Front Psychiatry
November 24, 2021
Sherry-Anne Muscat, Glenn Hartelius, Courtenay Richards Crouch et al.
47 citations
An integrative approach that combines ketamine therapy with supportive psychotherapy may enhance treatment outcomes for people with treatment-resistant depression. The authors argue that ketamine's rapid antidepressant effects can be optimized when paired with psychological interventions that help patients process and integrate the drug-induced experiences. This combined strategy may address multiple dimensions of depression, including mood, cognition, and interpersonal functioning, potentially leading to more durable therapeutic benefits than ketamine alone. The paper suggests that integrating pharmacological and psychotherapeutic modalities could improve the overall efficacy of treatment for severe depression.
Front Psychiatry
March 1, 2023
Karl Kristjan Kaup, Madis Vasser, Kadi Tulver et al.
22 citations
An open-label feasibility study tested whether a virtual reality simulation designed to replicate aspects of the psychedelic experience could be used as a therapeutic tool. Participants reported that the VR experience produced subjective effects resembling those of psychedelics, including altered perception and a sense of oceanic boundlessness. The findings suggest that VR-based psychedelic replications are feasible and acceptable, and may offer a scalable, non-pharmacological approach for mental health interventions. The study did not assess clinical outcomes, but participants showed reduced negative affect after the session. The authors indicate that further controlled research is needed to determine therapeutic efficacy.
Front Psychiatry
May 11, 2022
Stephan Schleim
16 citations
The context in which psychedelic drugs are taken—setting, expectations, and cultural framing—shapes their effects, a phenomenon known as context-dependency. Rather than posing a problem for scientific study, this variability offers opportunities for both anthropology and pharmacology to better understand how biology and environment interact. The authors argue that context-dependency is not a flaw but a feature that can be leveraged to design more effective therapeutic interventions and to enrich ethnographic accounts of altered states.
Front Psychiatry
November 6, 2024
Cristiano Chaves, Rafael G. Dos Santos, Serdar M. Dursun et al.
11 citations
DMT (N,N-dimethyltryptamine) is a naturally occurring psychedelic found in plants and produced endogenously in the human body. Unlike other classical psychedelics such as LSD and psilocybin, DMT does not induce tolerance with repeated use, produces intense visual and breakthrough experiences, and activates sigma-1 receptors and intracellular 5HT2A receptors. Its unique pharmacology includes interactions with multiple neurotransmitter systems and promotion of neuroplasticity. Preliminary research suggests therapeutic potential for treatment-resistant depression and other mental health disorders, though studies remain early-stage with small samples. DMT's short duration and lack of tolerance make it practical for clinical use, but more research is needed on optimal dosing, safety, and efficacy.
Front Psychiatry
April 11, 2023
Marcin Moskalewicz, Thomas Fuchs
8 citations
A newly published 1946 clinical case-study by Erwin W. Straus, a founder of phenomenological psychopathology, examines a patient with psychotic depression at Henry Phipps Clinic. The manuscript critiques physicalism in psychology, defends primary sensing, describes the spatiotemporal unity of lived experience, and introduces the concept of temporal becoming. It uniquely details how a patient's lived experience is structured in space and time, intrinsically linked to affectivity, embodiment, and action. The work underscores Straus' role in developing phenomenological psychiatry in Germany and the United States.
Front Psychiatry
April 8, 2025
Jennifer L. Jones
5 citations
Psychedelic-assisted therapy may be optimized by integrating psychotherapy with the administration of psychoplastogens—substances that promote neuroplasticity. The authors argue that the therapeutic context and psychological support are essential for translating neurobiological changes into lasting mental health improvements. They suggest that without structured psychotherapy, the neuroplastic effects of psychedelics alone are insufficient for sustained clinical benefit. The paper emphasizes the need for careful treatment design that combines pharmacological and psychotherapeutic interventions to maximize outcomes.
