were quantified by 2-dimensional GC-MS during and after dosing. RESULTS: Free plasma THC, 11-OH-THC, and THCCOOH concentrations 19.5 h after admission (before controlled oral THC dosing) were mean 4.3 (SE 1.1), 1.3 (0.5), and 34.0 (8.4) microg/L, respectively. During oral dosing, free 11-OH-THC and THCCOOH increased steadily, whereas THC did not. Mean peak plasma free THC, 11-OH-THC, and THCCOOH concentrations were 3.8 (0.5), 3.0 (0.7), and 196.9 (39.9) mug/L, respectively, 22.5 h after the last dose. Escherichia colibeta-glucuronidase hydrolysis of 264 cannabinoid specimens yielded statistically significant increases in THC, 11-OH-THC, and THCCOOH concentrations (P < 0.001), but conjugated concentrations were underestimated owing to incomplete enzymatic hydrolysis. CONCLUSIONS: Plasma THC concentrations remained >1 mug/L for at least 1 day after daily cannabis smoking and also after cessation of multiple oral THC doses. We report for the first time free plasma THC concentrations after multiple high-dose oral THC throughout the day and night, and after Escherichia colibeta-glucuronidase hydrolysis. These data will aid in the interpretation of plasma THC concentrations after multiple oral doses.
Authors: Tsadik T Abraham; Ross H Lowe; Stephane O Pirnay; William D Darwin; Marilyn A Huestis Journal: J Anal Toxicol Date: 2007-10 Impact factor: 3.367
Authors: Margaret Haney; Carl L Hart; Suzanne K Vosburg; Sandra D Comer; Stephanie Collins Reed; Richard W Foltin Journal: Psychopharmacology (Berl) Date: 2007-12-27 Impact factor: 4.530
Authors: Richard A Gustafson; Eric T Moolchan; Allan Barnes; Barry Levine; Marilyn A Huestis Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-12-05 Impact factor: 3.205
Authors: Erin L Karschner; Eugene W Schwilke; Ross H Lowe; W David Darwin; Harrison G Pope; Ronald Herning; Jean L Cadet; Marilyn A Huestis Journal: Addiction Date: 2009-10-05 Impact factor: 6.526
Authors: Olaf H Drummer; Jim Gerostamoulos; Helen Batziris; Mark Chu; John Caplehorn; Michael D Robertson; Philip Swann Journal: Accid Anal Prev Date: 2004-03
Authors: Garry Milman; Allan J Barnes; David M Schwope; Eugene W Schwilke; William D Darwin; Robert S Goodwin; Deanna L Kelly; David A Gorelick; Marilyn A Huestis Journal: Clin Chem Date: 2010-06-08 Impact factor: 8.327
Authors: David A Gorelick; Robert S Goodwin; Eugene Schwilke; David M Schwope; William D Darwin; Deanna L Kelly; Robert P McMahon; Fang Liu; Catherine Ortemann-Renon; Denis Bonnet; Marilyn A Huestis Journal: J Clin Psychopharmacol Date: 2011-10 Impact factor: 3.153
Authors: Dayong Lee; Ryan Vandrey; Garry Milman; Mateus Bergamaschi; Damodara R Mendu; Jeannie A Murray; Allan J Barnes; Marilyn A Huestis Journal: Anal Bioanal Chem Date: 2013-07-06 Impact factor: 4.142
Authors: David A Gorelick; Robert S Goodwin; Eugene Schwilke; Jennifer R Schroeder; David M Schwope; Deanna L Kelly; Catherine Ortemann-Renon; Denis Bonnet; Marilyn A Huestis Journal: Am J Addict Date: 2013 Sep-Oct