Relating Observed Psychoactive Effects to the Plasma Concentrations of Delta-9-Tetrahydrocannabinol and Its Active Metabolite: An Effect-Compartment Modeling Approach.
Rakesh Awasthi, Guohua An, Maureen D Donovan, Laura L. Boles Ponto
Journal of Pharmaceutical Sciences February 2018 DOI: 10.1016/j.xphs.2017.09.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or modeling paper Peer reviewed |
|---|---|
| Intervention | THC |
| Topics | Cannabis |
| Keywords | Clinical pharmacokinetics Metabolism Metabolite kinetics Pharmacokinetic/pharmacodynamic models Pharmacokinetics/pharmacodynamics Population pharmacokinetics |
| Key points | The authors propose that a hypothetical effect-compartment model can link predicted effect-site concentrations of THC, but not plasma concentrations, to reported "highness" after intravenous THC. Estimated equilibration half-lives differed between THC and its active metabolite THC-OH, indicating they equilibrate between plasma and the effect site at different rates. |
Abstract
The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the "hypothetical" effect-site compartment to the observed psychoactive effects. A "hypothetical" effect-compartment model was developed using literature data to characterize the observed delay in peak "highness" ratings compared with plasma concentrations of the psychoactive agents following intravenous administration of THC. A direct relationship was established between the reported psychoactive effects ("highness" or intoxication) and the predicted effect-site concentrations of THC. The differences between estimated equilibration half-lives for THC and THC-OH in the effect-compartment model indicated the differential equilibration of parent drug and the active metabolite between plasma and the effect-site. These models contribute to the understanding of the pharmacokinetic-pharmacodynamic relationships associated with marijuana use and are important steps in the prediction of pharmacodynamic effects related to the psychoactive components in marijuana.
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| Out of Harm's Way?: Illicit Drug Use, Medicalization and the Law | 2003 | Theoretical or philosophical paper |