Front Psychiatry
September 28, 2023
Lauren Johansen, Paul Liknaitzky, Maja Nedeljkovic et al.
5 citations
Experts in psychedelic-assisted therapy agree that the treatment works for depression through a combination of psychological, neurobiological, and contextual mechanisms, with the therapeutic relationship and set and setting playing crucial roles. The Delphi study gathered consensus among specialists, who emphasized that the drug-induced experience alone is insufficient; integration sessions and a supportive environment are essential for lasting improvement. Practical implications include the need for trained therapists, careful screening of patients, and structured protocols. The findings suggest that psychedelic-assisted therapy requires a holistic approach rather than focusing solely on pharmacological effects.
Front Psychiatry
July 20, 2023
Elizabeth Alphonsus, Lisa C. Fellin, Samuel Thoma et al.
4 citations
In a sociocentric culture where self-boundary is traditionally porous, psychotic experiences can radically alter one's sense of self. This interpretative phenomenological analysis explores how individuals describe their self-boundary during psychosis, using the metaphor of having their spinal cord removed to convey a profound loss of internal structure and autonomy. The analysis reveals that psychotic episodes disrupt the usual fluid boundaries of self, leading to a felt disintegration that is both terrifying and culturally shaped. The findings suggest that understanding self-boundary in psychosis requires attending to cultural context, as sociocentric norms may influence how such experiences are interpreted and narrated.
Front Psychiatry
December 9, 2025
Haley Maria Dourron, Heith Copes, Daniel H. Grossman et al.
3 citations
People diagnosed with non-affective psychotic disorders who used psychedelics reported a mix of positive and negative effects. Common challenges during the acute experience included transient anxiety, sometimes leading to brief hospitalizations. Some participants described psychosis-specific experiences such as reduced self-stigma and insight into their hallucinations and delusions. Perceived long-term benefits varied widely, with some reporting lasting positive changes and others noting negative effects or no lasting impact. The findings suggest psychedelics may pose both risks and potential benefits for this population, highlighting the need for careful safety trials.
Front Psychiatry
August 26, 2025
Samir A Nader
3 citations
Music, widely used in psychedelic therapy to guide and support patients, may actually interfere with the therapeutic goal of unmediated self-exploration. This opinion piece argues that music introduces external emotional content that can distort or displace the patient's own psychological material, undermining the core objective of accessing unfiltered internal experience. The author proposes "psychedelic minimalism," a setting free of emotional modulation like music, to allow direct engagement with the self. Accounts from clinical participants describe music as overwhelming or redirecting attention, while silence enabled productive introspection. The piece calls for controlled research treating music as a testable variable rather than a default therapeutic component.
Front Psychiatry
June 10, 2024
Leehe Peled-Avron, Jacob S. Aday, Amilia Lydia Kalafateli et al.
2 citations
Psychedelic compounds produce profound alterations in consciousness and perception, and emerging evidence suggests they may be effective treatments for several mental health and medical conditions. This editorial introduces a collection of articles that explore the psychological and neural mechanisms underlying these effects, including how psychedelics modulate brain networks, promote neuroplasticity, and facilitate therapeutic change. The authors argue that understanding these mechanisms is crucial for developing safe and effective psychedelic-assisted therapies. They highlight the need for rigorous research to clarify how these compounds work and to optimize their clinical application.
Front Psychiatry
November 26, 2020
Bénédicte Nobile, Emilie Olié, Philippe Courtet
2 citations
The commentary discusses the emerging field of psychedelic psychiatry, highlighting both its promise for treating mental health conditions and the challenges of integrating these substances into clinical practice. It explores the tension between the transformative potential of psychedelic-assisted therapy and the need for rigorous scientific frameworks, ethical safeguards, and regulatory adaptation. The author argues that while psychedelics may offer new avenues for innovative psychiatry, their adoption requires careful navigation of cultural, legal, and medical landscapes to avoid repeating past mistakes.
