The pharmacological activity of the fatty acid conjugate 11-palmitoyloxy-Δ9-tetrahydrocannabinol

Haggerty, G. C.; Deskin, Randy; Kurtz, P. J.; Fentiman, Allison F.

doi:10.1016/0041-008x(86)90266-8

Cited by 15 publications

(7 citation statements)

References 24 publications

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“…24 The exact composition of the material accumulated in fat is still unknown; a substantial proportion seems to consist of fatty acid conjugates of 11-OH-THC. 25,26 Metabolism THC is mainly metabolized in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of the cytochrome P450 (CYP) complex. Average plasma clearance rates have been reported to be 11.8 ± 3 L per hour for women and 14.9 ± 3.7 L per hour for men.…”

Section: Distributionmentioning

confidence: 99%

Review of Biologic Matrices (Urine, Blood, Hair) as Indicators of Recent or Ongoing Cannabis Use

Mußhoff¹,

Madea²

2006

Therapeutic Drug Monitoring

218

151

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Especially for cannabinoids, analytical procedures for the verification of recent use and generally for the assessment of the extent of drug abuse are of interest in clinical and forensic toxicology. For confirmation of abstinence, urine analysis seems to be a useful tool. Serial monitoring of THC-COOH to creatinine ratios can differentiate between recent drug use and residual THC-COOH excretion (THC-COOH/creatinine ratio Z0.5 compared with previous specimen ratio). For an assessment of the extent of cannabis use, the determination of free and bound THC-COOH and especially of THC and 11-OH-THC glucuronides are suggested as useful but need further confirmation. Blood analysis is preferred for the interpretation of acute effects after cannabis abuse. The cannabis influence factor (CIF) was demonstrated as a better tool to interpret the concentrations of THC and its metabolites in blood in forensic cases and therefore it was proposed to assume absolute driving inability because of cannabis intoxication from a CIF Z10. Additionally, a higher CIF is indicative of a recent cannabis abuse. Also discrimination between occasional use of cannabis and regular drug consumption is possible by analysis of THC-COOH in blood samples because of the long plasma half-life of THC-COOH and its accumulation in the blood of frequent cannabis consumers. In routine tests, blood samples have to be taken within a prescribed 8-day-period, and a THC-COOH concentration >75 ng/mL is assumed to be associated with regular consumption of cannabis products, whereas plasma THC-COOH concentrations <5 ng/mL are associated with occasional consumption. In contrast to other illicit drugs, hair analysis lacks the sensitivity to act as a detector for cannabinoids. THC and especially the main metabolite THC-COOH have a very low incorporation rate into hair and THC is not highly bound to melanin, resulting in much lower concentrations in hair compared with other drugs. Additionally, THC is present in cannabis smoke and also can be incorporated into the hair only by contamination. For the determination of the main metabolite THC-COOH in the picogram or femtogram per milligram range, which indicates an active consumption, special analytical procedures, such as GC/MS/MS techniques, are required.

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Section: Distributionmentioning

confidence: 99%

Review of Biologic Matrices (Urine, Blood, Hair) as Indicators of Recent or Ongoing Cannabis Use

Mußhoff¹,

Madea²

2006

Therapeutic Drug Monitoring

218

151

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“…However, the detection times of 7-13 h for THC and 5-11 h for THC-OH were much longer. The THC plasma peaks are characterized by very high interindividual variability 12 24 Fig. 6 Urine levels of total THC-COOH (N=12).…”

Section: Discussionmentioning

confidence: 99%

“…This wide detection window is mainly due to multicompartment kinetics, multiphase distribution and elimination, and high affinity for lipid tissue [21][22][23]. For example, fatty acid conjugates of hydroxylated cannabinoids have been identified as long-retained metabolites [22,24]. It is problematic to predict the time of drug use and the degree of impairment of the physical and psychological performance on the basis of urinary THC-COOH levels [20].…”

Section: Introductionmentioning

confidence: 99%

Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

et al. 2010

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Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes.

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“…However, a high degree of accumulation occurs in less vascularised tissues and finally in body fat Kreuz and Axelrod 1973;Johansson et al 1989a), which represents the major long-term storage site, resulting in concentration ratios between fat and plasma of up to 10 4 : 1 (Harvey et al 1982). The exact composition of the material accumulated in fat is still unknown; but a substantial proportion seems to consist of fatty acid conjugates of 11-OH-THC (Leighty et al 1976;Haggerty et al 1986). …”

Section: Eliminationmentioning

confidence: 99%

Toxicology of Specific Substances

Jones

Mußhoff

Kræmer

et al. 2014

Handbook of Forensic Medicine

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The pharmacological activity of the fatty acid conjugate 11-palmitoyloxy-Δ9-tetrahydrocannabinol

Cited by 15 publications

References 24 publications

Review of Biologic Matrices (Urine, Blood, Hair) as Indicators of Recent or Ongoing Cannabis Use

Review of Biologic Matrices (Urine, Blood, Hair) as Indicators of Recent or Ongoing Cannabis Use

Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

Toxicology of Specific Substances

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