Frontier mental health research: psychedelics & drug studies

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41 papers

MDMA

Based on 29 papers

Research shows that MDMA given together with structured therapy can help some people with hard-to-treat mental health problems. Most evidence and trials focus on post-traumatic stress disorder (PTSD), and many studies report big symptom drops when MDMA is used inside carefully run therapy programs (not as a daily pill) [15063,15135,15086]. Scientists agree the drug is given in a supervised clinical setting with hours of preparation and follow-up therapy. They also agree that safety looks acceptable in these controlled trials, but there are important limits: harms may be underreported, the exact brain mechanisms are not fully known, and trials so far include mostly white participants and are still growing in size and scope [15096,15065,15061,15095,15078].

Key findings

  • Most MDMA research for mental health focuses on treating post-traumatic stress disorder (PTSD). 15063 15135 15081
  • Researchers have also tested MDMA and other psychedelic drugs for depression, anxiety, and addiction, but those areas are less developed than the PTSD work. 15098 15135 15068 15058
  • In trials, MDMA is almost always given together with psychotherapy, plus hours of preparation before the drug session and follow-up sessions afterward. 15096 15065 15063 15087
  • Studies usually use one or a few supervised drug sessions inside a wider therapy program rather than daily medication. 15086 15063
  • Clinical trials report large or clinically meaningful symptom reductions for PTSD after MDMA-assisted therapy in several studies and later-stage trials. 15063 15135 15086
  • Under controlled research conditions, safety profiles are generally reported as acceptable, but reviewers warn that side effects and harms are often not tracked consistently and may be underreported. 15135 15061 15046
  • How MDMA helps is still debated: ideas include boosting social openness, easing fear or rigid patterns in the brain, and promoting short-term plasticity, but the exact biological and psychological mechanisms are not settled. 15086 15135 15091 15081
  • Important unknowns and debates remain: trials need larger and more diverse groups of people, standard ways to report side effects, clearer rules about who will be helped, and regulators have not made universal approvals yet. 15095 15061 15078 15079

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah E. Kleiman, Kelly Parker-Guilbert, et al.
Nature Medicine Summary & key facts 2021 901 citations

This randomized, double-blind phase 3 trial tested MDMA-assisted therapy versus placebo with the same therapy in 90 adults with severe PTSD. Participants had three drug sessions plus preparatory and integration therapy, and were assessed 18 weeks after starting. The MDMA group had larger drops in PTSD symptoms and in functional…

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Sleep and Wakefulness Research

RETRACTED ARTICLE: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials

Michael C. Mithoefer, Allison A. Feduccia, Lisa Jerome, Anne Mithoefer, Mark T. Wagner, Zach Walsh, et al.
Psychopharmacology Summary & key facts 2019 357 citations

This paper pooled data from six randomized, double‑blind phase‑2 trials of MDMA‑assisted psychotherapy for adults with PTSD (total N=103). After two blinded MDMA sessions, the MDMA group showed larger reductions in clinician‑rated PTSD symptoms than the control group (mean difference −22.0 points on the CAPS‑IV, P < 0.001) and a…

Cannabis and Cannabinoid Research Posttraumatic Stress Disorder Research Psychedelics and Drug Studies MDMA

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

Mitchell, Jennifer M., Ot’alora G., Marcela, van der Kolk, Bessel, et al.
Nature Summary & key facts 2023 347 citations

This multi-site, randomized, double-blind phase 3 trial tested MDMA-assisted therapy (MDMA-AT) versus placebo with the same therapy in 104 people with moderate to severe PTSD. Blinded assessors found larger average reductions in PTSD symptoms and in functional impairment for the MDMA-AT group than for the placebo group. The MDMA group…

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Tryptophan and brain disorders

Inclusion of people of color in psychedelic-assisted psychotherapy: a review of the literature

Timothy I. Michaels, Jennifer Purdon, Alexis Collins, Monnica T. Williams
BMC Psychiatry Summary & key facts 2018 247 citations