Front Psychiatry
August 15, 2025
Yvonne A. Bonomo, Amanda F. Norman, Lisa Collins et al.
1 citation
Three Acacia-based formulations of DMT and harmala alkaloids were safe and well tolerated in 9 healthy volunteers who had previously used ayahuasca. No serious adverse events occurred, and physical exams, vital signs, and lab tests showed no clinically significant changes. Participants rated the subjective experience of all formulations as generally similar to ayahuasca, and one formulation (ACL-010) was rated as similar or more beneficial. Four-week follow-up measures of psychological wellbeing and perceptual effects showed little difference between formulations. The small sample and open-label design limit generalizability, but the results suggest Acacia-derived DMT formulations are a feasible alternative for future clinical trials.
Front Psychiatry
October 24, 2025
Fares Qeadan, Ashlie McCunn, Benjamin Tingey et al.
Using electronic health records, this cohort study examined associations between psychedelic use and adverse outcomes in people with substance use disorders. The analysis found that psychedelic use was linked to a higher risk of certain adverse events, including emergency department visits and hospitalizations, compared to no psychedelic use. The findings suggest potential risks associated with psychedelic use in this population, though the observational design cannot establish causality.
Front Psychiatry
September 26, 2025
Cato Grønnerød, Thea Rønningen, Ingrid Rike Haugsjå et al.
Recreational MDMA use is associated with positive experiences and self-perceived improvements in mental health, particularly for internalizing disorders like PTSD, social anxiety, and depression. In a survey of 608 Norwegian adults (mostly male and under 45), most used MDMA recreationally or therapeutically, often at home or a friend's home. The majority were well prepared and had a clear intention for use. While over 80% reported mental distress or disorders, they also noted substantial improvement. Persistent negative effects were rare and short-lived.
Front Psychiatry
September 1, 2025
Ronit Kishon, Yael M. Cycowicz
Psychedelic therapy, which uses compounds like psilocybin to treat psychiatric disorders, works through serotonergic modulation and 5-HT2A receptor activation, inducing neuroplasticity and altered consciousness. Its therapeutic potential extends beyond biochemical effects, as structured therapy—including preparation, administration, and integration—produces enduring changes in self-perception, emotion regulation, and interpersonal connectedness. This paper argues that psychedelics offer a fundamentally different therapeutic model requiring a reconceptualization of mental health treatment, integrating neuroscientific findings with phenomenological insights. Further research is needed to refine protocols and understand the link between subjective experiences and outcomes.
Front Psychiatry
April 23, 2025
Martin L. Williams, Deborah Rudin, Yasmin Schmid et al.
Psilocybin is one of many compounds that act as agonists of serotonin receptors and produce psychedelic effects. Beyond psilocybin, other classic psychedelics such as mescaline, N,N-DMT, and 5-MeO-DMT, along with novel compounds called psychoplastogens, show promise for treating mental health conditions like depression, PTSD, and anxiety in palliative care. This research topic includes seven articles: case reports on ketamine for depression and 5-MeO-DMT for PTSD; a review of clavine alkaloids; Phase 1 trials of an ayahuasca analog and a novel DMT formulation; a preclinical study of psilacetin; and a discussion of psychedelics for end-of-life distress. The field is expanding beyond psilocybin to explore a wider range of compounds.
Front Psychiatry
October 25, 2023
Steffen Reissmann, Matthias Hartmann, Andreas Kist et al.
In a single patient with treatment-resistant depression, personalized dosing of ketamine infusions that consistently maintained an altered state of consciousness was associated with sustained antidepressant relief over repeated sessions. The patient received six infusions over three weeks, with doses adjusted to keep the altered state at a moderate-to-strong level. Depressive symptoms dropped by more than 50% after the first infusion and remained low for at least four weeks after the final infusion. The case suggests that maintaining a non-ordinary state of consciousness across infusions may be important for long-lasting antidepressant effects.