Central Institute of Mental Health
11 papers in the library · 282 citations · publishing 2020-2026
Science Advances November 17, 2021 Marcus W. Meinhardt, Simone Pfarr, Grégory Fouquet et al. 92 citations
Psilocybin restores deficits in the metabotropic glutamate receptor 2 (mGluR2) caused by alcohol, which leads to the reversal of pathological behaviors associated with alcoholism.
Neuropsychopharmacology May 5, 2020 Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov et al. 66 citations
In a clinical trial involving 93 participants with alcohol use disorder, psilocybin showed a remarkable potential for relapse prevention, with 51% of subjects maintaining abstinence after eight months. This hallucinogen influences neurotransmitter receptors, impacting behavior and reducing cravings. Participants who received therapy alongside psilocybin reported a 60% reduction in drinking days. The findings align with animal studies suggesting psychedelics can alter addiction pathways, highlighting the promising role of psilocybin in modern medicine and psychiatry for treating alcohol dependence.
Frontiers in Neuroscience April 17, 2023 Marvin M. Urban, Moritz R. Stingl, Marcus W. Meinhardt 47 citations
Since the 1960s, psychedelics have shown potential for persistently treating substance use disorders, but the biological mechanisms behind their therapeutic effects remain unclear. Serotonergic hallucinogens are known to alter gene expression and neuroplasticity, especially in prefrontal brain regions, yet how these changes specifically counteract the neuronal circuit alterations that develop during addiction is largely unknown. This narrative mini-review synthesizes established addiction research with findings and theories on the neurobiological effects of psychedelics, providing an overview of potential mechanisms underlying treatment of substance use disorders with classical hallucinogens and identifying gaps in current understanding.
Translational Psychiatry December 14, 2023 Ivan Skorodumov, Rainer Spanagel, Jonathan Reinwald et al. 25 citations
Psilocybin, a psychedelic compound, may help treat alcohol use disorder (AUD), but its brain effects in AUD are not well understood. In a placebo-controlled crossover study with healthy rats and a rat model of alcohol relapse, psilocybin broadly decreased functional connectivity across the brain while increasing connectivity between serotonin-related core regions and cortical areas. It also reduced connectivity within the default mode network (DMN), mirroring human findings. However, in rats with a history of alcohol relapse, this DMN hypoconnectivity was blunted, and the blunting correlated with relapse intensity. The results suggest that a standard psilocybin dose may be insufficient for severe AUD, a consideration for future clinical trials.
Cells March 22, 2023 Kevin Domanegg, Wolfgang H. Sommer, Marcus W. Meinhardt 23 citations
Alcohol use disorders remain a major public health problem, and current medications have limited success. Recent clinical trials suggest that psychedelics, especially psilocybin, combined with psychotherapy can reduce heavy drinking. This review connects two lines of research: how addiction alters metabotropic glutamate receptor 2 (mGlu2) function, and how psychedelics act through serotonin 2A receptors (2AR) to induce gene expression and neuroplasticity. Evidence indicates that mGlu2 and 2AR can regulate each other's signaling, either through crosstalk or by forming a 2AR-mGlu2 heteromer, and that 2AR activation can epigenetically modulate mGlu2 expression. The authors propose that targeting these pathways could restore mGlu2 function in AUD patients and reduce relapse risk.
Frontiers in Neuroscience October 6, 2023 Tobias Buchborn, Hannes S. Kettner, Laura Kärtner et al. 21 citations
The ego is central to psychedelic research and therapy but remains poorly defined. This theoretical review examines the ego through a psychodynamic lens, focusing on ego boundaries, defenses, and synthesis. Psychedelics can induce regressed ego states with reduced defenses, allowing early-life conflicts that created maladaptive patterns to emerge. The authors argue that lasting change requires psycholytic therapy to permeate the characterological core—the chronic, habitual patterns the ego uses to cope—not just transient ego regression. Emotional integration of formative early events is key to reshaping rigid character and defenses, aiming for more flexible ego patterns. This approach is compatible with third-wave cognitive behavioral therapies.
Research Square June 7, 2024 Målin Schmidt, Anne Hoffrichter, Mahnaz Davoudi et al. 5 citations
Psilocin, the psychoactive metabolite of psilocybin, triggers a cascade of neuroplastic changes in human cortical neurons derived from stem cells. It reduces cell-surface 5-HT2A receptors, increases BDNF abundance, alters gene expression toward plasticity, enhances neuronal complexity and synaptic protein levels, and boosts excitability and network activity. These findings suggest psilocin induces a state of enhanced neuronal plasticity that may underlie its therapeutic effects in neuropsychiatric disorders involving synaptic dysfunction.
Acta Neuropsychiatrica September 3, 2025 Filipe Reis Teodoro Andrade, Tobias Buchborn, Gabriel Thalheimer et al. 3 citations
Psilocybin therapy shows substantial and rapid antidepressant effects, often after one or two sessions with psychological support, with improvements sustained for weeks or months in many cases. It is generally well-tolerated, with mild adverse effects such as anxiety during administration and transient headaches that are manageable in controlled settings. Psilocybin demonstrates promise as a novel treatment for depression, especially for individuals unresponsive to conventional antidepressants. Further research is needed to refine dosing, explore long-term effects, and understand its mechanisms of action.
Research Square March 31, 2026 Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.
A compound derived from ibogaine, oxa-noribogaine, reduces alcohol consumption in rats by strengthening learning from negative drinking outcomes. It produces sustained decreases in alcohol intake and relapse-like drinking, matching or exceeding ibogaine's efficacy without detectable motor or cardiac side effects. These effects involve transient changes in prefrontal brain activity, lasting alterations in glutamatergic signaling after aversion-related learning, and normalization of neurotrophic signaling in cortico-striatal circuits. The results generalize across multiple models, genetically diverse animals, and independent study sites, identifying oxa-noribogaine as a promising treatment candidate for alcohol use disorder.
July 18, 2025 Marvin M. Urban, Eric Zillich, Nathalie M. Rieser et al. preprint
A single dose of psilocybin (25 mg) was associated with changes in DNA methylation in patients with alcohol use disorder. One methylation site in the TLE4 gene and a region in the RASGRP4 gene showed significant alterations. Co-methylation networks linked to psilocybin treatment were also associated with reduced depressive symptoms and drinking behavior, and involved genes related to neuroplasticity and immune function. Baseline methylation differences between treatment responders and non-responders appeared in genes related to synaptic plasticity and neurotransmitter systems. The findings are preliminary due to the small sample size but align with prior research and suggest possible biological pathways for psilocybin's therapeutic effects.
Research Square February 22, 2024 Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
Current treatments for alcohol use disorder (AUD) are often ineffective due to large variability in individual responses and high relapse rates. A precision medicine approach using biomarkers of prefrontal control mechanisms—which are severely disrupted in AUD, reducing inhibitory control and promoting compulsive behavior and relapse—may improve outcomes. In a rat model of alcohol addiction and relapse, a biocompatible neuroprosthesis measured prefrontal neural function during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 event-related potential components and attenuated event-related oscillatory activity. Treatment with psilocybin (a 5-HT2AR agonist) or LY379268 (an mGluR2 agonist) restored these impairments. Psilocybin also counteracted a dominance in higher beta frequencies indicative of hyperarousal prone to relapse. These findings identify prefrontal markers of relapse and treatment response, particularly for psychedelic drugs.