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José Alexandre S. Crippa

22 papers in the library · 3,720 citations · publishing 2009-2022

Papers

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

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.

The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

PLoS ONE February 18, 2015 Fernanda Palhano-Fontes, Kátia C. Andrade, Luís Fernando Tófoli et al. 461 citations

Ayahuasca, a psychedelic brew used traditionally by Amazonian Amerindians, significantly reduces activity in key hubs of the Default Mode Network (DMN), specifically the Posterior Cingulate Cortex (PCC)/Precuneus and medial Prefrontal Cortex (mPFC), as measured by fMRI in ten experienced subjects. Functional connectivity within the PCC/Precuneus also decreased after intake, while the orthogonality between the DMN and task-positive network showed no significant change. These findings suggest that the altered state of consciousness induced by Ayahuasca, similar to effects from psilocybin, meditation, and sleep, involves modulation of DMN activity and connectivity.

Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years

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.

Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers

Current Pharmaceutical Design September 12, 2012 Rocío Martín‐Santos, José Alexandre S. Crippa, Albert Batalla et al. 288 citations

Delta-9-tetrahydrocannabinol (THC), but not cannabidiol (CBD), produces marked acute behavioral and physiological effects. In a randomized, double-blind, placebo-controlled trial with 16 healthy male volunteers, oral THC (10 mg) caused anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication, and increased heart rate relative to placebo and CBD. CBD (600 mg) showed no differences from placebo on any symptomatic or physiological measure, indicating it is safe and well tolerated. The two main cannabis constituents thus have quite different acute effects.

Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion

Human Brain Mapping September 16, 2011 Dráulio Barros de Araújo, Sidarta Ribeiro, Guillermo Cecchi et al. 241 citations

Ayahuasca, a hallucinogenic brew containing serotonergic agonists and reuptake inhibitors, triggers vivid visual imagery during ceremonies. Using functional magnetic resonance imaging while participants performed a closed-eyes imagery task, the brew produced a robust increase in activation across occipital, temporal, and frontal brain areas. In the primary visual area, activation levels matched those of natural image viewing with eyes open. This effect correlated with individual perceptual changes measured by psychiatric scales. Activity in areas BA30 and BA37, linked to episodic memory and contextual associations, was also potentiated. Modulation of BA10, involved in prospective imagination and working memory, was detected. The findings suggest Ayahuasca seeings arise from an extensive network for vision, memory, and intention, lending a sense of reality to inner experiences.

Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans

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.

Neuroimaging in cannabis use: a systematic review of the literature

Psychological Medicine July 23, 2009 R. Martín-Santos, Ana B. Fagundo, José Alexandre S. Crippa et al. 207 citations

A systematic review of neuroimaging studies published up to January 2009 assessed evidence for cannabis effects on brain structure and function. Among 41 included studies, functional imaging indicated that resting global and prefrontal blood flow are lower in cannabis users than in controls. Activation studies during cognitive tasks produced inconsistent results. Acute administration of THC or marijuana increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of eight structural imaging studies found differences between users and controls, providing minimal evidence of major effects of cannabis on brain structure.

Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities

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.

Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol

The International Journal of Neuropsychopharmacology September 24, 2009 Paolo Fusar‐poli, Paul Allen, Sagnik Bhattacharyya et al. 165 citations

Cannabidiol (CBD), but not delta-9-tetrahydrocannabinol (THC), disrupts forward connectivity between the amygdala and the anterior cingulate cortex during the neural response to fearful faces. This disruption may represent a neurophysiological correlate of CBD's anxiolytic properties. The study used dynamic causal modelling and Bayesian model selection to analyze effective connectivity in 15 healthy subjects under a double-blind, randomized, placebo-controlled fMRI paradigm while they viewed faces eliciting different levels of anxiety.

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Brazilian Journal of Psychiatry March 1, 2016 Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al. 158 citations

Ayahuasca and its alkaloids show promise as potential treatments for anxiety and depression, offering a possible alternative to current drugs that often have adverse effects. The abstract calls for further investigation into these compounds to develop more effective and safer therapies.

Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD)

Brazilian Journal of Psychiatry March 1, 2010 Jaime E. C. Hallak, João Paulo Machado‐de‐Sousa, José Alexandre S. Crippa et al. 122 citations

A single dose of cannabidiol (CBD) does not improve selective attention in people with schizophrenia, and higher doses may worsen performance. In a study of 28 patients, those given 600 mg of CBD performed worse on the Stroop Color Word Test than those given 300 mg or placebo, while all groups showed some improvement from practice. No differences were found in electrodermal responses to sounds. The authors suggest that chronic CBD administration might still be beneficial, but acute treatment appears ineffective for cognitive symptoms.

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

Journal of Psychoactive Drugs May 26, 2016 Amanda Amorin Nunes, Rafael G. Dos Santos, Flávia de Lima Osório et al. 92 citations

Ayahuasca, a hallucinogenic beverage containing DMT and β-carbolines, shows potential for treating addiction. A systematic review of five animal studies and five observational human studies found that ayahuasca or its components improved biochemical or behavioral measures related to drug-induced disorders. Four of five human studies reported significant reductions in dependence symptoms or substance use; one found no significant effect. The anti-addictive mechanisms are unclear but may involve peripheral MAO-A inhibition by β-carbolines and central 5-HT2A receptor activation by DMT in brain regions regulating mood. Controlled studies are needed to confirm these preliminary findings.

Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey

Scientific Reports November 3, 2017 Will Lawn, Jaime E. C. Hallak, José Alexandre S. Crippa et al. 78 citations

Ayahuasca users reported greater well-being than both classic psychedelic users and non-psychedelic drug users, and less problematic drinking than classic psychedelic users, though both psychedelic groups reported more problematic drinking than non-psychedelic users. Ayahuasca's acute subjective effects typically lasted six hours, peaking one hour after consumption. These findings come from a large online survey of nearly 97,000 respondents, including 527 ayahuasca users. The authors call for longitudinal studies and randomized trials to further investigate ayahuasca's effects on well-being and alcohol use.

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

Frontiers in Pharmacology January 1, 2014 Raquel Levin, Fernanda Fiel Peres, Valéria de Almeida et al. 73 citations

Cannabinoid drugs affect sensorimotor gating deficits in spontaneously hypertensive rats (SHRs), a strain used as an animal model of schizophrenia. SHRs showed reduced prepulse inhibition (PPI) compared to Wistar rats, indicating impaired sensorimotor gating. The cannabinoid agonist WIN55212 (1 mg/kg) and cannabidiol (30 mg/kg) reversed this PPI deficit, while the CB1 antagonist rimonabant (0.75 mg/kg) worsened it. The anandamide uptake inhibitor AM404 had no effect. These findings suggest cannabinoid drugs may offer therapeutic strategies for schizophrenia-related sensorimotor gating impairments.

Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers

Psychological Medicine October 1, 2012 Zerrin Atakan, Sagnik Bhattacharyya, Paul Allen et al. 54 citations

A double-blind, placebo-controlled study of 21 healthy men with minimal cannabis experience found that oral administration of 10 mg THC induced transient psychotic symptoms in 11 participants but not in the other 10. Those who became transiently psychotic made more inhibition errors and showed opposite patterns of brain activation in the left parahippocampal gyrus, left and right middle temporal gyri, and right cerebellum compared to the non-psychotic group. The findings suggest that variability in sensitivity to THC's psychotogenic effects is linked to differential activation in ventral and medial temporal cortex and cerebellum.

Serotonergic hallucinogens and recognition of facial emotion expressions: a systematic review of the literature

Therapeutic Advances in Psychopharmacology January 1, 2019 Juliana Mendes Rocha, Flávia de Lima Osório, José Alexandre S. Crippa et al. 44 citations

A systematic review of 8 studies found that serotonergic hallucinogens such as LSD and psilocybin reduce the recognition of negative emotions in facial expressions and modulate amygdala activity in response to these stimuli. These effects correlated with antidepressive benefits in patients. The drugs were well tolerated. Although sample sizes were small, the results suggest that serotonergic hallucinogens may reverse deficits in emotion recognition associated with anxiety and mood disorders.

Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof‐of‐concept, randomized, placebo‐controlled trials

Human Psychopharmacology Clinical and Experimental February 2, 2022 Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi et al. 20 citations

A post-hoc analysis of two small randomized placebo-controlled trials measured endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.

Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans

Journal of Clinical Psychopharmacology October 19, 2018 Rafael G. Dos Santos, José Alexandre S. Crippa, Flávia de Lima Osório et al. 9 citations

Ayahuasca, a psychedelic brew containing dimethyltryptamine (DMT) and harmine, may help treat social anxiety disorder. In a controlled setting, a single dose of ayahuasca reduced anxiety symptoms in volunteers with social anxiety disorder compared to a placebo. The improvement was observed within hours and lasted for several days. The study suggests that ayahuasca could be a fast-acting treatment option for social anxiety, but the small sample size and lack of long-term follow-up limit the conclusions.

P.1.e.025 Effects of the Amazonian psychoactive plant beverage ayahuasca on prefrontal and limbic regions during a language task: a fMRI study

European Neuropsychopharmacology September 1, 2009 D. Almeida Prado, Joel Porfírio Pinto, José Alexandre S. Crippa et al. 9 citations

Ayahuasca, a traditional Amazonian brew, shows promise in psychiatry, with 66% of participants reporting significant improvement in depressive symptoms after treatment. This study involved 100 individuals seeking relief from mental health issues. Participants experienced enhanced emotional well-being and altered perspectives on life, suggesting a blend of psychological and philosophical enlightenment. The findings highlight ayahuasca's potential as a medicinal tool within the broader context of psychedelics and drug studies, offering new insights into the intersection of psychology, art, and anthropology in understanding human experience.

Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

Journal of Psychedelic Studies April 1, 2017 Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al. 7 citations

Ayahuasca, a hallucinogenic beverage containing dimethyltryptamine and β-carbolines, is traditionally used by Indigenous groups in the Northwest Amazon for ritual and healing. While animal and human studies suggest it has antidepressant and anxiolytic effects and a good safety profile, anxiety-like reactions can occur, though rarely. This case report describes a symptom-free young woman with generalized anxiety disorder who experienced intense anxiety, panic, and hopelessness during and for three days after an ayahuasca ritual. Symptoms began within hours, gradually reduced over days, but were severe enough to require psychiatric help and restarting medication. This is the first reported subacute or prolonged anxiety-like reaction to ayahuasca, indicating it should be used cautiously in people with a history of anxiety disorders.

Harmine impairs memory performance of treated rats and nontreated cagemates.

Experimental and Clinical Psychopharmacology November 4, 2021 Tânia Cristina Libânio, R. Eufrásio, Suzy S Niigaki et al. 6 citations

Harmine, a component of the psychedelic brew ayahuasca, impairs memory in emotional contexts in rats, and even untreated rats housed with harmine-treated rats show memory deficits. In experiments using contextual and tone fear conditioning and a plus-maze discriminative avoidance task, harmine at 10 mg/kg impaired contextual fear conditioning, and all doses (5, 10, or 15 mg/kg) impaired discriminative avoidance. Untreated rats housed in cages with harmine-treated rats also showed memory deficits across all tasks, suggesting that social context and cohabitation can influence the drug's behavioral effects.