Toxicology cannabinoids

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

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). 

B. Widdop. Screening for Drugs of Abuse (II) Cannabinoids, Lysergic Acid Diethylamide, Buprenorphine, Methadone, Barbiturates, Benzodiazepines and Other Drugs. Annals of Clinical Biochemistry 34 (5) (1997) 460-510 Shannon, M. Toxicology Reviews Physostigmine. Pediatric Emergency Care 14 (3) (1998) 224-226. 

Braude MC. Toxicology of cannabinoids. In Paton WM, Crown J, editors. Cannabis and its Derivatives. Oxford Oxford University Press, 1972 89-99. 

Pertwee, R. (2002). Sites and mechanism of action. In F. Grotenhermen 8c E. Russo (Eds.), Cannabis and cannabinoids Pharmacolojfy, toxicology and therapeutic potential (pp. 73-88). London Haworth. 

ElSohly MA (2002) Chemical constituents of cannabis. In Grotenhermen F, Russo E (eds) Cannabis and Cannabinoids Pharmacology, Toxicology and Therapeutic Potential. Haworth Press, New York, pp 27-36... 

Foltz RL (1984) Analysis of cannabinoids in physiological specimens by gas chromatography/mass spectrometry. In Baselt RC (ed) Advances in analytical toxicology. Biomedical Publications, Foster City, pp 125-157... 

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]. 

Felder, C.C. and Glass, M. (1998) Cannabinoid receptors and their endogenous agonists. Annual Review of Pharmacology and Toxicology 38 179-200. 

Gieringer, D. (2001) Medical use of cannabis experience in California, in Cannabis and Cannabinoids Pharmacology, Toxicology, and Therapeutic Potential, lids. F. Grotenhermen and E. Russo, pp. 153-170, Haworth Press, Binghamton, NY. 

King, D. L., Fukui, P., Schultheis, S. K., and Donnell, C. M. (1992). Evaluation of a thin-layer chromatographic method for the detection of cannabinoid (THC) metabolite using a microcolumn/disk extraction technique. In Recent Developments in Therapeutic Drug Monitoring and Clinical Toxicology, I. Sunshine (Ed.). Marcel Dekker, New York, pp. 521-.525. 

There are numerons reports for the gas chromatographic determination of THC and its metabolites, ll-nor-A-9-tetrahydrocannibinol-9-carboxylic acid (THC-COOH) and ll-hydroxy-A-9-tetrahydrocannibinol (11-OH-THC) in urine and blood. THC is not normally found in urine, so it must be determined in blood at levels around 2-4 ng/mL. The TMS derivative is the most widely used derivati-zation procedure with GCMS for the determination of cannabinoids. In addition to the obvious advantages of derivatizing the THC metabolites, the acidic constituents of cannabis mnst be derivatized because they can easily decarboxylate above 80°C. Almost aU gas chromatographic procedures today use fused-silica capillary columns for this analysis. Determination of THC in blood is routinely done in forensic toxicological samples, and the detection and quantification of the two THC metabolites in mine is a routine procedure for proof of cannabis use in workplace testing. Several of the procedures used for this type of analysis are listed in Table 16.9. 

Segall, Y., Quistad, G.B., Sparks, S.E., et al., 2003. Toxicological and structural features of organophosphorus and organosulfur cannabinoid CBl receptor ligands. Toxicol. Sci. 76, 131-137. 

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