5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats.

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Grammatical impairment in schizophrenia: An exploratory study of the pronominal and sentential domains.

Schizophrenia (SZ) is a severe mental disorder associated with a variety of linguistic deficits, and recently it has been suggested that these deficits are caused by an underlying impairment in the ability to build complex syntactic structures and complex semantic relations. Aiming at contributing to determining the specific linguistic profile of SZ, we investigated the usage of pronominal subjects and sentence types in two corpora of oral dream and waking reports produced by speakers with SZ and participants without SZ (NSZ), both native speakers of Brazilian Portuguese. Narratives of 40 adult participants (20 SZ, and 20 NSZ-sample 1), and narratives of 31 teenage participants (11 SZ undergoing first psychotic episode, and 20 NSZ-sample 2) were annotated and statistically analyzed. Overall, narratives of speakers with SZ presented significantly higher rates of matrix sentences, null pronouns-particularly null 3Person referential pronouns-and lower rates of non-anomalous truncated sentences. The high rate of matrix sentences correlated significantly with the total PANSS scores, suggesting an association between the overuse of simple sentences and SZ symptoms in general. In contrast, the high rate of null pronouns correlated significantly with positive PANSS scores, suggesting an association between the overuse of null pronominal forms and the positive symptoms of SZ. Finally, a cross-group analysis between samples 1 and 2 indicated a higher degree of grammatical impairment in speakers with multiple psychotic episodes. Altogether, the results strengthen the notion that deficits at the pronominal and sentential levels constitute a cross-cultural linguistic marker of SZ.

Speech graph analysis in obsessive-compulsive disorder: The relevance of dream reports.

Obsessive-compulsive disorder (OCD) is a distressing disorder characterized by the presence of intrusive thoughts, images or urges (obsessions) and/or behavioral efforts to reduce the anxiety (compulsions). OCD lifetime prevalence varies between 1% and 3% in the general population and there are no reliable markers that support the diagnosis. In order to fill this gap, Computational Psychiatry employs multiple types of quantitative analyses to improve the understanding, diagnosis, prediction, and treatment of mental illnesses including OCD. One of these computational tools is speech graphs analysis. A graph represents a network of nodes connected by edges: in non-semantic speech graphs, nodes correspond to words and edges correspond to the directed link between consecutive words. Using non-semantic speech graphs, we compared free speech samples from OCD patients and healthy controls (HC), to test whether speech graphs analysis can grasp structural differences in speech between these groups. To this end, 39 OCD patients and 37 HC were interviewed and recorded during six types of speech reports: yesterday, dream, old memory, positive image, negative image and neutral image. Also, the Obsessive-Compulsive Inventory-Revised (OCI-R) and the Yale Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess symptom severity. The graph-theoretical structural analysis of dream reports showed that OCD patients have significantly smaller lexical diversity, lower speech connectedness and a higher recurrence of words in comparison with HC. The other five report types failed to show differences between the groups, adding to the notion that dream reports are especially informative of speech structure in different psychiatric states. Further investigation is necessary to completely assess the potential of this tool in OCD.

LSD and language: Decreased structural connectivity, increased semantic similarity, changed vocabulary in healthy individuals.

Language has been explored as a window into the mind. Psychedelics, known to affect perception and cognition, seem to change language, but a systematic, time-dependent exploration is lacking. Therefore, we aimed at mapping the psychedelic effects on language over the time course of the acute and sub-acute effects in an explorative manner. For this, 24 healthy volunteers (age [mean±SD, range]: 35±11, 25-61 years; 33% women) received 50 µg lysergic acid diethylamide (LSD) or inactive placebo in a randomized, double-blind, placebo-controlled, crossover study. We assessed different language productions (experience reporting, storytelling), components (structure, semantics, vocabulary) and time points (+0 h to +24 h). Language productions included 5-min experience reporting (+1.5 h, +6.5 h) and 1-min storytelling (+0 h, +2 h, +4 h, +6 h, +24 h). Language structure was assessed by computing speech topology (SpeechGraphs), semantics by semantic distances (FastText), vocabulary by word categories (LIWC). LSD, compared to placebo, changed language structure, including decreased verbosity, lexicon, global and local connectivity (+1.5 h to +4 h); decreased semantic distances between neighbouring words and overall words (+2 h to +24 h); and changed vocabulary related to grammar, persons, time, space and biological processes (+1.5 h to +24 h). In conclusion, low to moderate LSD doses changed language over diverse production types, components and time points. While simpler and disconnected structure and semantic similarity might reflect cognitive impairments, changed vocabulary might reflect subjective perceptions. Therefore, language under LSD might provide a window into the psychedelic mind and automated language quantifications should be better explored as valuable tools to yield more unconstrained insights into psychedelic perception and cognition.

LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model.

BACKGROUND: For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 µg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined. RESULTS: LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience. CONCLUSIONS: The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.

Imagetic and affective measures of memory reverberation diverge at sleep onset in association with theta rhythm.

The 'day residue' - the presence of waking memories into dreams - is a century-old concept that remains controversial in neuroscience. Even at the psychological level, it remains unclear how waking imagery cedes into dreams. Are visual and affective residues enhanced, modified, or erased at sleep onset? Are they linked, or dissociated? What are the neural correlates of these transformations? To address these questions we combined quantitative semantics, sleep EEG markers, visual stimulation, and multiple awakenings to investigate visual and affect residues in hypnagogic imagery at sleep onset. Healthy adults were repeatedly stimulated with an affective image, allowed to sleep and awoken seconds to minutes later, during waking (WK), N1 or N2 sleep stages. 'Image Residue' was objectively defined as the formal semantic similarity between oral reports describing the last image visualized before closing the eyes ('ground image'), and oral reports of subsequent visual imagery ('hypnagogic imagery). Similarly, 'Affect Residue' measured the proximity of affective valences between 'ground image' and 'hypnagogic imagery'. We then compared these grounded measures of two distinct aspects of the 'day residue', calculated within participants, to randomly generated values calculated across participants. The results show that Image Residue persisted throughout the transition to sleep, increasing during N1 in proportion to the time spent in this stage. In contrast, the Affect Residue was gradually neutralized as sleep progressed, decreasing in proportion to the time spent in N1 and reaching a minimum during N2. EEG power in the theta band (4.5-6.5 Hz) was inversely correlated with the Image Residue during N1. The results show that the visual and affective aspects of the 'day residue' in hypnagogic imagery diverge at sleep onset, possibly decoupling visual contents from strong negative emotions, in association with increased theta rhythm.

Microelectrode implants, inflammatory response and long-lasting effects on NADPH diaphorase neurons in the rat frontal cortex.

At present, one of the main therapeutic challenges comprises the development of technologies to improve the life quality of people suffering from different types of body paralysis, through the reestablishment of sensory and motor functions. In this regard, brain-machine interfaces (BMI) offer hope to effectively mitigate body paralysis through the control of paralyzed body parts by brain activity. Invasive BMI use chronic multielectrode implants to record neural activity directly from the brain tissue. While such invasive devices provide the highest amount of usable neural activity for BMI control, they also involve direct damage to the nervous tissue. In the cerebral cortex, high levels of the enzyme NADPH diaphorase (NADPH-d) characterize a particular class of interneurons that regulates neuronal excitability and blood supply. To gain insight into the biocompatibility of invasive BMI, we assessed the impact of chronic implanted tungsten multielectrode bundles on the distribution and morphology of NADPH-d-reactive neurons in the rat frontal cortex. NADPH-d neuronal labeling was correlated with glial response markers and with indices of healthy neuronal activity measured by electrophysiological recordings performed up to 3 months after multielectrode implantation. Chronic electrode arrays caused a small and quite localized structural disturbance on the implanted site, with neuronal loss and glial activation circumscribed to the site of implant. Electrodes remained viable during the entire period of implantation. Moreover, neither the distribution nor the morphology of NADPH-d neurons was altered. Overall, our findings provide additional evidence that tungsten multielectrodes can be employed as a viable element for long-lasting therapeutic BMI applications.