The authors reviewed psychedelic-assisted psychotherapy studies published from 1993 to 2017 to see how many people of color took part. They found 18 studies with about 280 people. About 82% of participants were non-Hispanic White, while only small percentages were African American, Latino, Asian, indigenous, or mixed race. Because so…

Natural Compound Pharmacology Studies Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ayahuasca LSD

Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development

Eduardo Ekman Schenberg
Frontiers in Pharmacology Summary & key facts 2018 229 citations

This paper describes psychedelic-assisted psychotherapy, which means giving drugs like ketamine, MDMA, psilocybin, LSD or ibogaine together with guided therapy. The authors say this approach has shown promising safety and benefits so far, even for people who did not get better with usual treatments. They also argue that these therapies…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ibogaine Ketamine

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Antonio Inserra, Danilo De Gregorio, Gabriella Gobbi
Pharmacological Reviews Summary & key facts 2020 215 citations

This review looked at many studies about classic psychedelics (like psilocybin and LSD), MDMA, ketamine, and plant medicines (like ayahuasca). The authors explain how these drugs can change the brain’s wiring, calm inflammatory processes, and shift key brain chemicals. Those actions may help explain why small clinical trials and animal…

Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Tryptophan and brain disorders Ayahuasca Ketamine

The psychedelic renaissance and the limitations of a White-dominant medical framework: A call for indigenous and ethnic minority inclusion

Jamilah R. George, Timothy I. Michaels, Jae Sevelius, Monnica T. Williams
Journal of Psychedelic Studies Summary & key facts 2019 212 citations

This paper reviews the recent comeback of psychedelic research and points out that much of that work borrows from indigenous healing traditions. The authors say Indigenous people, ethnic and racial minorities, women, and other marginalized groups are often left out of research and the mainstream story about psychedelic medicine. The…

Biochemical Analysis and Sensing Techniques Chemical synthesis and alkaloids Psychedelics and Drug Studies MDMA Psilocybin

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Joost J. Breeksema, Alistair Niemeijer, Erwin Krediet, Eric Vermetten, Robert A. Schoevers
CNS Drugs Summary & key facts 2020 207 citations

Researchers collected and read 15 studies where patients described their own experiences with psychedelic treatments for mental disorders. These studies looked at about 180 patient accounts across different drugs and different illnesses. Even though the drugs and treatment settings were very different, many patients described similar helpful processes, such as…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ayahuasca Ibogaine

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity

Robin Carhart‐Harris, Kevin Murphy, Robert Leech, David Erritzøe, Matthew B. Wall, B. Ferguson, et al.
Biological Psychiatry Summary & key facts 2014 181 citations

In a double-blind, placebo-controlled study, 25 healthy volunteers each took a single 100 mg dose of MDMA or placebo (one week apart) while their brains were scanned. MDMA produced clear increases in positive mood and caused localized decreases in blood flow in parts of the right medial temporal lobe (including…

Forensic Toxicology and Drug Analysis Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Psychedelic medicine: a re-emerging therapeutic paradigm

Kenneth W. Tupper, Evan Wood, Richard Yensen, Matthew W. Johnson

Researchers around the world have started clinical studies again to see if psychedelic drugs can help treat serious mental health problems. This work picks up after research that stopped around the 1950s. Scientists are running controlled studies to test whether these substances can safely reduce problems like depression, anxiety, addiction…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ketamine LSD

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline

Allison A. Feduccia, Lisa Jerome, Berra Yazar‐Klosinski, Amy Emerson, Michael C. Mithoefer, Rick Doblin
Frontiers in Psychiatry Summary & key facts 2019 168 citations

This review explains why the FDA gave Breakthrough Therapy Designation to MDMA-assisted psychotherapy for PTSD. It summarizes six Phase 2 trials (2004–2017) in which MDMA was given in up to three 8-hour sessions combined with preparatory and follow-up therapy, and pooled analyses showed a large effect on PTSD symptoms and…

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Treatment of Major Depression
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