Psychedelic Research Papers

This neuroimaging study (n=20) aimed to understand the effects of DMT (20mg) on the human brain. The researchers used EEG-fMRI (electroencephalography-functional MRI) to measure brain activity before, during, and after administering DMT to healthy volunteers. They found that DMT increased global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient.

This balanced-order crossover study (n=20) investigates the effects of LSD (75µg) on the pain neural network using fMRI in healthy subjects. The study finds that LSD modulates brain regions involved in pain processing, showing differences in activity and connectivity compared to placebo, and highlights potential implications for future cognitive science and pharmacology research.

This seminal fMRI study (n=30) found decreases in blood flow of hub regions in the brain (thalamus, ACC, PCC). The study is the first to report on these findings with psilocybin (2mg iv ~15mg oral). There was a decoupling between the medial prefrontal cortex and the posterior cingulate cortex and this decoupling is hypothesized to be responsible for the psychedelic state.

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.

This double-blind, randomized, placebo-controlled, and crossover study (n=15) investigated the effects of oral psilocybin (14mg/70kg) on the predictive processing of somatosensory tactile stimulation using simultaneous EEG–fMRI recording. Psilocybin produced robust perceptual alterations of bodily awareness and self-experience that were related to decreased brain response to surprising tactile stimuli.

This case-control fMRI study (n=38 males) found that long-term ayahuasca users showed significantly higher psychological resilience scores and altered emotional brain reactivity patterns compared to controls. Machine learning algorithms achieved 75% accuracy in distinguishing users from non-users.

This interview study (n=15) investigated the phenomenology of individuals under the acute influence of psilocybin (intravenously injected - quicker onset) in an fMRI scanner.

This cross-sectional fMRI study (n=67) found that experienced psychedelic users (≥10 lifetime experiences) showed faster and more accurate recognition of angry facial expressions alongside diminished neural responses to anger in limbic and salience network regions, enhanced responses to happiness in parietal and sensorimotor areas, and reduced emotional differentiation in default mode network regions compared to non-users.

This secondary analysis of an RCT fMRI study (n=40) of meditation practitioners during a 3-day retreat found that DMT-harmine ('pharmahuasca', 120mg/120mg buccal) increased functional connectivity within the visual network and between visual and attention networks, whilst meditation alone reduced between-network connectivity, with no evidence of prolonged cortical gradient disruption characteristic of acute psychedelic effects, suggesting distinct neural mechanisms for meditation versus psychedelic-augmented meditation.

This within-subjects fMRI study (n=19) investigated changes in brain function before versus after psilocybin (with psychological support) in patients with treatment-resistant depression. After treatment, all patients showed decreased depressive symptoms and changes in brain functioning.

This analysis of fMRI data (n=15) examined how LSD (75μg) affects local brain activity and connectivity, finding that LSD decreased both measures in somatosensory/visual areas, with additional activity decreases in Default Mode and Fronto-Parietal networks and connectivity decreases in subcortical regions, with these changes occurring primarily in brain regions with high densities of D2 and 5HT1a receptors, suggesting complex neurobiological mechanisms underlying LSD's effects.

This double-blind, placebo-controlled, within-subjects fMRI study (n=19) investigated the effect of MDMA on the recollection of favorite and worst autobiographical memories (AMs). Positive memories were rated as more positive and negative memories as less negative after MDMA use. Several brain regions were found to be active during AM recollection and related to memory valance.

This double-blind, placebo-controlled, fMRI study (n=24) found that LSD (100 μg) reduced activity in brain areas responsible for self-processing and social cognition. This also translated to subjective effects and reduced joint attention.

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.

This randomized, double-blind, placebo-controlled cross-over study (n=17) investigates the effects of subanesthetic ketamine (105 mg/70kg) on resting-state functional connectivity in healthy male subjects and found an increase of connectivity between the executive control network (i.e. prefrontal cortex ) and other resting-state networks, such as the anterior cingulum and the frontal gyrus, and decreased connectivity between executive control network and salience network. Increased connectivity is taken to reflect positive psychotic symptoms (e.g. delusions, conceptional disorganization, hallucinatory behavior), whereas the decreased connectivity was taken to reflect negative psychotic symptoms (e.g. difficulties in abstract thinking, withdrawal) and as a sign of decreased visual perception in these subjects.

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.

This pre-print review article of fMRI studies with psychedelics finds that there are no studies that use the same analysis techniques. They propose eight steps to standardize measurements and propose future fMRI studies to be done.

