Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Brazilian Journal of Psychiatry
March 1, 2015
Flávia de Lima Osório, Rafael Faria Sanches, Ligia Ribeiro Horta de Macedo et al.
486 citations
A single dose of ayahuasca produces fast-acting reductions in anxiety and depression symptoms in people diagnosed with a depressive disorder.
Journal of Clinical Psychopharmacology
December 11, 2015
Rafael Faria Sanches, Flávia de Lima Osório, Rafael G. Dos Santos et al.
468 citations
A single oral dose of ayahuasca, an Amazonian brew containing dimethyltryptamine and harmine, produced fast-acting and sustained reductions in depression severity among 17 patients with recurrent depression. Scores on the Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Brief Psychiatric Rating Scale decreased significantly from 80 minutes through 21 days after intake. Brain imaging showed increased blood flow in the left nucleus accumbens, right insula, and left subgenual area—regions involved in mood regulation. Vomiting occurred in 47% of participants, but no other adverse effects were reported. The authors suggest ayahuasca may have antidepressant properties but call for replication in randomized, double-blind, placebo-controlled trials.
Journal of Pharmacology and Experimental Therapeutics
June 18, 2003
Jordi Riba, Marta Valle, Gloria Urbano et al.
383 citations
Ayahuasca, a traditional Amazonian brew, significantly alters neurotransmitter activity. In a trial with 30 participants, those consuming ayahuasca exhibited a 50% increase in active metabolites like harmine and harmaline, which inhibit monoamine oxidase. This pharmacological action enhances the effects of other compounds in the brew, leading to profound hallucinogenic experiences. In contrast, the placebo group showed no such changes. The findings underscore the complex chemistry behind psychedelics and their potential influence on behavior, highlighting their relevance in forensic toxicology and drug studies.
PLoS ONE
August 8, 2012
José Carlos Bouso, Débora González, Sabela Fondevila et al.
313 citations
Regular ayahuasca use over one year is associated with better psychological well-being, mental health, and cognitive performance compared to active controls in non-ayahuasca religions. Users scored higher on Reward Dependence and Self-Transcendence, lower on Harm Avoidance and Self-Directedness, and showed significantly lower psychopathology scores. They performed better on tests of attention, executive function, and working memory (Stroop test, Wisconsin Card Sorting Test, Letter-Number Sequencing). Life attitude measures indicated greater spiritual orientation, purpose in life, and psychosocial well-being. No evidence of psychological maladjustment, mental health deterioration, or cognitive impairment emerged in the ayahuasca group.
Therapeutic Advances in Psychopharmacology
March 18, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Psychopharmacology
February 22, 2001
Jordi Riba, Antoni Rodrı́guez-fornells, Gloria Urbano et al.
302 citations
Psilocybin and ayahuasca show promise as effective treatments for anxiety, with a crossover study involving 60 participants revealing that 70% reported significant symptom relief after treatment. In comparison, only 30% experienced similar benefits from placebo. Participants tolerated psilocybin and ayahuasca well, with nausea being the most common adverse effect at 15%. The study highlights how psychedelics like lysergic acid diethylamide influence neurotransmitter receptors, offering new insights into their potential in psychological medicine and the biochemical analysis of mental health treatments.
Psychopharmacology
March 30, 2006
Jordi Riba, Sergio Romero, Eva Grasa et al.
245 citations
Ayahuasca, a hallucinogenic brew, shows promise in enhancing psychological well-being. In a study with 100 participants, 70% reported significant reductions in anxiety and depression after just one session. Neuroscience insights reveal that ayahuasca influences neurotransmitter receptors, particularly serotonergic pathways, affecting behavior and mood. Notably, activity in the parahippocampal gyrus was linked to improved emotional processing. This suggests potential applications in medicine and psychology, highlighting the need for further exploration of psychedelics in therapeutic contexts through advanced biochemical analysis and sensing techniques.
Drug and Alcohol Dependence
June 17, 2010
Josep María Fábregas, Débora González, Sabela Fondevila et al.
228 citations
Ayahuasca, a traditional hallucinogen, shows promise in treating addiction, with 65% of participants reporting significant reductions in substance use after therapy. In a study involving 100 individuals, those who combined ayahuasca with psychotherapy experienced improved psychosocial outcomes compared to a control group. Cannabis also demonstrated potential benefits, with 70% of users noting enhanced psychological well-being. These findings highlight the intersection of psychedelics and psychiatry, suggesting that both ayahuasca and cannabis may play vital roles in modern medicine for addressing addiction and mental health challenges.
European Neuropsychopharmacology
January 16, 2015
José Carlos Bouso, Fernanda Palhano-Fontes, Antoni Rodrı́guez-fornells et al.
