The International Journal of Neuropsychopharmacology
March 29, 2015
Joan Francesc Alonso, Sergio Romero, Miguel Ángel Mañanas et al.
105 citations
Ayahuasca, a psychedelic containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine, temporarily disrupts neural hierarchies in the human brain by reducing top-down control and increasing bottom-up information transfer. In ten healthy male volunteers with prior psychedelic experience, transfer entropy analysis of brain oscillations showed that frontal sources decreased their influence over central, parietal, and occipital sites, while posterior sources increased their influence over anterior locations. Decreases in anterior-to-posterior transfer entropy correlated with the intensity of subjective effects, and the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced.
Frontiers in Pharmacology
March 20, 2018
Joaquim Soler, Matilde Elices, Elisabet Domínguez‐clavé et al.
104 citations
A single weekend of four ayahuasca sessions improved the capacity for non-judgmental acceptance as much as an eight-week mindfulness-based stress reduction (MBSR) course, though MBSR produced larger overall gains in mindfulness. Both interventions were tested in separate groups of ten participants each. MBSR training led to greater increases in overall mindfulness scores and in a composite index sensitive to meditation practice. However, ayahuasca sessions induced comparable increases specifically in the Non-Judging subscale of the Five Facet Mindfulness Questionnaire, which measures acceptance—the ability to take a detached, less judgmental stance toward distressing thoughts and emotions. The findings suggest that a small number of ayahuasca sessions can improve acceptance as effectively as longer, costlier interventions.
Journal of psychopharmacology (Oxford, England)
July 1, 2012
Fernando Caudevilla-Gálligo, Jordi Riba, Mireia Ventura et al.
99 citations
The psychoactive drug 2C-B, an analogue of mescaline, is increasingly used as a rave and club drug. Analysis of drug samples in Spain showed that the percentage containing 2C-B doubled between 2006 and 2009, shifting from powder to tablet form with low falsification rates. Recreational users typically took about 20 mg orally. Subjective effects included perceptual changes similar to those from ayahuasca and Salvia divinorum, but not from amphetamine or MDMA. Pleasure and sociability were comparable to MDMA, while incapacitation was lower than with the other psychedelics studied. The findings indicate 2C-B is consistently present in Spain's illicit market, producing psychedelic-like perceptual effects but with lower impairment and higher pleasurable effects akin to entactogens.
Drug Testing and Analysis
July 28, 2014
Jordi Riba, Ethan H. Mcilhenny, José Carlos Bouso et al.
96 citations
When N,N-dimethyltryptamine (DMT) is taken orally, it produces no psychedelic effects and no DMT appears in urine, because monoamine oxidase (MAO) breaks it down almost completely into indole-3-acetic acid (97% of recovered compounds). By contrast, smoking DMT yields full psychoactivity, with unmetabolized DMT and DMT-N-oxide rising to 10% and 28% of recovered compounds, while indole-3-acetic acid drops to 63%. An inverse relationship between the ratio of these metabolites and subjective effects indicates that smoking shifts metabolism from efficient MAO-dependent breakdown to less efficient CYP-dependent pathways, enabling psychoactivity.
Psychopharmacology
June 20, 2013
José Carlos Bouso, Josep María Fábregas, Rosa María Antonijoan et al.
96 citations
Acute ayahuasca intake impaired working memory, as measured by increased errors on the Sternberg task, but reduced stimulus-response interference, shown by faster reaction times on the Stroop task with maintained accuracy. Performance on the Tower of London task, which assesses executive function, worsened only in occasional users, not in long-term experienced users. Greater lifetime ayahuasca use was associated with less impairment on the Tower of London. The findings suggest that prior exposure to ayahuasca may protect against acute cognitive disruption, possibly due to compensatory or neuromodulatory effects.
Drug Testing and Analysis
April 19, 2012
Jordi Riba, Ethan H. Mcilhenny, Marta Valle et al.
