What’s Legal, Where — Psychedelic Law in 2026

Stimulant drugs like cocaine and methamphetamine acutely enhance the release of monoamine neurotransmitters, particularly dopamine, to induce euphoria, motivation, hyperlocomotion, and strong sleep suppression. Chronic stimulant use can lead to the development of stimulant use disorder (SUD), which is characterized by risky, excessive, or uncontrolled drug intake and an inability to cease use. At time of writing, there is no FDA-approved pharmacological treatment for SUD. Though symptoms and comorbidities of SUD vary, studies on abstinent stimulant-users repeatedly identify sleep disorder as a symptom that persists long into abstinence and drives relapse to stimulant use. This review discusses the use of the vinegar fly Drosophila melanogaster to identify the neural and genetic pathways mediating this sleep disorder. The fly has a long history of use in neurogenetics research, boasting efficient and low-cost husbandry, an extremely well-studied genome, widely available tools for manipulating neurons and genes with high spatiotemporal specificity, and a connectome cataloguing each neuron and synapse in the fly brain. Additionally, the fly rest state is a face-valid model of sleep in mammals, as it shares key features and is regulated by conserved neurotransmitter systems; flies also respond similarly to stimulant drugs, again mediated by common monoamine signals. As such, flies represent an excellent and under-utilized invertebrate model for studying sleep deficits in stimulant abstinence. This review describes methods available for studying sleep and stimulant use in Drosophila , highlighting key findings in the existing literature relevant to this phenotype while indicating where the literature is lacking. Identification of the genetic and neural pathways mediating stimulant-induced sleep disorder in flies will shed light on the critical role of dopamine systems in sleep regulation, facilitating the development of more efficacious treatments for SUD.

Silent synapses represent a unique class of synaptic connections that are non-functional at rest but possess the potential to become functional, serving as a critical reservoir for neural plasticity. Their activation mechanisms not only challenge traditional models of synaptic maturation but also provide novel insights into brain function regulation and disease pathology. This article provides a systematic review of the regulatory mechanisms underlying silent synapse activation, encompassing pre-synaptic calcium signaling-mediated vesicle cycling and active zone (AZ) optimization, post-synaptic α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) membrane insertion and post-synaptic density protein 95 (PSD-95) anchoring, Mg 2+ blockade release by N-methyl-D-aspartate receptor (NMDAR), as well as synergistic integration of upstream signaling pathways. Additionally, it explores the roles of astrocytes, epigenetic modifications, ubiquitin-proteasome systems, and autophagy-lysosomal systems in multi-level regulatory processes. Notably, abnormal regulation of silent synapses exhibits two contrasting pathological patterns in diseases: “desilencing impairment” (e.g., Alzheimer’s disease, depression) and “abnormally excessive desilencing” (e.g., drug addiction, chronic pain), which establishes a theoretical framework for targeted interventions. The study further evaluates the applicability and limitations of emerging technologies—including high-resolution imaging, single-cell omics, optogenetics, and AI-driven brain-inspired computing—in silent synapse research, while systematically summarizing clinical advancements, current challenges, and future directions, aiming to inform both fundamental neuroscience studies and therapeutic interventions.

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition arising from exposure to severe trauma, characterized by intrusive memories, avoidance, negative alterations in cognition and mood, and hyperarousal.Despite advances in understanding its neurobiology, effective pharmacotherapies remain limited.Dysregulation of the hypothalamic-pituitary-adrenal axis is a hallmark of PTSD, though findings on systemic cortisol levels remain inconsistentsuggesting that local, tissue-specific glucocorticoid metabolism may play a particularly relevant role beyond circulating hormone concentrations.The enzymes 11-hydroxysteroid dehydrogenases (11-HSDs), particularly 11-HSD1, regulate intracellular glucocorticoid availability in the brain and periphery and may contribute to region-specific modulation of stress-related neurocircuitry.This focused mini-review synthesizes available preclinical and clinical evidence on the involvement of 11-HSDs in PTSD.Preclinical studies consistently implicate 11-HSD1 in fear memory processing and stress adaptation, while emerging human data suggest a more complex and context-dependent role.Notably, recent neuroimaging findings indicate that higher brain 11-HSD1 availability may be associated with lower severity of specific symptom domains, raising the possibility of adaptive or compensatory mechanisms in chronic PTSD.Although the current clinical evidence base remains limited, these observations support the view that local glucocorticoid metabolism represents a biologically meaningful dimension of PTSD pathophysiology.Further integrative studies combining neuroimaging, molecular, and clinical approaches are needed to better define the contribution of 11-HSD enzymes to PTSD pathophysiology and to evaluate their potential as candidate molecular pathways for future research.