Review article Plants and the central nervous system E.A. Carlini * Department of Psychobiology, Paulista School of Medicine, Federal University of Sa ˜o Paulo, Rua: Botucatu, 862 Ed. Cie ˆncias Biome ´dicas, 1o andar, CEP 04023-062, Sa ˜o Paulo, SP, Brazil Received 2 November 2002; received in revised form 20 March 2003; accepted 31 March 2003 Abstract This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS) In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp (Ma Huang), Paullinia spp (guarana ´), Catha edulis Forssk (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill and the mixture of Psychotria viridis Ruiz and Pav and Banisteriopsis caapi (Spruce ex Griseb.) C.V Morton Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp and Piper methysticum G Forst.), were also analysed. Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed. D 2003 Published by Elsevier Science Inc. Keywords: Medicinal plants; Plant adaptogens; Khat; Ephedra spp.; CNS plants; Guarana ´; Ayahuasca; Iboga; Passiflora; Valeriana; Kava-kava 1. Introduction Mind-altering drugs, especially plants, have always fas- cinated human beings Surrounded by mystic superstitions, magic thoughts and religious rituals, they have always occupied man’s attention Among the plants used by humans, those able to alter the conscience and the sensorium have drawn special consideration In fact, due to their astonishing effects, the psychodysleptic drugs (according to the Delay and Deniker, 1961, nomenclature), also called hallucin- ogenic drugs, have occupied much of the researchers’ time, directed most of their thoughts and efforts towards attempts to understand their mechanism of action, and, hence, to un- derstand human behavior, thoughts, humor, sensations, etc. However, the challenge of trying to unravel the mecha- nisms of action on mood, humor, cognition, sensorium, etc., led to an inconvenience: to ignore, or to face as low priority, the fact that plants could also have beneficial properties to treat mental disease and some psychic ailments Further- more, as most of the plants were first used by the so-called primitive cultures, their occasional use by the White occi- dental culture was relegated to a second plan, being con- sidered as sorcerer’s therapeutics In this respect, it is pertinent to quote a sentence from the first description in 1651 of a Mexican hallucinogenic plant (ololiuqui): ‘‘A thousand visions and satanic hallucinations appeared to them’’ (Hofmann, 1982). A perverse result of such posture was a neglect of and probably more, a disdain, for all kinds of therapeutics based on plants. Thus, until recently, very little attention was given by the scientific community to the benefits, as accepted by folk medicine, of the therapeutic usefulness of plants endowed with psycholeptic and psychoanaleptic (Delay and Deniker, 1961) properties. Fortunately, this bad tide has recently turned due to several reasons, among them the wrong belief that plants, by originating directly from nature, must be less toxic than synthetic drugs Another important aspect for this turning point was the realization by the pharmaceutical industry that plants, after all, could be a good business as more and more 0091-3057/03/$ – see front matter D 2003 Published by Elsevier Science Inc. doi:10.1016/S0091-3057(03)00112-6 * Tel.: +55-11-5539-0155; fax: +55-11-5084-2793. E-mail address: carlini@psicobio.epm.br (E.A. Carlini). www.elsevier.com/locate/pharmbiochembeh Pharmacology, Biochemistry and Behavior 75 (2003) 501–512