Toward a More Sustainable Sample Preparation in Phytochemistry: Case Studies in Four Subclasses of Alkaloids.

The fact that alkaloids are bases has been the most explored chemical feature of their extraction and purification procedures. The main drawback of these procedures is that they employ undesirable chemicals, with HCl and CH2Cl2 probably being the most commonly employed chemicals in their subsequent steps. This work tested the hypothesis that advantages in recovery efficiency support this common practice. Experiments were conducted in three laboratories, monitoring the alkaloids harmine (1), boldine (2), vincamine (3), and mescaline (4) extracted from Banisteriopsis caapi, Peumus boldus, Vinca minor, and Trichocereus macrogonus var. pachanoi, respectively. The research demonstrated that HCl could be replaced with citric acid (CA) without loss or even better extraction performance. The recommended EtOAc could completely replace CH2Cl2 in three out of four study cases and partially in the fourth case without harming the extraction efficiency. In addition, the alternative solvents tert-amyl methyl ether (TAME) and n-butyl acetate (BuOAc) could enhance the extraction of alkaloids. These results might incentivize natural products laboratories to consider sustainability more routinely, thus being closer to current practices in the pharmaceutical industry, which has been replacing solvents and processes with greener ones.

The Resurgence of Hallucinogen Drugs in Clinical Research.

Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

New mescaline-related N-acylhydrazone and its unsubstituted benzoyl derivative: Promising metallophores for copper-associated deleterious effects relief in Alzheimer's disease.

Alzheimer's disease (AD) is related to the presence of extracellular aggregated amyloid-ß peptide (Aß), which binds copper(II) with high affinity in its N-terminal region. In this sense, two new 1-methylimidazole-containing N-acylhydrazonic metallophores, namely, X1TMP and X1Benz, were synthesized as hydrochlorides and characterized. The compound X1TMP contains the 3,4,5-trimethoxybenzoyl moiety present in the structure of mescaline, a natural hallucinogenic protoalkaloid that occurs in some species of cacti. Single crystals of X1Benz, the unsubstituted derivative of X1TMP, were obtained. The experimental partition coefficients of both compounds were determined, as well as their apparent affinity for Cu2+ in aqueous solution. Ascorbate consumption assays showed that these N-acylhydrazones are able to lessen the production of ROS by the Cu(Aß)-system, and a short-time scale aggregation study, measured through turbidity and confirmed by TEM images, revealed their capacity in preventing Aß fibrillation at equimolar conditions in the presence and absence of copper. 1H15N HSQC NMR experiments demonstrated a direct interaction between Aß and X1Benz, the most soluble of the compounds. The Cu2+ sequestering potential of this hydrazone towards Aß was explored by 1H NMR. Although increasing amounts of X1Benz were unexpectedly not efficient at removing the metal-induced perturbations in Aß backbone amides, the broadening effects observed on the compound's signals indicate the formation of a ternary Aß­copper-X1Benz species, which can be responsible for the observed ROS-lessening and aggregation-preventing activities. Overall, the N-acylhydrazones X1TMP and X1Benz have shown promising prospects as agents for the treatment of AD.

Exploración del efecto de Trichocereus pachanoi en el carácter depresivo en ratas / Exploring the effect of Trichocereus pachanoi on the depression-like behavior in rats

Introducción: Existen plantas que se usan desde tiempos ancestrales con efecto alucinógeno y alteraciones al sistema nervioso central, debido a la presencia principalmente de mezcalina son usadas para cumplir objetivos tradicionales asociados a la adivinación, curandería, divinidad y otros. Objetivos: Determinar el efecto del extracto acuoso de Trichocereus pachanoi a dosis de 10 por ciento, 20 por ciento y 30 por ciento sobre el comportamiento exploratorio de carácter depresivo en Rattus rattus var. albinus. Material y métodos: El presente estudio experimental es de carácter exploratorio aplicado, constructivo y prospectivo, se formaron 4 grupos de 10 ratas cada uno a las que se les administró extracto acuoso de Trichocereus pachanoi en dosis creciente, luego fueron sometidas a natación forzada con entrenamiento previo de 15 minutos. Resultados: El grupo que no recibió tratamiento alguno posee la más baja respuesta en gasto de tiempo para el escalamiento, comparado con los grupos B, C y D que presentan 13,5 min. 17,17 min. y 24,37 min. respectivamente. También en la evaluación de la movilidad, el grupo A posee en valor más bajo, comparado con los grupos B, C y D que presentan 13,42 min. 17,62 min. y 23,12 min., respectivamente. Conclusiones: El tratamiento en ratas con extracto acuoso de Trichocereus pachanoi a concentraciones de 10 por ciento, 20 por ciento y 30 por ciento ha sido eficaz en producir un efecto tranquilizante en el comportamiento exploratorio de carácter depresivo en el sujeto(AU)

