Cannabinoids pharmacokinetics

Keywords Cannabinoids Pharmacokinetics Tetrahydrocannabinol Cannabidiol Absorption Distribution Metabolism Excretion Interpretation Oral fluid Sweat Hair Plasma Urine Alternate matrix Marijuana... 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

Pharmacological and metabolic studies on cannabinoids (Fig. 1) have suffered from a lack of knowledge of their physico-chemical properties and the insensitivity of assays of A -tetrahydrocannabinol 1, and its metabolites in biological fluids. Unambiguous, sensitive, specific and accurate quantification is required for forensic toxicology and pharmacokinetic studies which can be correlated with the time course of the psychoactive effects (2). 

Kosel BW, Aweeka FT, Benowitz NL, Shade SB, Hilton JF, Lizak PS, Abrams DI. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002 16(4) 543-50. 

The most abundant member of this group is the cannabinoid Al-THC-7-oic-acid. When tested in humans as well as in the rhesus monkey, this cannabinoid did not show the behavioral activity or the cardiovascular effects characteristic of the parent substance, THC. (Perez-Reyes, M. In Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs, Barnett, G. and Chiang, N. (eds), Biomedical Press, 1985, pages 287-310 Mechoulam, R. and Edery, M. ln Marijuana, Mechoulam, R. (ed.), Academic Press, New York, 1973). Thus, little attention has been given to the possible pharmacodynamic properties of this metabolite or any of the other acid metabolites of THC. 

Pharmacokinetics and Metabolism ofthe Plant Cannabinoids, zl -Tetrahydrocannabinol, Cannabidiol and Cannabinol... 

In a recent controlled cannabinoid administration study of THC-containing hemp oils and dronabinol, the pharmacokinetics and pharmacodynamics of oral THC were evaluated. Up to 14.8 mg of THC was ingested by six volunteers each day in three divided doses with meals for five consecutive days (Nebro et al. 2004). There was a 10-day washout phase between each of the five dosing sessions. THC was quantified in plasma by solid-phase extraction followed by positive chemical ionization GC/MS. THC and 11-OH-THC were rarely detected in plasma following the two lowest doses of 0.39 and 0.47 mg/day THC, while peak plasma... 

AgureU S, HaUdin M, Lindgren JE, Ohlsson A, Widman M, GUlespie H, HoUister L (1986) Pharmacokinetics and metabolism of delta-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev 38 21-43... 

Chiang CN, Rapaka RS (1987) Pharmacokinetics and disposition of cannabinoids. In Rapaka RS, Makriyannis A (eds) NIDA research monograph—structure-activity relationships of the cannabinoids. National Institute on Drug Abuse, Rockville, pp 173-188... 

Gross SJ, Worthy TE, Nerder L, Zimmermann EG, Soares JR, Lomax P (1985) Detection of recent cannabis use by saliva delta-9-THC radioimmunoassay. J Anal Toxicol 9 1-5 Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin... 

Guy GW, Robson PJ (2004a) A phase 1, double blind, three-way crossover study to assess the pharmacokinetic profile of cannabis based medicine extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers (GWPK0215). J Cannabis Ther 3 121-152... 

As with the natural cannabinoids, the metabolism of nabilone appears to be extensive and complex. Of particular interest are the primary metabolites - the reduction products of the 1-oxo moiety. While in rats both enantiomers present in the racemate were reduced in vitro and in vivo to the (IS)-alcohol, in dogs one of the enantiomers gave both the (lS)-ol and the (l/ )-ol. The pharmacokinetic picture also differed. While the total carbinol metabolites accounted for 90% of metabolites in dog plasma after 24 h, in humans even after 8 h only 10% were carbinols. However, the doses administered were not fully comparable. These differences in metabolism (or possibly related ones) seem to account for a difference in toxicity. Rats, monkeys and apparently humans differ in their metabolism (and toxicological profile) from the dog, in which some deaths were observed upon prolonged administration [ 162]. 

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