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.

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). CONCLUSIONS: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

[Healthcare difficulties among people who have a drug use problem: an integrative review]. / Dificuldades no cuidado em saúde para as pessoas que fazem uso problemático de drogas: uma revisão integrativa.

The scope of this study was to understand the difficulties involving healthcare for people with a drug use problem within the context of specialized mental health services, both nationally and internationally. It involves an integrative review conducted in the PubMed, LILACS, Web of Science, SCOPUS, and EMBASE databases, with the following key words: Drug Users; Mental Health Services; Health Care. Eighteen studies were selected, the inclusion criteria being primary studies, available in full, published in English, Spanish and Portuguese, between January 2016 and January 2021. The inclusion criteria were primary studies, available in full, published in English, Spanish and Portuguese, during the period from January 2016 through January 2021. The analysis identified that the difficulties in healthcare for people with a drug use problem are linked to the dimensions of public health policies, models of care adopted, and the stakeholders involved, and that these aspects are interrelated. It also emphasizes the need for specialized training, as well as further in-depth research that addresses the therapeutics of the drug use problem, and the development of new healthcare technologies for this population group.

O estudo teve como objetivo conhecer as dificuldades para o cuidado em saúde de pessoas que fazem uso problemático de drogas, dentro do contexto dos serviços especializados em saúde mental nacionais e internacionais. Trata-se de uma revisão integrativa realizada nas bases de dados PubMed, LILACS, Web of Science, Scopus e Embase, com os descritores: usuários de drogas; serviços de saúde mental; cuidado em saúde. Foram selecionados 18 estudos, sendo os critérios de inclusão: estudos primários, disponíveis na íntegra, publicados nos idiomas inglês, espanhol e português, no período de janeiro de 2016 a janeiro de 2021. A partir da análise, identificou-se que as dificuldades para o cuidado de saúde de pessoas que fazem uso problemático de drogas estão ligadas às dimensões das políticas públicas em saúde, aos modelos de cuidados adotados e aos atores envolvidos, e que tais pontos se relacionam. Ressalta-se, ainda, a necessidade de formação específica, bem como a condução de novas pesquisas que abordem, com profundidade, a terapêutica do uso problemático de drogas e a produção de novas tecnologias de cuidado em saúde para essa população.

Ayahuasca's therapeutic potential: What we know - and what not.

The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in diverse clinical conditions in human (clinical, cross-sectional, observational, and qualitative) and preclinical (animal and in vitro) studies. In addition to summarizing and discussing the most commonly studied conditions, such as depression, anxiety, and substance use disorders (SUD), we also examine less frequently studied psychiatric, neurological, and physical conditions. Moreover, we discuss evidence from epidemiological studies on the impact of regular, long-term ayahuasca use on health and psychosocial outcomes. Overall, evidence for depression and SUD is more consistent, with numerous and diverse studies. However, a growing body of evidence suggests that other conditions equally relevant to public health might be promising targets for ayahuasca's therapeutic effects. This includes preliminary studies indicating potential for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses (e.g., cancer, chronic conditions). Moreover, preliminary evidence in long-term ayahuasca users does not suggest detrimental effects but possible benefits for individual and collective health. In light of the emerging evidence of psychedelic drugs as therapeutic agents, it is essential to further investigate in rigorous designs the therapeutic potential of ayahuasca in conditions other than depression.

Spiritual Well-Being Among Users and Non-Users of Psychedelics: A Cross-Sectional Study.

This study evaluated the psychometric properties of the Spiritual Well-Being Scale (SWBS) in a Brazilian sample. We analyzed spiritual well-being, defined as existential well-being (EWB) and religious well-being (RWB), among individuals with varying religious and spiritual experiences, both users and non-users of psychedelics. The online cross-sectional survey was conducted in Brazil, from April to June 2022. The psychometric analyses demonstrated reliability and validity based on the internal structure and the relationship with satisfactory external variables concerning the RWB and EWB factors of the SWBS. Validity evidence was shown for both factors (RWB, EWB) with adequate reliability ratings. However, the RWB factor, which was entirely replicated, demonstrated the best group differentiation and internal consistency. Although both factors showed validity, the RWB factor exhibited superior psychometric indices for validity, group discrimination, and reliability. Regarding psychedelics, the association with RWB and EWB demonstrates a U-shaped pattern, as participants who never use these substances typically exhibit higher RWB and EWB indices, succeeded by frequent users. This finding underscores the need for additional studies to further explore the intricate interplay between psychedelics and spiritual well-being.

