Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. ...

Migraine is a common and disabling neurological disorder that involves activation or the perception of activation of the trigeminovascular system. Cannabinoid (CB) receptors are present in brain and have been suggested to be antinociceptive. Here we determined the effect of cannabinoid receptor activation on neurons with trigeminovascular nociceptive input in the rat. Neurons in the trigeminoce...

Anandamide and 2-arachidonoylglycerol (2-AG), two endogenous ligands of the CB1 and CB2 cannabinoid receptor subtypes, inhibit the proliferation of PRL-responsive human breast cancer cells (HBCCs) through down-regulation of the long form of the PRL receptor (PRLr). Here we report that 1) anandamide and 2-AG inhibit the nerve growth factor (NGF)-induced proliferation of HBCCs through suppression...

Previous studies using a rat 5-choice serial reaction time task have established a critical role for dopamine D2 receptors in regulating increments in motor impulsivity induced by acute administration of the psychostimulant drugs amphetamine and nicotine. Here we investigated whether cannabinoid CB1 and/or μ-opioid receptors are involved in nicotine-induced impulsivity, given recent findings in...

Cannabinoid receptors have been implicated in the regulation of blood flow in the cerebral vasculature. Because the nucleus accumbens (NAc) shows high levels of central cannabinoid receptor 1 (CB1) expression we examined the effects of cannabinoids on the local transient alkaline shifts and increases in extracellular oxygen induced by electrical stimulation of the medial forebrain bundle (MFB) ...

BACKGROUND Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. METHODS Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg a...

Two types of cannabinoid receptor have been discovered so far, CB(1) (2.1: CBD:1:CB1:), cloned in 1990, and CB(2) (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the oth...

Current cannabinoid research is based on a number of major discoveries made by Professor Raphael Mechoulam. In the mid-1960s, he, together with Professor Yechiel Gaoni, identified in the plant Cannabis sativa, the psychoactive component of marijuana and hashish, D-tetrahydrocannabinol (THC), determined its chemical structure (Gaoni and Mechoulam, 1964; Mechoulam and Gaoni, 1967) and synthesized...

The use of cannabis sativa preparations as recreational drugs can be traced back to the earliest civilizations. However, animal models of cannabinoid addiction allowing the exploration of neural correlates of cannabinoid abuse have been developed only recently. We review these models and the role of the CB1 cannabinoid receptor, the main target of natural cannabinoids, and its interaction with ...

BACKGROUND AND PURPOSE Our previous study has demonstrated that the rapid tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was possibly mediated through an endocannabinoid system-related mechanism. The purpose of this study was to investigate whether activation of epsilon protein kinase C (εPKC) was involved in EA pretreatment-induced neuroprotection via cannabinoid recept...