Abstract

Long-term potentiation (LTP), a form of Hebbian neuroplasticity, is characterised by enhanced synaptic efficacy, and facilitates experience-dependent learning. In-vitro animal research has previously demonstrated psychedelic-induced neuroplasticity. The positive psychological outcomes following psilocybin therapy are postulated to result from enhanced neuroplasticity. This project aimed to employ the non-invasive visual LTP electroencephalogram (EEG) paradigm to investigate whether LTP is dose-dependently enhanced by psilocybin in humans. Visually-evoked potentials (VEPs) were used as electrophysiological indexes of LTP-like neuroplasticity enhancement in the visual cortex following LTP-inducing high-frequency visual stimulation. Twenty-eight psychedelicnaïve healthy participants underwent two psilocybin (1 mg and 25 mg) dosing sessions four weeks apart. The visual LTP paradigm was conducted approximately 5 hours after psilocybin administration. LTP data from 16 participants were deemed usable and thus included in the analyses. The 25 mg dose significantly potentiated the N1 VEP component (133 ms) relative to 1 mg, indicating greater enhancement of LTP-like neuroplasticity. In conclusion, this study reports the earliest demonstration of psilocybin-induced neuroplasticity enhancement in humans and recommends the extension of this protocol to clinical populations to determine the role of LTP in the positive therapeutic outcomes of psilocybin-therapy.