Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
Lysergic acid diethylamide (LSD), a well-known hallucinogen, significantly influenced mood and perception in a recent crossover study involving 60 participants. Those receiving LSD reported a 70% reduction in feelings of derealization and depersonalization compared to a placebo. Additionally, serotonin receptor activity was linked to improved prepulse inhibition, suggesting potential benefits for psychosis and schizophrenia. While heart rate increased by 15% and blood pressure rose moderately, adverse effects remained minimal, highlighting the need for further exploration of psychedelics in clinical psychology and psychiatry.
Biological psychiatry
February 1, 2023
Friederike Holze, Peter Gasser, Felix Müller et al.
294 citations
LSD-assisted therapy produced long-lasting reductions in anxiety and comorbid depression symptoms up to 16 weeks in patients with anxiety related to a life-threatening illness. In a double-blind, placebo-controlled crossover trial with 42 patients, LSD treatment led to significant decreases in anxiety scores compared to placebo, with a large effect size. Similar improvements were seen in depression ratings. Positive acute subjective drug effects and mystical-type experiences correlated with long-term anxiety reductions. Mild, transient side effects occurred in 19% of patients, and one serious adverse event (acute transient anxiety) was reported.
Neuropsychopharmacology
November 16, 2019
Friederike Holze, Patrick Vizeli, Felix Müller et al.
250 citations
LSD, MDMA, and d-amphetamine all increased heart rate, blood pressure, body temperature, and pupil size, but LSD produced the strongest alterations in consciousness, mystical experiences, ego dissolution, and emotional excitation. MDMA increased feelings of good drug effects, liking, and high more than d-amphetamine, and only MDMA raised oxytocin levels. d-Amphetamine boosted activity and concentration relative to LSD. None of the substances changed brain-derived neurotrophic factor. The findings highlight distinct subjective and endocrine profiles that may inform dosing in psychedelic-assisted therapy.
Neuropsychopharmacology
June 1, 2016
Patrick C. Dolder, Yasmin Schmid, Felix Müller et al.
249 citations
LSD acutely enhances feelings of happiness, trust, and closeness to others, increases explicit and implicit emotional empathy, impairs recognition of sad and fearful faces, and boosts prosocial behavior and desire for social interaction. These effects were observed in two placebo-controlled, double-blind, crossover studies with 24 participants receiving 100 μg and 16 receiving 200 μg of LSD. All participants were healthy, mostly hallucinogen-naive adults aged 25 to 65. The findings suggest that LSD alters emotional processing and sociality in ways that may support its use as an adjunct to psychotherapy for anxiety in patients with life-threatening illness.
Neuropsychopharmacology
October 15, 2020
Friederike Holze, Patrick Vizeli, Laura Ley et al.
243 citations
Lysergic acid diethylamide (LSD) produces dose-dependent subjective effects starting at 25 µg, with a ceiling for good drug effects at 100 µg, while ego dissolution and anxiety increase further at 200 µg. The average duration of subjective effects lengthens from 6.7 to 11 hours across the 25–200 µg range. LSD moderately raises blood pressure and heart rate. The serotonin 5-HT2A receptor antagonist ketanserin (40 mg) given before 200 µg LSD prevents the response, indicating that LSD's full psychedelic effects are primarily mediated by 5-HT2A receptor activation. These results assist dose finding for future LSD research.
Neuropsychopharmacology
February 25, 2022
Friederike Holze, Laura Ley, Felix Müller et al.
223 citations
In healthy volunteers, 100 and 200 micrograms of LSD and 30 milligrams of psilocybin produce comparable subjective effects, including alterations of mind that are qualitatively and quantitatively very similar. The 15 milligram psilocybin dose produces clearly weaker subjective effects. The 200 microgram dose of LSD induces higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 microgram dose. LSD at both doses has clearly longer effect durations than psilocybin. Psilocybin increases blood pressure more than LSD, whereas LSD increases heart rate more than psilocybin, though both show comparable overall cardiostimulant properties. Any differences between LSD and psilocybin appear dose-dependent rather than substance-dependent, except for the differential effects on heart rate and blood pressure.
Acta Psychiatrica Scandinavica
September 21, 2017
Felix Müller, Claudia Lenz, Patrick C. Dolder et al.
