Frontier mental health research: psychedelics & drug studies

Each month our editorial team sifts through hundreds of papers and curates notable findings—for practitioners and informed readers who want to stay current with the evidence. Subscribe to the monthly Research Digest for expert analysis and concise summaries of key papers.

18 papers

Ketamine for Anxiety

Based on 18 papers

Research on ketamine for anxiety is early but shows some promising signs. A small number of clinical trials report that ketamine can reduce anxiety symptoms for some people, sometimes for weeks after treatment. However, the studies are few, varied in how they were done, and often small, so we do not yet have strong, clear proof. Scientists have ideas about how ketamine may work. It acts on the brain’s glutamate system and seems to change how brain circuits connect and adapt. But measurements like blood BDNF (a protein linked to brain change) do not show a clear pattern after these drugs, so the biological story is still incomplete. Safety and the role of therapy around the drug are important topics that need more study.

Key findings

  • Some clinical trials report that ketamine can reduce anxiety symptoms in people with diagnosed anxiety disorders. 15068
  • Ketamine can act quickly in mood disorders, with clinical studies showing fast symptom drops in depression; this fast action is one reason researchers test it for anxiety too. 10149 15068
  • The overall evidence for ketamine in anxiety is limited. Trials are few, often small, and use different methods, so conclusions are tentative. 15068 15085
  • Researchers think ketamine works mainly through the glutamate system and by increasing brain plasticity (the brain’s ability to change), based on animal and human studies. 15091 10148
  • Blood measurements of BDNF (a protein tied to brain change) do not show a reliable increase after drugs like ketamine in pooled human studies, so blood BDNF is not a clear marker of ketamine’s effects. 15129
  • Common short-term risks seen with ketamine and similar psychedelic-assisted treatments include dissociation (a strange or detached feeling), faster heart rate, dizziness, and headache; careful screening and preparation are recommended in therapy programs. 10149 15065 15099
  • Non-drug factors matter. Studies of psychedelic and ketamine-assisted therapy emphasize preparation, safe setting, and follow-up therapy as important for safety and outcomes, but methods vary between clinics and trials. 15065 15063 15085
  • Key questions remain: how long benefits last, the best dose and schedule for anxiety, who benefits most, and long-term safety. More large, well-controlled trials are needed. 10149 15068

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

Roger S. McIntyre, Mohammad Alsuwaidan, Bernhard T. Baune, Michael Berk, Koen Demyttenaere, Joseph F. Goldberg, et al.
World Psychiatry Summary & key facts 2023 586 citations

Treatment-resistant depression means depression that does not get better after usual treatments. Scientists do not all agree on one clear definition, which makes it hard to know exactly how common it is or which treatments work best. Using the definition that regulators often use, about 30% of people with depression…

Electroconvulsive Therapy Studies Transcranial Magnetic Stimulation Studies Treatment of Major Depression Ketamine

Management of Treatment-Resistant Depression: Challenges and Strategies

Daphne Voineskos, Zafiris J. Daskalakis, Daniel M. Blumberger

This paper is a careful review of research about treatment-resistant depression. The authors looked through medical studies to see how doctors define this kind of depression, what makes it hard to assess, and which treatments have been tried. They describe drug strategies like adding lithium or thyroid hormone, switching antidepressant…

Electroconvulsive Therapy Studies Treatment of Major Depression Tryptophan and brain disorders Ketamine Psilocybin

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression

Amit Anand, Sanjay J. Mathew, Gerard Sanacora, James W. Murrough, Fernando S. Goes, Murat Altinay, et al.
New England Journal of Medicine Summary & key facts 2023 233 citations

Researchers ran a clinical trial that directly compared ketamine treatment with electroconvulsive therapy (ECT) in people whose major depression had not improved with other treatments and who did not have psychosis. The trial found that ketamine was “noninferior” to ECT, which means ketamine worked at least as well as ECT…

Electroconvulsive Therapy Studies Treatment of Major Depression Tryptophan and brain disorders 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

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

Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms

John H. Krystal, Ege T. Kavalali, Lisa M. Monteggia
Neuropsychopharmacology Summary & key facts 2023 188 citations

This review explains how ketamine can lift depression symptoms much faster than standard antidepressants. Researchers describe the clinical results, how doctors usually give ketamine, and the brain changes it seems to cause. They also say that the treatment must be given carefully because small dose changes matter, the exact brain…

Neuroscience and Neuropharmacology Research Treatment of Major Depression Tryptophan and brain disorders Ketamine

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

Legal highs: staying on top of the flood of novel psychoactive substances

David Baumeister, Luis M. Tojo, Derek K. Tracy

This review explains the fast-growing problem of so-called "legal highs", which are better called novel psychoactive substances or NPS. Unknown labs keep making slightly different chemicals to avoid bans, and this led to about 80 new substances being spotted in one year. The paper groups these drugs into five main…

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

The Therapeutic Potential of Psychedelic-assisted Therapies for Symptom Control in Patients Diagnosed With Serious Illness: A Systematic Review

Lucas Oliveira Maia, Yvan Beaussant, Ana Cláudia Mesquita Garcia

This paper looked at 20 clinical trials to see whether therapies that use psychedelic drugs together with talking therapy can help people who have serious, life‑limiting illnesses. The review found that these therapies often helped with psychological and spiritual problems like anxiety, low mood, and fear of dying. The drugs…

Chemical synthesis and alkaloids Complementary and Alternative Medicine Studies Psychedelics and Drug Studies Ketamine LSD

Psychedelic Commercialization: A Wide-Spanning Overview of the Emerging Psychedelic Industry

Jacob S. Aday, Brian S. Barnett, Dan Grossman, Kevin S. Murnane, Charles D. Nichols, Peter S. Hendricks
Psychedelic Medicine Summary & key facts 2023 49 citations

This article is a broad review of the new psychedelic industry. The authors look at how psychedelic drugs and clinics moved from decades-old research into a fast-growing business with hundreds of companies and big investment. They describe what companies are trying to sell, point out major scientific, legal, and ethical…

Chemical synthesis and alkaloids Diverse academic research themes Psychedelics and Drug Studies Ayahuasca Ibogaine

The Emerging Field of Psychedelic Psychotherapy

Gregory Barber, Scott T. Aaronson
Current Psychiatry Reports Summary & key facts 2022 48 citations

This review looks at recent research where drugs like MDMA and psilocybin are given inside carefully run therapy programs. People get hours of preparation, one or more drug sessions, and several follow-up therapy sessions to help make sense of the experience. Trials so far show big improvements for some people…

Chemical synthesis and alkaloids Diverse academic research themes Psychedelics and Drug Studies Ayahuasca Ibogaine

Psychedelic therapies reconsidered: compounds, clinical indications, and cautious optimism

Jennifer Mitchell, B. Anderson
Neuropsychopharmacology Summary & key facts 2023 44 citations

This review describes a rapid rise in medical research on psychedelic drugs over the past five years. Several later-stage clinical trials have been published, and many different drugs — including psilocybin, MDMA, ketamine, LSD, ayahuasca, and ibogaine — are being tested for conditions such as depression, post‑traumatic stress, addiction, obsessive‑compulsive…

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