The genus Psilocybe has been characterized by central nervous system (CNS) effects and as a source of therapeutic drugs such as the alkaloids psilocybin and psilocin—secondary metabolites that produce rapid anxiolytic and antidepressant effects in preclinical and clinical studies. Furthermore, these mushrooms also contain bioactive primary metabolites, for example, the interesting case of...
MoleculesSeptember 13, 2026Andrzej Günther, Barbara Bednarczyk-Cwynar, Michał Tomczyk
Amanita muscaria contains two structurally related neuroactive isoxazole metabolites, ibotenic acid (IA) and muscimol (MUS), which differ markedly in pharmacological activity. IA acts as an agonist at NMDA and metabotropic glutamate receptors, whereas MUS is a potent GABAergic agonist. This review critically evaluates their chemistry and biosynthesis, biological variability, post-harvest...
MoleculesSeptember 7, 2026Katarzyna Gawłowska, Katarzyna Kaja Nowakowska, Julia Wiktoria Makówka et al.
Standard pharmacotherapy for mental disorders, including depression and anxiety, is supported by extensive clinical validation and international treatment guidelines. However, it is frequently associated with limitations such as adverse side effects, low patient adherence, and the risk of relapse. Conventional approaches rely primarily on antidepressants, anxiolytics, mood stabilizers,...
Nitrous oxide (N2O), commonly known as laughing gas, is widely used for its anesthetic and analgesic properties in medical settings. However, its recreational abuse has escalated, leading to severe neurological complications including cognitive impairment, yet the underlying mechanisms remain poorly understood. In this study, male C57BL/6 J mice were exposed to either normal air inhalation or...
Chronic pain is a complex disorder of central nervous system maladaptation, perpetuated not only by ascending nociceptive transmission but also by entrenched prior expectations. Conventional analgesics typically fail to reverse this cognitive rigidity and the ensuing pathological cycles. Classic psychedelics, however, are emerging as a promising avenue to help address this therapeutic impasse....
Cumulative reports of psychiatric and neurological outcomes due to synthetic cathinones continue to raise public concern. However, the understanding of the neurotoxic mechanism of action is still poorly understood, particularly for the under-explored αPHP, one of the main MDPV derivatives. In particular, the effects of this synthetic drug on neural stem/progenitor cell cultures are still...
MoleculesJuly 1, 2026S. Filipiuc, Carmen Solcan, B. Tamba et al.
Background and Objectives: Synthetic cannabinoids (SCs) are new psychoactive substances associated with acute intoxications. Experimental data obtained under controlled and comparable conditions remain limited for this category of compounds. This descriptive, hypothesis-generating screening study aimed to characterize the acute toxicity profile of three SCs, JWH-007, AM-694, and MAB-CHMINACA....
Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ionization mass spectrometry imaging...
New psychoactive substances (NPS) are a heterogeneous group of recreational drugs that mimic the actions and psychoactive effects of existing pharmaceutical products or recreational drugs. As NPS can be highly potent, even exceeding their template compound's potency, there are frequent reports of non-fatal and fatal intoxications. One principal target for hallucinogenic and psychedelic drugs,...
Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of...
MoleculesFebruary 4, 2026Monica Patrícia Esperança, N. N. S. Gomes, Maria Graça Campos1 citation
Substance Use Disorder (SUD) constitutes a major and persistent global public health burden, accounting for approximately 600,000 deaths annually, largely driven by opioid use. Despite substantial advances in addiction neuroscience, currently approved therapeutic strategies remain limited in efficacy, as they predominantly target isolated neurobiological processes and fail to concurrently...
MoleculesJanuary 9, 2026Anna Trynda, Katarzyna Karwowska, Weronika Karpowicz et al.
Synthetic cathinones are cathinone analogues that humans have artificially created. The first compounds appeared on the European market in 2005. They belong to a class of drugs called stimulants, classified as new psychoactive substances. Synthetic cathinones are very popular; people use these drugs because they are cheaper "substitutes" for other stimulants. They produce psychostimulant and...
MoleculesJanuary 8, 2026Anna W Sobańska, Andrzej M Sobański, Elżbieta Brzezińska1 citation
A total of 250 known and novel compounds-ketamine and serotonergic psychedelics or their analogues-designed to target depression, addictions and/or other mental or neurological disorders and developed as "recreational" (illegal) drugs from three chemical families, ergolines, tryptamines and phenylethylamines, were investigated in the context of their ability to cross the human placenta. Using a...
Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging...
MoleculesFebruary 18, 2025Veronica de Melo Sacramento, Vanessa de Andrade Royo, Pedro Henrique Fonseca Veloso et al.2 citations
Diplopterys pubipetala (Malpighiaceae) is a liana native to the Brazilian Cerrado biome, traditionally used in Ayahuasca preparations. Despite its cultural importance, research on its chemical composition and biological activities, which may have therapeutic potential, is limited. This study investigated the volatile and non-volatile secondary metabolites of D. pubipetala leaves, their...
Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated...
Depression is a chronic, severe, and often life-threatening neurological disorder. It not only causes depression in patients and affects daily life but, in severe cases, may lead to suicidal behavior and have adverse effects on families and society. In recent years, it has been found that sub-anesthetic doses of ketamine have a rapid antidepressant effect on patients with treatment-resistant...
MoleculesFebruary 22, 2024Hanbo Yao, Xiaodong Wang, Jiaxin Chi et al.9 citations
Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and...
Peyote (Lophophora williamsii) is a cactus that contains various biologically active alkaloids—such as pellotine, anhalonidine, hordenine and mescaline. Here, mescaline induces the psychoactive effects of peyote through the activation of the serotonin 5-HT2A receptor and the subsequent release of calcium (Ca2+) from the endoplasmic reticulum (ER). Moreover, an evaluation of the therapeutic...
MoleculesOctober 13, 2023Alexander Dushkov, Zuzana Vosáhlová, Alexander Tzintzarov et al.
The fungus Amanita muscaria is universally recognizable for its iconic appearance; it is also widely regarded as poisonous, inedible, and even deadly. In spite of that, there have been documented cases of use of A. muscaria-containing preparations against various diseases, including cancer, to no apparent ill effect. The search for compounds that can be used to treat cancer among various plants...
MoleculesSeptember 4, 2023Maite L Docampo-Palacios, Giovanni A. Ramirez, Tesfay T Tesfatsion et al.
Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of...
G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activated agonist-receptor G-protein complex...
MoleculesAugust 24, 2023Nevena Tomašević, Maja Vujović, E. Kostić et al.5 citations
Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HT2AR, the enclosed study summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure–activity relationship (3-D...
Molecular-level investigations of the Central Nervous System have been revolutionized by the development of computational methods, computing power, and capacity advances. These techniques have enabled researchers to analyze large amounts of data from various sources, including genomics, in vivo, and in vitro drug tests. In this review, we explore how computational methods and informatics have...
Alzheimer's disease (AD) is a brain disease with a peculiarity of multiformity and an insidious onset. Multiple-target drugs, especially Chinese traditional medicine, have achieved a measure of success in AD treatment. Evodia rutaecarpa (Juss.) Benth. (Wuzhuyu, WZY, i.e., E. rutaecarpa), a traditional Chinese herb, has been identified as an effective drug to cure migraines. To our surprise, our...