Frontier mental health research: psychedelics & drug studies

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26 papers

Anxiety

Based on 52 papers

Research points to two clear groups of treatments for anxiety. First, ordinary approaches like exercise — especially walking and other regular physical activity — have strong, high-quality evidence showing medium-sized reductions in anxiety symptoms. These are proven in many randomized trials and reviews. Second, newer substance-assisted therapies (often called psychedelic‑assisted therapy) are promising. Small clinical trials and reviews show reductions in anxiety and related problems after carefully supervised doses of drugs such as psilocybin, MDMA, ketamine, and ayahuasca. However, these drug approaches are mostly early-stage or done in special research settings and need more, larger trials before they can become routine care. People thinking about or treating anxiety should know that drug‑assisted therapies are almost always given together with serious psychological support. How the drug is given, the preparation before it, and follow-up therapy matter a lot. There are also safety and equity issues to watch: some psychedelics can have rare lasting side effects, many studies are small, and people of color have been underrepresented in trials. For now, exercise has the clearest and broadest evidence. Other treatments are promising but still need more testing and careful medical oversight.

Key findings

  • Many high-quality reviews find regular physical activity reduces anxiety by a medium amount across many trials. 8792
  • Walking specifically lowers anxiety symptoms compared with doing nothing, based on 26 randomized trials pooled together. 8785
  • Clinical trials and reviews report that psychedelic-assisted therapies (drugs given with therapy) reduced anxiety symptoms in people diagnosed with anxiety disorders. 15068 15063 15056
  • For post‑traumatic stress disorder (a trauma-related anxiety condition), MDMA given with psychotherapy produced large benefits in several controlled trials. 15063
  • Psychedelic drugs appear to change the brain in ways that could help anxiety and mood problems. Lab and imaging studies report increased brain plasticity (the brain’s ability to form new connections) and changes in inflammation and brain networks after substances like psilocybin, DMT, and other psychedelics. 15132 15050 15091 15135
  • Ketamine produces fast antidepressant effects and has been tested as an alternative to electroconvulsive therapy; it has also been studied for anxiety-related conditions in some trials. 10149 10160 15068
  • Most studies of psilocybin and other classic psychedelics are small and done with close medical and psychological support, so experts say larger, well‑controlled trials are still needed before routine use. 15056 15078
  • How people are prepared and supported matters a lot: many guides and reviews agree that screening, setting expectations, building trust, and follow‑up therapy are core parts of substance‑assisted psychotherapy. 15065 15092 15063
  • People of color were underrepresented in many psychedelic-assisted psychotherapy studies, which limits how well the results apply to different ethnic groups. 15095
  • There are risks to be aware of: rare but long-lasting perceptual problems (called HPPD) and other psychological or physical side effects have been reported after hallucinogen use, so safety monitoring is important. 15048 15087

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

RETRACTED ARTICLE: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials

Michael C. Mithoefer, Allison A. Feduccia, Lisa Jerome, Anne Mithoefer, Mark T. Wagner, Zach Walsh, et al.
Psychopharmacology Summary & key facts 2019 357 citations

This paper pooled data from six randomized, double‑blind phase‑2 trials of MDMA‑assisted psychotherapy for adults with PTSD (total N=103). After two blinded MDMA sessions, the MDMA group showed larger reductions in clinician‑rated PTSD symptoms than the control group (mean difference −22.0 points on the CAPS‑IV, P < 0.001) and a…

Cannabis and Cannabinoid Research Posttraumatic Stress Disorder Research Psychedelics and Drug Studies MDMA

Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review

Jerome Sarris, Justin Sinclair, Diana Karamacoska, Margaret Davidson, Joseph Firth
BMC Psychiatry Summary & key facts 2020 243 citations

This 2019 systematic review looked at human studies of medicinal cannabis and cannabis-derived isolates for major psychiatric disorders. The authors found that the evidence is very new and limited, so it is too early to recommend cannabis medicines for psychiatric conditions. Some small or isolated studies suggest benefits for a…

Cannabis and Cannabinoid Research Infant Health and Development Sleep and Wakefulness Research

Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline

Allison A. Feduccia, Lisa Jerome, Berra Yazar‐Klosinski, Amy Emerson, Michael C. Mithoefer, Rick Doblin
Frontiers in Psychiatry Summary & key facts 2019 168 citations

This review explains why the FDA gave Breakthrough Therapy Designation to MDMA-assisted psychotherapy for PTSD. It summarizes six Phase 2 trials (2004–2017) in which MDMA was given in up to three 8-hour sessions combined with preparatory and follow-up therapy, and pooled analyses showed a large effect on PTSD symptoms and…

