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Peyote (Lophophora williamsii) is a cactus that contains various biologically active alkaloids—such as pellotine, anhalonidine, hordenine and mescaline. Here, mescaline induces the psychoactive effects of peyote through the activation of the serotonin 5-HT2A receptor and the subsequent release of calcium (Ca2+) from the endoplasmic reticulum (ER). Moreover, an evaluation of the therapeutic benefits of mescaline is also currently the subject of research. It is important to consider that the outcome of taking a psychedelic drug strongly depends on the mindset of the recipient and the context (set and setting principle), including ceremonies and culture. This overview serves to summarise the current state of the knowledge of the metabolism, mechanism of action and clinical application studies of peyote and mescaline. Furthermore, the benefits of the potential of peyote and mescaline are presented in a new light, setting an example for combining a form of treatment embedded in nature and ritually enriched with our current highly innovative Western medicine.

A phytochemical analytical study was conducted to address the question of whether the mescaline concentration in Lophophora williamsii (peyote) is dependent on the maturity and/or size of the plant. Samples of crown tissue (4 g each) biopsied from mature peyote cacti and whole small regrowth crowns (2-4 g each) were collected from the same population in the Tamaulipan Thornscrub ecoregion of South Texas. For each of the two groups (mature and small regrowth), the individual tissue samples were pooled, desiccated, and ground to powder. The alkaloids were extracted with methanol at 25°C, followed by evaporation of the methanol to dryness, then acid-base cleanup with water and dichloromethane. The mescaline concentration in each of the extracts was then determined by HPLC. Quantitative analyses provided evidence that the small crowns that develop in response to harvesting contain a lower mescaline concentration—about half as much—compared to that of crowns of mature unharvested plants in the same population. The deficiency in the mescaline concentration of these regrowth buttons (new crowns) exacerbates the problem posed by the small size of the buttons; that is, it further increases the number of buttons that must be consumed to obtain an efficacious dose for ceremonial use by members of the Native American Church (NAC). That means that either the NAC members must consume less than the traditional amount of peyote, or there will be increased demand for peyote. Any increase in demand, reflected in the price, will engender more intensive harvesting, which will inevitably have adverse effects on both the supply of sacrament for the NAC and the conservation status of L. williamsii wherever the harvesters have access to peyote populations. Se hizo un estudio fitoquímico analítico para determinar si la concentración de mescalina de Lophophora williamsii (peyote) depende de la madurez y/o el tamaño de la planta. Se recogieron muestras de teiido de la corona (4 g cada una) tomadas por biopsia en individuos maduros de peyote y muestras de coronas pequeñas enteras recrecidas (2-4 g cada una) de la misma población en la ecorregión del matorral espinoso tamaulipeco en el sur de Texas. Para cada uno de los dos grupos (maduros y pequeños recrecidos), las muestras individuales de tejido fueron combinados, secados, y molidos hasta polvo. Los alcaloides fueron extraídos con metanol a 25°C, seguido de evaporación del metanol hasta sequedad, y después una limpieza ácida- alcalina con agua y diclorometano. La concentración de mescalina en cada uno de los extractos fue determinada entonces por HPLC. Los análisis cuantitativos mostraron que las coronas pequeñas que se desarrollan como consecuencia del la cosecha contienen una concentración de mescalina más baja—aproximadamente la mitad—en comparación a la de coronas de plantas maduras no cosechadas en la misma población. La deficiencia en la concentración mescalínica de estas coronas recrecidas exacerba el problema causado por el tamaño pequeño de las mismas; es decir, aumenta aún más el número de \"botones\" (coronas) que tienen de consumirse para obtener una dosis eficaz para el uso ceremonial por miembros de la Native American Church (NAC). Eso significa que o los miembros de la NAC tienen que consumir menos cantidad tradicional de peyote, o habrá un aumento en la demanda de peyote. Cualquier aumento en la demanda, reflejado en el precio, engendrará recolección más intensiva, la cual inevitablemente tendrá efectos adversos, tanto en la provisión del sacramento para la NAC como en el estado de conservación de L. williamsii dondequiera que los peyoteros tengan acceso a las poblaciones de peyote.

The peyote cactus, Lophophora williamsii, is presently classified as a Schedule 1 Controlled Substance in the USA, with an exemption for use as a sacrament in bona fide religious ceremonies of the Native American Church (NAC). Any botanist or other researcher seeking to work with peyote or any of its alkaloids, must com-ply with applicable (nontrivial) regulatory requirements. This paper presents an examination of the prohibition efforts that paved the way for current peyote regulation, accompanied by documentation of the religion-based political origins of such efforts, which involved the \"acculturation\" of Native Americans (i.e., the destruction of American Indian cultures). We also look at the historical emergence of a nationally organized and coordinated effort by missionaries and other prohibitionists to sell a federal anti-peyote law to Congress, which manifested itself repeatedly over a period of more than fifty years, before finally realizing success in the Controlled Substances Act of 1970. In view of ongoing changes in the legal/regulatory status of Cannabis sp. (another Schedule 1 plant that was targeted for illegality during the prohibitionists' rise to political predominance), we compare and contrast the two plants with speculation on peyote’s future.

Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote.

Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT 2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov , and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study ( n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task ( p = 0.03) and no differences in the others (all p > 0.05). Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.

