Psychedelic Research Papers

Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience
This pre-print single-blind study (n=14) used multimodal neuroimaging techniques (fMRI + EKG) to investigate brain activity and autonomic physiology during DMT (20mg) altered state of consciousness. Results reveal unique brain activity substates, with increased superior temporal lobe activity and hippocampal deactivation under DMT, correlating with auditory distortions and meaningfulness of the experience, respectively. Moreover, increased heart rate under DMT correlates with hippocampal and medial parietal deactivation, suggesting a potential link between sympathetic regulation and positive mental health outcomes following psychedelic administration.
Biorxiv
February 2024
Cited by 0
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
Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties
This cell & mice study explores the psychopharmacological profile of amino-substituted 5-MeO-tryptamines, focusing on their interactions with serotonin receptors and transporters, as well as their psychoactive and thermoregulatory properties. The study demonstrates selectivity for 5-HT1AR over 5-HT2AR among examined compounds using radioligand binding methodologies and computational docking analyses, and 5-MeO-pyr-T was identified as the most potent partial 5-HT releaser.
Molecular Psychiatry
March 2024
Cited by 0
Adolescent Psychedelic Use and Psychotic or Manic Symptoms
This observational study (n=16.255) investigates the association between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents, utilizing a genetically informative design. Results suggest that psychedelic use may be associated with reduced psychotic symptoms after adjusting for other drug use, while associations with manic symptoms seem to be linked to genetic vulnerability to schizophrenia or bipolar I disorder.
JAMA Psychiatry
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
Safety pharmacology of acute psilocybin administration in healthy participants
This pooled analysis (n=85; doses=113) of three randomized crossover studies evaluates the safety pharmacology of psilocybin (15-30mg). Psilocybin induced stronger effects at higher doses, with 25 mg and 30 mg doses showing increased anxiety. However, overall, psilocybin was found to be safe in terms of acute psychological and physical harm, with no serious adverse reactions reported, suggesting its potential safety for controlled research settings.
Neuroscience Applied
March 2024
Cited by 0
Salience, Sensemaking, and Setting in Psilocybin Microdosing: Methodological Lessons and Preliminary Findings of a Mixed Method Qualitative Study
This pre-print (n=13) investigates the subjective experiences of individuals engaging in psilocybin microdosing in their daily lives. Combining momentary ecological assessments and retrospective interviews, participants reported varied effects, including loosening of mental structures, increased salience of external stimuli, flexible cognition, and ego-dystonic contents.
OSF Preprints
March 2024
Cited by 0
IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital
This longitudinal study (n=71) examines five years of real-world clinical data on the use of IV low-dose ketamine alongside standard care for outpatients with depression (MDD & TRD). Results indicate a significant reduction in depressive symptoms and suicide ideation by treatment endpoint, with 55% of patients responding to treatment. Side effects were transient and mild for 78% of patients, with a dropout rate of 11%. Multivariate analysis suggests that demographic variables did not impact treatment efficacy or tolerability.
Psychiatry Research
March 2024
Cited by 0
The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients
This pharmacokinetic study (n=14) on ibogaine (700mg/70kg) for opioid use disorder (OUD) finds significant variability in ibogaine clearance, strongly correlated with CYP2D6 genotype. Ibogaine plasma concentrations correlate with QTc prolongation and cerebellar effects, while neither ibogaine nor noribogaine correlate with the severity of opioid withdrawal symptoms.
Journal of Psychopharmacology
March 2024
Cited by 0
Childhood trauma, challenging experiences, and posttraumatic growth in ayahuasca use
This observational study (n=231) examines the relationship between childhood trauma, challenging experiences during acute ayahuasca effects, and posttraumatic growth. Results show that individuals with histories of childhood trauma were not at higher risk of adverse experiences during ayahuasca use, nor did they exhibit different levels of posttraumatic growth compared to those without such histories. Additionally, experiencing more challenges during acute ayahuasca effects did not correlate with increased posttraumatic growth.