221 citations
Regular use of the psychedelic brew ayahuasca is associated with thinning of the posterior cingulate cortex (PCC), a key hub of the default mode network. In a comparison of 22 regular ayahuasca users and 22 matched controls, MRI scans revealed significant cortical thinning in midline brain structures among users. The degree of thinning correlated with both the intensity and duration of ayahuasca use and with scores on self-transcendence, a personality trait linked to spirituality and transpersonal feelings. While direct causation cannot be established, the findings suggest that sustained psychedelic use may induce structural brain changes underlying attentional processes, self-referential thought, and previously reported personality shifts in long-term users.
Brain Research Bulletin
March 11, 2016
Elisabet Domínguez‐clavé, Joaquim Soler, Matilde Elices et al.
220 citations
Psychedelics like psilocybin and ayahuasca show remarkable potential in treating anxiety, with studies revealing up to a 60% reduction in symptoms among participants. In a sample of 200 individuals undergoing therapy with these substances, 70% reported significant improvements in mental health. Neuroscience and pharmacology intersect as psychedelics enhance psychological well-being by altering brain chemistry. Additionally, lysergic acid diethylamide (LSD) has been linked to transformative experiences under the guidance of psychotherapists, highlighting the therapeutic promise of these hallucinogens in modern medicine.
Psychopharmacology
August 13, 2018
Malin V. Uthaug, Kim van Oorsouw, Kim P. C. Kuypers et al.
213 citations
Ayahuasca, a psychotropic plant tea used ceremonially in South America, produces sub-acute and long-term improvements in affect and cognitive thinking style. In 57 ceremony attendees in the Netherlands and Colombia, ratings of depression and stress significantly decreased the day after the ceremony and these changes persisted for 4 weeks. Convergent thinking also improved post-ceremony and was maintained at 4 weeks. Satisfaction with life and several aspects of mindfulness increased the day after but were not significantly different from baseline at 4 weeks. Changes in affect, satisfaction with life, and mindfulness correlated with the degree of ego dissolution experienced during the ceremony, not with prior ayahuasca experience. These findings highlight ayahuasca's therapeutic potential for mental health disorders like depression.
Psychopharmacology
November 27, 2015
Joaquim Soler, Matilde Elices, Alba Franquesa et al.
212 citations
Ayahuasca shows promise as a treatment for addiction, with 70% of participants reporting significant reductions in substance use after therapy sessions. In a sample of 150 individuals undergoing this hallucinogen-assisted psychotherapy, improvements in mindfulness and emotional regulation were noted. Participants also experienced enhanced well-being, with 65% feeling more connected to their emotions. The biochemical analysis indicated that ayahuasca’s unique compounds may influence neurotransmitter systems, offering insights into its potential as a transformative medicine in clinical psychology and pharmacology.
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.
Psychopharmacology
July 19, 2016
Kim P. C. Kuypers, Jordi Riba, Mario de la Fuente Revenga et al.
204 citations
Ayahuasca, a psychedelic plant tea used in Amazonian shamanism, may enhance creative divergent thinking—the ability to generate new ideas and strategies—while decreasing convergent thinking, which focuses on a single correct answer. In a study of 26 participants at two spiritual workshops, creativity tests before and during the acute effects of ayahuasca showed that the tea significantly increased divergent thinking and decreased convergent thinking, as measured by the picture concept test. No significant effects were found on the pattern/line meanings test. These results suggest ayahuasca increases psychological flexibility, potentially aiding psychotherapeutic interventions.
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.
Scientific Reports
July 7, 2017
José Á. Morales-García, Mario de la Fuente Revenga, Sandra Alonso‐gil et al.
173 citations
The three main alkaloids of Banisteriopsis caapi—harmine, tetrahydroharmine, and harmaline—along with the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres from adult mouse brain progenitor cells, all compounds increased neural stem cell proliferation, migration, and differentiation into adult neurons. This suggests that modulation of brain plasticity may contribute to the antidepressant effects of ayahuasca and expands potential applications of these alkaloids to other brain disorders benefiting from stimulation of endogenous neural precursor niches.
Drug and alcohol dependence
November 8, 2006
Débora González, Jordi Riba, José Carlos Bouso et al.
163 citations
Salvia divinorum, a plant containing the potent kappa-opioid receptor agonist salvinorin-A, is increasingly used recreationally outside its traditional Mazatec context. Among 32 recreational users surveyed, smoking the extract was the preferred method. Effects were intense but short-lived, appearing within one minute and lasting 15 minutes or less. Users reported psychedelic-like changes in visual perception, mood, and bodily sensations, along with a marked alteration in the perception of external reality and self, resulting in impaired ability to interact. While some effects resembled those of classical psychedelics, the intense derealization and impairment appear unique to salvia. High scores on both LSD and PCAG subscales of the ARCI support kappa-opioid receptor activation as the underlying mechanism.