91 citations
Ayahuasca, an Amazonian tea containing β-carboline alkaloids (harmine, harmaline, tetrahydroharmine) and the psychedelic DMT, is used worldwide, but its metabolism in humans had not been systematically studied. In 10 healthy men given freeze-dried ayahuasca (1.0 mg DMT/kg), less than 1% of DMT was excreted unchanged; about 50% was recovered as indole-3-acetic acid, 10% as DMT-N-oxide, and total DMT plus metabolites reached 68%. Harmala alkaloids were excreted as O-demethylated and conjugated metabolites, but recoveries varied from 9% to 65%. The findings indicate alternative metabolic routes for DMT beyond monoamine-oxidase and that O-demethylation plus conjugation is important but not the only pathway for harmala alkaloids.
Journal of Chromatography B
October 11, 2002
Mercedes Yritia, Jordi Riba, Jordi Ortuño et al.
84 citations
A method to measure the four main alkaloids in ayahuasca (DMT, harmine, harmaline, and tetrahydroharmine) plus two major metabolites (harmol and harmalol) in human plasma is described. DMT is extracted with n-pentane and quantified by gas chromatography with nitrogen-phosphorus detection, achieving 74% recovery, precision and accuracy better than 9.9%, and a limit of quantification of 1.6 ng/ml. The beta-carbolines and metabolites are measured by high-performance liquid chromatography with fluorescence detection after solid-phase extraction, with recoveries above 87%, accuracy and precision better than 13.4%, and limits of quantification from 0.3 to 1.0 ng/ml. The methods allow adequate characterization of the pharmacokinetics of these compounds, including two major metabolites not previously described.
Psychopharmacology
November 7, 2018
Elisabet Domínguez‐clavé, Joaquim Soler, Juan Carlos Pascual et al.
81 citations
A single session of ayahuasca improved emotion regulation and mindfulness-related capacities in 45 volunteers. Participants showed significant increases in observing, acting with awareness, non-judging, and non-reacting on the Five Facet Mindfulness Questionnaire, as well as improvements in decentering and reductions in emotional non-acceptance, emotional interference, and lack of control on the Difficulties in Emotion Regulation Scale. Among the 12 participants with borderline personality disorder (BPD)-like traits, improvements were seen in emotional interference and lack of control but not in mindfulness capacities. The findings suggest ayahuasca may have therapeutic potential for emotion dysregulation, including in individuals with BPD.
The International Journal of Neuropsychopharmacology
June 5, 2015
Marta Valle, Montserrat Puntes, Jimena Coimbra et al.
75 citations
Salvinorin-A, a compound from the plant Salvia divinorum that activates kappa-opioid receptors, produces dose-dependent changes in perception and body awareness. In eight healthy volunteers with prior psychedelic experience, vaporized salvinorin-A at 0.25, 0.50, and 1 mg caused detachment from external reality, elaborate visions, and auditory phenomena. Lower doses increased bodily sensations, while the highest dose produced a complete loss of contact with the body. The effects on body awareness followed an inverted-U pattern, suggesting the kappa-opioid receptor plays a key role in regulating sensory perception, interoception, and the sense of body ownership.
Psychopharmacology
November 20, 2007
Manel J. Barbanoj, Jordi Riba, S. Clos et al.
74 citations
Ayahuasca, a traditional South American psychoactive beverage containing DMT and beta-carboline alkaloids, did not impair subjective sleep quality or disrupt sleep initiation and maintenance in 22 healthy male volunteers, unlike d-amphetamine which delayed sleep onset, disrupted maintenance, and reduced deep sleep. Both ayahuasca and d-amphetamine reduced REM sleep duration and increased high-frequency EEG power during stage 2 sleep. However, while d-amphetamine decreased slow-wave sleep power in the first night cycle (an indicator of sleep pressure), ayahuasca enhanced it. The findings suggest that serotonergic psychedelics interact with brain circuits regulating REM and slow-wave sleep.
Psychopharmacology
December 1, 2002
Jordi Riba, Antoni Rodrı́guez-fornells, Manel J. Barbanoj
71 citations
Ayahuasca, a South American psychotropic plant tea containing the psychedelic DMT and beta-carboline alkaloids, produces diverging effects on two measures of neural gating. In a double-blind, crossover trial with 18 healthy volunteers who had prior psychedelic experience, ayahuasca caused significant dose-dependent reductions in P50 suppression, an operational measure of sensory gating. However, no significant effects were found on prepulse inhibition of startle (PPI), a measure of sensorimotor gating, or on startle response habituation at any prepulse-to-pulse interval tested. These findings indicate that ayahuasca disrupts sensory gating while leaving sensorimotor gating unaffected at the doses administered.
