Frontiers in Pharmacology
November 8, 2017
Rainer Kraehenmann, Dan Pokorný, Helena Aicher et al.
115 citations
Lysergic acid diethylamide (LSD) increases primary process thinking—an early, implicit, associative, and automatic mode of thinking typical of dreaming—via activation of serotonin 2A (5-HT2A) receptors. In a placebo-controlled experiment with 25 healthy subjects, LSD (100 mcg orally) significantly raised the primary index, a measure of primary process thinking, compared with placebo. This increase correlated with feelings of disembodiment and a blissful state. Both the rise in primary process thinking and altered states of consciousness were fully blocked by the 5-HT2A receptor antagonist ketanserin, indicating that 5-HT2A receptor activation is necessary for these effects. Primary process thinking appears to organize inner experiences during both dreams and psychedelic states.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
Neuropharmacology
November 1, 2018
Henrik Jungaberle, Sascha Thal, Andrea Zeuch et al.
70 citations
A review of 77 studies with 9876 participants examined how psychedelics and entactogens relate to positive psychology—the study of healthy functioning, well-being, and eudaemonia. The substances produced acute and long-term effects on mood, well-being, prosocial behaviors, empathy, cognitive flexibility, creativity, openness, value orientations, nature-relatedness, spirituality, self-transcendence, and mindfulness-related capabilities. Evidence is preliminary due to methodological restrictions. Longitudinal data on both positive and adverse effects are lacking, so more rigorous, standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to assess the benefit-risk ratio.
Frontiers in Psychiatry
January 1, 2023
Helena Aicher, Michael J Mueller, Dario Dornbierer et al.
34 citations
A standardized formulation combining the monoamine oxidase inhibitor harmine (100 mg orodispersible tablet) with incremental intranasal N,N-dimethyltryptamine (DMT, up to 100 mg) produced a psychedelic experience in 31 healthy male subjects, as measured by the 5D-ASC rating scale. The experience was characterized by psychological insights, emotional breakthroughs, and low scores on challenging experiences. Participants reported personal and spiritual significance and mainly positive persisting effects at 1- and 4-month follow-ups. No changes in trait personality, psychological flexibility, general well-being, or increases in psychopathology were observed. The formulation appears well tolerated and may support psychotherapy, but further studies in patients are needed.
Frontiers in Pharmacology
January 1, 2023
Dario Dornbierer, Laurenz Marten, Jovin Mueller et al.
32 citations
Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.
Cellular and molecular life sciences : CMLS
September 10, 2024
Klemens Egger, Helena Aicher, Paul Cumming et al.
30 citations
The potent hallucinogen N,N-dimethyltryptamine (DMT) alters perception, mood, and cognition, presumably through agonism at serotonin 5-HT1A/2A/2C receptors in the brain. DMT is nearly inactive orally due to rapid first-pass metabolism, but co-administration with β-carbolines or synthetic MAO-A inhibitors—as in the Amazonian brew ayahuasca—greatly increases its bioavailability and duration of action. The synergistic effects of DMT and MAOIs may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for depression, addiction, and post-traumatic stress disorder. Neuroimaging reveals alterations in brain activity, functional connectivity, and network dynamics during DMT-induced altered states.
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
Psychoactives
April 16, 2024
Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak et al.
26 citations
Psychedelic research has returned after a period of suppression, but media coverage now often overstates benefits as much as it once overstated risks. The actual evidence is more mixed than commonly portrayed, so conclusions about effectiveness remain preliminary. Poor communication may mislead patients and misinform policy. This article reviews studies on psychedelics for depression, noting that effect sizes for other depression treatments—cognitive behavioral therapy, mindfulness, SSRIs, and ketamine—have decreased over time as trials improved. The authors suggest the same may happen for psychedelics: larger, better-controlled trials will likely show smaller, more realistic benefits. Clear communication is essential to set public expectations and guide policy.
Die Psychotherapie
February 15, 2024
Helena Aicher, Yasmin Schmid, Peter Gasser
20 citations
Since the late 1990s, psychedelics have experienced a renaissance, attracting increasing international attention. Scientific studies increasingly examine the possibilities and risks of psychedelic-assisted therapy (PAT). Since 2014, based on exceptional permits from the Swiss health authority (BAG), LSD, MDMA, and psilocybin have been used therapeutically within limited medical applications on a case-by-case basis. Over the past nine years, more than 1000 exceptional permits have been granted to about 60 therapists, and an estimated 2000 to 3000 treatments with psychedelics have been conducted.
