Dimethyltryptamine and harmine, components of ayahuasca, prevented cocaine-induced apoptosis in SH-SY5Y human neuroblastoma cells
Gilles Salles, Carolina Aparecida de Faria Almeida, Isabella de Carvalho Alves, Giulia de Assis Braz, Flávia B. Lopes, João Paulo S. Fernandes, Daniela Aparecida Chagas‐paula, Albert Katchborian‐neto, Matheus Fernandes Alves, Vítor Bruno, Beatriz Aparecida Passos Bismara Paranhos, Tânia Marcourakis, Larissa Helena Torres, Raphael Caio Tamborelli Garcia
Archives of Toxicology November 12, 2025 DOI: 10.1007/s00204-025-04208-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Human SH-SY5Y neuroblastoma cells |
| Interventions | DMT harmine cocaine |
| Duration | 48-hour exposure |
| Topics | Ayahuasca 5-MeO-DMT DMT |
| Keywords | Harmine Apoptosis Flow cytometry Pharmacology Viability assay Toxicity Western blot Mtt assay Propidium iodide Neuroprotection Parthenolide In vitro Neuroblastoma Programmed cell death Cell cycle Monoamine oxidase |
| Key points | DMT and harmine, isolated and combined, provided partial neuroprotection against cocaine-induced toxicity in SH-SY5Y cells. |
Abstract
Ayahuasca is a psychoactive brew traditionally used in religious rituals by indigenous Amazonian populations and South American syncretic religions such as Santo Daime and União do Vegetal. Its psychoactive effects are primarily due to N,N-dimethyltryptamine (DMT), while harmine (HRE), a β-carboline alkaloid, inhibits monoamine oxidase (MAO), enabling DMT's oral bioavailability. Recent studies demonstrate Ayahuasca's therapeutic potential in treating substance use disorders, including cocaine use disorder, which involves neurotoxic effects. However, no in vitro studies to date have evaluated the neuroprotective potential of Ayahuasca compounds in this context. This study investigated the effects of DMT and HRE, isolated and combined, on cocaine-induced toxicity in human SH-SY5Y neuroblastoma cells. Cells were exposed for 48 h to various concentrations of DMT and HRE (0.1-1000 µM), cocaine (0.5-5 mM), and DMT:HRE combinations (10:10 to 10:100 µM). The non-toxic concentrations of DMT (10 µM) and HRE (10 µM), both isolated and combined (10:20 µM DMT:HRE), were co-incubated with the lethal concentration 50 (LC50) of cocaine (2.5 mM) to assess neuroprotection. Cell viability was evaluated by MTT assay, apoptosis by flow cytometry using annexin-V/propidium iodide staining, and protein expression of apoptosis-related markers (Bax, Bcl-2, and caspase-8) by western blot. The results showed increased cell viability in co-treatment groups (cocaine + DMT and/or HRE) when compared to cocaine-only groups. Flow cytometry revealed partial to complete protection against apoptosis in co-treated cells. Western blot demonstrated reduced caspase-8 expression in cells treated with Ayahuasca compounds plus cocaine versus cocaine alone. In conclusion, DMT and HRE-isolated and combined-provided partial neuroprotection against cocaine-induced toxicity in SH-SY5Y cells. These findings support Ayahuasca-derived alkaloids as candidates for further investigation in neuroprotection and substance use disorder treatment.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |
Citations in the library
Cites 19
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Current Drug Abuse Reviews June 1, 2013
- Ayahuasca: Pharmacology, neuroscience and therapeutic potential Brain Research Bulletin March 11, 2016
- N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Translational Psychiatry September 28, 2020
and 14 more in the library