IntroductionMajor depressive disorder remains a prevalent world-wide health problem. Currently available antidepressant medications take weeks of dosing, do not produce antidepressant response in all patients, and have undesirable ancillary effects.Areas coveredThe present opinion piece focuses on the major inroads to the creation of new antidepressants. The...
Purpose of the reviewWe aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action.Recent findingsPsilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effect...
Clinical studies provide evidence that ketamine and psilocybin could be used as fast-acting antidepressants, though their mechanisms and toxicity are still not fully understood. To address this issue, we have examined the effect of a single administration of ketamine and psilocybin on the extracellular levels of neurotransmitters in the rat frontal cortex an...
Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has be...
IntroductionA limited number of preliminary open-label (n = 3) and placebo-controlled clinical trials (n = 5) have suggested psilocybin and LSD as potential rapid antidepressants. In this context, there is a growing need to verify and document their safety and tolerability as therapeutic agents, discuss the challenges associated with their administration, an...
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Function...
Promising outcomes of Psilocybin-Assisted Therapy (PAT) for depression have generated concerted efforts to replicate, extend, and refine protocols to maximize efficacy. Psychotherapy research reveals that clients benefit most when important components of treatment align with their personal preferences. One open question related to PAT concerns the importance...
RationaleKetamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. It is currently debatable whether these are essential for their therapeutic actions. As depressed patients report that the "time is dragging," we hypothesized that ketamine and psilocybin-like compounds may pr...
BackgroundPreliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.AimsThis study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who rece...
BackgroundPsychedelics, such as psilocybin represent one of the most promising current therapeutic approaches in psychiatry.ObjectivePsychedelics seem to have not only potent antidepressant effects. Do they also work particularly quickly, i.e. within one day?Material and methodsThe available literature on clinical studies of psychedelics in depressive syndro...
Drugs that target the human serotonin 2A receptor (5-HT2AR) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT2AR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous ne...
IntroductionThere is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis.MethodsWe systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in...
The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double-blind, placebo-controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretrea...
Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occur...
Rapid-acting antidepressants disprove the dogma that antidepressants need several weeks to become clinically effective. Ketamine, the prototype of a rapid-acting antidepressant, is an N-methyl-D-aspartate (NMDA) receptor blocking agent. A single i.v. application of ketamine induces rapid changes in glutamatergic neurotransmitter systems, leading to preferent...
Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of...
The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has inspired tremendous interest in the underlying neurobiological mechanisms. We review preclinical and clinical evidence supporting neuroplasticity as a convergent downstream mechanism of action for these novel fast-acting antidepressants. Through their primary glutamat...
BackgroundPrevious studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients).MethodsPublished studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines,...
Approximately 30% of people treated for a major depressive episode will not achieve remission after two or more treatment trials of first-line antidepressants and are considered to have treatment-resistant depression (TRD). Because the odds of remission decrease with every subsequent medication trial, it is important for clinicians to understand the characte...
The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical anti...
