Increased global integration in the brain after psilocybin therapy for depression.
Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D. Sexton, Matthew B. Wall, David Erritzøe, Leor Roseman, David Nutt, Robin Carhart-Harris
Nat Med April 11, 2022 DOI: 10.1038/s41591-022-01744-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial and double-blind phase II randomized controlled trial Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression and patients with major depressive disorder |
| Interventions | Psilocybin Escitalopram |
| Dose | 10 mg and 25 mg (open-label trial); 2 × 25 mg oral psilocybin or 2 × 1 mg oral psilocybin plus daily escitalopram 10-20 mg (RCT) |
| Duration | 7 days apart (open-label trial); 3 weeks apart for psilocybin doses, plus 6 weeks of daily placebo or escitalopram (RCT); fMRI recorded at baseline and 1 day after 25-mg dose (open-label) or 3 weeks after second psilocybin dose (RCT) |
| Topics | Depression Neuroplasticity Psilocybin Psychedelic-assisted therapy |
| Keywords | Psilocybin therapy Psilocybin treatment Psychedelic medicine Depressive symptoms Mental health Mood disorder Clinical depression Mental illness Brain connectivity Neural connectivity Brain integration Brain function Brain activity Neural integration Global integration Brain regions communication Brain research Neurobiology Cognitive neuroscience Brain science Neuroimaging Brain studies |
| Citations | 432 |
| Registration | NCT03429075 |
| Key findings | Psilocybin's antidepressant action correlates with global increases in brain network integration, as indicated by decreased fMRI brain network modularity. |
Abstract
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1 d after the 25-mg dose. Beck's depression inventory was the primary outcome measure ( MR/J00460X/1 ). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ('psilocybin arm') or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ('escitalopram arm'). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose ( NCT03429075 ). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.
In the evidence
This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.
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Antidepressant response to psilocybin was rapid and sustained and correlated with decreased fMRI brain network modularity, while escitalopram response was milder with no such change.
Synthesized
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In both trials, the antidepressant response to psilocybin was rapid, sustained, and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration.
Synthesized
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Psilocybin's antidepressant action correlated with global increases in brain network integration, as indicated by decreased fMRI brain network modularity.
Synthesized
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Psilocybin's antidepressant response was rapid, sustained, and correlated with decreased fMRI brain network modularity, suggesting increased global integration.
Synthesized
Comparable studies
Other randomized controlled trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Healthy adults, mostly hallucinogen-naïve | 2011 | Randomized controlled trial | n = 18 |
| Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder Adults aged 25–65 with DSM-IV alcohol dependence and at least 4 heavy drinking days in... | 2022 | Randomized controlled trial | n = 95 |
| Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. Adults diagnosed with major depressive disorder and no unstable somatic conditions | 2023 | Double-blind, randomised clinical trial | n = 52 |
| Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin Healthy participants | 2012 | Randomized controlled trial | n = 10 |
| The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world Adults who had a planned psychedelic experience (online surveys) and adults with major... | 2022 | Scale validation with data from two prospective observational online surveys and a double-blind randomized controlled trial | n = 1,278 |