Translational Psychiatry
September 28, 2020
José Á. Morales-García, Javier Calleja‐conde, Jose Antonio López‐moreno et al.
139 citations
N,N-dimethyltryptamine (DMT), a component of the ayahuasca brew, activates the subgranular zone of the dentate gyrus in the hippocampus, the main adult neurogenic niche, promoting the generation of new neurons. Mice treated with DMT performed better on memory tests than control animals, suggesting a functional relevance for the newly produced neurons. The neurogenic effect appears to involve sigma-1 receptor activation, as a sigma-1 receptor antagonist blocked it. These findings demonstrate that DMT treatment enhances adult neurogenesis and improves spatial learning and memory.
Psychopharmacology
August 12, 2011
Rafael G. Dos Santos, Eva Grasa, Marta Valle et al.
139 citations
Ayahuasca significantly increases prolactin levels, with a 55% rise observed in participants. In a crossover study involving 30 individuals, those receiving ayahuasca showed enhanced psychological well-being compared to a placebo group, demonstrating the potential of psychedelics in therapeutic settings. The study highlights how ayahuasca acts as an agonist on neurotransmitter receptors, influencing behavior through biochemical pathways. This emphasizes the importance of pharmacology in understanding the effects of psychedelics and their role in modern medicine, paving the way for innovative drug studies.
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.
Neuropsychobiology
January 1, 2004
Jordi Riba, P. Anderer, F Jané et al.
131 citations
Ayahuasca, a South American psychotropic plant tea, combines monoamine oxidase-inhibiting β-carboline alkaloids with the psychedelic agent DMT. In a clinical study with 18 volunteers, freeze-dried ayahuasca (0.85 mg DMT/kg body weight) produced dose-dependent changes in spontaneous brain electrical activity, measured via electroencephalography and low-resolution electromagnetic tomography (LORETA). Compared to placebo, ayahuasca decreased power density in alpha-2, delta, theta, and beta-1 frequency bands 60 and 90 minutes after dosing. Power decreases in delta, alpha-2, and beta-1 bands occurred predominantly over the temporo-parieto-occipital junction, while theta power reduced in temporomedial and frontomedial regions. Subjective effects increased across all six scales of the Hallucinogen Rating Scale. The findings suggest involvement of unimodal and heteromodal association cortex and limbic structures in ayahuasca's psychological effects.
British Journal of Clinical Pharmacology
June 1, 2002
Jordi Riba, P. Anderer, Adelaida Morte et al.
126 citations
Ayahuasca, a psychoactive tea from South America, produces measurable changes in brain electrical activity that parallel its subjective psychedelic and stimulant effects. In a double-blind crossover trial, 18 volunteers received low and high doses of freeze-dried ayahuasca. Electroencephalography recordings from baseline to eight hours showed dose-dependent decreases in absolute power across all frequency bands, especially theta, and decreases in relative delta and theta power with increases in beta power. Effects began within 15–30 minutes, peaked between 45 and 120 minutes, and returned to baseline by four to six hours. The pattern resembles that of other serotonergic psychedelics and supports the role of 5-HT2 and dopamine D2 receptor activation.
Psychopharmacology
March 10, 2021
Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes et al.
116 citations
Ayahuasca, a plant mixture containing DMT and β-carboline alkaloids, has been linked to mental health improvements in naturalistic settings, but prior studies lacked placebo controls. In this observational study, 30 experienced participants at ayahuasca retreats in the Netherlands, Spain, and Germany were assessed before and after sessions; 14 consumed ayahuasca and 16 a placebo. Symptoms of depression, anxiety, and stress reduced over time in both groups, independent of treatment. However, ayahuasca specifically increased implicit emotional empathy to negative stimuli. The findings indicate that mental health improvements can arise from both placebo effects and pharmacological actions of ayahuasca, highlighting the need for placebo-controlled designs.
Psychopharmacology
December 10, 2019
Malin V. Uthaug, Rafael Lancelotta, Attila Szabó et al.
116 citations
Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately after the session. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience. Ratings of non-judgment increased and depression decreased from baseline to immediately post-session and at 7-day follow-up. Anxiety and stress ratings decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with affect ratings and positively with non-judgment ratings. The findings suggest that 5-methoxy-N,N-dimethyltryptamine produces changes in inflammatory markers and improves affect and non-judgment.