Alcohol use disorder needs more effective treatments because relapse rates remain high. Psychedelics, such as ayahuasca, have been used to treat substance use disorders. Our study aimed to evaluate the effects of ayahuasca on ethanol-induced behavioral sensitization (EIBS). Swiss mice received 2.2 g/kg ethanol or saline IP injections every other day across nine days (D1, D3, D5, D7, and D9),...
Rationale: Previous studies with the serotonergic hallucinogens LSD and psilocybin showed that these drugs induced changes in personality traits, such as increases in Openness. However, results are inconsistent, and the effects of ayahuasca on personality were never investigated in a controlled trial. Objectives: To assess the effects of ayahuasca on personality in two randomized,...
In modern society, depression is one of the most common mental illness; however, its pathophysiology is not yet fully understood. A great body of evidence suggests that depression causes changes in neuroplasticity in specific regions of the brain which are correlated to symptom severity, negative emotional rumination as well as fear learning. Depression is correlated with atrophy of neurons in...
Prepulse inhibition (PPI) of startle is a sensorimotor gating phenomenon perturbed in a variety of neuropsychiatric conditions. Psychedelics disrupt PPI in rats and humans, but their effects and involvement of the serotonin 5-HT2A receptor (5-HT2AR) in mice remain unexplored. We tested the effect of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.5 mg/kg, i.p.) on startle...
The newfound antidepressant efficacy of ketamine has provided opportunities for the development of new-generation, rapid-acting, glutamate-based antidepressants. We previously identified that methoxetamine (MXE), a ketamine analog, and an N-Methyl-d-aspartate (NMDA) receptor antagonist, produced rapid and sustained antidepressant effects in mice. MXE (R, S (±)-MXE) is a racemic mixture...
Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored. Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R...
Background: Psilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans. Aim: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy...
While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test...
PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of ketamine as a treatment for treatment-resistant depression (TRD). It covers the epidemiology, risk factors, pathophysiology, and current treatment modalities regarding Major Depressive Disorder (MDD) and TRD. It provides background on the mechanism of action of ketamine, its history, current approved and...
Introduction: Microdosing refers to the repetitive administration of tiny doses of psychedelics (LSD, Psilocybin) over an extended period of time. This practice has been linked to alleged cognitive benefits, such as improved mood and creativity, potentiated by targeting serotonergic 5-HT2A receptors and facilitating cognitive flexibility. Nonetheless, in the absence of robust, quantitative and...