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Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man

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Abstract

The relationship between each of two pharmacologic effects (tachycardia and psychological “high”) of delta-9-tetrahydrocannabinol (THC) and plasma THC concentration was investigated in three male and three female experienced marihuana smokers. Each subject smoked one 1% THC cigarette on two occasions separated by 2 h. Heart rate and subjective psychological self-rating were determined frequently throughout the 4 h study period. Data were analyzed by calculating the area under the parameter versus time curves, constructing hysteresis plots, and calculating the decay rate constants from pharmacologic effect versus time plots. In both males and females, dose inhaled and psychological response were apparently equivalent for the first and second cigarettes. While all subjects exhibited marked tachycardia in response to the first cigarette, heart rate in both male and female subjects was not increased as markedly during the second cigarette. Interestingly, female subjects had less tachycardiac response than males during the second cigarette. Hysteresis plots revealed that both heart rate and subjective psychological effects were elicited in an effect compartment which was “deep” relative to the reference plasma compartment. The time courses of tachycardiac and psychological responses lagged behind the plasma THC concentration-time profile. Zero-order decay rate constants for subjective psychological rating did not change substantially from the first to second cigarette. This study suggests that plasma THC concentration is a poor predictor of simultaneously occurring physiological and psychological pharmacologic effects.

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Author notes

  1. S. Michael Owens

    Present address: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, 85721, Tucson, AZ, USA

Authors and Affiliations

  1. Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA

    David M. Cocchetto

  2. Department of Phathology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA

    S. Michael Owens

  3. Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA

    Mario Perez-Reyes & Stephanie DiGuiseppi

  4. Department of Clinical Research, Burroughs Wellcome Company, Research Triangle Park, North Carolina, USA

    Loren L. Miller

Authors
  1. David M. Cocchetto
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  2. S. Michael Owens
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  3. Mario Perez-Reyes
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  4. Stephanie DiGuiseppi
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  5. Loren L. Miller
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Cocchetto, D.M., Owens, S.M., Perez-Reyes, M. et al. Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man. Psychopharmacology 75, 158–164 (1981). https://doi.org/10.1007/BF00432179

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  • DOI: https://doi.org/10.1007/BF00432179

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