The suboptimal efficacy of currently available drugs in mental health care points towards a large and unmet clinical need to investigate novel approaches to combine pharmacotherapy and psychotherapy. Recently, psychedelic compounds such as ketamine, psilocybin, LSD and dimethyltryptamine (DMT) were discovered to alleviate symptoms of anxiety and depression in a rapid-acting manner.

Our goal is to investigate the therapeutic potential of psychoactive compounds to reverse maladaptive neurobehavioral patterns in stress-related mood disorders and to enhance psychotherapeutic learning capabilities. Based on these findings, we are developing novel transformation-based treatments for the safe, rapid-acting and sustainable treatment of affective disorders.

Iterative research and development program towards process-oriented transformative psychotherapy

As an alternative to widely used symptom- and substitution-oriented treatments in psychiatry, we develop novel process-oriented paradigms that are less focused on specific symptoms and their substitution by means of psychotropic drugs, but rather aim at directly resolving underlying maladaptive processes. Our iterative research and development program is based on clinical evidence that psychedelic compounds in supportive settings facilitate transformative experiences that are followed by rapid and sustainable decreases in anxiety, depression, posttraumatic stress and addictive behaviors.

Psychotherapy research is moving away from the era of protocols for symptom-based diagnostic categories towards personalized, transdiagnostic and modular approaches. For clinical trials with psychedelic compounds, we develop a specifically tailored process-based treatment manual to investigate the temporal dynamics of changeable transdiagnostic processes using ecological momentary assessment (EMA) technologies. This manual will allow the comparative empirical assessment of the potential of psychedelic compounds to specifically enhance the therapeutic efficacy of psychotherapeutic interventions in different patient populations.

Multimodal brain imaging study of ayahuasca-analogue psychointegrative compounds in healthy subjects

Within this project, ​we are developing a standardized and quality-controlled botanical extract analogue to traditional ayahuasca preparations with the goal to assess its safety and tolerability in healthy subjects. Using state-of-the-art multimodal neuroimaging technology we will investigate how pharmacological modulation of glutamate- and serotonin-responsive cerebral circuits predict behavioral change in terms of enhanced adaptive neuroplasticity, emotion regulation, psychological flexibility, and mindfulness-related capabilities.

Clinical studies about efficacy of ayahuasca-based psychotherapy for stress-related affective disorders


While ketamine and psilocybin have been researched extensively in the past decades, the plant medicine ayahuasca currently stimulates a tremendous public and scientific interest due to its antidepressant, anxiolytic and anti-addictive properties ​(​Frecska, 2016; ​​Labate, 2013). ​Ayahuasca has been used in the Amazon as traditional indigenous medicine but is currently spreading all over the world with increasing numbers of Westerners seeking treatment in established retreat centers in South America​ ​(​​​Tupper, 2008). ​

This rapid dissemination points to 1) an unmet need for increased psychosocial well-being through rapid and sustainable relief from various mental health problems and 2) the observational evidence that ayahuasca provides a pharmacological tool to facilitate transformational processes with beneficial health outcomes. In this context, Reconnect aims to further investigate biomechanisms and clinical efficacy of ayahuasca-assisted psychotherapy for stress-related mood disorders.

Developing machine learning methods for characterizing, predicting and optimizing the contextual factors of psychotropic drug effects


In contrast to conventional antidepressant drugs, the neuroplasticity-inducing properties of ayahuasca highlight the importance and modulatory role of contextual factors for beneficial effects on mental health. This project aims at analyzing epidemiological data from the Global Ayahuasca Survey providing information about ayahuasca consumption, beneficial health effects and side effects, as well as a broad range of bio-psycho-social context variables.

The translational application of machine learning algorithms developed in this project will: 1) promote improvements in safety and tolerability of pharmacologically-assisted therapy concepts, 2) derive empirically testable hypotheses for clinical studies, and 3) translate epidemiological findings towards effective personalized medicine.

