Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms
In a double‑blind, placebo‑controlled within‑subject study of 19 individuals with major depression, a single 0.3 mg/kg dose of psilocybin produced a twofold increase in auditory‑evoked theta (4–8 Hz) power at two weeks that correlated with reductions in GRID‑HAM‑D‑17 scores, whereas placebo produced no change. This sustained theta enhancement—interpreted as an EEG correlate of long‑term potentiation—may serve as a biomarker of psilocybin‑induced neuroplasticity underlying its antidepressant effects.
Authors
- Skosnik, P. D.
- Sloshower, J.
- Safi-Aghdam, H.
Published
Abstract
Background
Evidence suggests that serotonergic psychedelics (e.g. psilocybin), have rapid-acting and long-lasting antidepressant effects after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that these drugs promote neuroplasticity. However, this has not been conclusively demonstrated in humans.
Aims
We hypothesized that relative to placebo, psilocybin would: (1) increase electroencephalographic (EEG) correlates of neuroplasticity, (2) reduce depression symptoms, and (3) changes in EEG would correlate with improvements in depression.
Methods
In this double-blind, placebo-controlled, within-subject study, individuals with major depressive disorder (MDD; n = 19) were administered placebo followed by psilocybin (0.3 mg/kg) in a fixed order (placebo, followed by psilocybin 4 weeks later). EEG indices of neuroplasticity (tetanus-induced long-term potentiation) as assessed via auditory evoked theta (4–8 Hz) power and measures of depression (GRID Hamilton Rating Scale for Depression-17 (GRID-HAM-D-17)) were measured at several time-points after placebo and psilocybin (24 h and 2 weeks after each session).
Results
EEG theta power doubled in amplitude 2 weeks after a single psychedelic dose of psilocybin but not after placebo. Further, improvements in depression symptoms 2 weeks after psilocybin were correlated with increases in theta power.
Conclusions
The increased theta power observed represents evidence of sustained changes in the brain following psilocybin. Given the correlation with enhancement in depressive symptoms, changes in theta may represent an EEG biomarker of the sustained effects of psilocybin, and may shed light on potential mechanisms of psilocybin’s antidepressant effect. Taken together, these results complement the emerging notion that psilocybin, and perhaps other psychedelics, can produce long-term alterations in neuroplasticity.
Research Summary of 'Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms'
Introduction
Skosnik and colleagues situate this study within renewed interest in serotonergic psychedelics, particularly psilocybin, for neuropsychiatric disorders. Prior clinical studies have reported rapid and sustained therapeutic effects of one or two doses of psilocybin across conditions including depression, anxiety and substance use, but the biological mechanisms that could produce both fast onset and durable benefit remain uncertain. Preclinical work shows that psilocybin promotes structural synaptic changes (dendritic growth, spinogenesis, synaptogenesis) and increased synaptic strength, giving rise to the hypothesis that psychedelics act as "psychoplastogens"; however, electrophysiological evidence of increased neural plasticity in humans has not been conclusively demonstrated. The authors note that long-term potentiation (LTP) — a persistent increase in synaptic strength following high-frequency stimulation thought to support learning and memory — can be indexed non-invasively in humans using sensory stimulation and electroencephalography (EEG), for example via an auditory tetanus paradigm that elicits evoked theta-band activity. The study tested three linked hypotheses: that, relative to placebo, psilocybin would (1) increase EEG correlates of neuroplasticity, operationalised primarily as auditory-evoked theta (4–8 Hz) power and tetanus-induced LTP-like changes; (2) reduce depressive symptoms; and (3) show that EEG changes would correlate with clinical improvement. The work aimed to provide electrophysiological evidence in people with major depressive disorder (MDD) for sustained plasticity-related brain changes following a single moderate dose of psilocybin (0.3 mg/kg).
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Skosnik, P. D., Sloshower, J., Safi-Aghdam, H., Pathania, S., Syed, S., Pittman, B., & D’Souza, D. C. (2023). Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms. Journal of Psychopharmacology, 37(7), 687-697. https://doi.org/10.1177/02698811231179800
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