Nootropic effects of LSD: Behavioral, molecular and computational evidence.

The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we show that LSD treatment enhanced performance in a novel object recognition task in rats, and in a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. To gain insight into the relation of neural plasticity, aging and LSD-induced cognitive gains, we emulated the experiments in rats and humans with a neural network model of a cortico-hippocampal circuit. Using the baseline strength of plasticity as a proxy for age and assuming an increase in plasticity strength related to LSD dose, the simulations provided a good fit for the experimental data. Altogether, the results suggest that LSD has nootropic effects.

LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility.

Psychedelics acutely impair cognitive functions, but these impairments decline with growing experiences with psychedelics and microdoses may even exert opposing effects. Given the recent evidence that psychedelics induce neuroplasticity, this explorative study aimed at investigating the potential of psychedelics to sub-acutely change cognition. For this, we applied a randomized, double-blind, placebo-controlled, crossover study with 24 healthy volunteers receiving 50 µg lysergic acid diethylamide (LSD) or an inactive placebo. Sub-acute changes in cognition were measured 24 h after dosing, including memory (Rey-Osterrieth Complex Figure, ROCF; 2D Object-Location Memory Task, OLMT; Rey Auditory-Verbal Learning Test, RAVLT), verbal fluency (phonological; semantic; switch), design fluency (basic; filter; switch), cognitive flexibility (Wisconsin Card Sorting Test, WCST), sustained and switching attention (Trail Making Test, TMT), inhibitory control (Stroop Task) and perceptual reasoning (Block Design Test, BDT). The results show that when compared to placebo and corrected for Body Mass Index (BMI) and abstinence period from psychedelics, LSD sub-acutely improved visuospatial memory (ROCF immediate recall points and percentage, OLMT consolidation percentage) and phonological verbal fluency and impaired cognitive flexibility (WCST: fewer categories achieved; more perseveration, errors and conceptual level responses). In conclusion, the low dose of LSD moderately induced both "afterglow" and "hangover". The improvements in visuospatial memory and phonological fluency suggest that LSD-assisted therapy should be explored as a novel treatment perspective in conditions involving memory and language declines such as brain injury, stroke or dementia.

LSD and creativity: Increased novelty and symbolic thinking, decreased utility and convergent thinking.

BACKGROUND: Controversy surrounds psychedelics and their potential to boost creativity. To date, psychedelic studies lack a uniform conceptualization of creativity and methodologically rigorous designs. AIMS: This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 µg of LSD or inactive placebo. Near drug peak, a creativity task battery was applied, including pattern meaning task (PMT), alternate uses task (AUT), picture concept task (PCT), creative metaphors task (MET) and figural creativity task (FIG). Creativity was assessed by scoring creativity criteria (novelty, utility, surprise), calculating divergent thinking (fluency, originality, flexibility, elaboration) and convergent thinking, computing semantic distances (semantic spread, semantic steps) and searching for data-driven special features. RESULTS: LSD, compared to placebo, changed several creativity measurements pointing to three overall LSD-induced phenomena: (1) 'pattern break', reflected by increased novelty, surprise, originality and semantic distances; (2) decreased 'organization', reflected by decreased utility, convergent thinking and, marginally, elaboration; and (3) 'meaning', reflected by increased symbolic thinking and ambiguity in the data-driven results. CONCLUSION: LSD changed creativity across modalities and measurement approaches. Three phenomena of pattern break, disorganization and meaning seemed to fundamentally influence creative cognition and behaviour pointing to a shift of cognitive resources 'away from normal' and 'towards the new'. LSD-induced symbolic thinking might provide a tool to support treatment efficiency in psychedelic-assisted therapy.

Low-dose LSD and the stream of thought: Increased Discontinuity of Mind, Deep Thoughts and abstract flow.

