Modulation of neuroplasticity in humans after acute intake of antidepressant, anxiolytic and adaptogenic herbs

Abstract

Herbal medicine represents one of the most frequently used complementary and alternative approaches for the treatment of psychiatric conditions such as depression, anxiety and sleep disturbance. Among the most used herbal medicines, Hypericum perforatum (HYP) extract, Valeriana officinalis extract (VE) and Rhodiola rosea extract (RRE) are the oldest and most thoroughly researched phytotherapeutic medications. Despite their widespread use, the mechanisms of action and the role of the different compounds of these herbal products are still a matter of debate and warrant the need to develop new approaches to investigate their effects in humans. Noninvasive brain stimulation protocols, such as Transcranial Magnetic Stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. TMS can be used to test the affect of acute drug intake at the system level in the cerebral cortex in humans. Pharmaco-TMS offers a broad array of measures of cortical excitability and offers the possibility to probe the activity of different forms of inhibitory and excitatory networks. Furthermore, tDCS is a safe noninvasive brain stimulation technique that, combined with TMS, has been shown to induce cortical plastic changes in humans that resemble Long-term potentiation and depression (LTP and LTD)-like plasticity. The studies presented in this thesis explored the neurophysiological effect of the acute intake of herbal products commonly used to treat psychiatric conditions. Study 1 explored the effect of HYP extract acute dose intake on cortical excitability and plasticity. The results indicated that HYP acute intake affected cortical plasticity induced by cathodal tDCS by modulating LTD-like plasticity in a similar manner of conventional antidepressants. Study 2 investigated the effects of a single dose intake of VE on cortical excitability. It was found that VE intake modulated intracortical facilitatory circuits explored by TMS. Study 3 studied the effect of a single oral dose of RRE intake on cortical excitability and plasticity. Results showed that RRE acute intake prevented cathodal tDCS-induced LTD and increased (non-significantly) LTP-like plasticity. The translational studies described in the thesis add to the understanding of how the herbal products used in psychiatry can affect brain circuitries in humans.