Frontier mental health research: psychedelics & drug studies

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34 papers

Psilocybin for Depression

Based on 34 papers

Research on psilocybin for depression is promising but still early. Small, carefully run studies that combine psilocybin with therapy often find big short-term drops in depressive symptoms, and some people keep improving for months. At the same time, the trials are usually small or open-label, and scientists still need larger, well-controlled studies and longer follow-up to be sure how well and how safely psilocybin works for different people. Scientists have some ideas about how psilocybin might help. Lab and brain-imaging studies point to effects on serotonin brain receptors, more flexible brain connections (called neuroplasticity), and changes in brain networks linked to rumination. But these biological signs are not all consistently measured yet, and the best ways to test them in people are still under development. Research also notes real risks in uncontrolled use, and that many study samples lack diversity, so we do not yet know how well results apply to everyone.

Key findings

  • Small clinical trials that paired psilocybin with therapy often showed large, rapid drops in depression or anxiety symptoms. 15132 15063 15056
  • In some studies a single or just a few psilocybin doses were followed by benefits that lasted for weeks to months for some people. 15086 15049 15132
  • Psilocybin works mainly on serotonin-related brain receptors and seems to make brain networks more flexible and less stuck in patterns linked to depression. 15132 15050 15060
  • Laboratory and early human work also suggests psilocybin can reduce inflammation in the brain and boost the brain's ability to form new connections (neuroplasticity), but this is still being worked out. 15132 15050 15049
  • Overall evidence is limited by small sample sizes, open-label designs (where people knew they got the drug), short follow-up times, and few large randomized controlled trials. 15056 15070 15078 15085
  • Clinical trials done under medical supervision generally report acceptable safety and manageable side effects, but psychological distress during sessions and other adverse reactions can happen and need careful medical and therapeutic support. 15135 15055 15063
  • Biological markers are not yet consistent: for example, pooled human studies did not find clear rises in blood BDNF (a protein linked to brain change) after psychedelic drugs, even though lab work shows brain changes. 15129 15050 15086
  • Researchers disagree about whether the special subjective 'psychedelic' experience is required for benefit. This debate makes it hard to design placebo-controlled trials where people do not know what they received. 15078 15086
  • People of color and other groups are underrepresented in psychedelic studies, so we cannot be sure study results apply to everyone. 15095 15094
  • In surveys, many people report using psychedelic mushrooms for mental health, but population surveys also find that users often score higher on anxiety and depression screens — which does not prove benefit and may reflect self-treatment or other factors. 15054

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

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

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

The therapeutic potential of psilocybin: a systematic review

Jan van Amsterdam, Wim van den Brink
Expert Opinion on Drug Safety Summary & key facts 2022 73 citations

This paper looked across existing studies of psilocybin and found that, when it is given along with psychotherapy or therapy-style support, it looks promising as a treatment for several mental health problems, including cases that did not get better with other treatments. But the authors say the current studies are…

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

From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders

Urszula Kozłowska, Charles D. Nichols, Kalina Wiatr, Maciej Figiel
Journal of Neurochemistry Summary & key facts 2021 71 citations

This review looks at research on psychedelic drugs, especially psilocybin. It says recent human studies show a single dose can give lasting relief from severe depression, and regulators have given two late-stage psilocybin trials special 'Breakthrough Therapy' status. The paper also pulls together lab and animal studies that suggest psychedelics…

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

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

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
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