
Psychedelics Guide › Psychedelic Science and Therapy: What the Evidence Says
After decades of research stifled by prohibition, the clinical study of psychedelics is experiencing a renaissance. Molecules such as psilocybin, LSD, MDMA, ketamine, and ibogaine are currently being investigated in controlled trials for depression, post-traumatic stress disorder (PTSD), addictions, and end-of-life distress. This page gathers and organizes everything we have published on psychedelic science and therapy, with the aim of distinguishing what the evidence already supports from what remains a hypothesis or a promise.
The most promising results come, for now, from highly controlled clinical settings: prior psychological screening, measured doses, therapeutic support, and preparation and integration sessions. This framework appears to be part of the effect itself, not merely a formality. It is worth keeping this in mind when reading headlines, as many trials are in early phases with small sample sizes, and several regulatory agencies are calling for more and better research before moving forward. It is a young field, where caution is a better guide than enthusiasm.
We write from a perspective of harm reduction and respect for individual autonomy: our intention is to inform, not to lecture. Anyone wishing to approach these substances deserves honest data—about what we know and what we still ignore—not sermons. “Set and setting,” the internal state and the environment, conditions the experience as much as the molecule; and in most countries, their use remains illegal except in authorized trials, an objective fact to consider when assessing one’s own context. Here you will not find dosing protocols, but a calm reading of what science is discovering and the ethical and regulatory debate that remains very much alive.
Featured Readings
- Psychedelic Psychotherapy Under Examination: What Does the Evidence Say?
- MDMA Psychotherapy: From the Merck Patent to PTSD
- Psilocybin and Depression: Breaking the Rumination Loop
- FDA Finalizes Psychedelic Guidance and Accelerates Psilocybin
- Psychedelic Visions and the Brain: Beyond Huxley
- Psychedelic Medicine: A Practical Guide for Patients, Clinicians, and the Future of Assisted Treatment
Recent Studies Supporting Therapeutic Potential
What the most recent clinical research (Nature, JAMA, NEJM, Lancet, PubMed) shows, recounted with rigor and without exaggeration.
- Psilocybin and Major Depression: What Recent Clinical Trials Say
- Psilocybin and Treatment-Resistant Depression: What the EPISODE Trial Says
- MDMA and PTSD: What Phase 3 Trials Say About Efficacy
- Psilocybin and Alcoholism: What the JAMA Randomized Trial Shows
- Psilocybin and Cancer: A Single Dose with Two-Year Benefits
- LSD and Generalized Anxiety: What the Phase 2b Trial Showed
- DMT and Depression: What the First Clinical Trials Show
- Ayahuasca and Depression: What the Placebo-Controlled Randomized Trial Showed
- Psilocybin and Anorexia Nervosa: The First Feasibility Study
- Ibogaine in Veterans with Brain Injury: What Stanford Found
- How Psychedelics Change the Brain: What Recent Evidence Shows
- 5-MeO-DMT and Treatment-Resistant Depression: What Early Trials Say
- Esketamine Monotherapy in Treatment-Resistant Depression: What the 2025 Trial Says
- Psychedelic Microdosing: What Placebo-Controlled Trials Say
- Psilocybin in Bipolar II Depression: What the JAMA Psychiatry Trial Showed
The Rebirth of Psychedelic Therapy: What the Evidence Says
An overview of the resurgence of clinical research: what trials promise, why it was interrupted for decades, and where regulation (FDA/EMA) stands. A starting point for reading the rest of the cluster with a critical spirit.
- Psychedelic Psychotherapy Under Examination: What Does the Evidence Say?
- LSD in Therapy: Why Research Was Really Halted
- Fuerteventura and Psychedelic Therapy: From Enthusiasm to Caution
- Psychedelic Medicine: A Practical Guide for Patients, Clinicians, and the Future of Assisted Treatment
- FDA Finalizes Psychedelic Guidance and Accelerates Psilocybin
- Project Ideaa: Integrative Therapy of Visionary Substances and Psycho-Spiritual Disciplines in Addiction Treatment
MDMA and Trauma: Empathogen-Assisted Psychotherapy
MDMA as an adjunct to psychotherapy for PTSD and other conditions: trial results, mechanisms of empathy and fear, and the cautions that led regulators to request more evidence.
- MDMA Psychotherapy: From the Merck Patent to PTSD
- Ann Shulgin. Lecture on the Use of MDMA in Psychotherapy
- Ann Shulgin. Lecture on the Use of MDMA in Psychotherapy
- MDMA, Fear, and Empathy: What Affective Neuroscience Says
- Ecstasy and the Brain: Between the Myth of Neurotoxicity and Clinical Reality
- MDMA, Empathy, and Compassion: Does It Transform Our Social Behavior?
- MDMA-Assisted Psychotherapy and Autism Spectrum Disorder
- MDMA and Pain Relief: Science, Risk, and Perspective
- MDMA and Social Bonding: Selective Empathy, Generosity, and Context
Psilocybin and LSD for Depression and Anxiety
What studies with classic psychedelics show in depression, treatment-resistant depression, end-of-life distress, or ADHD: neuroimaging, emotional modulation, and the limits of still-preliminary evidence.
