The Cannabinoid CB1 Receptor Antagonist, Rimonabant, as a Promising Pharmacotherapy for Alcohol Dependence: Preclinical Evidence

Colombo, Giancarlo; Orrù, Alessandro; Lai, P.; Cabras, Claudia; Maccioni, Paola; Rubio, Marina; Gessa, Gian Luigi; Carai, Mauro A.M.

doi:10.1007/s12035-007-0017-y

Cited by 55 publications

(45 citation statements)

References 62 publications

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“…All these effects have been found when antagonists are administrated either systematically or centrally, e.g., by microinjections into the NAc and VTA [208]. Due to the recent increase in the literature regarding CB1 receptors as a pharmacological target for the treatment of alcoholism, there have been several extensive reviews published [209][210][211]. Based on these studies and recent findings from our own group [212], it is plausible to conclude that the endocannabinoid system mediates not only alcohol intake but the motivational and emotional properties of alcohol intake, seeking and craving.…”

Section: B) Pharmacological Manipulations Of the Endogenous Cannabinomentioning

confidence: 99%

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

López-Moreno¹,

López-Jiménez²,

Gorriti³

et al. 2010

CDT

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Although the first studies regarding the endogenous opioid system and addiction were published during the 1940s, addiction and cannabinoids were not addressed until the 1970s. Currently, the number of opioid addiction studies indexed in PubMed-Medline is 16 times greater than the number of cannabinoid addiction reports. More recently, functional interactions have been demonstrated between the endogenous cannabinoid and opioid systems. For example, the cannabinoid brain receptor type 1 (CB1) and mu opioid receptor type 1 (MOR1) co-localize in the same presynaptic nerve terminals and signal through a common receptor-mediated G-protein pathway. Here, we review a great variety of behavioral models of drug addiction and alcohol-related behaviors. We also include data providing clear evidence that activation of the cannabinoid and opioid endogenous systems via WIN 55,512-2 (0.4-10 mg/kg) and morphine (1.0-10 mg/kg), respectively, produces similar levels of relapse to alcohol in operant alcohol self-administration tasks. Finally, we discuss genetic studies that reveal significant associations between polymorphisms in MOR1 and CB1 receptors and drug addiction. For example, the SNP A118G, which changes the amino acid aspartate to asparagine in the MOR1 gene, is highly associated with altered opioid system function. The presence of a microsatellite polymorphism of an (AAT)n triplet near the CB1 gene is associated with drug addiction phenotypes. But, studies exploring haplotypes with regard to both systems, however, are lacking.

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Section: B) Pharmacological Manipulations Of the Endogenous Cannabinomentioning

confidence: 99%

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

López-Moreno¹,

López-Jiménez²,

Gorriti³

et al. 2010

CDT

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“…Pharmacological blockade with rimonabant, a potent, selective, and orally active blocker of the central CB1 receptors [30] prevents habituation to ethanol drinking, when administered at the start of exposure to alcohol in genetically-selected alcohol-preferring rats [31][32][33][34]. Similarly, using different animal models of excessive alcohol drinking in which alcohol intake was already established, rimonabant (administered either acutely or repeatedly) reduced ethanol intake [35][36][37][38], and suppressed alcohol self-administration [39][40][41]. Notably, rimonabant augmented inhibitory postsynaptic potentials, revealing a tonic endocannabinoid activity that decreased inhibitory transmission in central amygdala [42].…”

Section: Cannabinoid Receptorsmentioning

confidence: 99%

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Leggio¹,

Cardone²,

Ferrulli³

et al. 2010

curr pharm des

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Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been focusing on identifying new neuropharmacological targets for alcohol dependence. This review will summarize recent research, which has identified new targets to treat alcohol dependence. A variety of systems have been investigated, such as the endocannabinoid system, modulators of glutamatergic transmission, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), nociceptin, glial cell line-derived neurotrophic factor (GDNF), acetaldehyde (ACD), substance P and Neurokinin 1 (NK1) receptor, nicotinic acetylcholine receptors (nAchRs), alpha-adrenergic receptor, and many others. Compared to preclinical studies, only a few clinical studies have been conducted so far. Thus, there is a critical need to translate successful preclinical results into human clinical trials. However, since some clinical studies have failed to replicate preclinical findings, future research will have not only to identify more efficacious medications, but also delineate the best match between a particular pharmacotherapy with a specific alcoholic subtype.

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“…Involved in the physiological processes of mood, appetite, painsensation, and memory, the endocannabinoid system plays an important role in the behavioral effects of alcohol [104]. There are currently two known subtypes of cannabinoid receptors: CB1 and CB2.…”

Section: Cannabinoid Receptorsmentioning

confidence: 99%

“…In contrast, blocking of this receptor decreases alcohol consumption (reviewed in: [103,104]). One potential CB1 antagonist, rimonabant has shown promise as a potential blocker of this receptor and decreasing ethanol intake in animal studies [105].…”

Section: Cannabinoid Receptorsmentioning

confidence: 99%

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Edwards

Kenna²,

Swift³

et al. 2011

CPD

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Harmful alcohol use is a risk factor in more than 60 diseases and injuries resulting in approximately 2.5 million deaths per year worldwide. In the United States (US) and Europe, there are only a few medications approved for alcohol dependence (AD) however, these medications have only been moderately effective and there is a crucial need for more effective treatments. This review briefly summarizes research on currently approved medications for AD, as well as promising medications like topiramate, baclofen and ondansetron. Topiramate is likely the most promising new treatment for AD, however, further research is needed to determine the optimal dose and appropriate length of treatment. Baclofen, a GABA(B) agonist, is a promising medication as a treatment for AD, especially for patients with AD and severe liver disease. Ondansetron has shown promising results as a potential medication for AD, but only within a certain subtype of individuals. This review also discusses more recent findings on other potential pharmacotherapies for AD, such as serotonin-specific reuptake inhibitors (SSRIs; i.e. sertraline), aripiprazole and prazosin, as well as on some examples of other potentially interesting new neuropharmacological targets (i.e. cannabinoid receptors, CRF, NPY, ghrelin). Finally, the present review also discusses the attempts to personalize medication for AD treatment by alcohol typology and pharmacogenetics.

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The Cannabinoid CB1 Receptor Antagonist, Rimonabant, as a Promising Pharmacotherapy for Alcohol Dependence: Preclinical Evidence

Cited by 55 publications

References 62 publications

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

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