Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms
Guss, J., Krause, R., Reed, S., Skinta, M. D., Sloshower, J. A., Wallace, R. M., Williams, M. T.
This double-blind, placebo-controlled, within-subject study (n=19) involved individuals with major depressive disorder (MDD). It investigated the effects of a single dose of psilocybin on electroencephalographic (EEG) correlates of neuroplasticity and depression symptoms. The results showed that EEG theta power doubled in amplitude two weeks after psilocybin administration. This increase was correlated with improvements in depression symptoms, suggesting that psilocybin may produce sustained changes in brain neuroplasticity and have antidepressant effects. Note that the improvement in depression scores was not significant vs placebo.
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.