The human body possesses enzymatic machinery to both synthesize and rapidly degrade N,N-dimethyltryptamine (DMT). This coexistence raises a question: does DMT serve an endogenous function, or is it a metabolic byproduct with no physiological role? DMT is structurally almost identical to serotonin and binds to the same serotonin receptors. Serotonin is universally accepted as a neurotransmitter...
Major depressive disorder (MDD) is a leading cause of disability worldwide, and currently available antidepressants remain limited by delayed onset of action, incomplete response, and adverse effects. Ketamine is a rapid-acting antidepressant, whereas xanomeline, an M1/M4 muscarinic receptor agonist, may represent a mechanistically distinct non-monoaminergic strategy. However, the molecular...
The paper is Article 1 of the Pali-Psycho series. It focuses on the empirical and clinical comparison axis: mindfulness, breath meditation, compassion cultivation, absorption states, affect labeling, default-mode-network findings, and selected positive-psychology parallels are treated as modern comparison points for Pali-canonical practice architectures. The central result is deliberately...
It is unclear how serotonin 2A receptors (5-HT 2A Rs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further demonstrated that 5-HT 2A R...
Microdosing and related low-dose psychoactive practices have become increasingly visible in discussions of mental health, cognition, creativity, emotional regulation, pain, sleep, spirituality, and psychological flexibility. However, the term microdosing is often used as if it referred to a single pharmacological phenomenon. More precisely, it describes a low-dose application pattern used...
Four clinical literatures — psychedelic-assisted therapy, accelerated transcranial magnetic stimulation, closed-loop deep brain stimulation, and reconsolidation-based trauma therapy — produce durable change from brief, often single, interventions in conditions the current standard of care has not solved. The convergence is not procedural. Each modality transiently induces a high-plasticity...
Background: Depression is a multifactorial disorder involving neurotransmitter dysregulation, HPA axis hyperactivity, neuroinflammation, and impaired neuroplasticity. While combination psychotherapy and pharmacotherapy remains first-line, ~30% of patients develop TRD. In the last few years ketamine has emerged as a rapid-acting therapeutic option for treatment-resistant cases. Aim: To review...
Introduction: Contemporary psychiatry is grappling with a profound stagnation in innovation. It is primarily relying on the chronic management of symptoms through traditional daily-dose pharmacotherapy. The emergence of psychedelics and ketamine marks a significant departure from this model. It is offering rapid-acting, interventional alternatives that target the underlying neurobiological...
Scientific ReportsJune 14, 2026Bar Eilat Yogev, Gal Levi, Noa Efroni et al.
Alcohol consumption before trauma is a prevalent but understudied risk factor for posttraumatic stress disorder (PTSD). This study investigated whether acute ethanol exposure prior to trauma modulates PTSD-like symptom development in rats, identified hippocampal mechanisms involved, and tested an early post-trauma intervention. Adult male Sprague-Dawley rats received ethanol (1.6 g/kg, 40% v/v,...
Cerca de 30% dos pacientes com transtorno depressivo maior não respondem a nenhum dos antidepressivos. Caracterizando a depressão resistente ao tratamento (DRT). Esta revisão narrativa teve como objetivo analisar criticamente as evidências sobre o uso da cetamina e da escetamina no tratamento da DRT, incluindo eficácia, mecanismos de ação, perfil de segurança e barreiras de acesso. Foram...