Major depressive disorder (MDD) remains a global health burden, with over 60% of patients failing to respond adequately to current treatments. Treatment-resistant depression (TRD), a form of MDD, highlights the urgent need for mechanistically novel antidepressants. Psychoplastogens—a class of fast-acting compounds that promote neuroplasticity—are emerging as promising alternatives to...
Importance: Psychedelic drugs possess acute psychoactive effects that can compromise blinding integrity in randomized clinical trials (RCTs). Functional unblinding, when participants or raters correctly identify treatment allocation based on subjective effects, may bias outcomes through expectancy effects, challenging the validity of efficacy estimates and regulatory acceptance. Objective: To...
Altered states of consciousness (ASC) represent a universal human capacity for accessing and transforming the subconscious mind, employed across cultures and millennia through diverse contemplative, somatic, pharmacological, ritual, and technological modalities. This comprehensive review synthesizes evidence from over 25 distinct disciplines spanning five clusters: (A) contemplative and...
Many terms have been invented to describe different types of hallucinogenic drugs, sometimes based on an analogy with the symptoms of schizophrenia, such as “psychotomimetic” and “phrenotropic.” “Psychedelics” refers to drugs that act as agonists at serotonin 5-HT2A receptors in the brain; they include psilocybin, 5-methoxydimethyltryptamine, and N,N-dimethyltryptamine (tryptamine derivatives),...
INTRODUCTION: After decades of regulatory marginalization, psychedelic compounds have reemerged as promising therapeutic tools in psychiatry, driven by unmet clinical needs in treatment-resistant mental disorders and by growing evidence of rapid and sustained effects on mood, cognition, and behavior. AREAS COVERED: This narrative review critically examined the current clinical and regulatory...
The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or "psychoplastogens," for psychiatric disorders. However, the widespread application of classical psychedelics-such as psilocybin and LSD-and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of...
Background: Opioid receptors are a commonly used target for treatment of pain conditions. Most opioids used in therapy are linked to adverse effects such as tolerance, dependence, and respiratory depression. Indole alkaloids acting on opioid receptors may provide a novel molecular mechanism to confer analgesic effects. Results: Indole alkaloids such as ibogaine and mitragynine act on μ-opioid...
Indigenous Peoples have cultivated and protected natural psychoactive medicines through ceremony, kinship, and spiritual responsibility across generations, yet their long-standing contributions have often been marginalized through extractive research, commercialization, and policy exclusion. It is Indigenous communities that have stewarded and gained expertise working with psychoactive...
Psychedelics are a diverse class of psychoactive compounds that profoundly alter perception, cognition, and emotional states. Recently, classical serotonergic agents, such as psilocybin and lysergic acid diethylamide (LSD), along with atypical agents such as methylenedioxymethamphetamine (MDMA, ecstasy) and ibogaine, have attracted renewed attention due to their rapid and sustained clinical...
The clinical use of psychedelic substances and Psychedelic-Assisted Therapy (PAT) is an area of growing interest that also raises significant social concerns and controversy. Despite existing legal restrictions, empirical research on substances such as psilocybin, mescaline, MDMA, LSD, DMT, and ibogaine has been developing, particularly in the treatment of conditions such as treatment-resistant...