Psychedelic Research Papers

A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity
This double-blind, randomized, controlled cross-over study (n=13) explores MDMA's (30-70mg) impact on tinnitus through behavioural and rs-fMRI assessments. No notable effects were observed at the lower dose. However, the 70 mg dose significantly reduced tinnitus annoyance and ignore ratings post-administration. Neurophysiological analysis revealed decreased connectivity in emotion and memory-related brain regions (hippocampal and amygdala) and increased connectivity in sensory processing and attention areas (right post-central gyrus, posterior and superior temporal gyrus, thalamus, and frontoparietal network) with MDMA versus placebo.
International Journal of Neuroscience
January 2020
Cited by 5
Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin
This open-label waitlist trial (n=30) assessed the feasibility of psilocybin-assisted psychotherapy (PAP/PAT) in a complex population with treatment-resistant depression (TRD), including major depressive and bipolar II disorders, baseline suicidality, and significant comorbidity. Participants received one, two, or three sessions of PAP with psilocybin (25mg), accompanied by preparation and integration psychotherapy sessions. Immediate treatment showed greater reductions in depression severity (MADRS) compared to the waitlist period, with a large effect size (g = 1.07, p < 0.01). Repeated doses were associated with further reductions in depression severity. Adverse events were transient, and the study demonstrated feasibility, preliminary antidepressant efficacy, safety, and tolerability in this population.
Medicine
February 2024
Cited by 1
Effects of Psychedelic Microdosing versus Conventional ADHD Medication Use on Emotion Regulation, Empathy, and ADHD Symptoms in Adults with severe ADHD symptoms: A Naturalistic Prospective Comparison Study
This prospective survey (n=233, 64, 44) explores microdosing's (MD) impact on emotional regulation (ER) and empathy in adults with severe ADHD symptoms. Positive effects on ER and empathy were observed, specifically in cognitive reappraisal, expressive suppression, perspective-taking, and personal distress. However, a comparison with those using only conventional medications (n=180, 50, 38 MD; n=37, 27, 28 conventional) revealed that after four weeks, only expressive suppression improvement persisted, and cognitive reappraisal and empathy enhancements disappeared.
European Psychiatry
February 2024
Cited by 0
Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study
This reanalysis of a Phase II study (n=11) investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants received psilocybin (25mg; n=5) or diphenhydramine (antihistamine; 50mg; n=6). Psilocybin increased activity in the medial and lateral prefrontal cortex and left caudate, while decreasing activity in several other brain regions. These findings suggest enhanced goal-directed action, improved emotional regulation, and diminished craving.
Scientific Reports
February 2024
Cited by 0
Psychedelics-assisted psychotherapy: Experiences with the limited medical use of LSD, MDMA, and psilocybin in Switzerland
This commentary (2024) provides insights into the current practice of psychedelics-assisted therapy (PAT) in Switzerland, based on legally permitted medical use since 2014. Over 1000 individual case permits have been issued, allowing approximately 2000-3000 treatments. The article discusses application procedures, treatment frameworks, and ethical considerations, highlighting the potential for integrating PAT into psychotherapy internationally while emphasizing the need for ongoing therapist education and quality assurance measures.
Die Psychotherapie
February 2024
Cited by 0
Exploring mechanisms of psychedelic action using neuroimaging
This review (2024) discusses the pivotal role of neuroimaging in modern psychedelic research, providing insights into the acute and longer-term therapeutic effects of these substances. Evidence from ffMRI, PET, and MEG/EEG studies informs computational models, offering a comprehensive understanding of the effects of psychedelics on human consciousness as well as supporting the advancement of psychedelic therapies.
Nature Mental Health
February 2024
Cited by 0
Processing of self-related thoughts in experienced users of classic psychedelics and non-users: a source localisation EEG study
This comparative study (dataset I: n=70, II: n=38) explores differences between naturalistic psychedelics users and non-users during the processing of self-related thoughts, using behavioural testing combined with EEG and source localization. Results from Dataset I suggest weaker increases in alpha and beta power in psychedelics users, primarily in brain regions linked to processing self-related information and memory. However, Dataset II did not replicate these effects, possibly due to sample size and spatial resolution limitations.