A quantitative textual analysis of the subjective effects of ayahuasca in naïve users with and without depression.

Ayahuasca is a brew with psychoactive properties that has been used as an entheogen for centuries, with more recent studies suggesting it is a promising treatment for some clinical disorders. Although there is an emerging scientific literature on its effects, to the best of our knowledge no study has explored the self-reported experiences of first-time ayahuasca users with quantitative textual analysis tools. Accordingly, the current study aimed to analyze the subjective experience of naive individuals with depression and healthy controls after consuming ayahuasca. For this purpose, responses from a subsample of participants from a previous clinical trial to open-ended questions regarding their experience with ayahuasca underwent textual analysis. Data from nine patients with treatment-resistant depression and 20 healthy individuals were included, and quantitative textual analysis was performed using IRaMuTeQ 0.7 alpha 2 and R 3.1.2. The analysis identified five clusters: alterations in the state of consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Additionally, findings suggest specific features of the experience of people with depression with ayahuasca, such as increased aversive bodily reactions. The results are consistent with previous findings indicating central axes of the psychedelic experience, and may inform therapeutic approaches using ayahuasca.

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.

Corrigendum: Ceremonial ayahuasca in amazonian retreats-mental health and epigenetic outcomes from a six-month naturalistic study.

[This corrects the article DOI: 10.3389/fpsyt.2021.687615.].

Ayahuasca and tobacco smoking cessation: results from an online survey in Brazil.

RATIONALE: Smoking-related disease is a major problem globally. Effective smoking cessation treatments are however limited. Increasing evidence suggests that psychedelics have potential as treatments for substance use disorders and may therefore prove an option in aiding smoking cessation. OBJECTIVES: To establish which factors predict smoking cessation in people who reported quitting or reducing smoking following ayahuasca consumption. METHODS: A retrospective cross-sectional mixed-method study (quantitative and qualitative design) was undertaken using data from an online survey evaluating peoples' experiences before and after drinking ayahuasca. Multivariate logistic regression was performed with smoking condition (cessation or reduction/relapse) as a dependent variable and demographics, smoking, ayahuasca-related variables and the mystical experience (MEQ30) as predicting factors. RESULTS: A total of 441 responses were grouped according to self-reported smoking status: cessation (n = 305) or reduction/relapse (n = 136) smoking. Logistic regression showed that mystical experience (OR: 1.03; 95% CI [1.00-1.05]) and frequency of ayahuasca intake (OR: 2.16[1.00-4.70]) were protective factors, while positive mood (measured by the MEQ30) during the ayahuasca experience was a risk factor (OR: 0.91[0.85-0.97]). Qualitative thematic analysis identified eight themes (e.g. acquired awareness, spiritual experience, increased motivation) related to the ayahuasca experience and the process of smoking cessation/reduction. CONCLUSIONS: Our results suggest that ayahuasca could be used as a potential tool for smoking cessation, and that effects may be mediated by mystical experience. Given the current burden of smoking-related disease and the limited treatment options, studies are needed to investigate the efficacy of psychedelics in smoking cessation.

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.

Adaptation and latent structure of the Brazilian version of the Ego Dissolution Inventory (EDI-BR): An exploratory study.

INTRODUCTION: Existing scales that seek to measure alterations in self-experience were based on studies conducted in developed countries. Therefore, the aim of this study was to evaluate the psychometric properties of the Ego-Dissolution Inventory (EDI), translate and adapt it to the Brazilian context. METHODS: Translation of the measure was made by two translators fluent in both English and Portuguese, with back-translation into English to ensure there was no loss of meaning. The scale was included in an online survey exploring substance use. A total of 528 participants answered the full scale. We calculated the Kaiser-Meyer-Olkin (KMO) measure to evaluate sampling adequacy, then ran Exploratory Analysis Factor (EFAs) to investigate the factor structure of the EDI. RESULTS: The scale showed acceptable psychometric properties, with excellent internal consistency and sampling adequacy for a factor analysis. Kaiser-Gutman's criteria and Hull's method pointed to a three-factor solution, while Parallel Analysis suggested a two-factor solution. All items showed salient loadings, with two items exhibiting cross-loading. Positive but weak correlations were found between EDI factors 1 and 2 and nature-relatedness. CONCLUSIONS: The validated scale showed solid psychometric properties, with potential differences in factor structure in relation to the English version. Considering validation as ongoing process, it is recommended to conduct studies comparing the scores of ego dissolution across distinct substances and different regions of the country.

