CANNABINOID CB1 ANTAGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG DEPENDENCE
by
Le Foll B, Goldberg SR. NIDA.
J Pharmacol Exp Ther. 2004 Nov 3
ABSTRACTThis review examines the development of cannabinoid CB1 receptor antagonists as a new class of therapeutic agents for drug addiction. Abused drugs (alcohol, opiates, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and psychostimulants, including nicotine) elicit a variety of chronically relapsing disorders by interacting with endogenous neural pathways in the brain. In particular, they share the common property of activating mesolimbic dopamine brain reward systems and virtually all abused drugs elevate dopamine levels in the nucleus accumbens. Cannabinoid CB1 receptors are expressed in this brain reward circuit and modulate the dopamine-releasing effects of Delta(9)-THC and nicotine. Rimonabant (SR141716), a CB1 receptor antagonist, blocks both the dopamine-releasing and the discriminative and rewarding effects of Delta(9)-THC in animals. Blockade of CB1 receptor activity by genetic invalidation also decreases rewarding effects of opiates and alcohol in animals. Although CB1 receptor blockade is generally ineffective in reducing the self-administration of cocaine in rodents and primates, it reduces the reinstatement of extinguished cocaine-seeking behavior produced by cocaine-associated conditioned stimuli and cocaine priming injections. Similarly, CB1 receptor blockade is effective in reducing nicotine-seeking behavior induced by re-exposure to nicotine-associated stimuli. Some of these findings have been recently validated in humans. In clinical trials, Rimonabant blocks the subjective effects of Delta(9)-THC in humans and prevents relapse to smoking in ex-smokers. Findings from both clinical and preclinical studies suggest that ligands blocking CB1 receptors offer a novel approach for patients suffering from drug dependence that may be efficacious across different classes of abused drugs.CB1
CB2
Rimonabant
Anandamide
Tolerant mice
Just say know
Cannabis: effects
Forgetful rodents
Endocannabinoids
Stoned chocaholics?
The nectar of delight
Charas versus bhang
Rodent cannabis abuse
Cannabinoid receptor subtypes
Cannabinoids and the zebra finch
Cannabinoid CB1 receptor and emotion
CB1 cannabinoid receptor knockout mice
CB1 cannabinoid receptor agonism isn't rewarding01 02 03 04 05 06 07 08 09 10 11 12 13 14 15
Refs
HedWeb
Future Opioids
BLTC Research
Utopian Surgery?
The Hedonistic Imperative
MDMA: Utopian Pharmacology
When Is It Best To Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family
