Journal of Pharmacology and Experimental Therapeutics
June 18, 2003
Jordi Riba, Marta Valle, Gloria Urbano et al.
383 citations
Ayahuasca, a South American psychedelic beverage combining DMT with MAO-inhibiting beta-carboline alkaloids, produces significant subjective perceptual and mood effects peaking 1.5 to 2 hours after oral administration. In a double-blind placebo-controlled trial with 18 experienced psychedelic users, doses of 0.6 and 0.85 mg DMT/kg increased diastolic blood pressure by 9 mm Hg at the high dose, while systolic pressure and heart rate rose modestly but not significantly. Peak DMT blood concentrations (Cmax) were 12.14 ng/ml and 17.44 ng/ml for low and high doses, respectively, coinciding with subjective effect peaks. Urinary normetanephrine increased, but deaminated monoamine metabolites did not decrease, and harmine plasma levels were negligible, suggesting harmine acts primarily in the gastrointestinal tract and liver to prevent DMT breakdown and allow its entry into the brain.
The International Journal of Neuropsychopharmacology
May 17, 2017
Frederic Sampedro, Mario de la Fuente Revenga, Marta Valle et al.
205 citations
A single dose of ayahuasca reduced glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex of 16 healthy volunteers, measured post-acutely with magnetic resonance spectroscopy. Connectivity increased between the posterior and anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Reduced glutamate+glutamine correlated with higher scores on the nonjudging subscale of the Five Facets Mindfulness Questionnaire, and increased anterior cingulate cortex-medial temporal lobe connectivity correlated with higher self-compassion scores. Post-acute neural changes predicted sustained elevations in nonjudging two months later, suggesting glutamate neurotransmission and altered default mode network connectivity underlie ayahuasca's psychological effects.
European Neuropsychopharmacology
March 26, 2016
Marta Valle, Ana Maqueda, Mireia Rabella et al.
175 citations
Ayahuasca, a psychoactive Amazonian tea, contains DMT and other compounds. In a double-blind, placebo-controlled study with 12 experienced users, ayahuasca reduced brain oscillations in delta, theta, and alpha frequency bands. The intensity of visual imagery correlated inversely with alpha-band current density in parietal and occipital cortex. Pretreatment with the 5-HT2A antagonist ketanserin blocked these neurophysiological changes, weakened the correlation between alpha activity and visual effects, and reduced subjective intensity. These results indicate that activation of the 5-HT2A receptor is central to ayahuasca's neurophysiological and visual effects in humans, despite the tea's chemical complexity.
Psychopharmacology
August 12, 2011
Rafael G. Dos Santos, Eva Grasa, Marta Valle et al.
139 citations
The human pharmacology of ayahuasca, an Amazonian tea containing the psychedelic DMT, was evaluated after repeated doses. In a double-blind, crossover, placebo-controlled trial, nine experienced psychedelic drug users received either a placebo followed by ayahuasca, or two ayahuasca doses four hours apart. DMT plasma concentrations, subjective and neurophysiological effects, and serum prolactin and cortisol were higher after two doses. When effects were adjusted for plasma DMT, no differences appeared for subjective, neurophysiological, autonomic, or immunological measures. A trend toward reduced systolic blood pressure and heart rate, and significant tolerance to growth hormone secretion, were observed after the second dose. No clear tolerance or sensitization occurred in psychological or most physiological variables.
Journal of Clinical Psychopharmacology
October 15, 2011
Rafael G. Dos Santos, Marta Valle, José Carlos Bouso et al.
136 citations
Ayahuasca, an Amazonian psychotropic tea containing DMT and β-carboline alkaloids, produced moderate sympathomimetic effects, significant increases in prolactin and cortisol, and time-dependent changes in immune cell populations in a double-blind crossover trial with 10 healthy volunteers. Pupil dilation occurred with both ayahuasca and amphetamine, but ayahuasca’s effects were milder. Prolactin rose only after ayahuasca, while cortisol peaked higher with ayahuasca than with amphetamine. Lymphocyte subsets shifted similarly for both drugs: CD4 and CD3 percentages decreased, and natural killer cells increased, with maximum changes at 2 hours and return to baseline by 24 hours.
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.
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.
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.
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.
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.
January 1, 2021
Marta Valle, Elisabet Domínguez‐clavé, Matilde Elices et al.
Ayahuasca shows promise in enhancing mindfulness, with a study involving 100 participants revealing that 75% reported significant improvements in psychological well-being after use. Neuroscience insights indicate that psychedelics like ayahuasca can alter brain connectivity, fostering emotional resilience. In a separate analysis of 200 psychotherapists, 80% acknowledged incorporating mindfulness techniques into their practices, suggesting a growing acceptance of these approaches. Additionally, emerging cannabinoid research highlights potential synergies between cannabis and psychedelics in therapeutic settings, offering new avenues for mental health treatment.