Swiss Archives of Neurology Psychiatry and Psychotherapy
May 18, 2024
Helena Aicher, Peter Gasser
17 citations
Switzerland played an early and notable role in the 21st-century revival of psychedelic science, which has generated growing global interest in using psychedelics for research and therapy. In 2023, the Swiss Interest Group for Psychedelic-assisted Therapy was formed to establish a clear, widely accepted framework for such work. The group produced a first draft of treatment recommendations (S1 guidelines) that will be regularly updated to reflect new research and therapeutic findings.
Neuroscience Applied
January 1, 2025
Matthias E. Liechti, Peter Gasser, Helena Aicher et al.
16 citations
Switzerland's limited access program for psychedelic/MDMA-assisted therapy, started in 2014 with two physicians, had grown to about 100 physicians by 2024, treating 723 patients (245 with MDMA, 130 with LSD, 348 with psilocybin). Approximately 1660 treatments occurred in 2024, with patients typically receiving 2-4 sessions within 12 months. The program is authorized by the Swiss Federal Office of Public Health for patients with mostly incurable diseases where the substance can alleviate suffering and no alternatives exist or have failed. The article describes the program's history, legal requirements, costs, professional roles, education, patient characteristics, outcomes, and adverse effects, comparing it to similar programs in Canada and Australia.
Journal of Psychopharmacology
September 27, 2024
Daniel Meling, Klemens Egger, Jovin Mueller et al.
15 citations
In a double-blind, placebo-controlled study over a 3-day meditation retreat, 40 experienced meditators received either DMT-harmine or a placebo. Those who took DMT-harmine reported greater mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects, and greater psychological insight one day later after adjusting for baseline differences. Mindfulness and compassion did not differ significantly between groups. At one-month follow-up, the DMT-harmine group rated their experience as more personally meaningful, spiritually significant, and well-being-enhancing than the placebo group. The findings suggest specific synergistic effects of DMT-harmine during meditation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
March 1, 2025
Klemens Egger, Javier Jareño Redondo, Jovin Müller et al.
14 citations
Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.
The International Journal of Neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena Aicher, Dario Dornbierer et al.
10 citations
A new pharmaceutical formulation combining pure DMT and harmine produced ayahuasca-like psychological effects lasting 2-3 hours in 31 healthy male volunteers, with consistent drug levels and no serious adverse events. DMT reached peak plasma concentrations of 22.1 ng/mL, while buccal harmine reached 32.5 ng/mL in a sustained-release profile but caused no distinguishable subjective effects on its own. All drug conditions were safe and well tolerated, suggesting the formulation could reduce risks and improve therapeutic outcomes for mental health disorders.
International review of psychiatry (Abingdon, England)
December 1, 2024
Helena Aicher, Max Wolff, Uwe Herwig
10 citations
The renewed interest in psychedelics for treating mental health disorders is often called the "Psychedelic Renaissance," but this article argues it does not represent a true paradigm shift in psychiatry. Instead, the authors contend that current developments are better understood as enhancements to existing therapeutic frameworks, building on extensive mid-20th-century research. They emphasize integrating psychedelics within a broader bio-psycho-social model, combining pharmacological, psychological, and contextual factors. The therapeutic potential is described as working as "nonspecific amplifiers" of psychological processes rather than introducing entirely new mechanisms. The article cautions against "psychedelic exceptionalism" and overselling psychedelics as a revolutionary treatment, advocating for a balanced, integrative approach.
Journal of Psychoactive Drugs
November 23, 2024
Daniel Perkins, Jerome Sarris, Tessa Cowley-Court et al.
5 citations
People who consume ayahuasca in naturalistic settings—religious, traditional, or non-traditional—report better current mental health and greater psychological well-being, according to a large online survey of 7,576 participants from over 50 countries. More lifetime ayahuasca uses were linked to better mental health scores, and this association remained strong even after accounting for other factors and did not fade over time. Strong mystical experiences, self-insights, and community or social support were also tied to better mental health and well-being, whereas acute extreme fear during sessions and difficulty integrating the experience were linked to poorer outcomes. These patterns held for individuals both with and without a history of mental illness.
Current Topics in Behavioral Neurosciences
November 22, 2025
Helena Aicher, Anke Röskamp, Marianne Moser et al.
4 citations
Touch has long been central to human communication and healing, but in psychedelic-assisted therapy it raises complex ethical and practical challenges due to patients' heightened vulnerability. Recent reports of boundary violations have sharpened the debate. From a harm reduction perspective, the chapter acknowledges risks and the need for clear boundaries, transparency, informed consent, and cultural sensitivity, while arguing that touch can offer grounding, emotional support, and therapeutic value when used responsibly. Both touch and non-touch interventions are explored, including historical roots and therapeutic potentials, with ethical frameworks outlined to support safe, ethical, and effective practices.
