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Ayahuasca

Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells

February 28, 2017 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

BACKGROUND:
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.
PURPOSE:
To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells.
METHODS/STUDY DESIGNS:
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.
RESULTS:
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.
CONCLUSION:
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. Phytomedicine, 28, 10-18. 10.1016/j.phymed.2017.02.008
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Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies

February 23, 2017 / Ayahuasca, DMT, Papers, Psychology, Publications / By / , ,

Abstract

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2017). Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies. Therapeutic Advances in Psychopharmacology, 2045125316689030. 10.1177/2045125316689030
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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

February 13, 2017 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca, Virola) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention, self-referential thought, and internal mentation. Historical and technical restrictions impaired understanding how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by dimethyltryptamine (5-methoxy-N,N-dimethyltryptamine, 5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico systems biology analyses support 5-MeO-DMT’s anti-inflammatory effects and reveal a modulation of proteins associated with the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. Proteins involved in long-term potentiation were modulated in a complex manner, with significant increases in the levels of NMDAR, CaMKII and CREB, but a reduction of PKA and PKC levels. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.

Dakic, V., Nascimento, J. M., Sartore, R. C., de Moraes Maciel, R., de Araujo, D. B., Ribeiro, S., … & Rehen, S. K. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N, N-dimethyltryptamine. bioRxiv, 108159.
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Science, spirituality, and ayahuasca: The problem of consciousness and spiritual ontologies in the academy

September 10, 2024 / Ayahuasca, Humanities & Art, Papers, Publications, Scienitific Discipline / By /

Abstract

Ayahuasca is a psychoactive brew from Amazonas, popularized in the last decades in part through transnational religious networks, but also due to interest in exploring spirituality through altered states of consciousness among academic schools and scientific researchers. In this article, the author analyzes the relation between science and religion proposing that the “demarcation problem” between the two arises from the relations among consciousness, intentionality, and spirituality. The analysis starts at the beginning of modern science, continues through the nineteenth century, and then examines the appearance of new schools in psychology and anthropology in the countercultural milieu of the 1960s. The author analyzes the case of ayahuasca against this historical background, first, in the general context of ayahuasca studies in the academic field. Second, he briefly describes three cases from Spain. Finally, he discusses the permeability of science to “spiritual ontologies” from an interdisciplinary perspective, using insights from social and cognitive sciences.

Apud, I. (2017). Science, spirituality, and ayahuasca: The problem of consciousness and spiritual ontologies in the academy. Zygon®, 52(1), 100-123. 10.1111/zygo.12315
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Potential Antitumor Effect of Harmine in the Treatment of Thyroid Cancer

February 8, 2017 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , ,

Abstract

Thyroid cancer is one of the most common types of cancer in endocrine system. In latest studies, harmine has been proved to inhibit the growth of several cancers in vitro and in vivo. In the current study, we evaluated the in vitro and in vivo anticancer efficiency of harmine against thyroid cancer cell line TPC-1. The in vitro cytotoxicity of harmine evaluated by XTT assay indicated that harmine suppressed the proliferation of TPC-1 cells in a dose- and time-dependent manner. Moreover, harmine dose-dependently induced apoptosis of TPC-1 cells through regulating the ratio of Bcl-2/Bax. The colony forming ability of TPC-1 cells was also time-dependently inhibited by harmine. The inhibitory effects of harmine on migration and invasion of TPC-1 cells were studied by wound scratching and Transwell assays. In vivo evaluation showed that harmine effectively inhibited the growth of thyroid cancer in a dose-dependent manner in nude mice. Therefore, harmine might be a promising herbal medicine in the therapy of thyroid cancer and further efforts are needed to explore this therapeutic strategy.

Ruan, S., Jia, F., & Li, J. (2017). Potential Antitumor Effect of Harmine in the Treatment of Thyroid Cancer. Evidence-Based Complementary and Alternative Medicine, 2017. 10.1155/2017/9402615
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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomised placebo-controlled trial

January 27, 2017 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Major Depressive Disorder affects about 350 million people worldwide, and about one-third of the patients are considered treatment-resistant. Furthermore, available antidepressants take usually two weeks for the onset of their antidepressant effect. Recent open label trials show that psychedelics, such as ayahuasca and psilocybin, hold promise as fast-onset antidepressants. Although promising, these studies were not controlled for the placebo effect. To address this issue, and to further test the antidepressant effects of ayahuasca, we conducted a parallel arm, double blind randomised placebo-controlled trial, in patients with treatment-resistant major depression. Thirty-five patients with treatment-resistant major depression received a single dose of ayahuasca or placebo. We measured as primary outcome the change in the Hamilton Depression Rating scale (HAM-D) seven days after the dosing session, and as secondary outcomes the changes in Montgomery-Asberg Depression Rating Scale (MADRS), and response rates at one day (D1), two days (D2) and seven days (D7) after dosing, and remission rates at D7. This study is registered with http://clinicaltrials.gov (NCT02914769). We observed robust evidence of rapid antidepressant effects of a single dosing session with ayahuasca when compared to placebo. HAM-D scores at D7 were significantly lower in patients treated with ayahuasca than in those treated with placebo (p=0.019; Cohen’s d=0.98). MADRS scores were significantly reduced in the ayahuasca group compared to the placebo group at all endpoints (at D1 and D2, p=0.04; at D7, p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d=0.84; D2: Cohen’s d=0.84; D7: Cohen’s d=1.49). Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group only at D7 (64% vs. 27%; OR = 4.95; p = 0.04; NNT = 2.66). Remission rate was not significantly different between groups. Our study provides new evidence of rapid antidepressant effects of ayahuasca for treatment-resistant major depression.

Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M., Pessoa, J., … & Tofoli, L. (2017). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomised placebo-controlled trial. bioRxiv, 103531. 10.1101/103531
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Determination of Tryptamines and β-Carbolines in Ayahuasca Beverage Consumed During Brazilian Religious Ceremonies

January 19, 2017 / Ayahuasca, Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Publications / By / , ,

Abstract:

Ayahuasca is a potent hallucinogenic beverage prepared from Banisteriopsis caapi in combination with other psychoactive plants. N,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantified in ayahuasca samples using a simple and low-cost method based on SPE and LC with UV diode-array detection. The experimental variables that affect the SPE method, such as type of solid phase and nature of solvent, were optimized. The method showed good linearity (r > 0.9902) and repeatability (RSD < 0.8%) for alkaloid compounds, with an LOD of 0.12 mg/L. The proposed method was used to analyze 20 samples from an ayahuasca cooking process from a religious group located in the municipality of Fortaleza, state of Ceará, Brazil. The results showed that concentrations of the target compounds ranged from 0.3 to 36.7 g/L for these samples.

Santos, M. C., Navickiene, S., & Gaujac, A. (2017). Determination of Tryptamines and β-Carbolines in Ayahuasca Beverage Consumed During Brazilian Religious Ceremonies. Journal of AOAC International. 10.5740/jaoacint.16-0337
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Harmine, a Novel DNA Methyltransferase 1 Inhibitor in the Leukemia Cell Line

January 17, 2017 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

DNA methylation followed by tumor suppressor gene repression plays a critical role in the leukemia development. So, DNA methyl transferase inhibitors have great importance in treatment of theses malignancies. Harmine, A beta carboline alkaloid derivative of Peganum harmala, had shown anti- proliferative effects on leukemic cell line. This study aimed to evaluate the effect of Harmine on DNMT1 (DNA methyl transferase 1) expression in a leukemic cell line. Cell proliferation and cell cycle analysis were studied in NB4 cell line after treatment with Harmine for 72 h. DNMT1 expression in treated cells was analyzed by real time PCR. Tumor suppressor gene hypometylation and reactivation was evaluated via MSP analysis and also real time PCR. Harmine reduced cell proliferation in NB4 cell line in a time and dose-dependent manner. 102 µg/ml of Harmine was increased amount of cells in G1 Phase of cell cycle (p < 0.05). Anti proliferative doses of Harmine, has suppressed DNMT1 gene in NB4 cell line. Down-regulated DNMT1 induced p15 tumor suppressor promoter hypomethylation and reactivation. Our data indicate that Harmine can be considered as a potential treatment for AML (Acute Myeloid Leukemia), and future studies are required to test the clinical efficacy of Harmine—whether used as a single agent or as an adjuvant—for AML treatment.

Oodi, A., Norouzi, H., Amirizadeh, N., Nikougoftar, M., & Vafaie, Z. Harmine, a Novel DNA Methyltransferase 1 Inhibitor in the Leukemia Cell Line. Indian Journal of Hematology and Blood Transfusion, 1-7. 10.1007/s12288-016-0770-z

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Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric illness?

January 1, 2017 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Ayahuasca is a traditional psychoactive sacrament that’s been used in Amazonian shamanic rituals for hundreds of years. Ayahuasca is notorious for its psychedelic properties produced from the combination of monoamine oxidase inhibitors (MAOIs) found in the Banisteriopsis caapi vine and N-N-dimethyltryptamine from Psychotria viridis or Diplopterys cabrerana. Recently, ritual use of ayahuasca has increased and garnered attention for its potential in treating mental illnesses, such as substance use and depressive disorders. Due to its MAOI properties, there are serious drug interactions that may be of concern among patients who participate in ayahuasca use. The objectives of this paper are to describe ayahuasca’s pharmacology, potential drug interactions, and clinical data for its treatment potential in psychiatric illness.

Malcolm, B. J., & Lee, K. C. (2017). Ayahuasca: An ancient sacrament for treatment of contemporary psychiatric illness?. Mental Health Clinician, 7(1), 39-45. 10.9740/mhc.2017.01.039

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Harmine stimulates proliferation of human neural progenitors

December 6, 2016 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Dakic, V., de Moraes Maciel, R., Drummond, H., Nascimento, J. M., Trindade, P., & Rehen, S. K. (2016). Harmine stimulates proliferation of human neural progenitors. PeerJ, 4, e2727. 10.7717/peerj.2727
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