Functional Alternatives to Alcohol

Review Endocrinology & Metabolism

Relating neurosteroid modulation of inhibitory neurotransmission to behaviour

Delia Belelli et al.

Summary: Neurosteroids acting on GABA(A) receptors may modulate behavior by influencing neuronal signaling. Although there are challenges, the potential as new medications, especially in treating postpartum depression, is being explored.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Development of neuroactive steroids for the treatment of postpartum depression

Handan Gunduz-Bruce et al.

Summary: Postpartum depression (PPD) is a common and serious condition that can impair maternal functioning and mother-infant attachment, affecting the emotional and cognitive development of children. While the exact pathophysiology is unclear, preclinical findings suggest that fluctuations in neurosteroid hormone levels may induce plasticity in GABA(A) receptors, potentially contributing to the manifestation of depressive symptoms. Controlled clinical trials have explored various pharmacological treatments for PPD, highlighting the potential of targeting GABAergic transmission with positive allosteric modulators as a novel therapeutic approach.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Article Clinical Neurology

Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

Elia M. Pestana Knight et al.

Summary: This study evaluated the efficacy and safety of ganaxolone in patients with CDKL5 deficiency disorder (CDD) and refractory epilepsy. The results showed that ganaxolone significantly reduced seizure frequency in CDD patients and was generally well tolerated. The study suggests a potential treatment benefit for ganaxolone in CDD and further long-term treatment is being assessed in the ongoing open-label extension phase.

LANCET NEUROLOGY (2022)

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Review Neurosciences

Keeping the Balance: GABAB Receptors in the Developing Brain and Beyond

Davide Bassetti

Summary: Gamma-aminobutyric acid (GABA) is the main neurotransmitter in the brain responsible for inhibiting neuronal activity. GABA(B) receptors play a crucial role in regulating proliferation, migration, and cell inhibition. They can shape neuronal activity and contribute to development by modulating the function of cells in response to varying levels of GABA concentration.

BRAIN SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Ketamine plus Alcohol: What We Know and What We Can Expect about This

Natalia Harumi Correa Kobayashi et al.

Summary: This review examines the toxicological mechanisms and physiological effects on different body systems of co-abusing ketamine and ethanol. It also discusses the potential shared molecular mechanisms that may lead to additional hazardous effects. The review points out the gaps in knowledge in this area and emphasizes the need for further research.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Substance Abuse

Recent Advances in the Potential of Positive Allosteric Modulators of the GABAB Receptor to Treat Alcohol Use Disorder

Eric Augier

Summary: The effects of alcohol on GABA transmission are crucial for AUD, where GABA(B) receptor agonists like baclofen have shown promise in preclinical models and some clinical studies for attenuating addiction-related behaviors. However, larger clinical trials have not confirmed its efficacy and side effects such as sedation are a concern. Positive allosteric modulators of the GABA(B) receptor offer a potentially better alternative, with preclinical studies consistently showing their effectiveness in treating addiction behaviors.

ALCOHOL AND ALCOHOLISM (2021)

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Review Nutrition & Dietetics

Alcohol's Impact on the Cardiovascular System

Michael Roerecke

Summary: Alcohol consumption has complex relationships with cardiovascular diseases, with conflicting associations depending on exposure measurement and outcomes. Methodological shortcomings and the need for large-scale longitudinal studies with detailed exposure and outcome measurements are highlighted. The less alcohol consumed, the better for individuals' cardiovascular health.

NUTRIENTS (2021)

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Review Nutrition & Dietetics

Alcohol and the Brain

David Nutt et al.

Summary: Alcohol affects the brain in various harmful ways, including damage during intoxication, withdrawal effects, and peripheral factors like poor diet and vitamin deficiencies. Prenatal alcohol exposure can also have lasting impacts on brain development.

NUTRIENTS (2021)

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Article Microbiology

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance

Nize Otaru et al.

Summary: Research investigated GABA production of Bacteroides and its protective role in acid stress, revealing the widespread presence of the GAD system in Bacteroides and its potential as the only amino acid-dependent acid tolerance system in the genus.

FRONTIERS IN MICROBIOLOGY (2021)

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Article Pharmacology & Pharmacy

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

Stephen P. H. Alexander et al.

Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.

BRITISH JOURNAL OF PHARMACOLOGY (2021)

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Article Biochemistry & Molecular Biology

Sesquiterpenes and sesquiterpenoids harbor modulatory allosteric potential and affect inhibitory GABAA receptor function in vitro

Dieter Janzen et al.

Summary: This study analyzed the modulatory potential of 11 SQTs at GABA(A) receptors to characterize their potential neurotropic activity. The research found differences in receptor modulation by SQTs in HEK293 cells and neurons, with the presence of gamma(2) and delta subunits being important for SQT modulation. Additionally, the study provided insight into how nutritional digestion can affect the neurotropic potential of natural compounds.

JOURNAL OF NEUROCHEMISTRY (2021)

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Review Nutrition & Dietetics

Alcohol's Impact on the Gut and Liver

Keith Pohl et al.

