Frontier mental health research: psychedelics & drug studies

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5 papers

Sadness or low mood

Based on 75 papers

Research shows several different ways can help with sadness or low mood. Right now, the strongest clinical evidence for a fast-acting drug comes from ketamine and its approved form esketamine. At the same time, a wave of studies on classic psychedelics (psilocybin, LSD, DMT) and entactogens (MDMA) looks promising, especially when the drug is given together with careful psychological support. However, most psychedelic studies are still small or early-stage. They often rely on the setting, preparation, and therapy as part of the treatment, so researchers say we need larger, controlled trials and more long-term safety data. Also, non-drug options like brain stimulation and standard psychotherapies remain important parts of treatment plans and have mixed but useful evidence.

Key findings

  • Ketamine has the strongest current clinical evidence among rapid-acting drug options for major depression. 15070
  • An intranasal form of ketamine (esketamine), given with a new oral antidepressant, produced faster and larger symptom improvements than a new antidepressant plus placebo in a randomized trial of treatment‑resistant depression. 12156
  • A direct clinical trial found ketamine treatment was at least as effective as electroconvulsive therapy (ECT) for some people with hard-to-treat nonpsychotic depression. 10160
  • Psychedelic-assisted psychotherapy (for example psilocybin, MDMA, LSD) has shown promising benefits for depression and PTSD in several trials, but most studies so far are small or early-stage and need larger, controlled follow-up studies. 15135 15056 15063 15085
  • Laboratory and early human studies suggest classic psychedelics can boost the brain’s ability to rewire (called neuroplasticity) and can reduce brain inflammation, but blood biomarkers like BDNF do not reliably reflect these brain changes yet. 15132 15050 15129
  • How the drug is given matters a lot: studies and treatment guides agree that preparation, the person’s mindset, the setting, and follow-up therapy (often called 'set, setting, and integration') shape safety and outcomes. 15065 15086 15096
  • There are real safety and equity concerns: some substances (for example ibogaine) carry serious cardiac or neurological risks, some people can develop lasting perceptual problems after hallucinogens, and people of color are often under‑represented in trials. 15085 15048 15095 15094
  • Non-drug brain treatments show mixed results. Small deep brain stimulation (DBS) studies reported large improvements in a few people with severe depression, while a large one‑year trial of vagus nerve stimulation did not show a clear difference on its main outcome but did show some secondary clinician- and patient-rated benefits. 10166 10163
  • Standard psychotherapies help many people but do not work for everyone: pooled data across trials find modest response rates for depression, and clinical guidelines recommend collaborative, personalized care and stepwise treatment plans for major depression. 12851 15076 13305
  • Combining treatments is an active research idea. Early studies suggest pairing ketamine with brain stimulation (like TMS) or combining mindfulness with psychedelic therapy may boost effects, but this is still experimental. 10162 15047

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

The Influence of the COVID-19 Pandemic on Social Anxiety: A Systematic Review

Reuben Kindred, Glen Bates

This systematic review looked at 33 studies about social anxiety during the COVID-19 pandemic. The studies suggest social anxiety increased in the general population. Women and people with low incomes appeared more likely to report higher social anxiety. Other links to higher social anxiety included poor coping, weaker social support,…

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes COVID-19 and Mental Health Perfectionism, Procrastination, Anxiety Studies

Psychedelic Mushrooms in the USA: Knowledge, Patterns of Use, and Association With Health Outcomes

Richard Matzopoulos, Robert Morlock, Amy Morlock, Bernard Lerer, Leonard Lerer
Frontiers in Psychiatry Summary & key facts 2022 41 citations

Researchers ran a national online survey of U.S. adults from November 2020 to March 2021 that was weighted to represent the adult population. They asked about use of psychedelic mushrooms (psilocybin), reasons for use, and mental health. Many users said they took mushrooms for general mental health and well-being. Users…

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

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders

Nataliya S. Vorobyeva, Alena A. Kozlova
Frontiers in Pharmacology Summary & key facts 2022 14 citations

This paper reviews research on three naturally occurring psychedelics: psilocybin, ibogaine, and N,N-dimethyltryptamine (the active part of the brew ayahuasca). It explains that these drugs work on the brain's serotonin system and summarizes growing studies that suggest they might help with problems like post-traumatic stress disorder, major depression, anxiety, and…

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

Indigenous-Amazonian Traditional Medicine’s Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study

Ilana Berlowitz, Ernesto García Torres, Caroline Maake, Ursula Wolf, Chantal Martin‐Soelch
Plants Summary & key facts 2023 13 citations

Researchers reported a single case where a traditional Amazonian healer gave a weeklong, ritual treatment that included drinking a liquid made from the native tobacco plant. The patient was a 37-year-old woman with diagnosed low mood, anxiety, and attention problems plus a long-term physical health issue. The team used both…

Complementary and Alternative Medicine Studies Medicinal Plant Extracts Effects Psychedelics and Drug Studies Other
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