OPEN Foundation

M. Li

Interaction of Sex and Age on the Dissociative Effects of Ketamine Action in Young Healthy Participants.


Ketamine is a drug that reduces depressive and elicits schizophrenia-like symptoms in humans. However, it is largely unexplored whether women and men differ with respect to ketamine-action and whether age contributes to drug-effects. In this study we assessed dissociative symptoms via the Clinician Administered Dissociative States Scale (CADSS) in a total of 69 healthy subjects aged between 18 and 30 years (early adulthood) after ketamine or placebo infusion. Dissociative symptoms were generally increased only in the ketamine group post-infusion. Specifically, within the ketamine group, men reported significantly more depersonalization and amnestic symptoms than women. Furthermore, with rising age only men were less affected overall with respect to dissociative symptoms. This suggests a sex-specific protective effect of higher age which may be due to delayed brain maturation in men compared to women. We conclude that it is crucial to include sex and age in studies of drug effects in general and of ketamine-action in specific to tailor more efficient psychiatric treatments. Clinical Trial Registration: EU Clinical Trials Register (EudraCT), trial number: 2010-023414-31.
Derntl, B., Hornung, J., Sen, Z. D., Colic, L., Li, M., & Walter, M. (2019). Interaction of sex and age on the dissociative effects of ketamine action in young healthy participants. Frontiers in neuroscience13,
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Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways


The effects of harmaline on the viability and apoptosis of human liver carcinoma were investigated in vitro. HepG2 cells were treated with harmaline (0‑10 µM), and the proliferation and apoptosis of HepG2 cells were investigated using an MTT assay and flow cytometry, respectively. The protein expression of cellular tumor antigen p53 (p53), cyclin‑dependent kinase inhibitor 1 (p21), tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand (FasL) and caspase‑8 was subsequently measured using western blotting. In addition, an ELISA was used to analyze caspase‑8/3 activity. Harmaline significantly increased p53, p21, Fas and FasL protein expression in HepG2 cells. Additionally, treatment with harmaline significantly increased the expression of caspase‑8 and caspase‑8/3 activity. The results from the present study suggest that harmaline suppresses the viability, but induces the apoptosis, of human liver carcinoma cells through upregulation of the p53/p21 and Fas/FasL signaling pathways.
Xu, B., Li, M., Yu, Y., He, J., Hu, S., Pan, M., … & Zhu, J. (2018). Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways. Oncology Letters15(2), 1931-1936. 10.3892/ol.2017.7495
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Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling


Harmine is a major constituent in a hallucinogenic botanical mixture ayahuasca and medical plant Peganum harmala L. The plant is used for various illnesses and exhibits anti-inflammatory activity. However, the active constituents remain unclear. Here, we screened the seven alkaloids in P. harmala for their anti-inflammatory activity using an nuclear factor-κB (NF-κB) reporter assay. We found that harmine and harmol could inhibit NF-κB transactivity. As the most abundant compound, harmine inhibited tumor necrosis factor-α (TNF-α)- and lipopolysaccharides (LPS)-induced NF-κB transactivity and nuclear translocation in mouse macrophage RAW 264.7 cells. The mRNA and protein levels of NF-κB downstream inflammatory cytokines also reduced. In an LPS-challenged mouse model, harmine markedly averted inflammatory damage of the lung, and decreased serum TNF-α, interleukin-1β (IL-1β) and IL-6 levels. Our data indicate that harmine may exert the anti-inflammatory effect by inhibition of the NF-κB signaling pathway and harmine is probably responsible for the anti-inflammatory effects of P. harmala.

Liu, X., Li, M., Tan, S., Wang, C., Fan, S., & Huang, C. (2017). Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling. Biochemical and Biophysical Research Communications. 10.1016/j.bbrc.2017.05.126
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Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells


Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear.
To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells.
The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot.
Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine.
Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine.
Li, C., Wang, Y., Wang, C., Yi, X., Li, M., & He, X. (2017). Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells. Phytomedicine28, 10-18. 10.1016/j.phymed.2017.02.008
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11 December - Panel discussion on the Metaphysics of Psychedelic Experiences