The relative brain uptake (extraction into brain) of delta-9-tetrahydrocannabinol (delta-9-THC) and the primary metabolite 11-OH-delta-9-tetrahydrocannabinol (11-OH-delta-9-THC) was measured after close intracarotid injection in rats of radiolabelled moities using labelled antipyrine as reference. The extraction percentage was of the same magnitude when injections were given in saline, 66 +/- 11% and 70 +/- 9% respectively after 5 sec., 59 +/- 4 and 67 +/- 8 respectively after 15 sec. While the extraction of 11-OH-delta-9-THC was the same when injected into plasma, the extraction of delta-9-THC was only about half of the extraction from saline, and also half the extraction of the metabolite from plasma. The higher uptake quantity of the metabolite into the brain may account for the relatively greater effect on the central nervous system of the metabolite than of the parent compound at equal concentrations in plasma. Moreover our experiments demonstrate that 11-OH-delta-THC formed in the liver after cannabis (delta-9-THC) administration may exert significant brain effects.
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