- Psilocybin and Depression: Breaking the Rumination Loop
- Psilocybin and Depression: Neuroimaging, Regulation, and the Search for a New Therapy
- Psilocybin: Emotional and Cognitive Modulation Under the Scientific Lens
- LSD at the End of Life: What Peter Gasser’s Trial Showed
- The Rebirth of LSD in Clinical Research for Palliative Care
- Applications of LSD in Psychotherapy: An Interrupted History
- Applications of LSD in Psychotherapy: An Interrupted History
- LSD Microdosing Does Not Outperform Placebo in ADHD, According to Review
DMT, Ketamine, and Ibogaine: New Clinical Frontiers
Beyond psilocybin: ultra-short-acting tryptamines (DMT, 5-MeO-DMT), ketamine in treatment-resistant depression, and ibogaine in addictions. Pathways with very different pharmacological profiles and regulatory statuses.
- DMT and Psychedelics: The Science That Prohibition Silenced
- Ultra-Short-Acting Tryptamines: DMT and 5-MeO-DMT in Psychedelic Medicine
- A Single Dose of DMT Reduces Treatment-Resistant Depression, According to Trial
- Ketamine: Between Anesthesia and Neuronal Regeneration
- A Rigorous Trial Questions the Efficacy of Ketamine in Depression
- Ibogaine and Addictions: The Evidence That Medicine Ignores
The Psychedelic Brain: Neuroscience of the Experience
How science attempts to explain visions, the mystical experience, and changes in consciousness: 5-HT2A receptors, brain networks, suggestibility, and the difficult challenge of measuring subjective experiences.
- Psychedelic Visions and the Brain: Beyond Huxley
- Ayahuasca Visions: What the Brain Says (Part II)
- Hallucinogens and Mystical Experience: What Science Says
- Mapping the Invisible: Science and Subjectivity in Evaluating Psychoactive Effects
- Mapping the Ineffable: The Science Behind Measuring Subjective Experiences
- LSD and Suggestibility: Between Therapy, Risk, and the Mind
- Long-Term Effects of Ritual Ayahuasca Use: Scientific Evidence and Risk Reduction
Addiction, Spirituality, and Personal Transformation
The intersection between Western science, the spiritual dimension, and the potential for personal transformation attributed to these experiences, read with caution and without idealization.
- Addiction, Spirituality, and Western Science
- ADDICTION, SPIRITUALITY, AND WESTERN SCIENCE*
- Psychedelics and Personal Transformation: Between the Threshold and the Community
Frequently Asked Questions
Is psilocybin useful for treating depression?
The results are encouraging. Several early-phase clinical trials have recorded notable reductions in depressive symptoms after one or two psilocybin sessions combined with psychotherapy, even in cases of treatment-resistant depression. However, these are small studies with short follow-up periods, and they have not yet translated into a generally available treatment: the most robust data comes from highly structured clinical settings. Promising, yes; conclusive, not yet.
Is psychedelic-assisted therapy the same as taking the substance on your own?
Not exactly. In trials, the substance is administered in measured doses within a therapeutic framework, with prior screening and preparation and integration sessions. That context—and not just the molecule—appears to explain a good portion of the results: the experience and the work surrounding it go hand in hand. Taking it on your own is something else, without that support framework; knowing the difference is, precisely, a way of taking care of yourself.
Has the FDA approved MDMA for PTSD?
Not yet. To date, the FDA has not given the green light to MDMA for PTSD: in 2024, it requested more research despite promising results from phase 3 trials. Some countries have followed their own regulatory paths and have moved faster. It is a situation in full evolution, so it is advisable to check updated sources before considering it closed in one direction or another.
How do psychedelics act on the brain?
Classic psychedelics act primarily as agonists of the serotonin 5-HT2A receptor. Neuroimaging studies suggest that they transiently reorganize brain activity and modulate networks such as the “default mode network,” linked to rumination and the sense of self. This is one of the most fascinating lines of current neuroscience, although it remains open: we are talking about ongoing findings, not a closed map, and effects that are temporary.
How does ketamine differ from classic psychedelics?
They are less similar than the common label suggests. Ketamine is a dissociative anesthetic with its own mechanism—it acts on the glutamatergic system—and is already used, in specific formulations and contexts, for treatment-resistant depression. Classic psychedelics (psilocybin, LSD, DMT) are mostly still in the research phase. They share clinical interest and a certain family resemblance, but not the pharmacological profile or the regulatory stage in which each one finds itself.
Is it safe and legal to use psychedelics for therapeutic purposes?
These are two different questions. Legally, in most countries, these substances can only be used within authorized trials; that is the objective fact to start from. Regarding safety, they are neither harmless nor a leap into the void: most people tolerate them well in controlled settings, but possible adverse reactions exist—episodes of intense anxiety, or increased vulnerability in those with certain backgrounds—and some contraindications that are worth knowing. That is why honest information, support, and, when they exist, regulated trials are the paths that best protect those interested in their therapeutic potential.