Hypericum perforatum extract modulates cortical plasticity in humans

Background: Hypericum perforatum (HYP) extract is one of the most commonly used complementary alternative medicines (CAMs) for the treatment of mild-to-moderate depression. Non-invasive brain stimulation protocols can be used to investigate the effect of psychoactive substances on the human brain. In this study, we explored the effect of a single dose of HYP extract (WS 5570) intake on corticospinal excitability and plasticity in humans. Methods: Twenty-eight healthy subjects were required to intake 900 mg of either HYP extract or placebo. Cortical excitability was assessed using single and paired transcranial magnetic stimulation (TMS). The electrophysiological parameters of motor threshold, recruitment of motor-evoked potentials (MEPs), cortical silent period (CSP), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were tested before and 2 and 5 h after the oral intake. Spinal and neuromuscular excitability and peripheral nerve excitability were measured by F response and M-wave. Cortical plasticity was induced using transcranial direct current stimulation (tDCS). Subjects received either HYP extract or placebo before anodal and cathodal tDCS of the primary motor cortex. Plasticity was assessed by MEP amplitudes. Results: HYP extract reversed cathodal tDCS-induced long-term depression (LTD)-like plasticity into facilitation, as compared to placebo. HYP extract did not have a significant effect on anodal tDCS-induced plasticity and TMS measures of motor cortex and spinal/neuromuscular excitability. Conclusions: Our findings suggest that a single oral dose of HYP extract modulates cortical plasticity in healthy subjects and provide new insight into its possible mechanism of action in humans.