Antipsychotic natural products

Psychoactive plants and plant natural products (NPs) were instrumental in early neuroscience research, and recreational or toxic NPs have played major roles in the discovery of virtually all neurotransmitter systems. Here, we review the contribution of NPs to psychosis, a heterogeneous neuropsychiatric condition characterized by conflicting perception of reality, including false believes (delusions) and perceptions that others do not perceive (hallucinations). Although the underlying biochemical mechanisms of psychosis remain insufficiently understood, NPs were found to either trigger or inhibit psychosis via discrete neuropharmacological mechanisms. Psychosis most frequently occurs in patients suffering from schizophrenia, a severe chronic mental disease that affects about 0.3% of the population worldwide. It is noteworthy that the plant alkaloid reserpine from the ancient antihypertensive and antipsychotic botanical drug Rauwolfia serpentina root (Indian snakeroot) was described around the same time as the first synthetic antipsychotic (neuroleptic) agent chlorpromazine in early 1950s. On the other hand, numerous psychoactive NPs like anticholinergic tropane alkaloids, psychostimulants, or classical hallucinogens are known to induce psychosis in some individuals by inhibiting cholinergic signaling, stimulating monoaminergic synapses, or other mechanisms. We discuss the preclinical and clinical evidence of potentially antipsychotic NPs and botanical drugs. Because prevention of psychosis is an unmet medical need, given its severity and impact in society, the conceivable effects of dietary NPs or botanical drugs as emerging modifiers of anxiety, paranoia and psychosis deserve attention beyond drug discovery