Neuropharmacology
June 1, 2026
Evan C Smith, Christos Iliopoulos-Tsoutsouvas, Markos-Orestis Georgiadis et al.
Despite being the most prevalently abused illicit drug class, the neurochemical effects of cannabinoids (CBs) in key reward-related brain regions are not fully understood. Here, we used in vivo microdialysis combined with liquid chromatograph mass spectrometry to delineate how single, intraperitoneal injections of delta-9-tetrahydrocannabinol (Δ9-THC), and synthetic partial (AM11101) and full...
Nature Communications
January 8, 2025
T. Thorsen, Yashraj Kulkarni, David A. Sykes et al.
Tetrahydrocannabinol (THC) is the principal psychoactive compound derived from the cannabis plant Cannabis sativa and approved for emetic conditions, appetite stimulation and sleep apnea relief. THC’s psychoactive actions are mediated primarily by the cannabinoid receptor CB1. Here, we determine the cryo-EM structure of HU210, a THC analog and widely used tool compound, bound to CB1 and its...
Molecular Pharmacology
December 2022
Taryn Bosquez-Berger, Sierra Wilson, Christos Iliopoulos-Tsoutsouvas et al.
The two main constituents of cannabis are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). While Δ9-THC pharmacology has been studied extensively, CBD-long considered inactive-is now the subject of vigorous research related to epilepsy, pain, and inflammation and is popularly embraced as a virtual cure-all. However, our understanding of CBD pharmacology remains limited, although CBD...
Cell
October 20, 2016
Tian Hua, Kiran Vemuri, Mengchen Pu et al.
Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å...
Journal of Pharmacology and Experimental Therapeutics
January 29, 2016
Brian D Kangas, Michael Z. Leonard, Vidyanand G Shukla et al.
The primary psychoactive ingredient of marijuana, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), has medicinal value but also produces unwanted deleterious effects on cognitive function, promoting the search for improved cannabinergic therapeutics. The present studies used a battery of touchscreen procedures in squirrel monkeys to compare the effects of different types of cannabinergic drugs on several...
Psychopharmacology
February 2014
Torbjörn U C Järbe, Brian J LeMay, Aneetha Halikhedkar et al.
The "subjective high" from marijuana ingestion is likely due to Δ(9)-tetrahydrocannabinol (THC) activating the central cannabinoid receptor type 1 (CB1R) of the endocannabinoid signaling system. THC is a weak partial agonist according to in vitro assays, yet THC mimics the behavioral effects induced by more efficacious cannabinergics. This distinction may be important for understanding...
Journal of Pharmacology and Experimental Therapeutics
March 2013
Brian D Kangas, Marcus S Delatte, V Kiran Vemuri et al.
Cannabinoid receptor 1 (CB(1)) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications. Recent laboratory studies suggest that the effects of CB(1) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility. However, little is known...
Psychopharmacology
March 2012
Torbjörn U C Järbe, Sherrica Tai, Brian J LeMay et al.
The endocannabinoid signaling system (ECS) has been targeted for developing novel therapeutics since ECS dysfunction has been implicated in various pathologies. Current focus is on chemical modifications of the hexahydrocannabinol (HHC) nabilone (Cesamet(®)). To characterize the novel, high-affinity cannabinoid receptor 1 (CB(1)R) HHC-ligand AM2389...
Behavioural Pharmacology
September 2011
Torbjörn U C Järbe, Hongfen Deng, Subramanian K Vadivel et al.
We examined four different cannabinergic aminoalkylindole ligands, including one drug (AM678=JWH018) found in herbal 'Spice' concoctions, for their ability to substitute for Δ(9)-tetrahydrocannabinol (THC), and the ability of the cannabinoid receptor 1-selective antagonist/inverse agonist rimonabant to block the substitution, 30 and 90 min after intraperitoneal injection. Rats trained to...
European Journal of Pharmacology
December 1, 2010
Torbjörn U C Järbe, Roger S Gifford, Alexandros Makriyannis
The objective was to examine the time course of the cannabinoid 1 receptor antagonist/inverse agonist rimonabant's ability to antagonize in vivo cannabinergic agonist effects. We used two behavioral procedures sensitive to the effects of ∆⁹-tetrahydrocannabinol (∆⁹-THC): rat drug discrimination (EXP-1) and suppression of fixed-ratio responding (FR) for food reinforcement (EXP-2). Two training...
Psychopharmacology
November 1, 2009
C B Willmore, D M Krall, F M Spears et al.
Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands. The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits. Rats were trained to perform operant ratio...
Psychopharmacology
April 2009
Torbjörn U C Järbe, Chen Li, Qian Liu et al.
To characterize in vivo the high-affinity CB(1) cannabinoid receptor (CB(1)R) selective anandamide analog AM1346 [alkoxyacid amide of N-eicosa-tetraenylamine] using drug discrimination. Substitution tests involved Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and R-(+)-methanandamide (mAEA), a metabolically stable analog of anandamide (AEA), as well as the CB(1)R antagonist/inverse agonist...
Journal of Pharmacology and Experimental Therapeutics
April 2007
Marcello Solinas, Gianluigi Tanda, Zuzana Justinova et al.
Anandamide is an endogenous ligand for brain cannabinoid CB(1) receptors, but its behavioral effects are difficult to measure due to rapid inactivation. Here we used a drug-discrimination procedure to test the hypothesis that anandamide, given i.v. or i.p., would produce discriminative effects like those of delta-9-tetrahydrocannabinol (THC) in rats when its metabolic inactivation was...
Behavioural Pharmacology
September 2005
P J McLaughlin, C M Brown, K M Winston et al.
Cannabinoid agonists have been shown to produce dose-related impairments in several measures of cognitive performance. However, it is unclear if low doses of cannabinoid CB1 agonists, or CB1 antagonists, can facilitate aspects of stimulus detection. The present study employed an operant procedure involving visual stimulus detection in rats. The task was found to be sensitive to the muscarinic...
Psychopharmacology
August 2001
Torbjörn U C Järbe, R J Lamb, S Lin et al.
(R)-methanandamide (AM-356), a metabolically more stable chiral analog of the endocannabinoid ligand anandamide, was used as a representative of fatty acid ethanolamide CB1 receptor ligands to characterize the discriminative stimulus functions of anandamides. Rats discriminated between 10 mg/kg (R)-methanandamide and vehicle administered IP 15 min prior to session onset. Another group of rats...
Psychopharmacology
December 1998
Torbjörn U C Järbe, R J Lamb, Alexandros Makriyannis et al.
The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than delta9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg delta9-tetrahydrocannabinol (delta9-THC) and vehicle. Different training...