Cannabinoid blood concentrations

Figure 5. Cannabinoid blood concentrations after iv administration of 1 mg of...

Anti-arthritic effect. Oral administration of AJA, a cannabinoid acid devoid of psychoactivity, reduced joint tissue damage in rats with adjuvant arthritis. Peripheral blood monocytes (PBM) and synovial fluid monocytes (SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AJA (0-30 mM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for messenger RNA (mRNA), and supernatants were collected for cytokine assay. Addition of AJA to PBM and SFM in vitro reduced both steady-state levels of interleukin-ly (IL-ly) mRNA and secretion of IL-ly in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 mM AJA (p < 0.05 vs untreated controls, n = 7). AJA did not influence tumor necrosis factor-a (TNF-a) gene expression in or secretion from PBM . 

Since radioimmunoassay has permitted the quantitation of substances present in concentrations as low as a few pg/ml of a biological fluid, and since the inherent selectivity of antibodies often make sample preparation requirements minimal and assay methodology simple, RIA has naturally been considered as a means for measuring blood levels of cannabinoid compounds. 

Similar results appeared when the rats were regularly given massive dosages. Nahas and Leger concluded, "Concentrations of cannabinoids in brain and testis remained lower than in the blood and did not reflect any significant accumulation of the drug in those tissues. ... 

The abuse of cannabis cannot be detected by thin-layer Chromatography or by conventional gas Chromatography because the concentrations of cannabinoids in urine are too low. Immunoassay, applied to either blood or urine, is the best method (see B. Law et ah, J. analyt. Toxicol., 1984, <5, 14-... 

A THC tetrahydrocannabinol is the major psychoactive ingredient in the Cannabisplant. A THC is responsible for both the psychiatric and therapeutic effects obtained from marijuana. Its receptor, the cannabinoid receptor, is located mainly tat the presynaptic gap. The areas of the brain most affected are the basal ganglia, cerebellum, cerebral cortex, and the hippocampus. The acute effects consist of degradation in short term memory, changes in sensory perception, reduced concentration, disturbances in motor abilities, hypothermia, increased blood pressure and heart rate, and reduced pain perception. 

Because protein-bound drug cannot diffuse through the dialysis probes, the concentrations of I and II in the brain and plasma are representative of the free drug. Figure 6 is a plot of the plasma and brain extracellular fluid concentrations of I and II on the same time scale. The parent compound is able to cross the blood—brain barrier much more efficiently than the metabolite. The lower limit of quantitation (LLQ) for each compound in brain dialysate and plasma were 500 pg/mb and 1 ng/mb, respectively. Other applications of atmospheric pressure ionization MS have been reported for drugs in dialysate [14,15]. In one recent study, atmospheric pressure chemical ionization (APCI) LC/MS resulted in attomole detection limits with a linear response over 4 decades for anandamide, an endogenous cannabinoid. 

Berdyshev et al. (1997) examined the effects of anandamide, palmitoylethanolamide and THC on the production of TNF-a, IL-4, IL-6, IL-8, IL-10, IFN-y, p55, and p75 TNF-a soluble receptors expressed by stimulated human peripheral blood mononuclear cells as well as [ H]-arachidonic acid release by non-stimulated and N-formyl-Met-Leu-Phe (fMLP)-stimulalcd human monocytes. Anandamide diminished IL-6 and IL-8 production at low nanomolar concentrations and inhibited the production of TNF-a, IFN-y, IL-4, and p75 TNF-a soluble receptors at higher concentrations (i.e., micromolar levels). Palmitoylethanolamide inhibited IL-4, IL-6, and IL-8 synthesis and the production of p75 TNF-a soluble receptors at concentrations similar to those of anandamide but did not affect TNF-a and IFN-y production. Neither anandamide nor palmitoylethanolamide influenced IL-10 synthesis. THC, on the other hand, exerted a biphasic effect on pro-inflammatory cytokine production. TNF-a, IL-6, and IL-8 synthesis was inhibited maximally by 3 nM THC but stimulated by 3 pM THC. A similar effect was observed for IL-8 and IFN-y. The level of IL-4, IL-10, and p75 TNF-a soluble receptors was diminished by 3 pM THC. [ H]-Arachidonate release was stimulated only by high THC and anandamide concentrations. Based on these observations, the investigators suggested that the inhibitory properties of anandamide, palmitoylethanolamide, and THC are determined by the activation of peripheral-type cannabinoid receptors (i.e., CB2) and that various endogenous fatty acid ethanolamides also participate in the regulation of the immune response. 

Compared to other drugs of abuse, analysis of cannabinoids presents some difficult challenges. THC and 11-OH-THC are highly lipophilic and present in low concentrations in body fluids. Complex specimen matrices, i.e., blood, sweat, and hair, may require multi-step extractions to separate cannabinoids from endogenous lipids and proteins. Care must be taken to avoid low recoveries of cannabinoids due to their high affinity to glass and plastic containers, and to collection devices for alternate matrices (Blanc et al. 1993 Bloom 1982 Christophersen 1986 Joern 1992). THC and THCCOOH are predominantly found in the plasma fraction of blood, where 95% to 99% are bound to lipoproteins. Only about 10% of either... 

Huestis MA, Henningfield JE, Cone EJ (1992c) Blood cannabinoids. IL Models for the prediction of time of marijuana exposure from plasma concentrations of delta-9-tetrahydro-cannabinol (THC) and ll-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH). J Anal Toxicol 16 283-290... 

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