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Treatment of Major Depression

MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study

Philip E. Wolfson, Julane Andries, Allison A. Feduccia, Lisa Jerome, Julie B. Wang, Emily D. Williams, et al.
Scientific Reports Summary & key facts 2020 161 citations

This small, randomized, double-blind pilot study tested MDMA-assisted psychotherapy for anxiety tied to life‑threatening illness. Eighteen people were enrolled (13 got MDMA, 5 got placebo) and had two blinded 8‑hour therapy sessions, with later open‑label MDMA sessions and 6‑ and 12‑month follow-ups. The MDMA group showed a larger drop in…

Cannabis and Cannabinoid Research Natural Compound Pharmacology Studies Psychedelics and Drug Studies

Use of cannabidiol in anxiety and anxiety-related disorders

Jessica W. Skelley, Crystal M. Deas, Zachary Curren, Jonathan Ennis
PubMed Summary & key facts 2020 133 citations

This systematic review looked at human studies of cannabidiol (CBD) for anxiety up to June 2019. Eight studies were included (6 small randomized controlled trials, 1 case series, and 1 case report). The studies tested CBD for anxiety in healthy volunteers, generalized anxiety disorder, social anxiety disorder, and PTSD-related anxiety.…

Bipolar Disorder and Treatment Cannabis and Cannabinoid Research Child and Adolescent Psychosocial and Emotional Development

Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

Madison Wright, Patricia Di Ciano, Bruna Brands

This review looked at animal and human studies of cannabidiol (CBD) for anxiety. In animals, CBD often reduced anxiety-like behaviors at low or medium doses but sometimes increased anxiety at high doses. Small human studies and public-speaking tests suggest CBD might reduce anxiety in healthy people and in social anxiety…

Cannabis and Cannabinoid Research Neurotransmitter Receptor Influence on Behavior

Developing a real-world evidence base for prescribed cannabis in the United Kingdom: preliminary findings from Project Twenty21

Chloe Sakal, Michael T. Lynskey, Anne Katrin Schlag, David Nutt
Psychopharmacology Summary & key facts 2021 44 citations

Project Twenty21 is the UK’s first medical cannabis registry. It began in August 2020 to collect real-world data because randomized trials are hard and NHS prescribing remained rare after medical cannabis was legalised in November 2018. By 12 March 2021, 678 people had joined; most were men and the most…

Cannabis and Cannabinoid Research Homelessness and Social Issues Sleep and related disorders

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

Ana Maria Raymundi, Thiago Rodrigues da Silva, Jeferson Machado Batista Sohn, Leandro J. Bertoglio, Cristina Aparecida Jark Stern
BMC Psychiatry Summary & key facts 2020 42 citations

This review looked at human studies up to July 2020 about THC (the main psychoactive part of Cannabis) and its effects on fear-related memories and anxiety. The authors report that low doses of THC can speed up extinction of aversive memories and lower anxiety in people, and that combining THC…

Cannabis and Cannabinoid Research Memory and Neural Mechanisms Neuroscience and Neuropharmacology Research

A Multi-Level Analysis of Biological, Social, and Psychological Determinants of Substance Use Disorder and Co-Occurring Mental Health Outcomes

Cecilia Ilaria Belfiore, Valeria Galofaro, Deborah Cotroneo, Alessia Lopis, Isabella Tringali, Valeria Denaro, et al.
Psychoactives Summary & key facts 2024 40 citations

Researchers looked at sixty studies to see how biology, social life, and psychology mix together to affect substance use problems and mental health. They found that brain systems, genes, childhood experiences, parenting, personality, and existing mood or anxiety problems all interact. This makes addiction and related psychiatric symptoms complicated, especially…

Bipolar Disorder and Treatment Cannabis and Cannabinoid Research Child and Adolescent Psychosocial and Emotional Development Cannabis Other

Cannabinoids and their therapeutic applications in mental disorders

María Scherma, Anna Lisa Muntoni, Gernot Riedel, Walter Fratta, Paola Fadda

This review looks at research on cannabis compounds and the body’s endocannabinoid system as possible treatments for depression, bipolar disorder, anxiety, PTSD, and schizophrenia. It says the evidence is mixed and mostly preliminary. Some studies show biological links between the endocannabinoid system and mood disorders, and early clinical work suggests…

Cannabis and Cannabinoid Research Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies
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