RATIONALE: Stream of thought describes the nature of the mind when it is freely roaming, a mental state that is continuous and highly dynamic as in mind-wandering or free association. Classic serotonergic psychedelics are known to profoundly impact perception, cognition and language, yet their influence on the stream of thought remains largely unexplored. OBJECTIVE: To elucidate the effects of LSD on the stream of thought. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy participants received 50 µg lysergic acid diethylamide (LSD) or inactive placebo. Mind-wandering was measured by the Amsterdam Resting State Questionnaire (ARSQ), free association by the Forward Flow Task (FFT) for three seed word types (animals, objects, abstract words). ARSQ and FFT were assessed at +0 h, +2 h, +4 h, +6 h, +8 h and +24 h after drug administration, respectively. RESULTS: LSD, compared to placebo, induced different facets of mind-wandering we conceptualized as "chaos" (Discontinuity of Mind, decreased Sleepiness, Planning, Thoughts under Control, Thoughts about Work and Thoughts about Past), "meaning" (Deep Thoughts, Not Sharing Thoughts) and "sensation" (Thoughts about Odours, Thoughts about Sounds). LSD increased the FFT for abstract words reflecting an "abstract flow" under free association. Overall, chaos was strongest pronounced (+2 h to +6 h), followed by meaning (+2 h to +4 h), sensation (+2 h) and abstract flow (+4 h). CONCLUSIONS: LSD affects the stream of thought within several levels (active, passive), facets (chaos, meaning, sensation, abstractness) and time points (from +2 h to +6 h). Increased chaos, meaning and abstract flow at +4 h indicate the utility of a late therapeutic window in psycholytic therapy.

Nonsemantic word graphs of texts spanning ∼ 4500 years, including pre-literate Amerindian oral narratives.

Non-semantic word graphs obtained from oral reports are useful to describe cognitive decline in psychiatric conditions such as Schizophrenia, as well as education-related gains in discourse structure during typical development. Here we provide non-semantic word graph attributes of texts spanning approximately 4500 years of history, and pre-literate Amerindian oral narratives. The dataset assessed comprises 707 literary texts representative of 9 different Afro-Eurasian traditions (Syro-Mesopotamian, Egyptian, Hinduist, Persian, Judeo-Christian, Greek-Roman, Medieval, Modern and Contemporary), and Amerindian narratives (N = 39) obtained from a single ethnic group from South America (Kalapalo, N = 18), or from a mixed ethnic group from South, Central and North America (non-Kalapalo, N = 21). The present article provides detailed information about each text or narrative, including measurements of four graph attributes of interest: number of nodes (lexical diversity), repeated edges (short-range recurrence), largest strongly connected component (long-range recurrence), and average shortest path (graph length).

A protocol to examine the learning effects of 'multisystem mapping' training combined with post-training sleep consolidation in beginning readers.

We have recently used randomized controlled trials to examine the impact of a short neuroscience-informed causal intervention using a targeted training to inhibit a deeply rooted visual mechanism (mirror invariance) that hinders literacy acquisition, combined with post-training sleep (for learning consolidation). Using this training protocol, we have shown unprecedented improvements in visual perception of letters, writing, and a two-fold increase in reading fluency in first graders. Here, we describe this ecologically valid school-based intervention protocol to probe inhibition of mirror invariance for letters, including the detailed training instructions, post-training sleep consolidation, as well as practical tips and potential adaptations to different school sizes. For complete details on the use and execution of this protocol, please refer to Torres et al., (2021).

Hippocampus-retrosplenial cortex interaction is increased during phasic REM and contributes to memory consolidation.

Hippocampal (HPC) theta oscillation during post-training rapid eye movement (REM) sleep supports spatial learning. Theta also modulates neuronal and oscillatory activity in the retrosplenial cortex (RSC) during REM sleep. To investigate the relevance of theta-driven interaction between these two regions to memory consolidation, we computed the Granger causality within theta range on electrophysiological data recorded in freely behaving rats during REM sleep, both before and after contextual fear conditioning. We found a training-induced modulation of causality between HPC and RSC that was correlated with memory retrieval 24 h later. Retrieval was proportional to the change in the relative influence RSC exerted upon HPC theta oscillation. Importantly, causality peaked during theta acceleration, in synchrony with phasic REM sleep. Altogether, these results support a role for phasic REM sleep in hippocampo-cortical memory consolidation and suggest that causality modulation between RSC and HPC during REM sleep plays a functional role in that phenomenon.