Summary: Alcohol is closely linked to the digestive system, affecting gut microbiome and liver function and structure. Excessive alcohol use can result in important micronutrient deficiencies and progression of liver disease, even leading to liver cancer and high mortality rates among chronic liver disease patients.

NUTRIENTS (2021)

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Review Nutrition & Dietetics

Alcohol and Cancer: Epidemiology and Biological Mechanisms

Harriet Rumgay et al.

Summary: Alcohol consumption contributes to approximately 4% of cancers worldwide, increasing the risk of various cancer types through mechanisms such as DNA damage, inflammation, and oxidative stress. Comprehensive alcohol control and cancer prevention strategies are needed to reduce the burden of alcohol-related cancers.

NUTRIENTS (2021)

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Article Psychiatry

Effect of Zuranolone vs Placebo in Postpartum Depression A Randomized Clinical Trial

Kristina M. Deligiannidis et al.

Summary: Zuranolone demonstrated significant improvements in core symptoms of depression in women with postpartum depression (PPD) and was generally well tolerated, supporting further development of zuranolone as a treatment for PPD.

JAMA PSYCHIATRY (2021)

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Review Biochemistry & Molecular Biology

Potential Roles for Gamma-Aminobutyric Acid Signaling in Bacterial Communities

Sarah J. Quillin et al.

Summary: The gut microbiome influences human neurology and behavior, with GABA signaling being a crucial component of the gut-brain axis. Research has also found that GABA mediates interkingdom signaling, involving interactions across multiple biological kingdoms.

BIOELECTRICITY (2021)

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Review Biochemistry & Molecular Biology

The versatile GABA in plants

Li Li et al.

Summary: Gamma-aminobutyric acid (GABA) plays multiple roles in plants, acting as a signal in gene transformation and development, as well as regulating plant responses to environmental stresses and attacks from pathogens and insects.

PLANT SIGNALING & BEHAVIOR (2021)

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Editorial Material Substance Abuse

France Grants an Approval to Baclofen for Alcohol Dependence

Benjamin Rolland et al.

ALCOHOL AND ALCOHOLISM (2020)

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Review Substance Abuse

A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies

A. Leslie Morrow et al.

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH (2020)

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Article Chemistry, Medicinal

Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABAAR) Modulators Acting at the Benzodiazepine Binding Site: An Update

Samuele Maramai et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Article Neurosciences

Realising the therapeutic potential of neuroactive steroid modulators of the GABAA receptor

Delia Belelli et al.

NEUROBIOLOGY OF STRESS (2020)

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Article Multidisciplinary Sciences

Shared structural mechanisms of general anaesthetics and benzodiazepines

Jeong Joo Kim et al.

NATURE (2020)

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Article Neurosciences

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

Alison L. Althaus et al.

NEUROPHARMACOLOGY (2020)

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Editorial Material Psychiatry

Why Less Is Always More in the Treatment of Alcohol Use Disorders

David J. Nutt et al.

JAMA PSYCHIATRY (2019)

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Article Clinical Neurology

The Australian drug harms ranking study

Yvonne Bonomo et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2019)

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Review Physiology

THE MICROBIOTA-GUT-BRAIN AXIS

John F. Cryan et al.

PHYSIOLOGICAL REVIEWS (2019)

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Article Multidisciplinary Sciences

GABAA receptor signalling mechanisms revealed by structural pharmacology

Simonas Masiulis et al.

NATURE (2019)

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Article Microbiology

GABA-modulating bacteria of the human gut microbiota

Philip Strandwitz et al.

NATURE MICROBIOLOGY (2019)

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Review Biochemistry & Molecular Biology

Structure-Dependent Activity of Natural GABA(A) Receptor Modulators

Serhat Sezai Cicek

MOLECULES (2018)

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Article Multidisciplinary Sciences

Structure of a human synaptic GABAA receptor

Shaotong Zhu et al.

NATURE (2018)

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Article Multidisciplinary Sciences

Structural basis of neurosteroid anesthetic action on GABAA receptors

Qiang Chen et al.

NATURE COMMUNICATIONS (2018)

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Article Psychiatry

Using Baclofen to Explore GABA-B Receptor Function in Alcohol Dependence: Insights From Pharmacokinetic and Pharmacodynamic Measures

Claire F. Durant et al.

FRONTIERS IN PSYCHIATRY (2018)

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Article Biochemistry & Molecular Biology

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites

Duncan Laverty et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

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Article Biochemistry & Molecular Biology

Structural basis for GABAA receptor potentiation by neurosteroids

Paul S. Miller et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

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Review Neurosciences

Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits

Karina P. Abrahao et al.

NEURON (2017)

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Review Neurosciences

The role of neuroimmune signaling in alcoholism

Fulton T. Crews et al.

NEUROPHARMACOLOGY (2017)

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Article Psychiatry

Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women

Kirsten Tillisch et al.