Curr Top Behav Neurosci
January 1, 2018
Dennis 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.
Journal of Psychoactive Drugs
June 1, 2005
Jordi Riba, Manel J. Barbanoj
58 citations
Since 1999, a research team at the Autonomous University of Barcelona has conducted clinical studies administering ayahuasca to healthy volunteers. The work addresses two needs: systematically establishing the safety and pharmacological profile of ayahuasca, a complex brew of active compounds, given growing interest in traditional indigenous practices; and advancing understanding of how psychedelics modify higher-order cognitive processes, which remains incomplete despite known molecular and electrophysiological effects. The article reviews methodological aspects, basic clinical findings, current laboratory research, and outlines two planned studies to further knowledge of ayahuasca's pharmacology.
Biomedical chromatography : BMC
March 1, 2012
Ethan H Mcilhenny, Jordi Riba, Manel J Barbanoj et al.
57 citations
A new single analytical method can directly measure 14 major alkaloid components of ayahuasca, including known and potential metabolites of N,N-dimethyltryptamine and harmala alkaloids, in human blood plasma. The method uses 96-well plate protein precipitation and filtration followed by HPLC-ion trap-ion trap-mass spectrometry with heated electrospray ionization to reduce matrix effects. It provides adequate sensitivity, specificity, and reproducibility for clinical research, expanding the list of compounds that can be monitored after ayahuasca administration while simplifying the analysis compared to previous combined techniques.
Biomedical chromatography : BMC
September 1, 2011
Ethan H Mcilhenny, Jordi Riba, Manel J Barbanoj et al.
51 citations
The primary metabolite of N,N-dimethyltryptamine (DMT) in humans after ayahuasca ingestion is the corresponding N-oxide, the first time this metabolite has been described in in vivo human studies. Very little DMT was detected in urine, despite monoamine oxidase inhibition by harmala alkaloids. The major harmala alkaloid excreted was tetrahydroharmine. A rapid, sensitive method using HPLC-electrospray ionization-selected reaction monitoring-tandem mass spectrometry was developed and applied to urine samples from three individuals administered ayahuasca, identifying and quantifying major constituents and metabolites. The protocol is suitable for toxicological and clinical research on ayahuasca.
Molecular Psychiatry
March 31, 2015
Jordi Riba, Marta Valle, Frederic Sampedro et al.
41 citations
Chronic cannabis users, even after a period of abstinence, are more prone to false memories—mistaking events that never occurred for real ones. Using functional magnetic resonance imaging, the study found that abstinent cannabis users showed reduced brain activity in areas critical for memory processing, including the lateral and medial temporal lobe, as well as in parietal and frontal regions involved in attention and monitoring. Cannabis consumption was inversely correlated with medial temporal lobe activity, indicating a specific detriment to episodic memory. These results suggest long-lasting impairments in memory and cognitive control mechanisms that support reality monitoring.
November 22, 2013
José Carlos Bouso, Jordi Riba
40 citations
Ayahuasca shows promise in treating addiction, with a study involving 80 participants revealing that 61% experienced significant reductions in substance use after therapy. Participants reported enhanced emotional processing and improved psychological well-being, suggesting ayahuasca's potential as a therapeutic tool. The treatment influenced neurotransmitter receptors, which may alter behavior patterns associated with addiction. With growing interest in psychedelics within psychiatry and pharmacology, ayahuasca stands out as a compelling candidate for future drug studies focused on addiction recovery and mental health improvement.
November 22, 2013
Xavier Fernández, Rafael G. Dos Santos, Marta Cutchet et al.
37 citations
Ayahuasca shows promise in reducing anxiety and altering personality traits, with a study involving 80 participants revealing a significant decrease in anxiety levels for 70% of users. Participants reported enhanced emotional resilience and lower worry, suggesting ayahuasca's potential role in clinical psychology and psychiatry. The effects may stem from its influence on neurotransmitter receptors, paralleling findings in cannabis research. The temperament and character inventory indicated shifts towards more adaptive personality profiles, highlighting the therapeutic potential of psychedelics in addressing psychopathology.
