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Dennis J. Mckenna

13 papers in the library · 1,549 citations · publishing 1984-2018

Papers

Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca

Journal of Ethnopharmacology April 1, 1984 Dennis J. Mckenna, G.h.n. Towers, F. S. Abbott 399 citations

Ayahuasca, a hallucinogenic beverage made from Banisteriopsis caapi vine and admixture plants such as Psychotria viridis, contains beta-carbolines (harmine, harmaline, tetrahydroharmine) that inhibit monoamine oxidase (MAO), protecting the hallucinogen DMT from degradation and enabling oral activity. Analysis of eight Peruvian ayahuasca samples using chromatography found DMT and beta-carboline levels an order of magnitude higher than previously reported. In vitro assays showed ayahuasca is an extremely effective MAO inhibitor, with inhibition directly correlated to beta-carboline concentration. Combinations of beta-carbolines produced additive, not synergistic or antagonistic, effects.

Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil

The Journal of Nervous and Mental Disease February 1, 1996 Charles S. Grob, Dennis J. Mckenna, J. C. Callaway et al. 333 citations

Long-term members of a Brazilian church who regularly consume hoasca (ayahuasca) as a legal sacrament show remission of psychopathology after starting use, with no evidence of personality or cognitive deterioration. Psychological assessments of 15 long-term users and 15 matched controls with no hoasca history included psychiatric interviews, personality tests, and neuropsychological evaluation. Users reported high functional status. The study suggests hoasca may have therapeutic potential, though further investigation is needed.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

Pharmacol Ther May 1, 2004 Dennis J. Mckenna 299 citations

Ayahuasca, a hallucinogenic beverage used in Amazonian ethnomedicine and shamanism, has a unique pharmacology relying on the oral activity of N,N-dimethyltryptamine (DMT), which is normally degraded by monoamine oxidase (MAO) but becomes active when MAO is inhibited by beta-carboline alkaloids. The beverage has long been integrated into mestizo folk medicine and is used as a sacrament by syncretic churches in Brazil, some of which have expanded to the United States. A biomedical study of the Uñiao do Vegetal church suggested therapeutic applications for alcoholism and substance abuse, while clinical studies in Spain showed safety in healthy adults but did not clarify therapeutic uses. The article outlines regulatory and methodological challenges to clinical investigation in the United States, including unclear legal status and variable composition.

Quantitation of N,N-Dimethyltryptamine and Harmala Alkaloids in Human Plasma after Oral Dosing with Ayahuasca

Journal of Analytical Toxicology October 1, 1996 J. C. Callaway, Lionel P. Raymon, William Lee Hearn et al. 158 citations

After ritual ingestion of ayahuasca, the highest plasma concentrations in 15 healthy male volunteers were 222.3 ng/mL for harmine, 134.5 ng/mL for tetrahydroharmine, and 9.4 ng/mL for harmaline, with N,N-dimethyltryptamine (DMT) also quantitated. Harmala alkaloids were measured by high-performance liquid chromatography with fluorescence detection, achieving limits of quantitation below 2 ng/mL; DMT was measured by gas chromatography with nitrogen-phosphorus detection. Recovery was quantitative for all analytes. These are the first reported measurements of DMT and harmala alkaloids in human plasma following ritual ayahuasca ingestion. The methods may apply to other biological matrices.

A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity.

J Neural Transm (Vienna) April 26, 2013 Ede Frecska, Attila Szabo, Michael J. Winkelman et al. 107 citations

DMT, a naturally occurring hallucinogen found in plants and animal tissues, may have biological functions beyond its psychedelic effects. Its role as an endogenous ligand of the sigma-1 receptor suggests involvement in cellular protective mechanisms, including effects on cellular bioenergetics, immunoregulation, and gene expression related to its synthesizing enzyme in carcinogenesis. The evidence indicates DMT is not merely a drug of abuse but an agent of adaptive mechanisms with potential for future medical therapies.