Adverse effects of ayahuasca: Results from the Global Ayahuasca Survey.

INTRODUCTION: Ayahuasca is a plant-based decoction native to Amazonia, where it has a long history of use in traditional medicine. Contemporary ritual use of ayahuasca has been expanding throughout the world for mental health purposes, and for spiritual and personal growth. Although researchers have been conducting clinical trials and observational studies reporting medical and psychological benefits, most of these do not report ayahuasca's immediate or medium-term adverse effects, so these are underrepresented in the literature. With the expansion of ayahuasca ceremonies from their traditional contexts to countries around the world, there is an important public health question regarding the risk/benefit balance of its use. METHODS: We used data from an online Global Ayahuasca Survey (n = 10,836) collected between 2017 and 2019 involving participants from more than 50 countries. Principal component analysis was performed to assess group effects. Logistic regression analysis was performed to test for adverse effects associated with history of ayahuasca use, clinical, context of use and spiritual effect variables. RESULTS: Acute physical health adverse effects (primarily vomiting) were reported by 69.9% of the sample, with 2.3% reporting the need for subsequent medical attention. Adverse mental health effects in the weeks or months following consumption were reported by 55.9% of the sample, however, around 88% considered such mental health effects as part of a positive process of growth or integration. Around 12% sought professional support for these effects. Physical adverse effects were related to older age at initial use of ayahuasca, having a physical health condition, higher lifetime and last year ayahuasca use, having a previous substance use disorder diagnosis, and taking ayahuasca in a non-supervised context. Mental health adverse effects were positively associated with anxiety disorders; physical health conditions; and the strength of the acute spiritual experience; and negatively associated with consumption in religious settings. CONCLUSIONS: While there is a high rate of adverse physical effects and challenging psychological effects from using ayahuasca, they are not generally severe, and most ayahuasca ceremony attendees continue to attend ceremonies, suggesting they perceive the benefits as outweighing any adverse effects. Knowing what variables might predict eventual adverse effects may serve in screening of, or providing additional support for, vulnerable subjects. Improved understanding of the ayahuasca risk/benefit balance can also assist policy makers in decisions regarding potential regulation and public health responses.

Ayahuasca Lyophilization (Freeze-drying) Protocol with Pre- and Post-procedure Alkaloids Quantification.

Ayahuasca is a psychoactive brew from the decoction of different Amazonian plants, traditionally used in several cultures, religions, and rituals. Scientific studies with ayahuasca are rapidly increasing due to its subjective effects and therapeutic potential. Although ayahuasca is traditionally used in its liquid presentation, lyophilized (freeze-dried) ayahuasca is often used in scientific experimentation settings. However, there is no standard process or guideline to freeze-dry ayahuasca nor comparison of the chemical profile between the liquid and freeze-dried presentations. Therefore, we describe a reproducible five-day protocol for ayahuasca lyophilization with alkaloids quantification by liquid chromatography coupled to tandem mass spectrometry of both the liquid and the final freeze-dried ayahuasca. By the end of the protocol, approximately 295 g of freeze-dried extract with similar alkaloids concentration were obtained from two liters of ayahuasca (dry matter: 14.75 %). The final extract was stored for three years inside a vacuum desiccator (approximately 6°C) with its texture quality preserved. Further studies should address the impact of different storage conditions and the lyophilization on the alkaloids' quantity of the freeze-dried ayahuasca, especially the use of heat in regards to the ß-carbolines.

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.

The influence of ceremonial settings on mystical and challenging experiences occasioned by ayahuasca: A survey among ritualistic and religious ayahuasca users.