Transformative Psychotherapy: an interview with Milan Scheidegger

Milan Scheidegger talks about the challenges of developing a novel treatment approach based on psychedelic medicines: read interview

Integrating ayahuasca into western healthcare: an interview with Milan Scheidegger

In the first part of our interview, we compared western psychedelic lab research to American indigenous use of psychedelics: read interview (part 1)

Here is part 2, in which we discuss translating specific aspects of indigenous psychedelic ritual into the context of western healthcare:
read interview (part 2)



ORCID iD iconorcid.org/0000-0003-1313-2208

Bewusstseinserweiternde Substanzen als neue Möglichkeit der Therapie
Scheidegger M.
Info Neurologie & Psychiatrie, 2018; 16(1): 28–30.

Psychedelic medicines and their role in shifting the paradigm from pharmacological substitution towards transformation-based psychiatry
Scheidegger M.
In: Labate BC, Cavnar C (eds): Ayahuasca Healing and Science. Cham, Switzerland: Springer, 2020 (in press).

Comparative phenomenology and neurobiology of meditative and psychedelic states of consciousness: Implications for psychedelic-assisted therapy
Scheidegger M.
In: Grob, C.S., Grigsby, J. (eds.): Handbook of Medical Hallucinogens. New York: Guilford Publications, 2020 (in press).

Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat.
Smigielski L, Kometer M, Scheidegger M, Kraehenmann R, Huber T, Vollenweider FX.
Nature Sci Rep. 2019 Oct 24;9(1):14914. doi: 10.1038/s41598-019-50612-3.

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects.
Smigielski L*, Scheidegger M*, Kometer M, Vollenweider FX.
Neuroimage. 2019 Apr 6. pii: S1053-8119(19)30295-2. doi: 10.1016/j.neuroimage.2019.04.009.

Comparing Mental Health across Distinct Groups of Users of Psychedelics, MDMA, Psychostimulants, and Cannabis.
Rougemont-Bücking A, Jungaberle H, Scheidegger M, Merlo MCG, Grazioli VS, Daeppen JB, Gmel G, Studer J.
J Psychoactive Drugs. 2019 Mar 6:1-11. doi: 10.1080/02791072.2019.1571258.

Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine.
Gärtner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Böker H, Hättenschwiler J, Seifritz E, Grimm S*, Scheidegger M*.
Eur Neuropsychopharmacol. 2019 Feb 25. pii: S0924-977X(19)30166-X. doi: 10.1016/j.euroneuro.2019.02.008.

Positive psychology in the investigation of psychedelics and entactogens: A critical review.
Jungaberle H, Thal S, Zeuch A, Rougemont-Bücking A, von Heyden M, Aicher H, Scheidegger M.
Neuropharmacology. 2018 Nov;142:179-199. doi: 10.1016/j.neuropharm.2018.06.034. Epub 2018 Jun 30. Review.

Aberrant working memory processing in major depression: evidence from multivoxel pattern classification.
Gärtner M, Ghisu ME, Scheidegger M, Bönke L, Fan Y, Stippl A, Herrera-Melendez AL, Metz S, Winnebeck E, Fissler M, Henning A, Bajbouj M, Borgwardt K, Barnhofer T, Grimm S.
Neuropsychopharmacology. 2018 Aug;43(9):1972-1979. doi: 10.1038/s41386-018-0081-1. Epub 2018 May 2.

In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.
Wyss PO, Bianchini C, Scheidegger M, Giapitzakis IA, Hock A, Fuchs A, Henning A.
Magn Reson Med. 2018 Aug;80(2):452-461. doi: 10.1002/mrm.27067. Epub 2018 Jan 17.

Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.
Holst SC, Sousek A, Hefti K, Saberi-Moghadam S, Buck A, Ametamey SM, Scheidegger M, Franken P, Henning A, Seifritz E, Tafti M, Landolt HP.
Elife. 2017 Oct 5;6. pii: e28751. doi: 10.7554/eLife.28751.

Neural underpinnings of prosexual effects induced by gamma-hydroxybutyrate in healthy male humans.
Bosch OG, Havranek MM, Baumberger A, Preller KH, von Rotz R, Herdener M, Kraehenmann R, Staempfli P, Scheidegger M, Klucken T, Seifritz E, Quednow BB.
Eur Neuropsychopharmacol. 2017 Apr;27(4):372-382. doi: 10.1016/j.euroneuro.2017.02.006. Epub 2017 Mar 8.