The International Journal of Neuropsychopharmacology
February 12, 2016
Marta Valle, Montserrat Puntes, Jimena Coimbra et al.
31 citations
Salvinorin-A, a terpene from the plant Salvia divinorum, induces an intense but short-lasting altered state of awareness similar to classical psychedelics, but it acts on kappa-opioid receptors rather than serotonin-2A receptors. In a double-blind, placebo-controlled study with 24 healthy volunteers experienced with psychedelics, inhalation of 1 mg of vaporized salvinorin-A severely reduced external sensory perception, caused intense visual and auditory modifications, and increased systolic blood pressure, cortisol, and prolactin. These effects were effectively blocked by the opioid antagonist naltrexone (50 mg orally) but not by the serotonin-2A antagonist ketanserin (40 mg orally), confirming that salvinorin-A's mechanism involves kappa-opioid receptor agonism and not serotonin-2A agonism.
Current topics in behavioral neurosciences
January 1, 2015
Dennis 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.
bioRxiv (Cold Spring Harbor Laboratory)
January 27, 2017
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
22 citations
preprint
A single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
Frontiers in Neuroscience
September 14, 2016
Attila Szabo, A. Kovács, Jordi Riba et al.
18 citations
N,N-dimethyltryptamine (DMT), an endogenous hallucinogen found in the human brain, activates the sigma-1 receptor (Sig-1R), an intracellular chaperone that helps manage cellular stress. This study tested whether DMT protects brain cells from hypoxia by activating Sig-1R. In cultured human cortical neurons, macrophages, and dendritic cells exposed to severe hypoxia (0.5% O2), DMT robustly increased cell survival through Sig-1R activation. This effect was linked to decreased expression and function of hypoxia-inducible factor 1 alpha (HIF-1α), suggesting DMT alleviates hypoxic stress independently of HIF-1. The results indicate DMT may be endogenously produced during stress to protect the brain from hypoxic or ischemic damage.
The international journal of neuropsychopharmacology
January 12, 2022
Genís Ona, Frederic Sampedro, Sergio Romero et al.
17 citations
Kappa opioid receptor (KOR) agonists like salvinorin-A produce psychotomimetic effects through largely unknown mechanisms. In a double-blind, crossover, randomized, placebo-controlled study, acute administration of salvinorin-A increased delta and gamma brain waves while decreasing alpha waves, as measured by electroencephalography. Single-photon emission computed tomography revealed significant decreases in regional cerebral blood flow across frontal, temporal, parietal, and occipital cortices, with increases in the medial temporal lobe, amygdala, hippocampal gyrus, and cerebellum. Subjective effects resembled other psychotomimetic drugs but were distinctly dissociative, with no dysphoria reported. KOR agonism by salvinorin-A induces dramatic psychotomimetic effects alongside generalized reductions in cortical blood flow and electrical activity.
Journal of Cardiovascular Pharmacology
February 25, 2015
Dimítrius Leonardo Pitol, Selma Siéssere, Rafael G. Dos Santos et al.
13 citations
Ayahuasca, a hallucinogenic brew used by Amazonian indigenous groups, contains β-carbolines that inhibit monoamine oxidase and dimethyltryptamine, a serotonin receptor agonist. Acute administration causes moderate cardiovascular effects in healthy volunteers, but long-term effects are unknown. In rats, ayahuasca (2-4 mL/kg) flattened and stretched vascular smooth muscle cells and altered collagen and elastic fiber arrangement. Chronic high-dose treatment increased media thickness and the ratio of media thickness to lumen diameter in the aorta. More research on cardiovascular function in long-term ayahuasca consumers is needed.
Frontiers in psychiatry
January 1, 2022
Otto Simonsson, José Carlos Bouso, Florian Kurth et al.
6 citations
The corpus callosum, a brain structure connecting the two hemispheres, was thicker in the isthmus region among 22 ayahuasca users compared to 22 matched controls. A positive correlation was observed between callosal thickness in the rostral body and the number of past ayahuasca sessions, though neither finding survived correction for multiple comparisons. No brain region was thicker in controls than in ayahuasca users, and no region was negatively linked to ayahuasca use. This provides preliminary evidence of an association between ayahuasca use and callosal structure, but replication with larger samples and longitudinal designs is needed.