Drug Science, Policy and Law
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
Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension
This randomized placebo-controlled trial (n=111) investigated the efficacy, safety, and tolerability of fixed low-dose oral esketamine (3x p/d 42d; 30-90mg; oral) in patients with treatment-resistant depression (TRD). Results indicate that fixed low-dose oral esketamine did not show benefit on depressive symptom severity compared to placebo, but individually titrated higher doses in the open-label extension phase demonstrated potential antidepressant properties.
Molecular Psychiatry
March 2024
Cited by 0
Perceived attachment history predicts psychedelic experiences: A naturalistic study
This survey (n=185) of an international Jewish sample with psychedelic experience explores the association between attachment-related variables and psychedelic experiences. Findings suggest that perceptions of an insecure attachment history are positively linked to various measures of psychedelic phenomenology, while adult attachment orientations show no significant relationship. Moreover, psychedelic experiences do not typically moderate the association between perceived insecure attachment history and present attachment insecurity.
Journal of Psychedelic Studies
March 2024
Cited by 0
Sublingual Ketamine for Depression and Anxiety: A Retrospective Study of Real-World Clinical Outcomes
This retrospective analysis (n=431) of at-home ketamine treatments (1x p/w, 50-400mg lozenges) for depression, generalized anxiety, and social anxiety found statistically significant improvements in symptoms measured via PHQ-9, GAD-7, and SAD-D-10 at all follow-up time points (1-2-3 months). Minor side effects were reported by 18.8% of patients, resolving within 24 hours, and the majority concluded treatment within ≤ 6 months. No significant differences were observed between treatment-resistant and non-resistant depression outcomes.
MedRvix
February 2024
Cited by 0
Conflict monitoring and emotional processing in 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine users - A comparative neurophysiological study
This comparative study (n=38 METH users, n=42 MDMA users, n=83 controls) examines the impact of chronic METH and MDMA use on conflict control processes in social-affective contexts. Both METH and MDMA users exhibit reduced behavioral effects in cognitive-emotional conflict processing, particularly regarding anger content. These effects are associated with stronger P3 event-related potential modulations, suggesting altered decision-making and stimulus-response mapping, potentially linked to noradrenergic dysfunctions. Understanding the role of noradrenaline in chronic users of substituted amphetamines represents a significant direction for future research in this area.
NeuroImage
March 2024
Cited by 0
Synthetic surprise as the foundation of the psychedelic experience
This hypothesis paper proposes that psychedelic agents like LSD and psilocybin induce altered states of consciousness by activating the 5-HT2A receptor system, leading to a state of "synthetic surprise." This concept is based on recent understandings of serotonin's role in signaling surprise and is framed within the predictive coding framework, where surprise is seen as a mismatch between expectations and sensory input. The paper suggests that psychedelics disrupt maladaptive patterns by dynamically interacting with top-down expectations and sensory data, with implications for their clinical use, particularly emphasizing their ability to induce surprise to promote therapeutic effects.
Neuroscience and Biobehavioral Reviews
February 2024
Cited by 0
Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity
This machine learning study (n=16) examines baseline resting-state functional connectivity (FC) measured with fMRI as a predictor of symptom severity in psilocybin-assisted therapy for treatment-resistant depression (TRD). Results show that FC of visual, default mode, and executive networks predicted early symptom improvement, with the salience network predicting responders up to 24 weeks after treatment.
Journal of Affective Disorders
February 2024
Cited by 0
Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations
This computational study investigates the membrane permeability of 12 selected tryptamines, aiming to elucidate the impact of various structural modifications on their permeation behaviour. Using classical molecular dynamics simulations and umbrella sampling techniques, the study finds that dimethylation of the primary amine group and methoxy substitution at position 5 increase permeability, while positional substitutions on the indole groups and protonation decrease permeability.
Biochemistry
February 2024
Cited by 0
Expectancy effects in psychedelic trials
This review (2024) explores the impact of participant expectations on psychedelic clinical trials. It highlights the challenge of maintaining blinding as doses increase and discusses the potential bias introduced by positive expectancy. The review covers expectancy effects in both micro- and macrodose trials, suggesting that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.
Biological Psychiatry
February 2024
Cited by 0
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

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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