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.

14 papers

Ketamine

Based on 42 papers

Researchers agree that ketamine can lift symptoms of major depression quickly for some people, often within hours to a day. Many trials show fast drops in suicidal thoughts and short-term mood improvement, but these effects usually fade over days to weeks unless treatment is repeated. Esketamine, a related nasal form, is approved for hard-to-treat depression and must be given in clinics with monitoring. Outside depression, scientists are testing ketamine for PTSD, anxiety, addiction, and other conditions. Early results are mixed or smaller for those problems. People still debate the best dose, how often to repeat treatments, how long benefits last, how much the drug experience or therapy around it matters, and what long-term risks (including possible misuse) might be.

Key findings

  • Ketamine can reduce depression symptoms very fast, sometimes within hours, and effects often peak around 24 hours after a single infusion. 10152 10149 15070
  • The antidepressant effect after one ketamine infusion usually lasts days to about two weeks, so many studies use repeated doses to keep benefits going. 12152 10149
  • Esketamine (a nasal spray) is approved for treatment-resistant depression and for depression with acute suicidal thoughts, and it must be given in a clinic with two-hour monitoring and blood-pressure checks. 10144 12156 15070
  • A common research method is an intravenous infusion of about 0.5 mg per kg over roughly 40 minutes; studies also test other routes like intranasal, subcutaneous, or intramuscular dosing. 10149 10159 12156 12152
  • Beyond depression, ketamine has shown early signs of helping with suicidal thoughts, PTSD, anxiety disorders, and some substance-use problems, but the evidence outside depression is smaller or less certain. 12152 9521 15068
  • Common short-term side effects include dissociation (a strange or detached feeling), sedation, higher blood pressure, dizziness, and brief psychosis-like sensations; these usually go away within a few hours. 12152 10159 10151 12156
  • Studies done under medical supervision report only a few clear cases of tolerance or dependence, so the addiction risk in clinical use seems low, but researchers say long-term risk is still uncertain. 8828 12152 12365
  • Scientists have evidence about how ketamine works, such as blocking NMDA receptors and boosting AMPA signaling, BDNF, and mTOR pathways that support brain plasticity, but the exact chain of events is still being worked out. 10147 10146 10148 9521 15070
  • Many published ketamine studies are small or have risks of bias, so experts call for larger, longer trials to answer questions about long-term safety, optimal dosing plans, and which patients will benefit most. 12152 10153 15129

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

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

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

Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment

Jenessa N. Johnston, Bashkim Kadriu, Josh Allen, Jessica R. Gilbert, Ioline D. Henter, Carlos A. Zarate
Neuropharmacology Summary & key facts 2023 59 citations

This paper reviews what scientists know about how ketamine and classic serotonergic psychedelics (like psilocybin and LSD) can lift depression quickly. The authors compare how the drugs work in the brain, point out that ketamine has the strongest clinical evidence so far, and say psychedelics show early promise but need…

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

Therapeutic mechanisms of psychedelics and entactogens

Boris D. Heifets, David E. Olson
Neuropsychopharmacology Summary & key facts 2023 59 citations

This paper reviews human and animal research on so-called psychedelics (like psilocybin and LSD) and entactogens (mainly MDMA). The authors say these drugs can produce fast improvements in mental health that sometimes last for months or longer. But we do not yet understand exactly how they work. Human studies point…

Biochemical Analysis and Sensing Techniques Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ketamine LSD

A century of research on psychedelics: A scientometric analysis on trends and knowledge maps of hallucinogens, entactogens, entheogens and dissociative drugs

Marco Solmi, Chaomei Chen, Charles Daure, Anne Buot, Michael Ljuslin, Vincent Verroust, et al.

Researchers looked at published papers about psychedelic drugs from the last century, using citation maps and other tools to see how the field changed up to March 2022. They found that research was small and mostly about safety for many decades, then grew a lot after the 1990s into a…

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

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

Psychedelics in the treatment of unipolar and bipolar depression

Oliver G. Bosch, Simon Halm, Erich Seifritz

This paper reviews past and recent research on classic psychedelics and some newer psychedelic-like drugs as treatments for unipolar and bipolar depression. Classic psychedelics named in the paper are LSD, psilocybin, mescaline, and ayahuasca. Early carefully controlled studies of psilocybin show encouraging results for unipolar depression, and ketamine (in the…

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

Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings

Nicolas Garel, Julien Thibault Lévesque, Dasha A. Sandra, Justin Lessard-Wajcer, Elizaveta Solomonova, Michael Lifshitz, et al.

Researchers looked back at recordings and interviews from 26 people who got ketamine infusions for treatment-resistant depression. They found that things people were exposed to in the days before treatment — especially digital media like videos — sometimes showed up inside their ketamine experiences and changed how emotional or “mystical”…

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

Therapeutic (Sub)stance: Current practice and therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A systematized review

Sascha Thal, Michelle Wieberneit, Jason M. Sharbanee, Petra Skeffington, Paris Baker, Raimondo Bruno, et al.
Journal of Psychopharmacology Summary & key facts 2022 23 citations

The authors reviewed 83 papers and guides about how therapists prepare people for substance-assisted psychotherapy — therapy that uses drugs like psilocybin, LSD, MDMA, or ketamine together with psychological support. They found clear agreement that good preparation before a drug session is important for safety and for helping people get…

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Ibogaine Ketamine
Summaries and links are for general information and education only. They are not a substitute for reading the original publication or for professional medical, legal, or other advice. Always refer to the linked source for the full study.