These have shown that presynaptic GABA-B receptors inhibit GABA release within the central amygdala154, and can therefore compensate for the excessive GABA-ergic inhibition that results in this brain area from impaired GABA-clearance. These findings, combined with our discovery that the impaired GABA-clearance promotes alcohol choice and compulsivity, point to a potential mechanism of action behind reports of beneficial effects obtained in alcoholism with the GABA-B agonist baclofen35,39,155. The failure so far to achieve more than at best marginal gains in alcoholism treatment through pharmacotherapy strongly suggest that business as usual in alcoholism research should not be considered an acceptable option. The disease burden from alcohol addiction, and the inability of existing medications to significantly improve outcomes in this condition provide a strong incentive for research to identify new pharmacotherapeutic mechanisms.
Animal data suggest that severely dependent individuals, in whom glutamatergic dysregulation is most pronounced, should be most likely to respond to acamprosate24. However, the exact molecular mechanism through which acamprosate exerts its effect remains unknown, and it has been suggested that it simply functions as a carrier of calcium-ions into the CNS25. The combination of modest efficacy, a short half-life that necessitates three times daily administration, and a high frequency of gastrointestinal side effects has led to a very limited clinical uptake of acamprosate.
Network meta-analysis and microsimulation studies suggest that nalmefene may have some benefits over placebo for reducing total alcohol consumption (35, 36). The approval of nalmefene in Europe was accompanied by some controversy (37); a prospective head-to-head trial of nalmefene and naltrexone could help clarify whether nalmefene has added benefits to the existing medications available for alcohol use disorder. Last, nalmefene was approved in Europe as a medication that can be taken “as needed” (i.e., on days when drinking was going to occur). Prior work has also demonstrated the efficacy of taking naltrexone only on days that drinking was potentially going to occur (38). The next drug approved for treatment of alcohol use disorder was acamprosate; first approved as a treatment for alcohol dependence in Europe in 1989, acamprosate has subsequently been approved for use in the United States, Canada, and Japan.
Evidence-based treatments
Ethanol is classified as a “depressant” because it has a generally slowing effect on brain activity through activation of γ-aminobutyric acid (GABA) pathways. In this post, we’ll explore the current science and some practical ideas on how to approach the topic. Scientific American is part of Springer Nature, which owns or has commercial relations with thousands of scientific publications (many of them can be found at /us). Scientific American maintains a strict policy of editorial independence in reporting developments in science to our readers.
- As a reminder to the reader that science does not stand still, recent findings have shown that, contrary to an article included in this volume, absinthe does not pose a particularly potent health threat.
- Its interfer- ence with the dopamine pathway was reported in 1997 (9), and a series of subsequent clinical trials have shown a high degree of efficacy (10).
- What is the science behind the addictive nature of the simple ethanol molecule, the key ingredient in drinking alcohol, and what are current researchers doing to tame its effects?
- Rather than reflecting activity of entire brain structures, such as the mPFC or the amygdala, these processes seem to reflect the activity of small neuronal populations that are sparsely distributed within the respective structure100,101,102.
PHARMACOLOGICAL APPROACHES TO THE TREATMENT OF ALCOHOL USE DISORDER
Fermented beverages clearly eased the difficulties of everyday life—the workers who built the pyramids of ancient Egypt and Mesoamerica were paid in beer. Alcohol also knitted together, or “lubricated,” the social fabric mesclun psychedelic of cultures by bringing humans together and warming them up to one another. Despite the popularity of alcoholic beverages the world over, their potential dangers play a sinister leitmotif in human history.
Advances in the science and treatment of alcohol use disorder
Ethanol is a natural product that is formed from the fermentation of grains, fruits, and other sources of sugar. It’s found in a wide range of alcoholic beverages including beer, wine, and spirits like vodka, whiskey, rum, and gin. Many of the articles in this collection take a medical view of alcohol, demonstrating how scientific knowledge of alcohol in relation to human physiology has advanced during the past century. Indeed, alcoholic beverages were a kind of universal medicine before modern synthetic drugs became available. Botanical compounds with medicinal properties could also be dissolved in an alcoholic medium to be applied to the skin or imbibed. The world’s ancient pharmacopoeias—Chinese, Indian, Egyptian and Greco-Roman—are dominated by such recipes.
Choice of alcohol over a natural reward: an experimental study in light and heavy social drinkers
With respect to behavioral treatments, there are numerous opportunities for the development of novel mobile interventions that could provide treatment and recovery support in near real time. This mobile technology may also extend the reach of treatments to individuals with alcohol use disorder, particularly in rural areas. On the basis of a contextual self-regulation model of alcohol use (90), it is critical to address the immediate situational context alongside the broader social, environmental, and familial context in which an individual experiences the world and engages in momentary decision-making. Ambulatory assessment, particularly tools celebrities that drink alcohol everyday that require only passive monitoring (e.g., GPS, heart rate, and skin conductance) and real-time support via mobile health, could provide immediate environmental supports and could extend the reach of medications and behavioral treatments for alcohol use disorder.
Circuit-specific manipulations using chemogenetic or optogenetic approaches will allow further mechanistic insights that also might guide neuromodulation-based therapies for addictive disorders122,123. For instance, a recent study in rats indicated that a history of alcohol dependence alters the functional connectivity of the anterior insula124. Chemogenetically silencing this structure using a DREADD (designer receptor exclusively activated by designer drug) changed alcohol’s interoceptive properties and approach behavior to the drug125. We believe that circuits-based manipulations need to be combined with functional neuroimaging both in animals and humans to better understand the effects of local interferences on large-scale brain network properties. Efficacy of treatment approaches such as contingency management, which provides systematic incentives for abstinence73, certainly supports the notion that behavioral choices in patients with addictions including AUD74 remain sensitive to reward contingencies. The critical question would seem to be whether addictive behaviors—for the most part—result from healthy brains responding normally to externally determined contingencies, or rather from a pathology of brain circuits that promotes suboptimal choices even when reward contingencies are within a normal range.
This perspective is neither new, nor foreign to mainstream neuroscience of addiction75,76,77,78,79. Consumption of alcohol has bac depends on what and continues to serve major roles in religious and cultural ceremonies around the world. But unlike most food products, in the last century, alcohol has been wrapped up in nearly perpetual controversy over its moral effects and health implications. When people talk about drinking “alcohol,” they’re almost always referring to the consumption of ethanol.