OSF Preprints
February 2024
Cited by 0
What Predicts Beneficial Outcomes in Psychedelic Use? A Quantitative Content Analysis of Psychedelic Health Outcomes
This analysis (n=240) of online trip reports examines the mechanisms behind the therapeutic potential of psychedelics, comparing metaphysical belief theory and predictive self-binding theory. Path analysis and structural equation modelling reveal that psychological insight, rather than metaphysical beliefs, uniquely predicts beneficial outcomes. Additionally, the positive effects of ego dissolution and therapeutic intent on beneficial outcomes are fully mediated by psychological insight, thereby supporting the predictive self-binding model over the metaphysical belief theory.
Journal of Psychoactive Drugs
February 2024
Cited by 0
Subjective long-term emotional and social effects of recreational MDMA use: the role of setting and intentions
This survey study (n=766) explores the consumption habits and perceived long-term social-emotional effects of MDMA use among individuals aged 18–61, primarily from Western countries. Utilizing a K-medoids clustering algorithm, researchers identified three consumption setting types—party settings with friends (n=388), private home settings (n=132), and mixed settings (n=246)—and three intention types—euphoria and energy (n=302), self-insight (n=219), and mixed intentions (n=245). The study found that individuals in the self-insight and mixed intentions clusters reported more long-term socio-emotional benefits compared to those seeking solely euphoria and energy, with no significant differences observed between the setting clusters.
Science Reports
February 2024
Cited by 0
Who Are You After Psychedelics? A Systematic Review and a Meta-Analysis of the Magnitude of Long-Term Effects of Serotonergic Psychedelics on Cognition/Creativity, Emotional Processing and Personality
This systematic review & meta-analysis (2024; s=10; n=304) synthesized data from contemporary studies, including both randomized and non-randomized controlled trials, to evaluate lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcome measures; however, a meta-analysis of emotional recognition outcomes revealed faster reaction times in the active treatment groups for disgust and sadness.
Neuroscience and Biobehavioral Reviews
February 2024
Cited by 0
Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study
This longitudinal study (n=54) investigates the effects of ayahuasca retreat experiences on gratitude, nature relatedness, and nature appreciation. Findings reveal significant increases in these factors at one-week and one-month follow-ups compared to baseline. Ratings of mystical experiences and awe during ayahuasca sessions weakly-to-moderately correlate with these increases, highlighting their potential role in post-ayahuasca changes. Participant age negatively relates to the occurrence of mystical experiences and awe, indicating diminished effects with increased age. The study emphasizes the quality of experiences over quantity in influencing post-ayahuasca changes, suggesting potential mental health benefits associated with prosocial changes in gratitude and nature relationships.
Journal of Psychoactive Drugs
February 2024
Cited by 0
Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA
This preclinical study (in cells) investigated methylone's potential for treating PTSD, comparing it with MDMA. Methylone showed rapid antidepressant and anxiolytic effects in preclinical models, affecting gene expression related to neuroplasticity in brain areas associated with PTSD and MDD. Unlike MDMA, methylone demonstrated no off-target effects at various receptors, indicating potential higher specificity, and suggesting its potential use in treating PTSD and other neuropsychiatric disorders.
Frontiers in Neuroscience
February 2024
Cited by 0
Effects of DMT on mental health outcomes in healthy volunteers
This placebo-controlled trial (n=13) and prospective study (n=17) examine the effects of DMT (iv) on mental health outcomes in healthy volunteers. Significant improvements in depression scores are observed 1-2 weeks after DMT administration in both datasets, with reductions in trait Neuroticism found only in the placebo-controlled sample. Correlations between acute peak experiences and changes in depression and trait anxiety are noted.
Scientific Reports
February 2024
Cited by 0
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
This randomized controlled trial (n=80) investigated the effects of microdosed LSD (10µg; 14x) on neural plasticity using a visual long-term potentiation (LTP) EEG paradigm. Participants received either LSD or placebo and completed the visual LTP paradigm both acutely and after six weeks of repeated microdosing. While event-related potential (ERP) analyses didn't show changes in visually induced LTP, dynamic causal modelling revealed alterations in laminar connectivity in the primary visual cortex, suggesting a more sensitive approach to assessing neural plasticity compared to traditional peak analysis methods.