This article explores the ancient tradition of shamanism and its many facets in Huichol Indian culture. The Huichol Indians (Wixárika, Wixáritari pl.) live predominately in the Mexican states of Jalisco and Nayarit in their remote mountain homelands of the Sierra Madre Occidental. Their shamans have been vital keepers of ancient esoteric knowledge and leaders, healers, and diviners for their people. The shamanic tradition is passed down primarily through family kin ties. The path to becoming a shaman and the plants and animals that are shamanic allies will be discussed. This is followed by an examination of the shaman’s power objects and the wide array of specialties acquired. Finally, the article addresses the challenges to shamans in the 21st century and their crucial role to the survival of Huichol culture and identity.

Here we report the 6-year results of a long-term study of the effects of harvesting on a wild population of the cactus Lophophora williamsii (peyote). Harvesting was performed using the best known technique: removing only the crown from the top of the plant. The two-year interval between harvests was chosen because it was similar to that observed by persons who harvest peyote for legally protected religious use by members of the Native American Church. Plants in the study were divided into three treatment groups: (1) control plants that were never harvested, (2) plants that were harvested only once, at the beginning of the study, and (3) plants that were harvested at the beginning of the study and every two years thereafter. Over the last two years of the study (2012‒2014), the survival rate was significantly lower (77%) in the plants harvested every two years than in the once-harvested plants (100%) and the unharvested control plants (98%). At the end of the 6th year of the study, average volume of living crown tissue per plant was significantly and substantially lower in the plants harvested every two years than in the once-harvested plants and the unharvested controls. The average volume of once-harvested plants was 27% lower than that of the controls, although this latter difference was not statistically significant. The modal number of crowns per plant varied with treatment and over time; in the plants harvested every two years it underwent a progression from 1 to 2 to 3 to 1 in response to successive harvests. The results of this study indicate that a six-year recovery period, following the harvesting of peyote in natural habitats, is probably not long enough to ensure long-term sustainability. Aquí reportamos los resultados de seis años de un estudio a largo plazo sobre los efectos de cosechar individuos del cactus Lophophora williamsii (peyote) en una población silvestre. La cosecha se hizo utilizando la mejor técnica que se conoce, recogiendo solamente la corona de la parte superior de la planta. El intervalo de dos años entre cosechas fue similar al utilizado por personas que cosechan peyote para uso jurídicamente protegido por los miembros de la Native American Church. Las plantas en el estudio fueron divididas en tres grupos de tratamiento: (1) las plantas de control que nunca fueron cosechadas, (2) las plantas que fueron cosechadas sólo una vez, al comienzo del estudio, y (3) las plantas que fueron cosechadas al comienzo del estudio y posteriormente cada dos años. En los últimos dos años del estudio (2012–2014), la tasa de supervivencia fue significativamente menor (76,5%) en las plantas cosechadas cada dos años, que en las plantas cosechadas una sola vez (100%) y las plantas de control que no fueron cosechadas nunca (97,7%). Al final del sexto año del estudio, el volumen promedio del tejido vivo de la corona por planta fue significativamente menor en las plantas cosechadas cada dos años, que en las plantas cosechadas una sola vez y las plantas de control que nunca fueron cosechadas. El número modal de coronas por planta varió con el tratamiento y con el tiempo; en las plantas cosechadas cada dos años hubo una progresión desde 1 a 2 a 3 a 1 en respuesta a las cosechas sucesivas. Los resultados de este estudio indican que un período de recuperación de seis años después de la recolección del peyote en el hábitat probablemente no es suficientemente largo como para asegurar la sostenibilidad a largo plazo.

Natural compounds in plants are often unevenly distributed, and determining the best sampling locations to obtain the most representative results is technically challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can provide the basis for formulating sampling guideline. For a succulent plant sample, ensuring the authenticity and in situ nature of the spatial distribution analysis results during MSI analysis also needs to be thoroughly considered. In this study, we developed a well-established and reliable MALDI-MSI method based on preservation methods, slice conditions, auxiliary matrices, and MALDI parameters to detect and visualize the spatial distribution of mescaline in situ in Lophophora williamsii. The MALDI-MSI results were validated using liquid chromatography–tandem mass spectrometry. Low-temperature storage at −80°C and drying of “bookmarks” were the appropriate storage methods for succulent plant samples and their flower samples, and cutting into 40 μm thick sections at −20°C using gelatin as the embedding medium is the appropriate sectioning method. The use of DCTB (trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile) as an auxiliary matrix and a laser intensity of 45 are favourable MALDI parameter conditions for mescaline analysis. The region of interest semi-quantitative analysis revealed that mescaline is concentrated in the epidermal tissues of L. williamsii as well as in the meristematic tissues of the crown. The study findings not only help to provide a basis for determining the best sampling locations for mescaline in L. williamsii, but they also provide a reference for the optimization of storage and preparation conditions for raw plant organs before MALDI detection. Key Points An accurate in situ MSI method for fresh water-rich succulent plants was obtained based on multi-parameter comparative experiments. Spatial imaging analysis of mescaline in Lophophora williamsii was performed using the above method. Based on the above results and previous results, a sampling proposal for forensic medicine practice is tentatively proposed.