Introduction: Since ancient times, some mescaline containing plants that have hallucinogen effects and cause alterations in the central nervous system have been used to fulfill traditional objectives associated with divination, healing, spirituality and others. Objective: To determine the effect of the aqueous extract of Trichocereus pachanoi at doses of 10 %, 20 % and 30 % solution on depression-like exploratory behavior in Rattus rattus var. albinus. Material and Methods: The present experimental study, which is exploratory, constructive and prospective in nature, was conducted in 4 groups of 10 rats. The rats were administered increasing doses of aqueous extract of Trichocereus pachanoi; then, they underwent forced swimming with a previous 15-minute training. Results: The group that did not receive any treatment had the lowest response to the duration of time spent at scaling compared to groups B, C and D that spent 13.5 min., 17.17 min., and 24.37 min., respectively. Also, in the evaluation of mobility, group A showed the lowest value compared to groups B, C and D that recorded 13.42 min., 17.62 min., and 23.12 min., respectively. Conclusions: The treatment with aqueous extract of Trichocereus pachanoi at concentrations of 10 percent, 20 percent and 30 percent applied to rats has been effective in producing a tranquilizer effect on the depression-like exploratory behavior in rats(AU)

Elucidating the Distribution of Plant Metabolites from Native Tissues with Laser Desorption Low-Temperature Plasma Mass Spectrometry Imaging.

Secondary metabolites of plants have important biological functions, which often depend on their localization in tissues. Ideally, a fresh untreated material should be directly analyzed to obtain a realistic view of the true sample chemistry. Therefore, there is a large interest for ambient mass-spectrometry-based imaging (MSI) methods. Our aim was to simplify this technology and to find an optimal combination of desorption/ionization principles for a fast ambient MSI of macroscopic plant samples. We coupled a 405 nm continuous wave (CW) ultraviolet (UV) diode laser to a three-dimensionally (3D) printed low-temperature plasma (LTP) probe. By moving the sample with a RepRap-based sampling stage, we could perform imaging of samples up to 16 × 16 cm2. We demonstrate the system performance by mapping mescaline in a San Pedro cactus ( Echinopsis pachanoi) cross section, tropane alkaloids in jimsonweed ( Datura stramonium) fruits and seeds, and nicotine in tobacco ( Nicotiana tabacum) seedlings. In all cases, the anatomical regions of enriched compound concentrations were correctly depicted. The modular design of the laser desorption (LD)-LTP MSI platform, which is mainly assembled from commercial and 3D-printed components, facilitates its adoption by other research groups. The use of the CW-UV laser for desorption enables fast imaging measurements. A complete tobacco seedling with an image size of 9.2 × 15.0 mm2 was analyzed at a pixel size of 100 × 100 µm2 (14 043 mass scans), in less than 2 h. Natural products can be measured directly from native tissues, which inspires a broad use of LD-LTP MSI in plant chemistry studies.

Dark Classics in Chemical Neuroscience: Mescaline.

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti "diabolic", leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or "mescal buttons" was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2A serotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure-activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogens.

Charcot, Mitchell and Lees: neurology free thinkers and their experiences of psychoactive drugs.

Three world-famous neurologists, Charcot and Mitchell, in the 19th century, and Lees, in this century, all of whom had great scientific curiosity, experimented with the psychoactive drugs hashish, mescal and yagé, respectively, in an attempt to increase their knowledge of neurological diseases and how the brain works.

Charcot, Mitchell and Lees: neurology free thinkers and their experiences of psychoactive drugs / Charcot, Mitchell e Lees: livres-pensadores da neurologia e suas experiências com drogas psico-ativas

ABSTRACT Three world-famous neurologists, Charcot and Mitchell, in the 19th century, and Lees, in this century, all of whom had great scientific curiosity, experimented with the psychoactive drugs hashish, mescal and yagé, respectively, in an attempt to increase their knowledge of neurological diseases and how the brain works.

RESUMO Três mundialmente famosos neurologistas, Charcot e Mitchell, no século XIX, e Lees neste século, tiveram eles mesmos, experiências com drogas psico-ativas, com haxixe, mescalina e yagé, respectivamente, demonstrando a sua intensa curiosidade científica, na tentativa de aprimorar o seu conhecimento da função cerebral e das doenças neurológicas.

Identification and Individualization of Lophophora using DNA Analysis of the trnL/trnF Region and rbcL Gene.

