Psychedelic Research Papers

Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder
This reanalysis of a trial (n=59) investigates the mechanisms underlying the efficacy of Psilocybin Therapy (PAT) versus Escitalopram Treatment in patients with depression (MDD) over a 6-week trial period. Acute psychological experiences such as "mystical experience" and "ego dissolution" were found to mediate the effect of treatment condition on depressive response, suggesting a mechanistic role of these experiences in the treatment of depression via PAT.
International Journal of Mental Health and Addiction
March 2024
Cited by 0
The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder
This randomized, waiting list-controlled clinical trial (n=24) for depression (MDD) assessed the therapeutic alliance between participants and intervention facilitators in psilocybin-assisted therapy (PAT). Therapeutic alliance significantly increased from the final preparation session to one-week post-intervention, with a stronger alliance predicting depression scores at various post-intervention time points. Stronger alliances were correlated with peak ratings of mystical experiences and psychological insight, which in turn were correlated with depression scores.
PLOS ONE
March 2024
Cited by 0
Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression
This post hoc analysis of a recent clinical trial comparing psilocybin to escitalopram with psychological support for depression (MDD) found that discontinuing SSRIs/SNRIs prior to psilocybin treatment led to reduced treatment effects on depression severity measures. However, there were no observed effects on the acute psychedelic experience. The study suggests that discontinuation of SSRIs/SNRIs before psilocybin treatment might impact treatment response.
Journal of Psychopharmacology
March 2024
Cited by 0
Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression
This reanalysis of an RCT (n=55) compared escitalopram and psilocybin (COMP360) for treating depression (MDD). Patients had higher expectancy for psilocybin, but only expectancy for escitalopram predicted therapeutic outcomes. Additionally, pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, suggesting psychedelic therapy may be less vulnerable to expectancy biases, and highly suggestible individuals may be primed for response to psilocybin treatment.
Psychological Medicine
January 2024
Cited by 0
Predicting the Intensity of Psychedelic-Induced Mystical and Challenging Experience in a Healthy Population: An Exploratory Post-Hoc Analysis
In a Phase I RCT (n=89), this analysis aimed to predict the intensity of mystical and challenging experiences during psilocybin therapy for depression. It found a strong positive correlation between psilocybin dosage and experience intensity. Age was negatively linked to challenging experiences. Personality traits had minimal impact, except for a positive connection between neuroticism and high-dose difficult experiences. No significant links were found with affect.
Neuropsychiatric Disease And Treatment
October 2023
Cited by 0
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial
This Phase II trial (n=104) evaluated the effects of a single dose of psilocybin (25mg) vs niacin (100mg) placebo in adults with moderate or severe depression (MDD). Psilocybin treatment significantly reduced depression scores (MADRS & Sheehan Disability Scale) compared to niacin up to day 43. While there were no serious treatment-emergent adverse events, psilocybin was associated with a higher rate of overall and severe adverse events.
JAMA Psychiatry
August 2023
Cited by 0
Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms
This double-blind, placebo-controlled, within-subject study (n=19) involved individuals with major depressive disorder (MDD). It investigated the effects of a single dose of psilocybin on electroencephalographic (EEG) correlates of neuroplasticity and depression symptoms. The results showed that EEG theta power doubled in amplitude two weeks after psilocybin administration. This increase was correlated with improvements in depression symptoms, suggesting that psilocybin may produce sustained changes in brain neuroplasticity and have antidepressant effects. Note that the improvement in depression scores was not significant vs placebo.
Journal of Contextual Behavioral Science
June 2023
Cited by 0
Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression
This pre-print analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.
MedRvix
June 2023
Cited by 0
How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change
This re-analysis of the psilocybin (25mg) versus escitalopram (antidepressant, 6 weeks) RCT finds that in the psilocybin arm, experiential avoidance reductions led to improvements in mental health outcomes (e.g. depression severity). Note: the trial itself was insignificant on the primary measure of depression.
Journal of Affective Disorders
May 2023
Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life
This re-analysis of the COMPASS Phase IIb RCT with psilocybin (25/10/1mg; COMP360) finds significantly higher scores on patient-reported depression severity, anxiety, positive affect, functioning, quality of life, and cognitive function. Though the main finding of the study was less impressive than hoped, all patient-reported measures show that the high dose of psilocybin (25mg) led to better outcomes.
Journal of Affective Disorders
February 2023
Cited by 0
Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial
This double-blind placebo-controlled study (n=56) found that one psilocybin-assisted therapy (16mg/70kg, 2 prep + 3 integration meetings) session significantly reduced depressive symptoms (MADRS & BDI) in those suffering from a major depressive disorder (MDD, n=26). Fourteen days after the intervention, 54% of those in the psilocybin group met remission criteria (<10 on MADRS).
EClinicalMedicine
December 2022
Cited by 0
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
This double-blind active-placebo controlled trial (n=233) tested the effect of a single dose of psilocybin (25/10/1mg) with supportive therapy for treatment-resistant depression. The primary endpoint at three weeks finds a significant reduction in depressive symptoms (MADRS, 12-point drop from baseline of 32) that was significantly greater in the 25mg group vs the 1mg (placebo) group (6.6 points larger drop). The response (>50% drop in MADRS score) in the 25mg group dropped from 37% at 3 weeks to 20% at 12 weeks.
New England Journal of Medicine
November 2022
Cited by 4
Psilocybin Therapy for Treatment Resistant Depression: Prediction of Clinical Outcome by Natural Language Processing