Cyclic alternation of quiet and active sleep states in the octopus.

Previous observations suggest the existence of 'Active sleep' in cephalopods. To investigate in detail the behavioral structure of cephalopod sleep, we video-recorded four adult specimens of Octopus insularis and quantified their distinct states and transitions. Changes in skin color and texture and movements of eyes and mantle were assessed using automated image processing tools, and arousal threshold was measured using sensory stimulation. Two distinct states unresponsive to stimulation occurred in tandem. The first was a 'Quiet sleep' state with uniformly pale skin, closed pupils, and long episode durations (median 415.2 s). The second was an 'Active sleep' state with dynamic skin patterns of color and texture, rapid eye movements, and short episode durations (median 40.8 s). 'Active sleep' was periodic (60% of recurrences between 26 and 39 min) and occurred mostly after 'Quiet sleep' (82% of transitions). These results suggest that cephalopods have an ultradian sleep cycle analogous to that of amniotes.

Zebrafish automatic monitoring system for conditioning and behavioral analysis.

Studies using zebrafish (Danio rerio) in neuro-behavioural research are growing. Measuring fish behavior by computational methods is one of the most efficient ways to avoid human bias in experimental analyses, extending them to various approaches. Sometimes, thorough analyses are difficult to do, as fish can behave unpredictably during an experimental strategy. However, the analyses can be implemented in an automated way, using an online strategy and video processing for a complete assessment of the zebrafish behavior, based on the detection and tracking of fish during an activity. Here, a fully automatic conditioning and detailed analysis of zebrafish behavior is presented. Microcontrolled components were used to control the delivery of visual and sound stimuli, in addition to the concise amounts of food after conditioned stimuli for adult zebrafish groups in a conventional tank. The images were captured and processed for automatic detection of the fish, and the training of the fish was done in two evaluation strategies: simple and complex. In simple conditioning, the zebrafish showed significant responses from the second attempt, learning that the conditioned stimulus was a predictor of food presentation in a specific space of the tank, where the food was dumped. When the fish were subjected to two stimuli for decision-making in the food reward, the zebrafish obtained better responses to red light stimuli in relation to vibration. The behavior change was clear in stimulated fish in relation to the control group, thus, the distances traveled and the speed were greater, while the polarization was lower in stimulated fish. This automated system allows for the conditioning and assessment of zebrafish behavior online, with greater stability in experiments, and in the analysis of the behavior of individual fish or fish schools, including learning and memory studies.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

Objective: To conduct Brazil's first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. Clinical trial registration: RBR-6sq4c9

Zebrafish tracking using YOLOv2 and Kalman filter.

Fish show rapid movements in various behavioral activities or associated with the presence of food. However, in periods of rapid movement, the rate at which occlusion occurs among the fish is quite high, causing inconsistency in the detection and tracking of fish, hindering the fish's identity and behavioral trajectory over a long period of time. Although some algorithms have been proposed to solve these problems, most of their applications were made in groups of fish that swim in shallow water and calm behavior, with few sudden movements. To solve these problems, a convolutional network of object recognition, YOLOv2, was used to delimit the region of the fish heads to optimize individual fish detection. In the tracking phase, the Kalman filter was used to estimate the best state of the fish's head position in each frame and, subsequently, the trajectories of each fish were connected among the frames. The results of the algorithm show adequate performances in the trajectories of groups of zebrafish that exhibited rapid movements.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil.

OBJECTIVE: To conduct Brazil's first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. METHODS: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. RESULTS: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. CONCLUSIONS: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. CLINICAL TRIAL REGISTRATION: RBR-6sq4c9.