Subcellular distribution of delta9-tetrahydrocannabinol in rat brain.
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Biomedical subjects
Publications and source records attributed to L Lemberger.
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A comparison of the psychologic and physiologic effects of intravenously administered Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-Delta(9)-THC) was carried out in nine casual marihuana smokers. A marked tachycardia and psychologic "high" occurred within 3-5 min after the i.v. administration of 11-OH-Delta(9)-THC (1 mg) to all subjects. In contrast, the peak psychologic "high" was delayed 10-20 min after the i.v. administration of Delta(9)-THC (1 mg). There was some individual variation in response among subjects. Psychologic effects correlated well with plasma levels of unchanged [(3)H]11-OH-Delta(9)-THC. About 75% of the administered radioactive dose was excreted in urine (25%) and feces (50%) after [(3)H]11-OH-Delta(9)-THC administration. The disposition, excretion, and metabolism of [(3)H]11-OH-Delta(9)-THC appear to be similar to that previously reported after [(14)C]Delta(9)-THC administration. These findings, in conjunction with the marked psychologic high seen after 11-OH-Delta(9)-THC, suggest that in man, Delta(9)-THC, the active constituent in marihuana, is converted to 11-OH-Delta(9)-THC, which is in part responsible for the psychologic effects.
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11-Hydroxy-Delta(9)-tetrahydrocannabinol, administered intravenously to man, produces psychologic and pharmacologic effects that persist for several hours. The drug and its metabolites are excreted in urine and feces for more than 1 week. The pharmacology, disposition, and metabolism of 11-hydroxy-Delta(9)-tetra-hydrocannabinol mimic that of Delta(9)-tetrahydrocannabinol, thus providing evidence that Delta(9)-tetrahydrocannabinol (the major active component of marihuana) is converted to the 11-hydroxy compound in man, the latter compound being responsible for the effects.
Twelve chronic marijuana users received triangle up(9)-tetrahydrocannabinol by smoking. The magnitude of their pulse increment was highly correlated with their subjective experiences. Three of the 12 subjects subsequently received triangle up(9)-tetrahydrocannabinol labeled with carbon-14; the time course of its concentration in plasma was highly correlated with the pulse increment. Subjective symptoms, however, appeared later and dissipated more slowly.
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Radioactively labeled delta-9-tetrahydrocannabinol (delta(9)THC) administered intravenously to chronic marihuana smokers disappeared from the blood plasma with a half-life of 28 hours as compared to 57 hours for nonusers of marihuana. Apparent volumes of distribution did not significantly differ between the two groups. Within 10 minutes after administration of delta(9)THC, 11-hydroxy-delta(9)THC is present in the plasma of nonusers and chronic users. This metabolite was also present in urine and feces of nonusers and long-term marihuana smokers. In addition, polar metabolites were excreted in urine and feces of both groups for more than 1 week.
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Delta(9)-Tetrahydrocannabinol (the major active component of marihuana) administered intravenously to normal human volunteers persists in plasma for more than 3 days (t(1/2) = 56 hours). Its metabolites appear in plasma within 10 minutes after administration and persist along with the precursor compound. Delta(9)-Tetrahydrocannabinol is completely metabolized in man, and the radioactive metabolites are excreted in urine and feces for more than 8 days.
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