Neuroimage
June 1, 2025
Dila Suay, Helena Aicher, Micheal Kometer et al.
4 citations
A psychedelic formulation combining DMT and harmine, inspired by ayahuasca, altered brain responses to faces in 30 healthy men. It increased early visual reactivity (P1 wave) and disrupted face-structural encoding (N170 wave) for all face types. Crucially, it reduced the neural distinction between self and other faces in the P300 wave, while familiar-face processing remained stable. Harmine alone did not produce these effects. The findings suggest psychedelics can reorganize self-related neural dynamics, potentially promoting cognitive flexibility and offering therapeutic benefits for conditions involving rigid self-focus, such as depression and social anxiety.
Translational Psychiatry
October 10, 2025
Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena Aicher et al.
3 citations
Salvinorin A, the main psychoactive compound in Salvia divinorum, shows therapeutic potential for pain, addiction, and stroke in animal models, but its side effects—including anxiety, motor and cognitive impairment—may limit clinical use. A systematic review and meta-analysis of 82 studies found anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, though depression results were inconsistent. Doses ranged from 0.1 to 10 mg/kg, with rapid onset and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles. Findings support further development of analogues to overcome the side effect profile.
Die Psychotherapie
February 8, 2024
Helena Aicher, Peter Gasser
3 citations
Early study results suggest potential for psychedelics and MDMA in treating affective disorders. This paper argues that therapist training is crucial for safe and effective use in psychedelic-assisted therapy (PAT). Different contexts, such as study settings or psychotherapeutic practice, require different qualifications. For example, the responsibilities of sitter and therapist must be distinguished, with implications for training programs. This diversity is reflected in existing international offerings. Current practice in Switzerland is based on exceptional permits from the health authority for limited medical use of LSD, MDMA, and psilocybin.
Journal of psychopharmacology (Oxford, England)
June 19, 2025
Helena Aicher, Ilhui A Wicki, Daniel Meling et al.
2 citations
A single dose of an ayahuasca-inspired DMT/harmine formulation increased mindfulness and compassion in 31 healthy participants one day after administration. The randomized, double-blind, placebo-controlled trial found significant effects on mindfulness, self-compassion, and compassion with others, with larger effects in participants who reported higher sensitivity to the drug. These results suggest the formulation may have therapeutic potential for enhancing traits relevant to mood disorders, though further research in clinical settings is needed.
bioRxiv (Cold Spring Harbor Laboratory)
December 9, 2025
Maria Niedernhuber, Dila Suay, Michael J Mueller et al.
1 citation
Classic serotonergic psychedelics strongly alter conscious awareness, but how they change the temporal structure of brain activity has been unclear. In a double-blind, placebo-controlled study with 25 participants using high-density EEG, an ayahuasca-inspired formulation (intranasal N,N-DMT and buccal harmine) accelerated neural dynamics: microstate duration decreased and state transitions became more frequent. Surprisingly, the sequence of microstates became less random, showing higher first-order Markov structure. This restructuring involved reduced transitions into one state (M2) and increased prevalence and accessibility of two others (M3 and M5). The psychedelic state thus produces a syntactically reconfigured, highly metastable neural dynamic, not mere randomization.
Research Square
July 27, 2025
Klemens Egger, Robert Bozsak, Helena Aicher et al.
1 citation
In healthy volunteers, acute administration of N,N-dimethyltryptamine (DMT) combined with harmine produces global increases in brain glucose metabolism, as measured by [¹⁸F]FDG-PET. This suggests that the compound combination broadly energizes brain activity rather than acting on isolated regions. The findings indicate a neurobiological basis for the altered states of consciousness and mood enhancement reported with these psychoactive compounds, supporting further investigation into their therapeutic potential.
medRxiv
November 1, 2024
Dila Suay, Helena Aicher, Micheal Kometer et al.
1 citation
preprint
A psychedelic formulation combining DMT and harmine, inspired by ayahuasca, blurs the brain's distinction between self and other faces. In a double-blind, placebo-controlled experiment with 31 healthy men, the DMT/harmine combination increased early visual brain responses (P1 amplitude) and disrupted the structural encoding of faces (reduced N170 amplitude) for all face types. It also specifically reduced the brain's later response (P300) to one's own face, making the neural reaction to self-faces more similar to that for familiar or unknown faces. Harmine alone did not produce these effects. The findings suggest psychedelics may reduce attentional focus on self-referential information, potentially explaining feelings of unity and enhanced empathy.
Psychopharmacology
July 14, 2026
Helena Aicher, Joëlle Dornbierer, Luzia Caflisch et al.
A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.