Progress in brain research
January 1, 2018
Felix Müller, Matthias E Liechti, Undine E Lang et al.
32 citations
Studies of hallucinogenic drugs on the resting brain show some consistent findings: psilocybin, LSD, and ayahuasca all decrease cerebral blood flow and increase global functional connectivity in the precuneus and thalamus. LSD also consistently reduces functional connectivity within distinct resting state networks. However, results for connectivity between networks and blood flow in other brain regions show little convergence. These studies are limited by small sample sizes and potential bias from unspecific drug effects on physiology and the vascular system. Current evidence suggests neuroimaging may help reveal the neural correlates of hallucinogenic effects.
PLoS ONE
September 10, 2013
Niklaus Denier, Hana Gerber, Marc Vogel et al.
32 citations
In 15 heroin-dependent patients receiving stable heroin-assisted treatment, heroin reduced blood flow in the left anterior cingulate cortex, left medial prefrontal cortex, and insula compared to placebo. These brain areas are involved in self-regulation and emotional processing. The findings suggest that heroin's effects on these regions may contribute to its ability to reduce craving and produce relaxation in maintenance therapy.
Frontiers in Psychiatry
October 22, 2020
Felix Müller, Markus Mühlhauser, Friederike Holze et al.
31 citations
A woman with severe, treatment-resistant depression and a complex personality disorder received weekly, ascending doses of LSD in an open psychiatric ward. Despite adequate dosing confirmed by blood tests, she experienced no substantial acute subjective drug effects. However, she showed rapid and significant improvements in depressed mood, emotional instability, low energy, and suicidal thoughts. Questionnaire scores also decreased in global severity and various psychopathological subscales. Improvements lasted about 7 days after each dose. The case suggests that LSD can induce rapid but transient beneficial effects on several symptoms, and that these improvements can occur without acute drug experiences, resembling the time course of ketamine's antidepressant effects.
Molecular psychiatry
April 1, 2025
Mihai Avram, Lydia Fortea, Lea Wollner et al.
26 citations
Lysergic acid diethylamide (LSD), d-amphetamine, and MDMA each reduce the integrity (within-network connectivity) of several brain networks, with LSD uniquely reducing integrity in the default-mode network. Contrary to expectations, amphetamines reduced integrity in more networks than LSD. LSD produced more pronounced decreases in between-network segregation, while amphetamines also induced increases. Seed-based connectivity mostly increased between networks across all substances, with LSD showing stronger effects than both amphetamines. All substances decreased global connectivity in visual areas, but LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings clarify distinctive neurobiological effects of psychedelics and support further investigation of their therapeutic potential.
The International Journal of Neuropsychopharmacology
November 22, 2017
André Schmidt, Felix Müller, Patrick C. Dolder et al.
25 citations
Modafinil, but not methylphenidate or MDMA, increased brain activity in a limbic-cortical-striatal-pallidal-thalamic circuit and the amygdala when healthy subjects viewed fearful faces. Activation in frontal brain regions correlated with increased feelings of fearfulness and depressiveness after modafinil. Despite modafinil's cognitive enhancement effects, potential adverse effects on emotion processing should be considered.
Med (New York, N.Y.)
June 4, 2025
Felix Müller, Hannes Zaczek, Anna M Becker et al.
21 citations
In a double-blind, low-dose controlled trial, 61 patients with moderate-to-severe major depressive disorder received supportive psychotherapy and either two high doses (100 μg then 200 μg) or two low doses (25 μg each) of LSD. At the primary endpoint two weeks after the second session, the high-dose group showed a greater average reduction in self-rated depression scores (11.8 points) compared to the low-dose group (3.9 points), a difference that approached but did not reach statistical significance. Clinician-rated scores also favored the high dose, but significance was lost after adjusting for baseline depression severity. Improvements were numerically maintained through 12 weeks. Adverse events were similar between groups. The authors suggest these exploratory results warrant a larger phase 3 trial.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
Frontiers in Pharmacology
June 28, 2017
Patrick C. Dolder, Edna Grünblatt, Felix Müller et al.
12 citations
A single 100 μg dose of LSD did not change the expression of the serotonin 5-HT2A receptor gene (HTR2A) or the early growth response genes EGR1, EGR2, and EGR3 in the whole blood of 15 healthy subjects, measured 1.5 and 24 hours after administration. This null finding contrasts with rodent studies showing that LSD acutely increases EGR1 and EGR2 expression in the brain and that repeated use reduces 5-HT2A receptor binding. Whether chronic LSD administration alters gene expression in humans remains unknown.
Swiss Medical Weekly
September 30, 2019
Felix Mller, Stefan Borgwardt
10 citations
LSD produces extensive alterations in functional brain connectivity, particularly increasing connectivity within the thalamocortical system. These changes align with models suggesting hallucinogenic drugs inhibit cerebral filtering of external and internal data. Recent neuroimaging studies in the UK and Switzerland using fMRI have revived research into LSD's neuronal effects, which were unclear despite decades of earlier psychiatric investigation into its potential for treating depression, anxiety, addiction, and personality disorders. However, these studies face limitations, including potential biases in neuroimaging measurements.
