The pharmacological interaction of compounds in ayahuasca: a systematic review

Ruffell, Simon; Netzband, Nige; Bird, Catherine; Young, Allan H.; Juruena, Mário F.

doi:10.1590/1516-4446-2020-0884

Cited by 20 publications

(20 citation statements)

References 59 publications

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“…It is composed of items relating to depression symptomatology such as hopelessness, irritability, cognitions such as guilt or feelings of being punished, as well as fatigue, weight loss, and lack of sexual interest (55). For the purposes of this study, we used the following cut-off points as recommended by the authors of the BDI-II: "not depressed" (0-13), "mild depression" (14)(15)(16)(17)(18)(19), "moderate depression" (20-28), "severe depression" (29-63) (56).…”

Section: Measures Beck Depression Inventory-second Editionmentioning

confidence: 99%

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Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

et al. 2021

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Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis. Overall, a statistically significant decrease in BDI-II (13.9 vs. 6.1, p < 0.001), STAI (44.4 vs. 34.3 p < 0.001) scores, and CORE-OM scores were observed (37.3 vs. 22.3 p < 0.001) at post-retreat, as well as a concurrent increase in SCS (3.1 vs. 3.6, p < 0.001). Psychometric improvements were sustained, and on some measures values further decreased at 6-month follow-up, suggesting a potential for lasting therapeutic effects. Changes in memory valence were linked to the observed psychometric improvements. Epigenetic findings were equivocal, but indicated that further research in candidate genes, such as sigma non-opioid intracellular receptor 1 (SIGMAR1), is warranted. This data adds to the literature supporting ayahuasca's possible positive impact on mental health when conducted in a ceremonial context. Further investigation into clinical samples, as well as greater analyses into the mechanistic action of ayahuasca is advised.

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Section: Measures Beck Depression Inventory-second Editionmentioning

confidence: 99%

“…While MAOIs and DMT are both somewhat psychoactive independently, unique phenomenology and pharmacodynamics arise from their interaction in ayahuasca brews ( 9 , 14 , 15 ). A recent review of the literature suggests that such effects are likely synergistic as opposed to simply additive ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

et al. 2021

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“…When DMT is administered without the other ayahuasca components, effects arise within minutes after ingestion when inhaled or injected, and last for 15 min (15). After intake of ayahuasca, effects are noticeable 30 min after ingestion, lasting for 3 h, with a peak at 1.5-2 h, corresponding with the peak in DMT plasma concentration, indicating a significant role for DMT in the pharmacology of ayahuasca (16).…”

Section: Introductionmentioning

confidence: 99%

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

2021

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Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.

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“…The harmalas and DMT are typically put into separate gelatin capsules, with the harmaline/ harmine being taken first and the DMT being taken 15 to 20 min later. The use of moclobemide, a reversible inhibitor of MAO-A, has also been reported in DMT "pharmahuasca" studies (Kaasik et al 2020;Ruffell et al 2020).…”

Section: Administration Of Dmt With and Without A Maoi: Doses Routes And Effectsmentioning

confidence: 91%

Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT

Barker

2022

Psychopharmacology

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As with all drugs, the route, form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and use as a therapeutic. This review will focus on these factors as they relate to the psychedelic N,N-dimethyltryptamine (DMT). It will examine the positive and negative aspects of different formulations and routes of administration of DMT and the observed effects from such administrations in the form of ayahuasca teas; oral “pharmahuasca”; injections by intravenous (IV) and intramuscular (IM) routes; inhalation, insufflation; and other routes; and high-dose, low-dose, and “micro-dose” effects. The review will consider possible oral route of administration alternatives that would not require concomitant use of a monoamine oxidase inhibitor. The review will then address the current research findings for DMT from in vivo and in vitro studies as well as the possibility that these findings may be revealing the role of endogenous DMT in normal brain function.

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The pharmacological interaction of compounds in ayahuasca: a systematic review

Cited by 20 publications

References 59 publications

Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT

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