Journal article
Relating Observed Psychoactive Effects to the Plasma Concentrations of Delta-9-Tetrahydrocannabinol and Its Active Metabolite: An Effect-Compartment Modeling Approach
Journal of pharmaceutical sciences, Vol.107(2), pp.745-755
02/2018
DOI: 10.1016/j.xphs.2017.09.009
PMID: 28942005
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.
Details
- Title: Subtitle
- Relating Observed Psychoactive Effects to the Plasma Concentrations of Delta-9-Tetrahydrocannabinol and Its Active Metabolite: An Effect-Compartment Modeling Approach
- Creators
- Rakesh Awasthi - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242Guohua An - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242Maureen D Donovan - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242Laura L Boles Ponto - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.107(2), pp.745-755
- DOI
- 10.1016/j.xphs.2017.09.009
- PMID
- 28942005
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/2018
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984051566802771
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