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Classical psychedelics for the treatment of depression and anxiety: A systematic review
Abstract
Background Depression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promising alternative for patients unresponsive to traditional treatments. This review aims to determine the efficacy and tolerability of psychedelics in the management of resistant depression.Methods Clinical trials investigating psychedelics in patients with depression and/or anxiety were searched via MEDLINE, EMBASE and PsychINFO. Efficacy was assessed by measuring symptom improvement from baseline, and tolerability was evaluated by noting the incidence and type of adverse effects reported. Risk of bias was assessed.Results Seven studies, with 130 patients, were analysed in this review. Three were conducted in patients with depression, two in patients with anxiety and two in patients with both. In a supportive setting, ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics were well-tolerated. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.Limitations At present, the number of studies on this subject is very limited; and the number of participating patients within these is also limited as the treatment under investigations is a relatively novel concept.Conclusions Though further evidence is required, psychedelics appear to be effective in significantly reducing symptoms of depression and anxiety and are well-tolerated.
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“Classic psychedelics, such as synthetic LSD and psilocybin, which is found in certain mushrooms, have shown promise as aids in psychotherapy e.g., for mood disorders and substance dependence [1, 5, 33].”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [5]
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“To date, reviews have focused on establishing treatment efficacy [30], understanding the neurological mechanisms of change [71], or have been broad in their aims (e.g. including a variety of drug classes or disorders [72, 73];).”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [30]
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Metadata
- Authors
- Muttoni, S., Ardissino, M., & John, C.
- Affiliations
- Imperial College London (GB)
- Chelsea and Westminster Hospital (GB)
- Corresponding author
- Ardissino, Maddalena
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 258
- Pages
- 11-24
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2964775179
- Cited by
- 256
- References
- 127
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 67 · 2023: 51 · 2022: 31 · 2021: 32 · 2020: 20 · 2019: 2
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Health › Religion, Spirituality, and Psychology
- Keywords
- psychedelics, psychedelic therapy, depression, anxiety, treatment-resistant depression, ayahuasca, psilocybin, lysergic acid diethylamide, treatment efficacy, tolerability, adverse effects
- MeSH terms
- Adult, Anxiety Disorders, Depressive Disorder, Female, Hallucinogens, Humans, Lysergic Acid Diethylamide, Psilocybin
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