Frontier mental health research: psychedelics & drug studies

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46 papers

Psilocybin

Based on 45 papers

Researchers are actively testing psilocybin (the active part of “magic mushrooms”) as a possible treatment for several mental health problems. Early clinical trials—usually done under medical supervision with therapy before and after the drug session—have found quick improvements in some people with major depression, anxiety linked to serious illness, and other hard-to-treat conditions (but the studies are still small). (15135,15063,15056) Scientists propose several ways psilocybin might help, such as changing how brain networks communicate, boosting the brain’s ability to form new connections, and lowering brain inflammation. However, the exact reasons are not settled. Safety in careful clinical settings looks acceptable so far, but harms may be underreported, and unsupervised use can carry real risks. More and larger trials are needed, and many groups (for example people of color) were not well represented in early studies. (15132,15050,15135,15061,15095,15056)

Key findings

  • Psilocybin is being tested for major depression, anxiety (including cancer‑related anxiety), substance use problems, and other mental health conditions. 15135 15063 15056
  • In research studies, psilocybin is usually given as one or a few full (hallucinogenic) doses together with hours of preparation and follow‑up psychotherapy. 15063 15065 15056
  • Some clinical trials report rapid and sometimes lasting reductions in depression and anxiety after only one or a few psilocybin sessions. 15132 15063 15049
  • Trials done with people who have serious illnesses (for example advanced cancer) often show lower anxiety, less depression, and reduced fear of dying after psychedelic‑assisted therapy. 15055 15063
  • Clinical studies run in controlled settings have generally reported acceptable safety and mostly short‑lived side effects, but reviews warn that studies often do not track or report harms in a consistent way. 15135 15055 15061
  • In community or illegal settings, psychedelic use (including psilocybin) has been linked to increases in psychotic or manic symptoms for some users, and users in unregulated settings report more negative experiences than people in clinical trials. 15133 15072 15080
  • Scientists do not agree on one single reason psilocybin might help. Evidence points to changes in brain networks, increased neuroplasticity (the brain’s ability to form new connections), and lower inflammation as possible mechanisms. 15132 15135 15050
  • Many studies so far are small, have limited long‑term follow‑up, and underrepresent people of color, so we do not yet know how well results generalize to all groups or how long benefits and harms last. 15056 15095 15064

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez, Peter C. Arden, Annie Baker, James Bennett, et al.
New England Journal of Medicine Summary & key facts 2022 980 citations

Compass Pathways reported early results from its first Phase 3 trial of synthetic psilocybin (COMP360) for treatment‑resistant depression. In 258 patients, the 25 mg dose showed a statistically significant improvement versus placebo on the MADRS depression scale at week 6 (a 3.6‑point difference, p < 0.001). The Data and Safety…

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

Psychedelics reopen the social reward learning critical period

Romain Nardou, Edward J. Sawyer, Young Jun Song, M. F. Wilkinson, Yasmin Padovan‐Hernandez, Júnia L. de Deus, et al.
Nature Summary & key facts 2023 303 citations

Researchers gave different psychedelic drugs to mice and found the drugs could reopen a window of brain plasticity used for learning social rewards. This reopened window went along with changes in a social hormone system in a key reward area of the brain and with changes in genes that control…

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

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

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance

Ricardo Jorge Dinis‐Oliveira
Drug Metabolism Reviews Summary & key facts 2017 217 citations

This review explains how the mushroom drugs psilocybin and psilocin are broken down in the body. Psilocybin is mainly a pro-drug that enzymes convert into the active compound psilocin. Psilocin is then further changed, and the main substance found in urine is psilocin-O-glucuronide, which matters for clinical and forensic testing.…

Chemical synthesis and alkaloids Forensic Toxicology and Drug Analysis Psychedelics and Drug Studies

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Kim P. C. Kuypers, Livia Ng, David Erritzøe, Gitte M. Knudsen, Charles D. Nichols, David E. Nichols, et al.
Journal of Psychopharmacology Summary & key facts 2019 213 citations

Microdosing means taking a very small, sub‑hallucinogenic amount of a psychedelic drug. Research so far is limited and mixed: some large observational studies report small-to-medium mood gains, but at least one randomized trial found no objective benefit. There is no standard definition of microdosing, potency and legality vary, and long‑term…

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

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

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

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review

Joost J. Breeksema, Bouwe Kuin, Jeanine Kamphuis, Wim van den Brink, Eric Vermetten, Robert A. Schoevers
Journal of Psychopharmacology Summary & key facts 2022 161 citations

Researchers reviewed studies of drugs that act on serotonin (so-called serotonergic psychedelics) and MDMA. They found that harms and bad reactions are not clearly defined in these studies and are probably reported less often than they actually happen. Some intense or frightening experiences during treatment might help people heal, but…

Chemical synthesis and alkaloids Forensic Toxicology and Drug Analysis Psychedelics and Drug Studies MDMA Psilocybin

Ethics and ego dissolution: the case of psilocybin

William Smith, Dominic Sisti
Journal of Medical Ethics Summary & key facts 2020 130 citations

Recent, early-phase trials suggest psychedelics—especially psilocybin—may help treat several mental and substance use disorders. The psychedelic experience can include loss of self-importance, feelings of unity or connection, ineffable insights, and encounters with ‘deep’ reality or God, and it can change a person’s personality and worldview. The authors argue these unusual…

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

Therapeutic effect of psilocybin in addiction: A systematic review

van der Meer, Pim B., Fuentes, Juan J., Kaptein, Ad A., et al.
www.frontiersin.org Summary & key facts 2023 111 citations

This systematic review searched for clinical trials of psilocybin for substance use problems up to September 2, 2022. The authors found four trials with 151 patients that tested psilocybin combined with psychotherapy for alcohol or tobacco use. These small trials, including one randomized placebo-controlled trial, reported reductions in heavy drinking…

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

The acute effects of classic psychedelics on memory in humans

C. J. Healy
Psychopharmacology Summary & key facts 2021 91 citations

This 2021 review of human studies found that classic psychedelics (for example psilocybin, LSD, ayahuasca) tend to reduce performance on standard memory tests in a dose-dependent way: low doses usually showed no impairment and higher doses caused more impairment. At the same time, these drugs often made autobiographical memories feel…

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