Journal of Clinical Psychopharmacology
December 30, 2022
Helena Rogg, Mihai Avram, Felix Müller et al.
8 citations
Ketamine treatment in patients with borderline personality disorder (BPD) may reduce symptom severity, but the evidence is preliminary and based on small samples. The review suggests that ketamine could be a potential therapeutic option for BPD, particularly for comorbid depression, though more rigorous studies are needed to confirm efficacy and safety. The authors note that existing studies have significant limitations, including lack of control groups and short follow-up periods.
Neuropsychobiology
January 1, 2008
Paolo Fusar‐poli, Stefan Borgwardt
7 citations
Albert Hofmann, a Swiss chemist, first synthesized LSD in 1938 but set it aside. In 1943, he accidentally ingested a small amount and experienced an extremely stimulated imagination. Three days later, on April 19, 1943, he intentionally took 250 micrograms of LSD to verify the effects, then rode his bicycle home—a ride now known as Bicycle Day. LSD was initially hailed as a tool for psychoanalysis and understanding schizophrenia, but in the 1960s figures like Timothy Leary promoted it as a path to spiritual enlightenment.
Cell Reports Medicine
May 7, 2026
Mihai Avram, Aurore Menegaux, Felix Müller et al.
1 citation
Lysergic acid diethylamide (LSD) may alleviate depression by altering white matter microstructure in the brain, potentially reflecting enhanced neuroplasticity. In a clinical trial of 61 patients with major depressive disorder, those receiving moderate-to-high doses (100 μg then 200 μg) showed increased fractional anisotropy in several white matter tracts, including the internal and external capsule, sagittal stratum, and fornix/stria terminalis. These microstructural changes correlated with improvements in depressive symptoms measured at 2, 6, and 12 weeks. The findings suggest that LSD-induced white matter changes are linked to antidepressant effects.
medRxiv
January 16, 2026
Kristian Larsen, Patrick M Fisher, Drummond E. Mcculloch et al.
1 citation
Classical psychedelics such as LSD, psilocybin, and mescaline produce distinct changes in brain complexity and entropy that are not seen with stimulants like MDMA or d-Amphetamine. Using resting-state fMRI data from three placebo-controlled crossover trials with 79 participants across 255 sessions, the study found that psychedelics specifically increased meta-state complexity, short-timescale multiscale entropy, and dynamic conditional correlation entropy. Both drug classes increased Lempel-Ziv and spatial complexity and decreased absolute modularity, but only psychedelics showed these unique complexity and entropy increases. These findings suggest that psychedelic-specific brain signal changes may help distinguish the acute psychedelic state from other psychoactive drug effects and could be relevant to understanding their therapeutic potential.
Psychedelics as Psychiatric Medications
March 1, 2023
Mihai Avram, Felix Müller, Stefan Borgwardt
1 citation
Lysergic acid diethylamide (LSD) is a potent perception-altering chemical that has been both revered and demonized since its discovery. Before its ban in the late 1960s, it was used to model aspects of psychosis and treat alcohol addiction and anxiety. Recent clinical trials show LSD can be administered safely in clinical settings to healthy volunteers and clinical groups. Small studies suggest potential therapeutic uses for anxiety. LSD's perception-altering effects involve agonism at the 5-HT2A receptor. Neuroimaging reveals LSD enhances signal diversity and complexity, decreases resting-state connectivity within intrinsic brain networks, and increases between-network connectivity, including thalamocortical connectivity.
Cell Rep Med
September 1, 2025
Mihai Avram, Stefan Borgwardt
Recent phase 2 randomized controlled trials indicate that psychedelics can reduce symptoms of depression, and phase 3 trials are now in progress. The biological and psychological processes behind these effects—including receptor activity, subjective experiences, and the role of context—are not yet fully explained. The authors review current clinical findings and mechanistic insights, then suggest directions for further investigation.
Fortschritte der Neurologie · Psychiatrie
April 1, 2024
Stefan Borgwardt, Tomislav Majić, Mihai Avram et al.
Classic psychedelics such as psilocybin, LSD, ayahuasca, and 5-MeO-DMT are attracting renewed psychiatric, psychotherapeutic, and neuroscientific interest, driven by recent clinical trials suggesting therapeutic benefits for treatment-resistant depression, substance use disorders, anxiety disorders, and existential distress in life-threatening physical illness. Despite these promising effects, the substances carry unique risks due to the phenomenology of their central nervous system effects, the temporal dynamics of their psychological impacts, and their biological action profile, distinguishing them from many other psychoactive drugs.
Current pharmaceutical design
January 1, 2012
Niklaus Denier, Marc Walter, Kerstin Bendfeldt et al.
A systematic review compared resting-state cerebral blood flow patterns in first-episode psychosis (FEP), acute cannabinoid intoxication, and acute opioid intoxication. The evidence was highly conflicting within each condition, but some consistent findings emerged: both positive symptoms of FEP and depersonalization after cannabis administration were linked to increased activity in the anterior cingulate cortex, a key region of the default mode network. The review included 22 studies with 279 FEP participants or controls, 315 participants receiving cannabinoids, and 113 receiving opioids.