BMC Psychiatry
February 2024
Psychedelics and sexual functioning: a mixed-methods study
This mixed-methods study combines data from two studies, one large naturalistic study (n=261) and one smaller controlled clinical trial (n=59), to investigate the post-acute effects of psychedelics on self-reported sexual functioning. It finds that naturalistic use of psychedelics is associated with improvements in sexual pleasure, communication, satisfaction with one’s partner, and physical appearance. Similarly, a controlled trial comparing psilocybin therapy with the SSRI escitalopram for depression shows that patients treated with psilocybin report positive changes in sexual functioning, unlike those treated with escitalopram.
Scientific Reports
February 2024
Cited by 0
Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study
This qualitative study (n=11) explores the experiences of treatment-resistant depression (TRD) patients undergoing a double-blind, randomized clinical trial with a single session of oral psilocybin treatment (1, 10, or 25 mg). Three major themes emerged: trust-building and expectation management challenges, navigating the experience, and the need for a more comprehensive treatment. Subthemes included distrust in mental healthcare, managing expectations, profound experiences during the session, and a desire for multiple psilocybin sessions. Insights from patients' perspectives suggest strategies for optimizing psilocybin treatment for TRD, such as individualized preparation, trust-building, additional sessions, and personalized therapy approaches.
Scientific Reports
February 2024
Cited by 0
Effects of hallucinogenic drugs on the human heart
This review (2024) outlines the effects of various hallucinogenic drugs on the human heart (contraction force & heart rate). These drugs, including bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, DMT, & 5-MeO-DMT, primarily stimulate serotonin receptors, particularly 5-HT2A receptors in the brain, leading to their hallucinogenic effects. However, they also impact the heart, potentially increasing cardiac contractility and heart rate, which could predispose individuals to arrhythmias.
Frontiers in Pharmacology
February 2024
Cited by 0
DMT induces a transient destabilization of whole-brain dynamics
This pre-print computational fMRI study (n=15) examines brain dynamics after DMT (iv; 20mg) administration, focusing on the onset of the psychedelic state. It reveals a peak destabilization of brain dynamics around 5 minutes post-administration and identifies a heightened reactivity phase, primarily affecting fronto-parietal and visual regions. The study links these changes to serotonin 5HT2a receptor density, suggesting these dynamics underpin the psychedelic state's complexity and flexibility.
Biorxiv
January 2024
Cited by 0
Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine
This in vitro and in vivo study investigates novel analogues of the designer drug 5-(2-methylaminopropyl) benzofuran (5-MAPB) as potential MDMA-like monoamine releasers. The research reveals that the S isomers of 5- and 6-(2-methylaminobutyl)benzofuran (5-MABB and 6-MABB) exhibit efficacy as releasing agents for serotonin, norepinephrine, and dopamine transporters. In contrast, the R isomers show reduced potency in inducing behavioural effects, suggesting the aminoalkyl benzofuran scaffold is a potential template for developing compounds with MDMA-like properties.
Journal of Pharmacology and Experimental Therapeutics
January 2024
Cited by 0
Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial
This Phase I study (n=44) investigates the safety, tolerability, pharmacokinetics, and -dynamic profile of escalating doses of SPL026 (DMT fumarate; 9-21.5mg) in psychedelic-naïve healthy participants. The RCT concludes that SPL026 was well-tolerated, showing an acceptable safety profile, with potential correlations between plasma concentration and psychometric measures.
Frontiers in Psychiatry
January 2024
Cited by 2
MDMA enhances positive affective responses to social feedback
This double-blind, placebo-controlled crossover trial (n=36) investigates the effects of two doses of MDMA (52.5-105mg/70kg) compared to both placebo and methamphetamine (20 mg) on responses to personalized social feedback in healthy adults. The study concludes that the higher dose of MDMA increases positive affective responses to social feedback, suggesting a potential mechanism by which MDMA may enhance social connection.
