Evidence map›Paper›PMID 36844032›Full record

ReviewFrontiers in psychiatry2022

Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action?

Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows, Jenna Baer, Joshua D Rosenblat, Daniel M Blumberger, Benoit H Mulsant, David J Castle

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Frontiers in psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07017478 (Mood Effects of Serotonin Agonists), which is not on this map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07017478 early_phase1completednot on this mapstarted 2025, after this paper: background citation

Mood Effects of Serotonin Agonists: Depression

TypeinterventionalSponsorUniversity of ChicagoRan2025 to 2026Enrolled41ConditionsLSD, Major Depressive Disorder, DepressionArmsLSD, Placebo
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  4. Moving beyond 5-HTPsychopharmacology · 2026
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  6. Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations.Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Muhammad Ishrat HusainCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Nicole LedwosCentre for Complex Interventions, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Elise FellowsCentre for Complex Interventions, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Jenna BaerCentre for Complex Interventions, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Joshua D RosenblatDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Daniel M BlumbergerCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Benoit H MulsantCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
David J CastleDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Current treatment options for major depressive disorder (MDD) have limited efficacy and are associated with adverse effects. Recent studies investigating the antidepressant effect of serotonergic psychedelics-also known as classic psychedelics-have promising preliminary results with large effect sizes. In this context, we conducted a review of the putative neurobiological underpinnings of the mechanism of antidepressant action of these drugs. Methods: A narrative review was conducted using PubMed to identify published articles evaluating the antidepressant mechanism of action of serotonergic psychedelics. Results: Serotonergic psychedelics have serotonin (5HT)2A agonist or partial agonist effects. Their rapid antidepressant effects may be mediated-in part-by their potent 5HT2A agonism, leading to rapid receptor downregulation. In addition, these psychedelics impact brain derived neurotrophic factor and immunomodulatory responses, both of which may play a role in their antidepressant effect. Several neuroimaging and neurophysiology studies evaluating mechanistic change from a network perspective can help us to further understand their mechanism of action. Some, but not all, data suggest that psychedelics may exert their effects, in part, by disrupting the activity of the default mode network, which is involved in both introspection and self-referential thinking and is over-active in MDD. Conclusion: The mechanisms of action underlying the antidepressant effect of serotonergic psychedelics remains an active area of research. Several competing theories are being evaluated and more research is needed to determine which ones are supported by the most robust evidence.

Indexed as

ayahuascaconnectivitydepressionhallucinogenLSDneurobiologypsilocybinpsychedelics

Identifiers

PMID36844032
PMCPMC9950579

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.