This proposal is a request for an ISA (K02) which would enhance my research career development and extend ongoing research concerning cannabioids and related compounds. The recent advances in our understanding of the neurochemical/physiological basis of cannabinoid action provide exciting background material for continuing efforts to further delineate the mechanism of action of cannabimimetic agents. The overall purpose of the proposed studies is to compare the structure-activity relationships of the subjective effects of delta-9-tetrahydrocannabinol (delta-9-THC) and other cannabimimetics with an analog [(R)-methanandamide] of the endogenous cannabinoid receptor ligand anandamide. The SAR between chemical structure and drug action reveals the structural requirements for a given drug effect or drug action. Though some studies suggest that delta-9-THC and anandamide as well as (R)-methanandamide share many similar properties, a one-on-one relationship has not been demonstrated. Studies from our own and other laboratories have shown the THC-like properties of synthetic cannabinoids and cannabimimetics are highly dependent on particular structural configurations. The proposed studies investigate potential stereoselectivity of known cannabimimetic compounds with regard to (R)-methanandamide. These studies also focus on identifying useful pharmacotherapies for cannabis abuse by effectively blocking the psychoactive, cannabimimetic properties. The present project will utilize drug discrimination procedures with rats as an animal model for assessing the psychoactive properties of delta-9-THC, (R)-methanandamide, and related compounds. Drug discrimination is the most commonly used paradigm for studying the subjective, intoxicating effects of drugs in preclinical psychopharmacology. A special feature of this proposal is the use of different training doses of THC to create different efficacy demands. Additionally, food maintained responding and open-field activity studies will also be conducted. By providing important information on the SAR of endogenous anandamide and exogenous delta-9-THC, as well as potential cannabimimetic antagonists, these studies will not only add to our understanding of the behavioral neurobiology of cannabis abuse and dependence, but may also lead to the development of effective pharmacological treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
2K02DA000253-08A1
Application #
6327045
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Schnur, Paul
Project Start
2000-07-01
Project End
2006-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
8
Fiscal Year
2001
Total Cost
$93,094
Indirect Cost
Name
Temple University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Järbe, Torbjörn U C; Deng, Hongfen; Vadivel, Subramanian K et al. (2011) Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (?(9)-tetrahydrocannabinol) discrimination for rats. Behav Pharmacol 22:498-507
Järbe, Torbjörn U C; Li, Chen; Vadivel, Subramanian K et al. (2010) Discriminative stimulus functions of methanandamide and delta(9)-THC in rats: tests with aminoalkylindoles (WIN55,212-2 and AM678) and ethanol. Psychopharmacology (Berl) 208:87-98
Järbe, Torbjörn U C; Li, Chen; Liu, Qian et al. (2009) Discriminative stimulus functions in rats of AM1346, a high-affinity CB1R selective anandamide analog. Psychopharmacology (Berl) 203:229-39
Jarbe, T U C; LeMay, B J; Olszewska, T et al. (2008) Intrinsic effects of AM4113, a putative neutral CB1 receptor selective antagonist, on open-field behaviors in rats. Pharmacol Biochem Behav 91:84-90
Jarbe, Torbjorn U C; Li, Chen; Vadivel, Subramanian K et al. (2008) Discriminative stimulus effects of the cannabinoid CB1 receptor antagonist rimonabant in rats. Psychopharmacology (Berl) 198:467-78
Jarbe, Torbjorn U C; DiPatrizio, Nicholas V; Li, Chen et al. (2007) Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats. Behav Pharmacol 18:673-80
Jarbe, Torbjorn U C; Liu, Quian; Makriyannis, Alexandros (2006) Antagonism of discriminative stimulus effects of delta(9)-THC and (R)-methanandamide in rats. Psychopharmacology (Berl) 184:36-45
Jarbe, T U C; DiPatrizio, N V (2005) Delta9-THC induced hyperphagia and tolerance assessment: interactions between the CB1 receptor agonist delta9-THC and the CB1 receptor antagonist SR-141716 (rimonabant) in rats. Behav Pharmacol 16:373-80
Jarbe, T U C; DiPatrizio, N V; Lu, D et al. (2004) (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats. Behav Pharmacol 15:517-21
Jarbe, T U; Lamb, R J; Lin, S et al. (2000) Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats: a systematic replication. Behav Pharmacol 11:81-6

Showing the most recent 10 out of 15 publications