149 citations
Lysergic acid diethylamide (LSD) alters consciousness by increasing functional connectivity between the thalamus and various cortical regions, particularly the right fusiform gyrus and insula. In 20 healthy participants given 100 μg LSD orally, thalamic connectivity changes correlated with subjective auditory and visual drug effects. These findings suggest that hallucinogenic effects may arise from enhanced cortical excitability through thalamocortical interactions, providing insight into the role of the 5-HT2A receptor in altered states of consciousness.
Translational Psychiatry
April 8, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
132 citations
A double-blind, placebo-controlled experiment with 0.17 mg/kg psilocybin shows that the drug affects creative thinking in time-dependent and task-specific ways. Immediately after consumption, psilocybin increased spontaneous creative insights but decreased deliberate, task-based creativity. Seven days later, participants generated more novel ideas. Brain imaging revealed that both acute and persisting effects were predicted by connectivity within and between networks of the default mode network. These results support historical claims that psychedelics can influence aspects of the creative process and may serve as tools for investigating creativity and its neural basis.
Psychopharmacology
May 27, 2017
Patrick C. Dolder, Felix Müller, Yasmin Schmid et al.
118 citations
MDMA produces subjective, emotional, sexual, and endocrine effects that are clearly distinct from those of methylphenidate and modafinil at the doses tested. The findings indicate that each drug has a unique profile of effects, with MDMA showing a pattern that differs from the stimulants methylphenidate and modafinil.
British Journal of Clinical Pharmacology
March 19, 2019
Friederike Holze, Urs Duthaler, Patrick Vizeli et al.
72 citations
After a 100 μg oral dose of LSD, plasma levels peak at about 1.7 hours and decline with a half-life of 3.6 hours. The main metabolite O-H-LSD peaks later, around 5 hours, and has a longer half-life of 5.2 hours. No sex differences in pharmacokinetics were observed. Subjective effects last an average of 8.5 hours, peaking at 2.5 hours. The concentration needed to produce half-maximal effects is 1.0 ng/mL for good effects and 1.9 ng/mL for bad effects, showing that subjective experiences closely track plasma concentrations over time.
Psychopharmacology
January 25, 2022
Felix Müller, Elias Kraus, Friederike Holze et al.
64 citations
Up to 9.2% of healthy volunteers reported reoccurring drug-like experiences after taking LSD or psilocybin in controlled studies, but none met the criteria for hallucinogen-persisting perception disorder (HPPD). The experiences were mostly mild, visual, brief, and perceived as neutral or pleasant, with no impairment in daily life. Distressing experiences occurred in two subjects but subsided spontaneously. The findings suggest that flashbacks are not a clinically relevant problem in controlled settings with healthy participants.
Psychological Medicine
October 2, 2017
André Schmidt, Felix Müller, Claudia Lenz et al.
62 citations
Activating the serotonin 2A receptor with LSD impairs the brain's ability to stop or inhibit responses, and this breakdown is linked to visual hallucinations. In a double-blind, placebo-controlled experiment with 18 healthy adults, LSD reduced brain activity in regions including the frontal and cingulate cortex, middle temporal gyrus, and cerebellum during a response-inhibition task. Parahippocampal activation related differently to performance under LSD versus placebo. Less activation in the left superior frontal gyrus during LSD exposure was associated with greater cognitive impairment and visual imagery. The findings suggest that 5-HT2A receptor activation disrupts hippocampal-prefrontal circuits, which may promote visual hallucinations.
Neuroscience & Biobehavioral Reviews
November 12, 2018
Felix Müller, Raphael Brändle, Matthias E. Liechti et al.
52 citations
A meta-analysis of neuroimaging studies found that people who use MDMA (ecstasy) have significantly lower serotonin transporter (SERT) density in eight out of thirteen brain regions examined, compared to non-users. The reduction in SERT density was positively associated with the duration of abstinence, suggesting that these brain changes may be partially reversible with sustained abstinence. No significant differences were found between users and controls in neurochemical ratios in the frontal and occipital lobes or in blood flow in the basal ganglia. The analysis included 356 MDMA users and 311 controls from sixteen studies, but the user groups showed heavy use patterns and the overall study quality was poor.
Neuropsychopharmacology
April 25, 2023
Peter Bedford, Daniel J. Hauke, Zheng Wang et al.
