Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ9-THC in humans discriminating Δ9-THC
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Allosteric modulator
Tetrahydrocannabinol
In vitro binding characteristics of Δ8-tetrahydrocannabinol (Δ8-THC) and its metabolites, 11-hydroxy-Δ8-THC (11-OH-Δ8-THC) and 11-oxo-Δ8-THC, as well as an inactive metabolite, Δ8-THC-11-oic acid, as a cannabinoid receptor site from bovine cortex were examined using the specific agonist [3H]CP-55940. 11-OH-Δ8-THC and 11-oxo-Δ8-THC strongly inhibited the specific binding of [3H]CP-55940. The Ki values of 11-OH-Δ8-THC and 11-oxo-Δ8-THC for the specific binding of [3H]CP-55940 were 52 and 143 nM, respectively, whereas that of Δ8-THC-11-oic acid was 917 nM. Scatchard plot analyses indicated that 11-OH-Δ8-THC and 11-oxo-Δ8-THC caused a significant increase in the apparent KD value without changing the apparent Bmax. These results reveal that active metabolites of Δ8-THC also competitively bind to the cannabinoid receptor as agonists.
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A blood concentration of tetrahydrocannabinol (THC) in the low nanograms-per-milliliter range is often claimed to result from drug use more than 24–48 h previously. The present investigation determined concentrations of cannabinoids in blood collected at least 24 h from smoking in an in-patient setting. During sampling, distinctive effects due to drug use could not be observed. The randomly collected samples from heavy (n = 16, > 1 joint/day), moderate (n = 15, ≤ 1 joint/day), and light (n = 6, < 1 joint/week) users of cannabis were analyzed for THC, 11-hydroxy-THC (OH-THC), and free 11-nor-9-carboxy-THC (THCCOOH) by gas chromatography-mass spectrometry as well as for glucuronidated THCCOOH by liquid chromatography-tandem mass spectrometry. THC was detectable in 9, 6, and 1 samples from heavy, moderate, and light users, respectively. Although cannabinoid concentrations were overlapping between groups, there was a trend towards higher concentrations of both conjugated and free THCCOOH in regular users compared to occasional users. The present findings appear to indicate that low levels of THC, or of THC along with OH-THC, may not unequivocally prove a very recent use of cannabis.
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Tetrahydrocannabinol
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Abstract Cannabinoid acids readily decarboxylate to the corresponding cannabinoid. Methods are available for the determination of Δ9-tetrahydrocannabinol (THC) and its acids (THCA) and published data on the levels of these compounds in cannabis are summarized. Using gas and liquid chromatography, fresh cannabis (64 samples) and cannabis resin (26 samples) from different countries were examined. Wide variations in the relative amounts of THCA and THC in cannabis were found. For cannabis resin, a wide range of values was also found (0·5: 1 to 6·1: 1), the lower values being in resins from the Indian sub-continent and the higher values in resins from the Mediterranean area. Total THC values were in the range 1·–10·6% in cannabis and 6·0–12·5% in cannabis resin.
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Delta-9-tetrahydrocannabinol
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Discriminative stimulus and reinforcing effects of the GABAA partial allosteric modulator imidazenll
s of the BAP/EBPS International Workshop on The Behavioural Pharmacology of Anxiety and Depression, Bath, UK, November 20-23: PDF Only
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Cannabis contains various cannabinoids, two of which have almost opposing actions: Delta9-tetrahydrocannabinol (Delta9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Delta9-THC and CBD in 140 individuals. Three clear groups emerged: ;THC only', ;THC+CBD' and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.
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Tetrahydrocannabinol
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