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 4, 2017
Felix Mueller, Claudia Lenz, Patrick C. Dolder et al.
124 citations
Lysergic acid diethylamide (LSD) reduces reactivity in the left amygdala and right medial prefrontal cortex when processing fearful faces, compared to a placebo. In a double-blind, randomized, crossover study, 20 healthy adults received either 100 μg of LSD or a placebo before undergoing functional magnetic resonance imaging (fMRI). Plasma LSD levels were measured before and after the scan. A significant negative correlation emerged between the reduced amygdala response to fearful stimuli and the subjective drug effects reported by participants. These findings indicate that LSD alters the engagement of brain regions involved in emotional processing.
Current Pharmaceutical Design
May 10, 2014
Johannes Wrege, André Schmidt, Anna Walter et al.
96 citations
A systematic review of 17 studies (13 meeting inclusion criteria) examined cannabis's effects on impulsivity, disinhibition, and motor control, with a focus on neuroimaging findings from acute and chronic use up to May 2012. Functional imaging studies indicate that chronic cannabis users have lower prefrontal blood flow than controls, while acute administration of THC or marijuana increases brain metabolism in several regions during impulsivity tasks. Structural imaging studies found reduced prefrontal volumes and white matter integrity in cannabis users, which may mediate abnormal impulsivity and mood. The review concludes that more longitudinal studies are needed to determine whether impulsivity precedes cannabis use or cannabis aggravates impulsivity and discontinuation.
Journal of Substance Abuse Treatment
July 1, 2022
Patrick Köck, Katharina Froelich, Marc Walter et al.
68 citations
Ibogaine and its alkaloids reduce withdrawal symptoms and craving in substance use disorders, and may also improve depression and trauma-related symptoms. However, severe medical complications and deaths have been reported, linked to neuro- and cardiotoxic effects. Two fatalities occurred among 705 individuals across 24 studies, which included two randomized controlled trials and 17 open-label studies. Ibogaine's distinct psychoactive and somatic effects set it apart from classic hallucinogens like LSD and psilocybin. Rigorous medical monitoring is needed for safe application.
Neuroscience & Biobehavioral Reviews
December 30, 2015
Felix Mueller, Claudia Lenz, Markus Steiner et al.
68 citations
Moderate use of MDMA (ecstasy) shows no convincing evidence of structural or functional brain alterations in neuroimaging studies. A review of 19 studies, each involving subjects with fewer than 50 lifetime episodes or under 100 tablets consumed, found no significant harmful effects. However, the lack of results is linked to high methodological variability in dosages and co-consumption of other drugs, low study quality, and small sample sizes.
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.
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.
Psychiatry Research
January 29, 2025
Felix Müller, Thomas Sauer, Corina Hänny et al.
11 citations
A 60-year-old man with recurrent depression and a history of delusions died after psilocybin-assisted therapy. Psilocybin-triggered delusions and emotional dysregulation may have contributed to the death. A weak therapeutic alliance hindered assessment of the patient's internal state. Delusional symptoms may contraindicate psychedelic interventions. The case emphasizes the need for thorough assessment and close follow-up in complex cases.
Frontiers in Psychiatry
January 23, 2024
Johannes Hauser, Jan Sarlon, Timur Liwinski et al.
10 citations
Listening to music during intranasal (es)ketamine treatment for therapy-resistant depression is linked to reduced anxiety and lower blood pressure, stable or increased dissociation, and tolerance for higher doses. In a review of 494 sessions from 37 patients, those who listened to music received higher average doses (131.5 mg vs. 116.7 mg), reported less anxiety (0.4 vs. 1.4 points), and had lower peak systolic blood pressure (137.9 vs. 140.3 mmHg) compared to those who did not. Music did not affect depression scores between sessions.
European Archives of Psychiatry and Clinical Neuroscience
June 1, 2025
Jan Sarlon, Else Schneider, Annette B Brühl et al.
2 citations
Adding a daily 30-day mindfulness mobile app (Headspace) to standard treatment helped reduce depression severity more than standard treatment alone in people with major depressive disorder. In a randomized trial with 83 patients, those using the app showed a significantly greater decrease in clinician-rated depression scores (HDRS) and lower systolic blood pressure after one month. Both groups improved from partial remission at hospital discharge, but the app group improved more. The total dropout rate was 29%. Short-term app-based mindfulness appears beneficial as a supplement to usual care.
Journal of Affective Disorders
January 21, 2026
Jan Sarlon, Deanne Thomi, Annette B Brühl et al.
1 citation
Intranasal racemic ketamine is non-inferior to esketamine for reducing depression symptoms in adults with treatment-resistant depression, with comparable symptom improvement over four weeks. However, remission rates were higher with esketamine (38.7%) than with racemic ketamine (15.6%), and racemic ketamine failed to meet non-inferiority for remission. Safety profiles were similar, though racemic ketamine caused slightly more transient blood pressure elevations. Racemic ketamine may be a cost-effective alternative where esketamine access is limited, but higher remission with esketamine warrants further study.
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.