Frontiers in Pharmacology
July 5, 2018
Eduardo Ekman Schenberg
242 citations
Psychedelic-assisted psychotherapy (PAP), involving professionally supervised use of ketamine, MDMA, psilocybin, LSD, and ibogaine within structured therapy programs, has shown safety and efficacy in clinical trials, even for treatment-resistant conditions. Beyond offering new treatments, PAP challenges the current psychiatric paradigm by questioning discrete diagnostic categories and advancing explanations for mental disorders that incorporate social and cultural factors, including adversity, trauma, and the therapeutic potential of non-ordinary states of consciousness. This model addresses the stalled innovation in psychiatric medications and the broader crisis in psychiatric diagnostics and explanations.
PLoS ONE
September 30, 2015
Eduardo Ekman Schenberg, João Felipe Morel Alexandre, Renato Filev et al.
115 citations
Ayahuasca, an Amazonian plant-based brew used ritually in Brazil and increasingly worldwide, produces a two-phase brain effect. Electroencephalogram recordings and blood measurements of the brew's compounds (DMT, harmine, harmaline, tetrahydroharmine, and their metabolites) showed that 50 minutes after ingestion, alpha brainwave power (8–13 Hz) decreased, mostly in the left parieto-occipital cortex. Between 75 and 125 minutes, slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) increased across multiple cortical regions, including left centro-parieto-occipital, left fronto-temporal, and right frontal areas. These brain changes were significantly linked to circulating levels of ayahuasca's active chemicals. The authors interpret these effects within cognitive and emotional frameworks relevant to ritual use and potential therapeutic applications.
Journal of psychopharmacology (Oxford, England)
November 1, 2014
Eduardo Ekman Schenberg, Maria Angélica De Castro Comis, Bruno Rasmussen Chaves et al.
110 citations
Ibogaine, an alkaloid used to treat drug dependence, is illegal in some countries but unregulated in Brazil, where it is combined with psychotherapy. A retrospective analysis of 75 former alcohol, cannabis, cocaine, and crack users (72% poly-drug users) found no serious adverse reactions or fatalities. 61% of participants remained abstinent. Those treated with ibogaine once reported a median abstinence of 5.5 months; those treated multiple times, 8.4 months. Both single and multiple treatments resulted in longer abstinence than before the first session. The findings suggest that physician-supervised ibogaine with psychotherapy can facilitate prolonged abstinence without fatalities, indicating it may be a safe and effective treatment for stimulant and other non-opiate drug dependence.
ACS Pharmacology & Translational Science
January 1, 2021
Konstantin Gerber, Inti García Flores, Angela Christina Ruiz et al.
54 citations
Since a 1957 Life Magazine article, chemical compounds from Psilocybe mushrooms have been the subject of many patent attempts, including recent ones for treating depression. The Mazatec indigenous communities, who have used these traditional medicines for millennia, are not included in any of these patents, despite international treaties that recognize indigenous rights to their intangible cultural heritage.
Journal of Psychedelic Studies
August 29, 2017
Eduardo Ekman Schenberg, Maria Angélica de Castro Comis, João Felipe Morel Alexandre et al.
39 citations
Patients with substance-related disorders who received ibogaine in a treatment program reported intense physical discomfort and a psychologically challenging experience, along with heightened memory retrieval—especially about past drug use—and vivid, dreamlike visions. The experience shared some features with other psychedelics but also differed markedly. The authors propose that ibogaine's subjective effects may function as simulations of threat and danger, drawing on an evolutionary theory of dreaming.
American Journal of Psychiatry
January 1, 2024
Eduardo Ekman Schenberg, Franklin King, João Eusébio Da Fonseca et al.
31 citations
Psilocybin has shown remarkable potential in psychiatry, with a study involving 100 participants revealing that 70% experienced significant reductions in anxiety and depression symptoms after treatment. This psychedelic compound, derived from mushrooms, is gaining traction in psychoanalysis and psychology for its therapeutic effects. Psychotherapists are increasingly scrutinizing its efficacy compared to traditional therapies. The chemical synthesis of psilocybin and its alkaloids could revolutionize mental health treatment, offering new avenues for those struggling with severe psychological conditions.
Journal of Psychedelic Studies
April 1, 2017
Eduardo Ekman Schenberg, Maria Angélica de Castro Comis, João Felipe Morel Alexandre et al.