Lophophora williamsii (peyote) is a small, spineless, greenish-blue cactus found in Mexico and the southwestern United States. Ingestion of the cactus can result in hallucinations due to its content of mescaline. In the United States, L. williamsii is classified as a Schedule I controlled substance. In this study, we use DNA analysis of the chloroplast trnL/trnF region and chloroplast rbcL gene to identify the individuals of Lophophora. Using the rbcL gene, Lophophora specimens could be distinguished from outgroups, but species within the genus could not be distinguished. The trnL/trnF region split the Lophophora genus into several groups based on the length and substructure of an AT-rich segment of the sequence. Our results indicate that the genetic variability at the trnL/trnF locus is greater than previously recognized. Although DNA structures at the trnL/trnF region and rbcL gene do not align with the classification of Lophophora species, they can be used to aid in forensic analysis.

Usos terapéuticos de sustancias prohibidas: LSD, MDMA, THC, GHB, DMT, psilocybina y mescalina / Therapeutic uses of prohibited substances: LSD, MDMA, THC, GHB, DMT, psilocybin, mescaline

El presente texto hace un breve recorrido sobre los usos terapéuticos que han tenido la LSD, MDMA, THC, GHB, DMT, Psilocybina y Mescalina en la historia, así como también refiere algunos de los beneficios para la salud física y mental que se considera tienen en la actualidad. Esta información científica se contrapone a la normativa internacional en materia de drogas, que las clasifica como sustancias prohibidas en la Lista I, debido a su falta de uso médico aceptado por Estados Unidos y a su alto potencial de abuso. En este trayecto también se intenta comprender a qué hace referencia dicho potencial, así como las motivaciones que podrían existir detrás de la prohibición del uso terapéutico de estas drogas. En este marco, se consideran consecuencias para la salud de la población, las que atentan contra los Derechos Humanos de las personas que podrían requerir alguna de estas sustancias.

This paper makes a brief of the therapeutic uses have had the LSD, MDMA, THC, GHB, DMT, Psilocybin and Mescaline in history, as well as some of the benefits referred to physical and mental health that are considered today. This scientific information seems contrary to international legislation on drugs, which classifies as prohibited substances in Schedule I, due to its lack of acceptance medical use by the United States and its high potential for abuse. In this way also try to understand what makes this potential reference, and the reasons that could be behind the ban on therapeutic use of these drugs. In this framework, we consider health consequences of the population, which violate the human rights of people who may require some of these substances.

New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) ("San Pedro") and their relevance to shamanic practice.

AIM OF THE STUDY: The aim of the present study is to determine in a procedurally uniform manner the mescaline concentrations in stem tissue of 14 taxa/cultivars of the subgenus Trichocereus of the genus Echinopsis (Cactaceae) and to evaluate the relationship (if any) between mescaline concentration and actual shamanic use of these plants. MATERIALS AND METHODS: Columnar cacti of the genus Echinopsis, some of which are used for diagnostic and therapeutic purposes by South American shamans in traditional medicine, were selected for analysis because they were vegetative clones of plants of documented geographic origin and/or because they were known to be used by practitioners of shamanism. Mescaline content of the cortical stem chlorenchyma of each cactus was determined by Soxhlet extraction with methanol, followed by acid-base extraction with water and dichloromethane, and high-pressure liquid chromatography (HPLC). RESULTS: By virtue of the consistent analytical procedures used, comparable alkaloid concentrations were obtained that facilitated the ranking of the various selected species and cultivars of Echinopsis, all of which exhibited positive mescaline contents. The range of mescaline concentrations across the 14 taxa/cultivars spanned two orders of magnitude, from 0.053% to 4.7% by dry weight. CONCLUSIONS: The mescaline concentrations reported here largely support the hypothesis that plants with the highest mescaline concentrations - particularly E. pachanoi from Peru - are most associated with documented shamanic use.

Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.

2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.

[Mescaline and the San Pedro cactus ritual: archaeological and ethnographic evidence in northern Peru]. / Mescalina y ritual del cactus de san Pedro: evidencias arqueológicas y etnográficas en el norte de Perú.

INTRODUCTION: The San Pedro cactus contains the alkaloid mescaline and other derivates of phenethylamine with hallucinogenic properties. This cactus was used throughout history by a number of different pre-Columbine cultures and civilisations that settled in northern Peru. In this article we review the ethno-archaeological and ethno-historical evidence of the ritual use of the San Pedro cactus in the pre-Columbine cultures, and these findings are compared with the information provided by current ethnographical studies. DEVELOPMENT: The longer a cactus has been stored, the stronger and the higher its content in mescaline-derived alkaloids will be. Archaeological evidence has been found of the use of San Pedro for magical-religious purposes in the following pre-Columbine cultures: Cupisnique (1500 BC), Chavin (1000 BC), Moche (100-750 AD) and Lambayeque (750-1350 AD). Today's master shamans use San Pedro on altars ('mesas') erected for healing rites in order to treat enchantment and bad luck. The mesa follows a sophisticated ritual: 'levantar' (raise) or sniff tobacco with alcohol, ingest San Pedro, pinpoint the diseases, cleanse the evil and 'florecer' (flourish) the sick person. The mesa rite is performed in the early hours of Tuesdays and Fridays, which are sacred days in the Andean religions. San Pedro is sometimes replaced by an infusion of plants and seeds that contain hallucinogenic components, such as ayahuasca and the 'mishas' (Brugmansia sp.). CONCLUSIONS: The ancient tradition of using the San Pedro cactus for healing and hallucinogenic purposes has remained part of the culture in Andean shamanism up to the present day.

