BACKGROUND: Major depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of s...
The proposed open-label, controlled study at the Johns Hopkins Center for Psychedelic and Consciousness Research (CPCR) will test the following primary hypotheses in adult patients with chronic PTSD who are currently taking a serotonin reuptake inhibitor: psilocybin therapy will be feasible and safe for participants, significantly remediate PTSD symptoms, an...
BACKGROUND: Current treatments for obsessive-compulsive disorder (OCD), including serotonin reuptake inhibitors and cognitive-behavioral therapy, are often insufficient. Psilocybin, a 5HT2a agonist psychedelic, has shown promise for treating OCD, but rigorous evidence is still needed. AIMS: This randomized clinical trial evaluated safety, tolerability, and b...
In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadians-about 6.3 million individuals-were prescribed at least one antidepressant, with fluoxetine remaining one of the most commonly used options (IQVIA, 2023). Benzodiazepine use, including drugs like alprazolam, rang...
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmissi...
The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment-resistant depression and has been reported to reduce symptoms of depression and anxiety. Psilocybin's active metabolite, psilocin, possesses a binding affinity for serotonin receptors as well as for the serotonin transporter (5-HTT). We recently reported that in contr...
Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and...
A meta-analysis comprising 17 randomized trials has found that rates of control group improvement in depression studies were lower in psilocybin trials than in studies of esketamine or a selective serotonin reuptake inhibitor (SSRI). The results suggest that psilocybin's overall efficacy in the treatment of depression might be overestimated.
Use of selective serotonin reuptake inhibitor (SSRI) antidepressants has been associated with reduced intensity of emotional experience. Conversely, some research has shown that use of psilocybin in patients with depression leads to an increase in responsiveness to emotional face stimuli, suggesting that the psychedelic generates a transient elevation in moo...
ImportancePsilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment ou...
Ketamine has transformed depression treatment by providing therapeutic relief within a single day, unlike monoaminergic antidepressants that require weeks to take effect. Here, we conducted whole-brain screening in mice to compare drug-evoked c-fos expression-acting as a marker of brain activity leading to protein synthesis-dependent forms of plasticity-foll...
This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in 'magic mushrooms', with the selective serotonin reuptake inhibitor (SSRI) escitalopram for major depressive disorder (MDD).
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT2A R). However, some aspects of 5-HT2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT2A R agonists. We developed an ex vivo...
Background: Psilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination. Methods: This is a 6-month follow-up study of a phase 2, double-blind...
A man with AUD achieves sobriety on treatment with an SSRI and naltrexone, but then stops taking the SSRI to participate in a psilocybin “ceremony.” What factors contributed to his subsequent relapse to alcohol use?
Psilocybin could be as effective as escitalopram - a selective serotonin reuptake inhibitor (SSRI) - in treating depressive symptoms, a study has found. A systematic review and network meta-analysis, published in the BMJ on 21 August 2024, looked at 19 placebo-controlled studies of oral monotherapy with either psychedelics (psilocybin, lysergic acid diethyla...
Ongoing antidepressant treatment is believed to alter the psychedelic effect of psilocybin, so most psilocybin trials have required withdrawal from antidepressants before enrollment. There has been recent evidence, however, that administration of a selective serotonin reuptake inhibitor (SSRI) does not significantly alter the acute subjective effects of psil...
Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, o...
Background: Psilocybin is being studied for depression, but little is known about how it interacts with common antidepressants. Limited data suggest that psilocybin’s effects may be diminished by serotonergic antidepressants acutely and even after a medication washout period. Aims: To learn the extent to which antidepressants may diminish the effects of psil...
