Abstract

The overall goal of this proposed research is to investigate tetrahydrocannabional (THC) receptors.
Our specific aims are to evaluate natural cannabinoids and their analogs for specific antagonistic activity of delta-8-THC-induced hypothermia, hypo-activity and analgesia in mice, TCH generalization in rats, and overt behavioral effects of THC in dogs. Analogs will include alkylating and non-alkylating agents.
The second aim i s to carry out biodispositional studies in order to localize THC binding sites centrally which will provide insight into the functionality of these receptors.
The third aim i s to characterize THC receptors using in vitro binding techniques. Several radiolabeled ligands, including THC, water soluble derivatives of THC and THC antagonists, will be used to study the binding sites in brain fractions. The discovery of a specific cannabinoid antagonist coupled with the in vitro characterization of a specific binding site will provide for the first time, compelling evidence for the existence of a THC receptor. Identification of such a receptor would provide insight into the mechanism responsible for THC's neuropharmacological and neurophysiological effects. These findings would lead to a search for the endogenous substrate for these receptors, the identification of which would provide a better understanding of the consequences of marihuana use.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003672-03
Application #
3208231
Study Section
(DABB)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Mitjavila, Jose; Yin, Danielle; Kulkarni, Pushkar M et al. (2018) Enantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons. Pharmacol Res 129:475-481
Barrus, Daniel G; Lefever, Timothy W; Wiley, Jenny L (2018) Evaluation of reinforcing and aversive effects of voluntary ?9-tetrahydrocannabinol ingestion in rats. Neuropharmacology 137:133-140
Kevin, Richard C; Lefever, Timothy W; Snyder, Rodney W et al. (2018) Kinetic and metabolic profiles of synthetic cannabinoids NNEI and MN-18. Drug Test Anal 10:137-147
Marusich, Julie A; Wiley, Jenny L; Lefever, Timothy W et al. (2018) Finding order in chemical chaos - Continuing characterization of synthetic cannabinoid receptor agonists. Neuropharmacology 134:73-81
Wiley, Jenny L; Owens, R Allen; Lichtman, Aron H (2018) Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Curr Top Behav Neurosci 39:153-173
Kevin, Richard C; Lefever, Timothy W; Snyder, Rodney W et al. (2017) In vitro and in vivo pharmacokinetics and metabolism of synthetic cannabinoids CUMYL-PICA and 5F-CUMYL-PICA. Forensic Toxicol 35:333-347
Grim, T W; Morales, A J; Thomas, B F et al. (2017) Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model. J Pharmacol Exp Ther 362:210-218
Lefever, Timothy W; Marusich, Julie A; Thomas, Brian F et al. (2017) Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice. Subst Abuse 11:1178221817701739
Lefever, Timothy W; Lee, Youn O K; Kovach, Alexander L et al. (2017) Delivery of nicotine aerosol to mice via a modified electronic cigarette device. Drug Alcohol Depend 172:80-87
Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A et al. (2017) Comparison of the discriminative stimulus and response rate effects of ?9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats. Drug Alcohol Depend 172:51-59

Showing the most recent 10 out of 284 publications