This preprint (2022) uses the Ising model of brain phase transition to assess fMRI BOLD data from a study in LSD was administered (n=15). Several different concepts from statistical physics were applied to the fMRI data to analyze individualized Ising temperature increases under the influence of LSD and placebo, showing that LSD ingestion shifts the system away from the critical point between paramagnetic and ferromagnetic phases to a more disordered state. Overall findings suggest that LSD increases the complexity of brain dynamics.

This study (n=9) tested the tolerability of psilocybin in an fMRI environment, and found high levels of tolerability. It found that full-dose psychedelic studies with fMRI equipment are viable.

This neuroimaging study (n=4) used positron emission tomography (PET) with a 5-HT2A receptor agonist radioligand (that would light up on scans) and cortical regions of interest (ROIs) to determine the regional occupancy of 5-HT2A receptors after oral administration of a psychoactive dose of psilocybin (10mg/70kg). Three areas with the greatest occupancy were within the default mode network (DMN). There was high variability across individuals.

This systematic review (s=51) examines fMRI studies on the acute effects of psychedelics like psilocybin, LSD, and ketamine on the human brain. The review highlights significant methodological inconsistencies across studies, including 54% not meeting contemporary Type I error correction or motion artefact control standards. Despite these limitations, convergent findings indicate that psilocybin and LSD affect the connectivity architecture of the sensorimotor-association cortical axis, while ketamine increases activation in the dorsomedial prefrontal cortex.

This within-subjects study (n=10) investigated the effect of ayahuasca on brain activity. Resting-state fMRI data was broadly consistent with the entropic brain hypothesis which holds that the effects of psychedelics are partially explained in terms of increased entropy of the brain’s functional connectivity.

This review (2023) charts the resurgence of interest in psychedelic therapy for treating addiction, beginning with historical studies from the mid-late 1900s, then examining real-world evidence from naturalistic, observational, and survey-based studies, and contemporary clinical trials ranging from first-in-human to Phase II. It also explores translational human neuropsychopharmacology techniques like fMRI and PET to understand the therapeutic mechanisms of psychedelics.

This theory-building preprint (2022) uses data from fMRI and PET scans (of the brain) to show how different pharmacological interventions (including psychedelics) interact with neurotransmitters. The results show opposite routes, but similar mechanisms, as to how psychedelics and anaesthetics (e.g. ketamine) interact with the brain (molecular chemoarchitecture).

This placebo-controlled within-subjects study (n=12) analysed fMRI data of participants' brain activity in response to LSD (75μg/70kg) with or without the influence of listening to music. Using a novel connectome-specific harmonic decomposition method, they found that brain states under the influence of LSD exhibit a wider and more flexible repertoire of activation patterns, which maintain a unique type of non-random stability in their co-activation over time.

In this neuroimaging study (n=14) data from participants who were given 75μg of intravenous LSD or placebo and brain activity was assessed using fMRI and a novel whole-brain computer model (in silico) approach. The largest deviations from normal brain function were found in the limbic network, the visual network and the default mode network (DMN). It was found that the computer model used allows for the exploration of changes in brain dynamics that can be challenging to observe via experiments in living subjects (in vivo).

This computational paper (2020) describes a model that predicts whole-brain activity in light of the functional coupling between neuroanatomical and neuromodulatory systems and applies this model to demonstrate how the effects of psilocybin on the brain arise out of the mutual interaction between serotonergic (5-HT2A) receptor modulation and the anatomy of the raphe nucleus. The results provide evidence for how the integration of dMRI (anatomy), fMRI (functional neuronal activity), and PET (neurotransmitter system) at the whole-brain level is necessary for properly predicting brain dynamics as a result of the mutual coupling between a dual system.

This fMRI analysis study (n=74 total) looks at how three different drugs - nitrous oxide, ketamine, and lysergic acid diethylamide (LSD) - affect the way different parts of the brain communicate with each other. By comparing brain scans taken before and during drug use, the study found that all three drugs reduced connectivity within certain networks in the brain, while enhancing connections between different networks. These effects were seen in areas of the brain that are important for our conscious experiences.

This double-blind placebo-controlled fMRI study (n=53) on ketamine (r-ketamine, continuous iv) and cognition found that ketamine increased metacognitive bias, negatively impacted metacognitive sensitivity, and increased activation of posterior brain areas.

This analysis of resting-state fMRI (n=15) of LSD (75μg) effects on the brain finds modifications in serotonin receptor-rich areas. The local signal amplitude and functional connectivity (FC) increased in the default mode network (DMN) and attention networks (rich in serotonin 2a receptors). A decrease was seen in limbic areas (with many serotonin 1a receptors).