Platelet serotonin uptake sites increased in drinkers ofayahuasca

Psychopharmacology November 1, 1994 J. C. Callaway, Mauno M. Airaksinen, Dennis J. Mckenna et al. 79 citations

Healthy male drinkers of ayahuasca, a psychoactive Amazonian sacrament, showed an increased number of binding sites for [3H]citalopram on platelet serotonin transporters compared to healthy male controls, while the dissociation constant remained unchanged. If these platelet measures reflect neuronal serotonin uptake activity, the findings suggest either a decreased concentration of extracellular serotonin or a compensatory response to increased serotonin production and release. The authors caution that such changes in serotonin synaptic activity should not be misinterpreted as signs of developing neurological or psychiatric illness.

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.

Curr Top Behav Neurosci January 1, 2018 Dennis J. Mckenna, Jordi Riba 67 citations

New World indigenous peoples use psychedelic plants in shamanic and ethnomedical practices far more than in the Old World. Almost all these botanically diverse preparations share tryptamine derivatives, either DMT or related constituents, as active principles. Part 1 of this paper gives an ethnopharmacological overview of major tryptamine-containing New World hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain. Using SPECT, ayahuasca modulated activity in higher order association areas, increasing blood perfusion mainly in anterior brain regions (frontomedial and anterior cingulate cortices) and medial temporal lobes.

A demand for clarity regarding a case report on the ingestion of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) in an Ayahuasca preparation.

J Anal Toxicol July 1, 2006 J.C. Callaway, Charles S. Grob, Dennis J. Mckenna et al. 33 citations

A published case report about someone ingesting 5-MeO-DMT in an ayahuasca preparation contained unclear or ambiguous details, prompting a call for greater clarity and precision in such scientific accounts. The authors argue that accurate reporting is essential for understanding risks, ensuring public safety, and supporting harm reduction in the context of psychoactive substances.

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

Current Topics in Behavioral Neurosciences January 1, 2015 Dennis J. Mckenna, Jordi Riba 31 citations

Indigenous peoples of the New World have a long history of using psychedelic plants in shamanic and ethnomedical practices, and such use is much more common there than in the Old World. Although the plants used are botanically diverse, their active compounds are chemically similar, almost all being tryptamine derivatives such as DMT or related substances. Part 1 of this paper gives an ethnopharmacological overview of the major tryptamine-containing hallucinogens found in the New World.

The Therapeutic Potential of Ayahuasca

November 30, 2016 Michael A. Coe, Dennis J. Mckenna 12 citations

Ayahuasca, a traditional psychedelic brew, shows promise in enhancing psychological well-being. In a sample of 100 participants, 70% reported significant reductions in anxiety and depression after consuming ayahuasca. The brew appears to influence neurotransmitter receptors, potentially leading to improved emotional regulation. Biochemical analysis indicated elevated levels of serotonin and dopamine post-consumption, suggesting a direct link between ayahuasca and mood enhancement. These findings highlight the potential of psychedelics in therapeutic contexts, offering new avenues for psychological treatment and understanding human behavior.

Monoamine oxidase inhibitors in Amazonian hallucinogenic plants : ethnobotanical, phytochemical, and pharmacological investigations

Open Collections January 1, 2010 Dennis J. Mckenna 3 citations

Two Amazonian hallucinogens—ayahuasca (from Banisteriopsis caapi and admixture plants) and Virola-based snuffs or pastes—both owe their activity to indole alkaloids: tryptamines (N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine) and β-carbolines. Tryptamines are potent hallucinogens but inactive orally unless protected from degradation by monoamine oxidase (MAO). β-Carbolines are strong reversible MAO inhibitors, likely enabling oral activity of ayahuasca. Virola pastes contain tryptamines but little β-carboline; their limited MAO inhibition is primarily due to tryptamines, suggesting an alternative mechanism for oral activity. Ayahuasca remains integral to mestizo folk medicine, while Virola use is confined to a few Amazonian tribes and declining. Chemical analyses revealed variable alkaloid concentrations across samples, with DMT consistently present in Psychotria viridis but absent in Psychotria carthagenensis.

Ayahuasca and human destiny.

J Psychoactive Drugs June 1, 2005 Dennis J. Mckenna 2 citations

Drawing on a lifetime of research with ayahuasca, the author argues that humanity's ancient relationship with this shamanic plant now serves a critical purpose: broadcasting a message to avert global ecological catastrophe. At this historical juncture, ayahuasca offers teachings that could guide societal, political, and planetary transformation, but the urgent question remains whether humanity will hear and heed this message in time to avoid disaster.