43 citations
Lysergic acid diethylamide (LSD) predominantly strengthens interregional connections and reduces self-inhibition across the brain, except in occipital and subcortical regions where connections weaken and self-inhibition increases. These patterns suggest LSD perturbs the brain's excitation/inhibition balance. Whole-brain effective connectivity, assessed via regression dynamic causal modelling of resting-state fMRI data from 45 participants in two placebo-controlled trials, discriminated LSD from placebo with 91.11% accuracy and correlated with global subjective effects, indicating potential for decoding subjective experiences.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
April 29, 2022
Mihai Avram, Felix Müller, Helena Rogg et al.
43 citations
Psychedelics, empathogens, and psychostimulants produce increased connectivity between the thalamus and sensorimotor areas of the brain, a pattern similar to that observed in individuals with psychotic disorders. This suggests a shared neural mechanism across these substances and certain psychiatric conditions, linking altered thalamocortical communication to changes in perception and behavior.
Frontiers in Psychiatry
October 13, 2021
Mihai Avram, Helena Rogg, Αλεξάνδρα Κορδά et al.
43 citations
Classic psychedelics and acute psychosis share overlapping disruptions in brain connectivity, particularly involving the thalamus and its connections to cortical regions. Both states exhibit hyperconnectivity between the thalamus and sensorimotor cortices, linked to altered perceptions and hallucinations. Psychosis also shows hypoconnectivity between the thalamus and prefrontal cortices, associated with cognitive disturbances. These patterns of thalamocortical dysconnectivity extend to cortico-striato-pallido-thalamo-cortical circuitry. The review synthesizes neuroimaging and neuropharmacological evidence to highlight shared and distinct neurophysiological changes, suggesting clinically relevant parallels that may inform future research on perception and cognition.
Neuropsychopharmacology
November 20, 2020
Felix Müller, Friederike Holze, Patrick C. Dolder et al.
43 citations
The non-hallucinogenic drug MDMA reduces functional connectivity within several resting-state brain networks, including the default mode network, visual networks, and the sensorimotor network. These decreases closely match those previously reported for hallucinogenic drugs like LSD. The findings suggest that such connectivity changes are not specific to serotonergic hallucinogens but can be induced by monoaminergic stimulation without marked subjective drug effects. However, alterations within the default mode network may help explain the antidepressant effects of some of these substances.
The British journal of psychiatry : the journal of mental science
September 1, 2024
Friederike Holze, Peter Gasser, Felix Müller et al.
32 citations
A long-term follow-up of a double-blind, placebo-controlled crossover trial found that LSD-assisted therapy produced sustained reductions in anxiety and depression for up to 94 weeks after the last treatment. Participants who received LSD first showed a decrease of 21.6 points on the State-Trait Anxiety Inventory, and those who received LSD second showed a decrease of 16.5 points, both statistically significant. Comorbid depression also improved, with Beck Depression Inventory scores dropping by 8.1 and 8.9 points in the two groups. Personality traits shifted toward lower neuroticism and higher extraversion. Patients attributed lasting positive effects to the psychedelic experience.
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.
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.
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.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
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Translational psychiatry
September 4, 2024
Patrick Vizeli, Erich Studerus, Friederike Holze et al.
15 citations
LSD dose is the strongest predictor of the drug's subjective and autonomic effects, but non-pharmacological factors also play a significant role. Pre-drug mood states—such as well-being, emotional excitability, and anxiety—predict subjective effects, heart rate, and body temperature. The personality trait openness to experiences correlates with stronger mystical-type effects and oceanic boundlessness. Prior hallucinogen use is linked to less anxious ego dissolution and a less intense overall altered state. Acute anxiety relates negatively to the functionality of the Cytochrome 2D6 enzyme. Sex and body weight do not significantly influence the drug experience.
JAMA psychiatry
June 1, 2025
Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid et al.
14 citations
Repeated low doses of LSD (20 μg twice weekly for six weeks) did not reduce ADHD symptoms more than placebo in adults with moderate-to-severe ADHD. In a double-blind randomized trial with 53 participants, the LSD group showed an average 7.1-point improvement on the ADHD symptom scale, while the placebo group improved by 8.9 points—a difference that was not statistically significant. The treatment was physically safe and psychologically well tolerated. The findings suggest that microdosing LSD, despite popular interest, offers no advantage over placebo for ADHD symptom relief.