Frontier mental health research: psychedelics & drug studies

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71 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

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Roland R. Griffiths, Matthew W. Johnson, Michael A. Carducci, Annie Umbricht, William A. Richards, Brian D. Richards, et al.
Journal of Psychopharmacology Summary & key facts 2016 2,068 citations

This randomized, double‑blind, cross‑over trial gave 51 patients with life‑threatening cancer two sessions of psilocybin (one very low dose and one high dose) spaced five weeks apart. The high dose (22–30 mg/70 kg) produced large drops in clinician‑ and self‑rated depression and anxiety, and increased quality of life, meaning, and…

Cannabis and Cannabinoid Research Complementary and Alternative Medicine Studies Psychedelics and Drug Studies

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences

Theresa M. Carbonaro, Matthew P. Bradstreet, Frederick S. Barrett, Katherine A. MacLean, Robert L. Jesse, Matthew W. Johnson, et al.
Journal of Psychopharmacology Summary & key facts 2016 526 citations

Psychedelic "bad trips" can be intense and sometimes last past the session. Surveys and studies report that a minority of users have serious short- or long-term problems, while other people later say the experience was meaningful or helpful. Risk and duration vary by dose, setting, and support, and studies give…

Body Image and Dysmorphia Studies Complementary and Alternative Medicine Studies Psychedelics and Drug Studies

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

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

Towards an understanding of psychedelic-induced neuroplasticity

Abigail E. Calder, Gregor Hasler
Neuropsychopharmacology Summary & key facts 2022 272 citations

This review looks at studies about classic psychedelics (like LSD, psilocybin, and DMT/ayahuasca) and their effects on neuroplasticity — the brain’s ability to change. Animal studies show these drugs can raise genes tied to plasticity and cause dendrite and synapse growth. Human results are mixed, especially when studies use blood…

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

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

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

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

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
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