New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

McKenna, Dennis J.; Riba, Jordi

doi:10.1007/7854_2015_368

Cited by 40 publications

(57 citation statements)

References 35 publications

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“…The authors interpreted their findings in terms of increased feed-forward or bottom-up information transfer and decreased feed-back or top-down control. Our findings would support 5-HT2A agonism as a key mechanism in the modification of brain dynamics induced by ayahuasca (McKenna and Riba, 2015).…”

Section: Discussionsupporting

confidence: 68%

Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Valle

Maqueda

Rabella

et al. 2016

European Neuropsychopharmacology

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142

104

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Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.

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Section: Discussionsupporting

confidence: 68%

Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Valle

Maqueda

Rabella

et al. 2016

European Neuropsychopharmacology

Self Cite

142

104

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“…A yahuasca is a hallucinogenic botanical brew prepared by decoction of the bark of the vine Banisteriopsis caapi together with the leaves of the shrub Psychotria viridis. 1 Banisteriopsis caapi contains β-carboline alkaloids (harmine, tetrahydroharmine, and harmaline) that act as reversible inhibitors of monoamine oxidase(MAO)-A, whereas P. viridis is rich in N,N-dimethyltryptamine (DMT), n hallucinogenic tryptamine that acts as a 5-HT 1A/2A/2C agonist. 1,2 The psychoactive effects of ayahuasca are produced by a combined action of β-carbolines and DMT: because DMT is metabolized by MAO-A in the gut and liver, peripheral MAO-A inhibition by β-carbolines allows DMT to reach systemic circulation and the brain, where it acts at frontal and paralimbic areas.…”

mentioning

confidence: 99%

“…1 Banisteriopsis caapi contains β-carboline alkaloids (harmine, tetrahydroharmine, and harmaline) that act as reversible inhibitors of monoamine oxidase(MAO)-A, whereas P. viridis is rich in N,N-dimethyltryptamine (DMT), n hallucinogenic tryptamine that acts as a 5-HT 1A/2A/2C agonist. 1,2 The psychoactive effects of ayahuasca are produced by a combined action of β-carbolines and DMT: because DMT is metabolized by MAO-A in the gut and liver, peripheral MAO-A inhibition by β-carbolines allows DMT to reach systemic circulation and the brain, where it acts at frontal and paralimbic areas. [1][2][3] Preclinical, observational, and experimental studies in healthy volunteers suggest that ayahuasca has antidepressive properties, 4 and we recently reported that administration of ayahuasca to 6 patients with recurrent major depressive disorder (MDD) was associated with fast-acting and enduring antidepressive effects.…”

mentioning

confidence: 99%

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression

Sanches¹,

Osório²,

Santos³

et al. 2016

Journal of Clinical Psychopharmacology

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407

434

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Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

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“…DMT ( 168 ) is the active component in ayahuasca. 115 Its biosynthesis occurs within plants via the shikimate pathway. 116 This pathway is also responsible for the biosynthesis of the amino acid tryptophan as well as various indole alkaloid precursors.…”

Section: The Hallucinogensmentioning

confidence: 99%

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

Chambers

DeSousa

Huseman

et al. 2018

ACS Chem. Neurosci.

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Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term “psychotropic drug” is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.

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New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

Cited by 40 publications

References 35 publications

Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

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