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.
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.
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.
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.
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.
Imaging Neurosci (Camb)
September 29, 2025
Klemens Egger, Daniel Meling, Firuze Polat et al.
1 citation
A randomized controlled trial investigated how the psychedelic compounds N,N-dimethyltryptamine (DMT) and harmine, administered during a meditation retreat, affect brain connectivity. Using resting-state fMRI, the study found that these compounds altered functional connectivity in neural networks, particularly in regions associated with self-referential thought and sensory integration. The changes in brain communication patterns were linked to enhanced psychological well-being and mental flexibility, suggesting that combining psychedelics with contemplative practices may promote neuroplasticity and cognitive enhancement. The results indicate that DMT and harmine can reorganize brain networks in ways that support meditative experiences and long-term benefits for brain health.
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.
medRxiv
Klemens Egger, Daniel Meling, Firuze Polat et al.
preprint
In a double-blind, placebo-controlled pharmaco-fMRI study, 40 meditation practitioners on a three-day retreat received either placebo or buccal DMT-harmine (120 mg each). Meditation alone increased network segregation across several resting-state networks, while DMT-harmine increased functional connectivity within the visual network and between visual and attention networks. Between-group differences showed increased connectivity between visual and salience networks in the DMT-harmine group. No prolonged cortical gradient disruption was observed, indicating a return to typical brain organization shortly after the experience. Meditation reduced connectivity between networks, whereas DMT-harmine increased within- and between-network connectivity, revealing distinct neural mechanisms.