Journal of Psychopharmacology
January 2024
Cited by 0
Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study
This prospective survey (n=161) examines the interactions between psychedelics and serotonergic antidepressants (SRIs), focusing on their effects on well-being and depressive symptoms. Utilizing multivariate analysis and linear mixed effect models, it compares subjective psychedelic experiences and post-use well-being between individuals on SRIs ('SRI +') and those not ('SRI −'). Findings indicate 'SRI −' participants experience more intense mystical, challenging, and emotional breakthroughs, while 'SRI +' participants have less intense experiences but similar improvements in well-being and depressive symptoms.
Journal of Psychopharmacology
January 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
Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine
This re-analysis (n=73) investigates the effects of low doses of LSD (13-26µg; n=21), THC (7.5-15mg), and methamphetamine (MA; 10-20mg) on neural complexity in healthy volunteers without inducing altered states of consciousness. Utilizing a within-subjects design over three laboratory visits, the study records resting state EEG data to measure Lempel-Ziv complexity and spectral power. Results demonstrate that only LSD, not THC or MA, dose-dependently increases neural complexity and reduces delta and theta power, while THC and MA respectively decrease and increase alpha power, primarily in frontal regions.
Neuropsychopharmacology
January 2024
Cited by 0
Microdosing psychedelics: Current evidence from controlled studies
This systematic review (s=14) compiles double-blind, placebo-controlled studies on microdosing LSD (5-20 μg) under laboratory conditions. It reports that acute low doses of LSD affect blood pressure, sleep, neural connectivity, mood, social cognition, and perceptions of pain and time, with noticeable effects at 10-20μg but not at 5μg. While no serious adverse effects were noted, repeated microdosing did not significantly change mood or cognition.
Biological Psychiatry
January 2024
Cited by 0
A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review
This systematic review (s=5) of randomized controlled trials (RCTs) compares oral psilocybin (25mg) and intranasal esketamine (56-84mg) with an oral antidepressant in adults with depression (TRD). The review showed significant depressive symptom reduction with psilocybin (Number Needed to Treat; NNT=5) and esketamine (NNT=7). Psilocybin has a Number Needed to Harm (NNH) of 5 for nausea, while esketamine induces mild side effects (NNH<10).
Journal of Affective Disorders
January 2024
Cited by 0
Older adults in psychedelic-assisted therapy trials: A systematic review
This systematic review (n=1400; s=36) aimed to assess the prevalence of older adults in psychedelic clinical trials and explore safety data. Only 19 participants aged 65 or older were identified, constituting less than 1.4% of all trial participants. Detailed safety data for 10 of these older adults revealed no serious adverse events, with only transient mild-to-moderate adverse events related to anxiety, gastrointestinal upset, and hypertension during psychedelic dosing sessions.
Journal of Psychopharmacology
January 2024
Cited by 0
Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression
This in vitro study examines functional selectivity between two 5-HT2A receptor agonists, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] and (R)-2,5-dimethoxy-4-trifluoromethylamphetamine [(R)-DOTFM], in the context of their impact on inflammation and airway hyperresponsiveness (AHR) in a murine asthma model. Despite similar in vitro activity and behavioral potency, (R)-DOTFM does not prevent inflammation or elevated AHR, in contrast to (R)-DOI, suggesting distinct anti-inflammatory mechanisms associated with certain psychedelics.
ACS Pharmacology and Translational Science
January 2024
Cited by 0
The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression
This open-label Phase IIa clinical trial (n=6) examines the efficacy of vaporized DMT in treating treatment-resistant depression (TRD). Patients experienced significant reductions in two depression scores (MADRS & PHQ-9), with 83% responding to treatment by day 7 and 66.67% achieving remission. The rapid onset and sustained antidepressant effects of vaporized DMT suggest its potential as a practical and accessible option in psychedelic treatments for depression within interventional psychiatry.
MedRvix
January 2024
Cited by 0
Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins
This review (2023) assesses the potential long-term impact of microdosing psychedelics on cardiac health, particularly focusing on LSD and psilocybin. Despite the increasing popularity of microdosing, concerns arise due to structural similarities between these substances and medications associated with cardiac fibrosis and valvulopathy. The review emphasizes the need for future studies to evaluate the safety of prolonged microdosing and discusses the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor.
Journal of Psychopharmacology
January 2024
Cited by 0

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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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