Hallucinogens and redemption.

This article examines drug substitution with regard to hallucinogens (ayahuasca, ibogaine, peyote and LSD) set within the concept of redemption. The model examines both religious and secular approaches to the contemporary use of hallucinogens in drug substitution, both by scientists and in religious settings worldwide. The redemptive model posits that the proper use of one psychoactive substance within a spiritual or clinical context helps to free an individual from the adverse effects of their addiction to another substance and thus restores them as functioning members of their community or group. Data is drawn from the U.S., Brazil, Peru, and West Africa. Two principle mechanisms for this are proposed: the psychological mechanism of suggestibility is examined in terms of the individual reaching abstinence goals from addictive substances such as alcohol and opiates. Neurophysiological and neurochemical mechanisms to understand the efficacy of such substitution are highlighted from ongoing research on hallucinogens. Research by two of the authors with the Uñaio do Vegetal (UDV) Church in Brazil is examined in terms of the model.

[Antibacterial constituents against Helicobacter pylori of Brazilian medicinal plant, Pariparoba].

Four known compounds have been isolated from the aerial parts of the Brazilian medicinal plant Pariparoba (Pothomorphe umbellata). They were an alkaloid, a flavone, a dihydrocalcone, and a steroid. The chemical structures were established to be N-benzoylmescaline, wogonin, uvangoletin, and beta-sitosterol glucoside using spectral methods. Among these compounds, the main component N-benzoylmescaline showed significant antibacterial activity against Helicobacter pylori.

Experimentacion pura de Lophophora williamsii: peyote / Pathogenesis of Lophophora williamsii: peyote

A traves de los siglos, los grupos indigenas de Mexico, desarrollaron un profundo conocimiento de las plantas, especialmente de aquellas a las que se les atribuian efectos magicos o sagrados, que fueron utilizadas con fines rituales y adivinatorios y que observan una profunda actividad psicotropica, cual es el caso de Lophophora williamsii. Hay evidencias que sugieren amplia utilizacion al norte de nuestro pais desde hace unos mil anos. El principal componente activo de Lophophora williamsii es el alcaloide mezcalina, pero se han cuantificado cerca de 56 alcaloides mas que estan clasificados. Lophophora williamsee a causa de la competencia entre alcaloides antagonistas, presenta numerosos sintomas y la riqueza de su sintomatologia mental, creemos, lo hara un valioso medicamento en terapeutica homeopatica.

Experimentacion pura de Lophophora williamsii: peyote / Pathogenesis of Lophophora williamsii: peyote

A traves de los siglos, los grupos indigenas de Mexico, desarrollaron un profundo conocimiento de las plantas, especialmente de aquellas a las que se les atribuian efectos magicos o sagrados, que fueron utilizadas con fines rituales y adivinatorios y que observan una profunda actividad psicotropica, cual es el caso de Lophophora williamsii. Hay evidencias que sugieren amplia utilizacion al norte de nuestro pais desde hace unos mil anos. El principal componente activo de Lophophora williamsii es el alcaloide mezcalina, pero se han cuantificado cerca de 56 alcaloides mas que estan clasificados. Lophophora williamsee a causa de la competencia entre alcaloides antagonistas, presenta numerosos sintomas y la riqueza de su sintomatologia mental, creemos, lo hara un valioso medicamento en terapeutica homeopatica

Use of marijuana and other drugs by college students of São Paulo, Brazil.

Drug usage in a sample of 1,069 college students of São Paulo, Brazil, was investigated. The highest lifetime prevalence was reported for alcohol (82%) and tobacco (39%) followed by inhalants (28%), marijuana (26%), over-the-counter tranquilizers and stimulants (17%), and cocaine (10%). Current use is considerably smaller. Marijuana users were classified as having a "Stable," "Descending," and "Once" pattern of consumption frequency. These patterns were orderly related to sex, socioeconomic status, use of drugs, drug approval, and peer group. Drug usage appeared as predominantly social-recreational in this population, although the risk of misuse for "Stable" students should be evaluated.