title: Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.
abstract: Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.
authors.affiliation: a Postdoctoral Fellow, Department of Neurosciences and Behavior, Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto , Brazil.|b Advisory Board, International Center for Ethnobotanical Education , Research & Service , Barcelona , Spain.|c National Institute of Science and Technology , Ribeirão Preto , Brazil.
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Dos Santos
authors.affiliation: d Professor, Department of Neurosciences and Behavior, Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto , Brazil.|e Researcher, National Institute of Science and Technology , Translational Medicine , Ribeirão Preto , Brazil.
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
mesh_terms: D000818:Animals; D031581:Banisteriopsis / Q000737:chemistry*; D003071:Cognition / Q000187:drug effects; D006213:Hallucinogens / Q000302:isolation & purification / Q000494:pharmacology*; D006247:Harmine / Q000302:isolation & purification / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D006213:Hallucinogens; D018696:Neuroprotective Agents; D006247:Harmine
keywords: Harmine; hippocampus; learning; memory; neuroprotection