The conceptual framework for the therapeutic approach used in phase 3 trials of MDMA-assisted therapy for PTSD.

Results from multiple recent studies support further evaluation of 3,4-methylenedioxymethamphetamine (MDMA) in conjunction with psychotherapy (i.e., MDMA-Assisted Therapy) in the treatment of post-traumatic stress disorder (PTSD).

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD).

Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.

Design, Setting, And Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support.

A Systematic Approach to Standardizing Drinking Outcomes From Timeline Followback Data.

Objective: The timeline followback (TLFB) interview is the gold standard for the quantitative assessment of alcohol use. However, self-reported "drinks" can vary in alcohol content. If this variability is not accounted for, it can compromise the reliability and validity of TLFB data.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.

Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.

Design, Setting, And Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8.

Mapping consent practices for outpatient psychiatric use of ketamine.

Background: Given increasing community-based and off-label use of ketamine for psychiatric indications, we examined current informed consent processes from a convenience sample of outpatient ketamine clinics to identify areas of congruence with current evidence and opportunities for growth.

Methods: Using a rubric developed from existing practice guidelines, we conducted an exploratory analysis of informed consent documents (IC-Docs) from 23 American clinics offering ketamine as a psychiatric treatment. Domains assessed included clinical content, procedures, and syntax.

Neurotoxicity of the Parkinson Disease-Associated Pesticide Ziram Is Synuclein-Dependent in Zebrafish Embryos.

Background: Exposure to the commonly used dithiocarbamate (DTC) pesticides is associated with an increased risk of developing Parkinson disease (PD), although the mechanisms by which they exert their toxicity are not completely understood.

Objective: We studied the mechanisms of ziram's (a DTC fungicide) neurotoxicity in vivo.

Methods: Zebrafish (ZF) embryos were utilized to determine ziram's effects on behavior, neuronal toxicity, and the role of synuclein in its toxicity.

Axon degeneration and PGC-1α-mediated protection in a zebrafish model of α-synuclein toxicity.

α-synuclein (aSyn) expression is implicated in neurodegenerative processes, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In animal models of these diseases, axon pathology often precedes cell death, raising the question of whether aSyn has compartment-specific toxic effects that could require early and/or independent therapeutic intervention. The relevance of axonal pathology to degeneration can only be addressed through longitudinal, in vivo monitoring of different neuronal compartments.

WldS and PGC-1α regulate mitochondrial transport and oxidation state after axonal injury.

Mitochondria carry out many of the processes implicated in maintaining axon health or causing axon degeneration, including ATP and reactive oxygen species (ROS) generation, as well as calcium buffering and protease activation. Defects in mitochondrial function and transport are common in axon degeneration, but how changes in specific mitochondrial properties relate to degeneration is not well understood. Using cutaneous sensory neurons of living larval zebrafish as a model, we examined the role of mitochondria in axon degeneration by monitoring mitochondrial morphology, transport, and redox state before and after laser axotomy.

Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease.

Parkinson disease (PD) is a neurodegenerative disorder particularly characterized by the loss of dopaminergic neurons in the substantia nigra. Pesticide exposure has been associated with PD occurrence, and we previously reported that the fungicide benomyl interferes with several cellular processes potentially relevant to PD pathogenesis. Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD.

Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types.

Background: Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function.

Generation and behavioral characterization of beta-catenin forebrain-specific conditional knock-out mice.

The canonical Wnt pathway and beta-catenin have been implicated in the pathophysiology of mood disorders. We generated forebrain-specific CRE-mediated conditional beta-catenin knock-out mice to begin exploring the behavioral implications of decreased Wnt pathway signaling in the central nervous system. In situ hybridization revealed a progressive knock-out of beta-catenin that began between 2 and 4 weeks of age, and by 12 weeks resulted in considerably decreased beta-catenin expression in regions of the forebrain, including the frontal cortex, hippocampus, and striatum.

The behavioral actions of lithium in rodent models: leads to develop novel therapeutics.

For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms.

Beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors.

Lithium inhibits glycogen synthase kinase-3 (GSK-3) at therapeutic concentrations; however, it is unclear if this inhibition and its downstream effects on specific signaling pathways are relevant to the treatment of bipolar disorder and depression. One of the targets of GSK-3 is the transcription factor beta-catenin. Normally active GSK-3 phosphorylates beta-catenin, leading to its degradation.