Navegando por Autor "Hallak, Jaime E.C."

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Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study
(2016) Sanches, Rafael Faria; Osório, Flávia de Lima; Santos, Rafael G. dos; Macedo, Ligia R.H.; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; Araújo, Dráulio Barros de; Riba, Jordi; Crippa, José Alexandre S.; Hallak, Jaime E.C.
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.
Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans
(2015) Bouso, José Carlos; Palhano-Fontes, Fernanda; Rodríguez-Fornells, Antoni; Ribeiro, Sidarta Tollendal Gomes; Sanches, Rafael; Crippa, José Alexandre S.; Hallak, Jaime E.C.; Araújo, Dráulio Barros de; Riba, Jordi
Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.
Nitroprusside single-dose prevents the psychosis-like behavior induced by ketamine in rats for up to one week
(Elsevier, 2015-03) Maia-de-Oliveira, Joao Paulo; Soares, Bruno Lobão; Ramalho, Thais; Gavioli, Elaine C.; Soares, Vanessa Paula; Teixeira, Leslie; Baker, Glen B.; Dursun, Serdar M.; Hallak, Jaime E.C.
Recently, we found a rapid and long-lasting improvement of symptoms in schizophrenic patients on antipsychotics after a single four-hour infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life. This improvement persisted for up to 4 weeks. Because these patients remained on antipsychotics after infusion of SNP was finished, the question arises about whether this improvement was due to SNP itself. We have now investigated whether SNP, alone, can produce preventive antipsychotic effects in rats treated with ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4 mg/kg, KET 25 mg/kg, or saline as follows: group1 — saline, group2 — SNP, group3 — KET, group4 — KET 12 h after SNP, group5 — KET 1 day after SNP, group6 — KET 2 days after SNP, and group7 — KET 1 week after SNP. The animals were filmed in an open field arena for 30 min and the videos were later analyzed by ANY-Maze software to measure activity and stereotypy. SNP significantly prevented the emergence of hyperactivity induced by KET when it was administered for up to 1 week before KET, and prevented the emergence of stereotypies when it was administered for up to 1 day before KET. These findings in rats, which have an even faster metabolic rate than humans, suggest that the long-lasting effects observed in our clinical trial with SNP in humans could have been due to SNP itself, and indicate for the first time that SNP may present preventive antipsychotic effects.
Seeing With the Eyes Shut: Neural Basis of Enhanced Imagery Following Ayahuasca Ingestion
(2011) Araújo, Dráulio Barros de; Ribeiro, Sidarta Tollendal Gomes; Cecchi, Guillermo A.; Carvalho, Fabiana M.; Sanchez, Tiago A.; Pinto, Joel P.; Martinis, Bruno S. de; Crippa, Jose A.; Hallak, Jaime E.C.; Antonio C. Santos, Antonio C.
The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid ‘‘seeings.’’ During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature.
Sodium nitroprusside, a nitric oxide donor for novel treatment of schizophrenia, may also modulate dopaminergic systems
(Elsevier, 2014-11) Soares, Bruno Lobão; Maia-de-Oliveira, Joao Paulo; Baker, Glen B.; Hallak, Jaime E.C.; Dursun, Serdar M.
“Schizophrenia is arguably the worst disease affecting mankind, even AIDS not excepted”. Since this statement in 1988 (Editors, 1988), schizophrenia still remains a major challenge to medicine, with up to 60% of patients not responding adequately to treatment despite the relatively large arsenal of antipsychotics currently available. By modulating the nitric oxide (NO) pathway, a new paradigm for schizophrenia treatment apparently involving modulation of nitric oxide (NO) has been proposed (Oliveira et al., 2011).

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Navegando por Autor "Hallak, Jaime E.C."