PSYCHOSOMATIC MEDICINE (2017)

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Article Biochemistry & Molecular Biology

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites

Duncan Laverty et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

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Article Biochemistry & Molecular Biology

Structural basis for GABAA receptor potentiation by neurosteroids

Paul S. Miller et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

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Review Pharmacology & Pharmacy

Borneol, a novel agent that improves central nervous system drug delivery by enhancing blood-brain barrier permeability

Qun-Lin Zhang et al.

DRUG DELIVERY (2017)

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Review Neurosciences

Potentiation of Gamma Aminobutyric Acid Receptors (GABAAR) by Ethanol How Are Inhibitory Receptors Affected?

Benjamin Forstera et al.

FRONTIERS IN CELLULAR NEUROSCIENCE (2016)

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Article Clinical Neurology

European rating of drug harms

Jan van Amsterdam et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2015)

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Review Psychology, Multidisciplinary

Neurotransmitters as food supplements: the effects of GABA on brain and behavior

Evert Boonstra et al.

FRONTIERS IN PSYCHOLOGY (2015)

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Review Neurosciences

Addiction as a stress surfeit disorder

George F. Koob et al.

NEUROPHARMACOLOGY (2014)

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Article Multidisciplinary Sciences

Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation

Ludovic Sauguet et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

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Article Behavioral Sciences

Ovarian hormones and the heterogeneous receptor mechanisms mediating the discriminative stimulus effects of ethanol in female rats

Christa M. Helms et al.

BEHAVIOURAL PHARMACOLOGY (2013)

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Article Biotechnology & Applied Microbiology

γ-Aminobutyric acid production by culturable bacteria from the human intestine

E. Barrett et al.

JOURNAL OF APPLIED MICROBIOLOGY (2012)

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Article Clinical Neurology

Substitution therapy for alcoholism: time for a reappraisal?

Jonathan Chick et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2012)

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Article Chemistry, Medicinal

GABAA Receptor Subtype-Selective Modulators. I. α2/α3-Selective Agonists as Non-Sedating Anxiolytics

John R. Atack

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2011)

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Article Chemistry, Medicinal

Bioassay-guided Fractionation of Lemon Balm (Melissa officinalis L.) using an In Vitro Measure of GABA Transaminase Activity

Rosalie Awad et al.

PHYTOTHERAPY RESEARCH (2009)

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Review Anatomy & Morphology

Functional role of local GABAergic influences on the HPA axis

William E. Cullinan et al.

BRAIN STRUCTURE & FUNCTION (2008)

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Article Plant Sciences

Anxiolytic Activity of a Phytochemically Characterized Passiflora incarnata Extract is Mediated via the GABAergic System

Oliver Grundmann et al.

PLANTA MEDICA (2008)

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Article Multidisciplinary Sciences

Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites

Alastair M. Hosie et al.

NATURE (2006)

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Review Neurosciences

A new look at the 5α-reductase inhibitor finasteride

Deborah A. Finn et al.

CNS DRUG REVIEWS (2006)

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Article Biochemistry & Molecular Biology

5α-reductase activity in Lycopersicon esculentum:: Cloning and functional characterization of LeDET2 and evidence of the presence of two isoenzymes

F Rosati et al.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY (2005)

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Review Neurosciences

Neurosteroids:: Endogenous regulators of the GABAA receptor

D Belelli et al.

NATURE REVIEWS NEUROSCIENCE (2005)

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Article Neurosciences

Evaluation of GABAergic neuroactive steroid 3α-hydroxy-5α-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats

K Hirani et al.

PSYCHOPHARMACOLOGY (2005)

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Article Neurosciences

Alcohol intoxication increases allopregnanolone levels in male adolescent humans

JM Torres et al.

PSYCHOPHARMACOLOGY (2004)

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Article Neurosciences

The reinforcing properties of alcohol are mediated by GABAA1 receptors in the ventral pallidum

HL June et al.

NEUROPSYCHOPHARMACOLOGY (2003)

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Article Neurosciences

Neuroactive steroid 3α-hydroxy-5α-pregnan-20-one modulates ethanol-induced loss of righting reflex in rats

RT Khisti et al.

BRAIN RESEARCH (2003)

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Article Neurosciences

Alcohol intoxication increases allopregnanolone levels in female adolescent humans

JM Torres et al.

NEUROPSYCHOPHARMACOLOGY (2003)

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Article Neurosciences

Lorazepam substitutes for the alcohol stimulus in social drinkers

A Jackson et al.

PSYCHOPHARMACOLOGY (2003)

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Article Endocrinology & Metabolism

New evidence of similarity between human and plant steroid metabolism: 5 alpha-reductase activity in Solanum malacoxylon

F Rosati et al.

ENDOCRINOLOGY (2003)

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Article Neurosciences

Behavioral action of ethanol in Porsolt's forced swim test: modulation by 3alpha-hydroxy-5alpha-pregnan-20-one

K Hirani et al.

NEUROPHARMACOLOGY (2002)

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Article Neurosciences

GABAA receptors containing α5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors:: An extended ethanol reward circuitry

HL June et al.

JOURNAL OF NEUROSCIENCE (2001)

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Functional Alternatives to Alcohol

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