29 citations
A treatment combining the psychedelic alkaloid ibogaine with cognitive-behavioral therapy led to improvements in craving, personal relationships, quality of life, and self-efficacy among people with substance use disorders, including cocaine dependence. These secondary outcomes were assessed through semi-structured interviews and qualitative content analysis. The findings support the therapeutic potential of ibogaine-assisted psychotherapy for treating substance use disorders, particularly for psychostimulants like cocaine and crack cocaine, for which effective treatments are lacking.
Archives of Clinical Psychiatry (São Paulo)
January 1, 2017
Eduardo Ekman Schenberg, Luís Fernando Tófoli, Daniel Rezinovsky et al.
28 citations
A Brazilian Portuguese version of the States of Consciousness Questionnaire (SOCQ) was produced, and the 30-item Mystical Experience Questionnaire (MEQ30) was validated in a sample of 1,504 Portuguese-speaking respondents who completed an online survey. Confirmatory factor analysis supported the same four-factor structure as the original English MEQ30, with factors showing excellent to acceptable reliability: mystical (0.95), positive mood (0.71), transcendence of time/space (0.83), and ineffability (0.81). The availability of these instruments allows systematic cross-cultural research on altered states of consciousness and mystical experiences in the Brazilian Portuguese-speaking population.
Transcultural Psychiatry
January 6, 2022
Eduardo Ekman Schenberg, Konstantin Gerber
18 citations
Recent clinical trials show evidence of therapeutic potential for ayahuasca in treating depression, but indigenous peoples have used ayahuasca therapeutically for centuries. The authors argue that epistemic injustices have been committed by attributing excessive authority to scientific studies over traditional knowledge, with practical, cultural, social, and legal consequences. They question epistemic authority based on double-blind design, molecularization discourse, and safety issues. A new approach is proposed to enforce indigenous rights, considering cases in Brazil, Peru, and Colombia. Indigenous peoples have the right to control their biocultural heritage and traditional medicine.
Journal of ethnopharmacology
February 10, 2024
Tiago Arruda Sanchez, Lucas Rego Ramos, Felipe Araujo et al.
12 citations
Ayahuasca, a traditional Amazonian beverage, attenuates brain activity in the amygdala—a region central to fear processing—when people view aversive (fearful or disgusted) faces, while enhancing activation in the insular cortex and right dorsolateral prefrontal cortex. Nineteen experienced male users underwent fMRI before and 50 minutes after ingesting ayahuasca. Self-reported anxiety and mental sedation also decreased. The findings suggest ayahuasca may promote emotion regulation in response to negative stimuli, with corresponding improvements in cognition.
Journal of Psychoactive Drugs
August 19, 2022
Marcio S. C. Longo, Bheatrix Bienemann, Marco Multedo et al.
10 citations
People who currently use ayahuasca/DMT, psilocybe mushrooms, LSD, cannabis, or MDMA/ecstasy score higher on nature relatedness than those who have never used these substances. After accounting for sociodemographic factors, only current and past use of ayahuasca/DMT remained positively associated with nature relatedness. Among those who reported an intention to use psilocybe mushrooms in the future, that intention was also linked to higher nature relatedness. The findings suggest that classic serotonergic psychedelics may have a unique relationship with nature relatedness, but the cross-sectional design cannot establish causation.
Pharmacology Research & Perspectives
April 1, 2025
Eduardo Ekman Schenberg
9 citations
Regulatory evaluation of psychedelic-assisted therapies, such as MDMA for PTSD and psilocybin for depression, faces methodological challenges because the standard requirement for two successful phase 3 randomized controlled trials (RCTs) lacks agreement on what constitutes success when psychoactive drugs are given alongside psychotherapy. This arrangement undermines the internal validity of estimated treatment effects compared with conventional controls. The paper reviews assumptions behind RCTs' gold-standard status in evidence-based medicine, highlighting limits of randomization and blinding and warning against the extrapolation fallacy. Trustworthiness that efficacy in RCTs will predict effectiveness in target populations depends on the type of treatment: low for stand-alone drugs, high for drug-assisted psychotherapies, due to different causal claims and external validities.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
8 citations
Psychedelic-assisted therapy (PAT) is a complex intervention combining pharmacological, psychotherapeutic, and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional randomized controlled trials may fail to capture these complexities. This position paper advocates applying the UK Medical Research Council's framework for complex interventions to PAT development and evaluation, emphasizing the need to articulate the theory of therapeutic change, structure intervention development into phases, account for contextual interactions, and incorporate stakeholder perspectives.
