OPEN Foundation

E. Gallardo

Evaluation of the Cytotoxicity of Ayahuasca Beverages

January 7, 2022 / Ayahuasca, Papers, Psychopharmacology, Safety, Toxicology / Leave a Comment / By / , , , , , , , , , ,

Abstract

Ayahuasca is a beverage consumed at shamanic ceremonies and currently has gained popularity on recreational scenarios. It contains beta-carboline alkaloids and N,N-dimethyltryptamine, which possesses hallucinogenic effects. Only a few studies have elicited the psychoactive effects and the dose of such compounds on neurological dopaminergic cells or animals. In this work, we aimed to study the cytotoxic effects of these compounds present in ayahuasca beverages and on five different teas (Banisteriopsis caapi, Psychotria viridis, Peganum harmala, Mimosa tenuiflora and Dc Ab (commercial name)) preparations on dopaminergic immortalized cell lines. Moreover, a characterization of the derivative alkaloids was also performed. All the extracts were characterized by chromatographic systems and the effect of those compounds in cell viability and total protein levels were analyzed in N27 dopaminergic neurons cell line. This is the first article where cytotoxicity of ayahuasca tea is studied on neurological dopaminergic cells. Overall, results showed that both cell viability and protein contents decreased when cells were exposed to the individual compounds, as well as to the teas and to the two mixtures based on the traditional ayahuasca beverages.

Simão, A. Y., Gonçalves, J., Gradillas, A., García, A., Restolho, J., Fernández, N., Rodilla, J. M., Barroso, M., Duarte, A. P., Cristóvão, A. C., & Gallardo, E. (2020). Evaluation of the Cytotoxicity of Ayahuasca Beverages. Molecules (Basel, Switzerland), 25(23), 5594. https://doi.org/10.3390/molecules25235594

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Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials

November 18, 2021 / Depression, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy / Leave a Comment / By / , , , ,

Abstract

Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = -4.589; 95% CI = -4.207 to -0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = -5.906; 95% CI = -7.852 to -3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = -6.032; 95% CI = -8.900 to -3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety.

Vargas, A. S., Luís, Â., Barroso, M., Gallardo, E., & Pereira, L. (2020). Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Biomedicines, 8(9), 331. https://doi.org/10.3390/biomedicines8090331

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A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics

February 10, 2017 / Other subjects, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , ,

Abstract

Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum) due to its hallucinogen properties.

Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa-opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200–500 μg of S. divinorum leaves is enough to produce these effects thus making it the most potent natural occurring hallucinogen known.

Due to its legal status in various countries, this compound has gained a worldwide popularity as a drug of abuse with an easy access through smartshops and internet.

Furthermore, salvinorin A gathered an increased interest in the scientific community thanks to its unique structure and properties, and various studies demonstrated that salvinorin A has antinociceptive, antidepressant, in some circumstances pro-depressant and anti-addictive effects that have yielded potential new avenues for research underlying salvinorin A and its semi-synthetic analogs as therapeutic agents.

Cruz, A., Domingos, S., Gallardo, E., & Martinho, A. (2017). A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics. Phytochemistry. 10.1016/j.phytochem.2017.02.001
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Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum

August 1, 2016 / Papers, Safety, Salvia / Salvinorin A, Toxicology / By / , ,

Abstract

S. divinorum is a psychoactive plant that has been consumed as a recreational drug of abuse in the last years. Salvinorin A is its main constituent, and is responsible for the observed psychoactive effects. Both S. divinorum and salvinorin A have become controlled drugs in several countries, but they are not listed in the Schedules of the United Nations Drug Conventions. Regarding the effects of S. divinorum consumption, almost all studies are based on in vivo or on surveys, and there are no studies in vitro on its toxicity. Furthermore, all studies are focused on the acute toxicological effects of the plant. So, it is of utmost importance to further investigate the effects of S. divinorum and salvinorin A, particularly using in vitro models, after prolonged exposures. In this context, the present work evaluated the in vitro toxicity induced by S. divinorum or salvinorin A in six cell lines, through MTT assays and LC50 determination. Overall, results showed that both S. divinorum and salvinorin A are cytotoxic, dose- and time-dependent. Also, Hep G2 and Caco 2 (to a lesser extent) cells showed lower sensitivity to S. divinorum and salvinorin A when compared to the other studied cell lines. To our knowledge, this is the first work focused on the in vitro toxicity of S. divinorum and salvinorin A using a variety of cell lines, which are extensively described in literature and have been widely used in several in vitro studies.
Martinho, A., M Silva, S., & Gallardo, E. (2016). Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum. Medicinal Chemistry, 12(5), 432-440. 10.2174/1573406411666151005105617
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Salvia divinorum: toxicological aspects and analysis in human biological specimens

June 9, 2016 / Ethnobotany, Other subjects, Papers, Publications, Salvia / Salvinorin A, Toxicology / By / , , ,

Abstract

The identification and quantitation of the main psychoactive component of Salvia divinorum (salvinorin A) in biological specimens are crucial in forensic and clinical toxicology. Despite all the efforts made, its uncontrolled abuse has increased quickly, exposing its users’ health to serious risks both in the short and long term. The use of alternative biological matrices in toxicological analyzes can be advantageous as complementary postmortem samples, or in situations when neither blood nor urine can be collected; they may be useful tools in those determinations, providing important information about prior exposure. The aim of this article is to present a brief summary of legal aspects of Salvia divinorum and salvinorin A, including the methods used for the determination of the latter in biological matrices.

Margalho, C., Corte-Real, F., López-Rivadulla, M., & Gallardo, E. (2016). Salvia divinorum: toxicological aspects and analysis in human biological specimens. Bioanalysis, (0). http://dx.doi.org/10.4155/bio-2016-0067

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30 April - Q&A with Rick Strassman

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