Effects of serotonin 2A/1A receptor stimulation on social exclusion processing.
Preller KH, Pokorny T, Hock A, Kraehenmann R, Stämpfli P, Seifritz E, Scheidegger M, Vollenweider FX.
Proc Natl Acad Sci U S A. 2016 May 3;113(18):5119-24. doi: 10.1073/pnas.1524187113. Epub 2016 Apr 18.

Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network.
Lehmann M, Seifritz E, Henning A, Walter M, Böker H, Scheidegger M*, Grimm S*.
Soc Cogn Affect Neurosci. 2016 Aug;11(8):1227-35. doi: 10.1093/scan/nsw034. Epub 2016 Apr 13.

Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation.
Scheidegger M, Henning A, Walter M, Lehmann M, Kraehenmann R, Boeker H, Seifritz E, Grimm S.
Hum Brain Mapp. 2016 May;37(5):1941-52. doi: 10.1002/hbm.23148. Epub 2016 Feb 25.

Effects of ketamine on cognition-emotion interaction in the brain.
Scheidegger M, Henning A, Walter M, Boeker H, Weigand A, Seifritz E, Grimm S.
Neuroimage. 2016 Jan 1;124(Pt A):8-15. doi: 10.1016/j.neuroimage.2015.08.070. Epub 2015 Sep 5.

Fast iterative pre-emphasis calibration method enabling third-order dynamic shim updated fMRI.
Fillmer A, Vannesjo SJ, Pavan M, Scheidegger M, Pruessmann KP, Henning A.
Magn Reson Med. 2016 Mar;75(3):1119-31. doi: 10.1002/mrm.25695. Epub 2015 May 7.

Glutamatergic and neurometabolic alterations in chronic cocaine users measured with (1) H-magnetic resonance spectroscopy.
Hulka LM, Scheidegger M, Vonmoos M, Preller KH, Baumgartner MR, Herdener M, Seifritz E, Henning A, Quednow BB.
Addict Biol. 2016 Jan;21(1):205-17. doi: 10.1111/adb.12217. Epub 2014 Dec 30.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.
Kraehenmann R, Preller KH, Scheidegger M, Pokorny T, Bosch OG, Seifritz E, Vollenweider FX.
Biol Psychiatry. 2015 Oct 15;78(8):572-81. doi: 10.1016/j.biopsych.2014.04.010. Epub 2014 Apr 26.

Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans.
Bosch OG, Rihm JS, Scheidegger M, Landolt HP, Stämpfli P, Brakowski J, Esposito F, Rasch B, Seifritz E.
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19597-602. doi: 10.1073/pnas.1317010110. Epub 2013 Nov 11.

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans.
Hulka LM, Treyer V, Scheidegger M, Preller KH, Vonmoos M, Baumgartner MR, Johayem A, Ametamey SM, Buck A, Seifritz E, Quednow BB.
Mol Psychiatry. 2014 May;19(5):625-32. doi: 10.1038/mp.2013.51. Epub 2013 Apr 30.

Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.
Scheidegger M*, Walter M*, Lehmann M, Metzger C, Grimm S, Boeker H, Boesiger P, Henning A, Seifritz E.
PLoS One. 2012;7(9):e44799. doi: 10.1371/journal.pone.0044799. Epub 2012 Sep 24.

Increased metabotropic glutamate receptor subtype 5 availability in human brain after one night without sleep.
Hefti K, Holst SC, Sovago J, Bachmann V, Buck A, Ametamey SM, Scheidegger M, Berthold T, Gomez-Mancilla B, Seifritz E, Landolt HP.
Biol Psychiatry. 2013 Jan 15;73(2):161-8. doi: 10.1016/j.biopsych.2012.07.030. Epub 2012 Sep 7.

(*) equal contribution

Disclaimer: The information on this website is not intended to encourage the use of ethnobotanicals or psychoactive substances. Transformative Psychotherapy specifically cautions against the use of psychedelics in violation of the law, without appropriate professional guidance and monitoring, or without careful personal evaluation of potential risks and hazards.