Therapeutic Advances in Psychopharmacology
January 1, 2024
Eduardo Ekman Schenberg
7 citations
A commentary responds to a call for greater methodological rigor in psychedelic research, agreeing that studies should adhere to principles of internal, external, and construct validity. The authors note that conclusions must not exceed what robust statistical inferences support. They find valuable the examples of past inadequacies and mistakes, including oversight by peer reviewers, and affirm that future research can benefit from increased rigor.
Trends in Psychiatry and Psychotherapy
October 18, 2022
Bheatrix Bienemann, Mariana Ridolfi, Marco Multedo et al.
5 citations
A validated scale for measuring ego dissolution demonstrated strong psychometric properties, though its factor structure may differ from the English version. Because validation is an ongoing process, further studies should compare ego dissolution scores across different substances and regions of the country.
PsyArXiv
February 23, 2025
Suresh Muthukumaraswamy, Matthew Baggott, Eduardo Ekman Schenberg et al.
3 citations
preprint
Psychedelic-assisted therapy (PAT) is a complex, multi-component intervention, yet most clinical trials evaluate it as a simple pharmaceutical treatment, limiting real-world validity. This position piece advocates applying the UK Medical Research Council's complex intervention framework to PAT, emphasizing theory of change, structured development, context, and stakeholder input. Pragmatic randomized controlled trials, informed by the PRECIS-2 tool, are proposed to align trial designs with real-world healthcare settings. The authors contrast drug-centric and psychotherapy-augmented views of PAT's efficacy, and recommend integrating qualitative data, adaptive designs, and comparative effectiveness research. A pluralistic evidentiary model is suggested to advance psychedelic medicine while avoiding past developmental pitfalls.
Transcultural Psychiatry
October 1, 2022
Eduardo Ekman Schenberg, Konstantin Gerber
2 citations
Ayahuasca, a psychedelic brew, significantly impacts users' mental health and worldview. In a study involving 200 participants, 76% reported enhanced emotional well-being and 65% experienced shifts in their understanding of reality. This suggests that ayahuasca may bridge gaps between psychology and sociology, revealing insights into human behavior and belief systems. Additionally, the findings highlight the potential for psychedelics to inform political science discussions on globalization and environmental ethics, while also prompting further exploration in cannabis research and biochemical analysis techniques.
October 1, 2024
Eduardo Ekman Schenberg
1 citation
preprint
Regulatory approval of MDMA-assisted therapy for PTSD by the FDA faces epistemological and methodological challenges, particularly the demand for two successful phase 3 randomized controlled trials when there is no agreement on what constitutes success for psychoactive drugs combined with therapy. These complex treatment arrangements undermine the internal validity of estimated average treatment effects compared to conventional controls. The paper reviews assumptions behind RCTs' gold-standard status in evidence-based medicine, emphasizing the need to avoid the extrapolation fallacy. Trustworthiness that efficacy in RCTs will predict effectiveness in target populations depends on the type of psychedelic treatment regulated: low for stand-alone drugs, high for drug-assisted psychotherapies, because these involve different causal claims with distinct external validities.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
Harvard Dataverse
July 4, 2015
Eduardo Ekman Schenberg
Ayahuasca consumption alters brain electrical activity and plasma biochemistry. EEG recordings showed increased theta and alpha power, while plasma samples revealed changes in cortisol, serotonin, and brain-derived neurotrophic factor (BDNF) levels. These results suggest that ayahuasca modulates neural oscillations and neuroendocrine markers, pointing to potential therapeutic applications for mood disorders.
Eduardo Ekman Schenberg
preprint
Between April and October 2024, expert bodies in the US and the Netherlands reached opposite conclusions on MDMA for PTSD. The FDA rejected Lykos Therapeutics' New Drug Application despite prior breakthrough therapy status, while the Dutch State Commission recommended making the treatment available as soon as possible. These contrasting decisions highlight epistemic differences in evidence assessment: the FDA's approach aligned with traditional Evidence-Based Medicine (EBM), whereas the Dutch approach resembled the newer EBM+ framework. Drawing on historical fatal examples and recent evidence-assessment debates (e.g., masking during COVID-19), the authors argue that shifting to EBM+ is essential for reliable assessments of psychedelic therapies.