This article of a language model (NLP, BART) finds that the audio from psychological support sessions (in the COMP360 trial for treatment-resistant depression, n=90 at 12 weeks) can predict clinical outcomes with high (85%) accuracy. The implications of this research signal that audio recordings can be used to predict who will respond to treatment and possibly aid in helping identify who would need more support.
Psyarxiv
August 2023
Cited by 0
A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression
This preprint (2022) reanalyses the data of a clinical trial in which the effects of psilocybin were compared to that of the SSRI escitalopram for major depressive disorder. Bayesian reanalysis found indeterminate evidence that psilocybin is superior that escitalopram using the QIDS SR-16 while strong evidence favoured psilocybin when using the BDI-1D and MADRS and extremely strong evidence when using the HAMD-17. The results support the idea that psilocybin outperformed escitalopram but was not clinically meaningful and, psilocybin is almost certainly non-inferior to escitalopram.
Psyarxiv
July 2022
Increased global integration in the brain after psilocybin therapy for depression
This fMRI study assessed the impact of psilocybin on brain function in two clinical trials of depression. In both trials, the antidepressant response to psilocybin was rapid and sustained, correlating with decreases in fMRI brain network modularity. Network cartography analyses indicated that serotonin (5-HT) 2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after a psilocybin treatment. Together, the findings from both studies point to global increases in brain network integration as an antidepressant mechanism in psilocybin therapy.
Nature Medicine
April 2022
Cited by 0
Methodological challenges in psychedelic drug trials: Efficacy and safety of psilocybin in treatment-resistant major depression (EPIsoDE) – Rationale and study design
This paper (2022) details the rationale and study design for an upcoming double-blind placebo-controlled trial (n=144) which will assess the safety and efficacy of using psilocybin in a cohort with treatment-resistant depression.
Neuroscience Applied
March 2022
Cited by 0
Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial
This paper (2021) lays out the protocol for a randomized, placebo-controlled trial exploring the safety and efficacy of using psilocybin-assisted therapy for the treatment of treatment-resistant major depressive disorder (MDD). Up to 60 participants will be selected and randomized to a single dosing session of 25mg psilocybin or placebo.
BMJ Open
Cited by 0
Decreased brain modularity after psilocybin therapy for depression
This preprint (2021) analyzed data from an open-label (n=16) and a randomized double-blind placebo-controlled study (n=43) of psilocybin (10 - 25mg) treatment for depression, in order to identify neural biomarkers underlying antidepressant efficacy. Psilocybin (but not escitalopram) decreased brain modularity across both trials, i.e. brain connectivity became less segregated, and this correlated with improvements in depressive symptomatology.
Research Square
May 2021
Cited by 0
The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action
This randomized, double-blind, placebo-controlled, within-subjects study (n=17) investigated the effects of psilocybin (18.2mg/70kg) on brain rhythms during sleep and found that it increased the transition period from wakefulness to REM sleep and reduced the duration of the REM period. These results are in line with the effects of other antidepressants and diametrically opposed to biomarkers of depression that include shortened wakefulness to REM transitions and increased REM duration and density.
Frontiers in Pharmacology
December 2020
Cited by 6
Trial of Psilocybin versus Escitalopram for Depression
This double-blind placebo-controlled study (n=59) compared psilocybin (2x25mg; 3 weeks apart) to escitalopram (SSRI) over a six-week period and found large improvements in depression scores for those suffering from depression (MDD) in both groups. On the main measure of depression, the QIDS-SR-16, there was no significant difference between both groups. The study did find significant differences, favoring psilocybin, on the HAM-D-17, MADRS, avoidance, flourishing, wellbeing, and suicidality.
New England Journal of Medicine
April 2021
Cited by 326
Psilocybin biases facial recognition, goal-directed behaviour, and mood state toward positive relative to negative emotions through different serotonergic subreceptors
In this double-blind, within-subjects, placebo-controlled study (n=17) it was investigated whether psilocybin does bias emotional processing away from negative information by activating 5-HT2A (Serotonin) receptors. It was indeed found that psilocybin enhanced mood and shifted emotional bias towards positive information. The 5-HT2A receptors played a crucial roll in the effects of psilocybin on emotional processing.
Biological Psychiatry
December 2012
Cited by 157
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer
This is the first (modern) double-blind placebo-controlled study (n=12) of psilocybin (14mg/70kg) for the treatment of (end-of-life) anxiety (and depression) related to cancer. Treatment led to a significant reduction in anxiety symptoms up to three months after treatment and improvements in depressive symptoms reached significance after six months.
Archives of General Psychiatry
September 2010
Cited by 1,185
Patient Experiences of Psilocybin-Assisted Psychotherapy: An Interpretative Phenomenological Analysis
This qualitative analysis of experiences may help form new hypotheses on why a psychedelic experience works. Found is that participants experienced strong emotions, partly conveyed by music.
Journal of Humanistic Psychology
April 2017
Cited by 238
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
This study (n=51) investigated the effects of a high dose of psilocybin (22 or 30mg/70kg) on depression and anxiety in patients with life-threatening cancer. It found significant improvements in clinician- and self-administered measures of depression and anxiety, even without psychotherapy (as many other studies provide). At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety.
Journal of Psychopharmacology
November 2016
Cited by 1,557
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial
This double-blind placebo-controlled study (n=29) for those suffering from anxiety and depression, related to cancer, improved significantly (60-80% of participants) after a single dose of psilocybin (21mg/70kg) in combination with psychotherapy.
Journal of Psychopharmacology
November 2016
Cited by 1,226

Find Psychedelic Papers

Find all relevant psychedelic research papers in our ever-growing database. Here we cover and connect the latest research and seminal papers. From early open-label psychedelic studies with healthy volunteers to large-scale double-blind, placebo-controlled trials.

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