Effects of the Naturalβ-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies

Harmine, a natural alkaloid found in ayahuasca and Syrian rue, shows neuroprotective and cognitive-enhancing effects in preclinical studies. A systematic review of two hippocampal cell culture studies and nine animal model studies found that harmine reduced excitotoxicity, inflammation, and oxidative stress, increased brain-derived neurotrophic factor levels, and improved memory and learning. These effects may involve monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreased reactive oxygen species, increased neurotrophic factors, and anti-inflammatory actions. Further preclinical and human research is needed.

Study at a glance

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.