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Rainer Spanagel

14 papers in the library · 211 citations · publishing 2020-2026

Papers

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Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder.

Translational Psychiatry May 26, 2026 Marvin M. Urban, Lea Zillich, Nathalie M. Rieser et al. 1 citation

The serotonergic hallucinogen psilocybin has shown potential as a treatment for psychiatric conditions like alcohol use disorder (AUD) and depression in clinical studies. Epigenetic mechanisms, including DNA methylation, are hypothesized to contribute to its lasting therapeutic benefits. In this exploratory study, we present the first methylome-wide analysis of psilocybin-induced changes in a...

Oxa-noribogaine reduces alcohol drinking through aversion learning and by altering glutamatergic activity in the mPFC

Research Square March 31, 2026 Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.

Abstract Alcohol use disorder is a major global health problem, and current treatments often fail to produce lasting reductions in harmful drinking1,2. Psychedelic-assisted therapies may promote durable behavioural change by enhancing brain plasticity during emotionally meaningful experiences, but progress has been limited by a lack of experimental models that capture these context-dependent...

Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons.

Elife March 27, 2026 Målin Schmidt, Anne Hoffrichter, Mahnaz Davoudi et al. 3 citations

Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from...

(R)-Ketamine reduces alcohol intake and alcohol seeking induced by reconsolidation of alcohol-related memories in female Marchigian Sardinian alcohol-preferring rats.

Psychopharmacology November 15, 2025 Elisabetta Ciccocioppo, Sara Massetti, Marcus W. Meinhardt et al.

Alcohol use disorder (AUD) represents a significant medical challenge, with available therapeutic approaches having limited efficacy. Emerging data suggest that psychedelic compounds could represent an alternative treatment for AUD. Among this class of molecules, ketamine, a dissociative psychedelic, shows promising properties. It reduces alcohol drinking in rodents and in humans it is used to...

Behavioral Neurobiology of Alcohol Addiction: A Decade of Great Challenges, New Hopes, and Hypes.

Current Topics in Behavioral Neurosciences July 12, 2025 Wolfgang H. Sommer, Rainer Spanagel

Over a decade after the first edition of "Behavioral Neurobiology of Alcohol Addiction," this chapter revisits the field at a critical juncture, marked by both persistent challenges and emerging opportunities. We reflect on the translational gap that has stalled the development of new treatments for alcohol use disorder (AUD), despite decades of promising preclinical findings. Particular...

A new module in the drug development process: preclinical multi-center randomized controlled trial of R-ketamine on alcohol relapse.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1, 2025 Marcus W. Meinhardt, Ivan Skorodumov, Jérôme Jeanblanc et al. 8 citations

The drug development process in psychiatry faces significant challenges due to low reproducibility rates in animal testing, which often leads to translation failures. To address this issue, we introduce a new approach in psychiatric drug development: a preclinical randomized controlled trial (preRCT). To demonstrate its potential utility, we conducted a multi-center preRCT using the alcohol...

Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Translational Psychiatry December 5, 2024 Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al. 6 citations

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse....

Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.

Neuroscience November 1, 2024 Veronika Pohořalá, Martin Kuchař, Rainer Spanagel et al. 3 citations

There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models....

Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons

Research Square June 7, 2024 Målin Schmidt, Anne Hoffrichter, Mahnaz Davoudi et al. 5 citations

Abstract Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons...

Prefrontal Electrophysiological Biomarkers and Mechanism-Based Drug Effects in a Rat Model of Alcohol Addiction

Research Square February 22, 2024 Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.

Abstract Current treatments for alcohol use disorder (AUD) show large heterogeneity in response and thus limited effectiveness and high relapse rates. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced...

Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats

Translational Psychiatry December 14, 2023 Ivan Skorodumov, Rainer Spanagel, Jonathan R Reinwald et al. 25 citations

Abstract Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in...

Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney’s lesions

European Archives of Psychiatry and Clinical Neuroscience November 7, 2023 Ana-Maria Iorgu, Andrei-Nicolae Vasilescu, Natascha Pfeiffer et al. 2 citations

Abstract S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HT 2A R) agonist, are reported as effective rapid-acting antidepressants. Both compounds increase glutamate signalling and evoke cortical hyperexcitation. S-ketamine induces neurotoxicity especially in the retrosplenial cortex (Olney’s lesions). Whether...

Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse

Neuropsychopharmacology May 5, 2020 Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov et al. 66 citations

For most psychiatric disorders, including alcohol use disorder (AUD), approved pharmacological treatments are limited in their effectiveness, and new drugs that can easily be translated into the clinic are needed. Currently, great hope lies in the potential of psychedelics to effectively treat AUD. The primary hypothesis is that a single session of psychedelic-guided psychotherapy can restore...