Recent studies have recognized the importance of non-pharmacological factors such as setting to induce or promote mystical experiences or challenging experiences among ayahuasca users. This study aimed to evaluate the association between the setting in which ayahuasca is consumed and the intensity of mystical and challenging experiences considering three ayahuasca using traditions (União do Vegetal, Santo Daime and neo-shamanic groups). A cross-sectional analysis was performed on survey data collected online from 2,751 participants. The Setting Questionnaire for the Ayahuasca Experience (SQAE) was used to evaluate six dimensions of the setting characteristics. The Mystical Experience Questionnaire (MEQ) and the Challenging Experience Questionnaire (CEQ) were used to quantify the psychedelic experience. Ratings on every SQAE setting dimension were negatively correlated with ratings of the CEQ (r values between 0.21 and 0.36) for all ayahuasca using traditions. Regression analysis revealed that ratings on four SQAE dimensions (Social, Comfort, Infrastructure and Decoration) explained 41% of the variance in CEQ ratings. Associations between SQAE and MEQ ratings were relatively weak and confined to the dimensions Leadership and Comfort, explaining 14% of the variance in MEQ ratings. Ratings of Social context were higher among members of União do Vegetal compared to Santo Daime and neo-shamanic members. Ratings of Infrastructure, Comfort and Decoration were more consistently correlated with MEQ in the neoshamanic tradition compared to the other traditions. This study shows that the setting is an important moderator of a challenging experience under ayahuasca. Maximizing the quality of the setting in which ayahuasca is taken will reduce the chance of a challenging experience while contributing positively to a mystical experience. The present findings can be considered when designing rituals and the (social) environment of ayahuasca ceremonies, and indicate that the SQAE questionnaire can be employed to monitor the influence of ceremonial settings on the ayahuasca experience.

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.

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.

The psychosis continuum in the general population: findings from the São Paulo Epidemiologic Catchment Area Study.

The aim of the study was to examine the psychosis continuum in a Latin-American community setting. Data were from the Brazilian São Paulo Epidemiologic Catchment Area Study, a cross-sectional survey conducted in two boroughs of the city of São Paulo. The Composite International Diagnosis Interview (version 1.1) was applied to a probabilistic sample of 1,464 adults, who were interviewed in their household, in order to identify the presence of psychotic symptoms. A subsample was assessed with Schedules for Clinical Assessment in Neuropsychiatry interview. We described the occurrence of psychotic symptoms, categorized into subgroups according to their clinical impact, disability, and help-seeking behavior. The correlation of socio-demographic variables, depressive symptoms, and alcohol and substance use disorders with those psychotic subgroups was analyzed. Polychotomic logistic regression tested the associations between subgroups of psychosis (clinical and subclinical) and the correlates. Of the total sample, 38.0% presented at least one lifetime psychotic symptom, 1.9% met the criteria for an ICD-10 diagnosis of non-affective psychosis, 5.4% presented clinically relevant psychotic symptoms, and 30.7% endorsed clinically non-relevant symptoms. The most common psychotic symptom was delusion with a plausible explanation (in 18.6%). The presence of any psychiatric diagnosis was associated with the presence of psychotic symptoms (OR range, 1.9-8.9). Subclinical psychosis subgroups were found to be associated with the 18-24 year age bracket, chronic depressive mood, and alcohol use disorder. Our results support the concept of a psychosis continuum in Latin-American populations, suggesting that different risk factors influence their manifestation across the continuum.

Determination of the Elemental Composition of Ayahuasca and Assessments Concerning Consumer Safety.

The consumption of ayahuasca, a brew prepared from the decoction of two Amazon plants, has increased worldwide in the last decades. This fact raised questions about the safety in its oral administration. In this sense, information concerning the chemical composition of ayahuasca is essential to find a comprehensive reply. Therefore, the aim of this study consisted of determining the elemental composition of ready-to-consume ayahuasca samples produced in Brazil, in order to evaluate the safety in the oral administration of this beverage, considering recommended macroelement and microelement daily intake values and the permitted limits of potentially toxic heavy metals. Real ayahuasca samples, obtained from Brazilian religious groups, underwent microwave radiation-assisted acid decomposition, and Li, Al, Mn, Fe, Co, Cu, Zn, As, Cd, Hg, and Pb concentrations were determined by ICP-MS, while Ca, Mg, K, and P concentrations were determined by ICP OES. Method accuracy was assessed by analyte addition and recovery assays. Recoveries ranged from 80 and 118%, indicating satisfactory accuracy. Limit of detection (LOD) and limit of quantification (LOQ) values were lower than 1 mg L-1 for the macroelements determined by ICP OES and lower than 3.5 µg L-1 for the microelements determined by ICP-MS. The concentrations of the elements determined in the samples were lower than the recommended or tolerable limits; hence, it is possible to affirm that ayahuasca presents safe administration levels regarding total elemental content.

The ritual use of ayahuasca during treatment of severe physical illnesses: a qualitative study.

Diseases that threaten life raise existential questions that can be a source of psychological distress. Studies with psychedelics demonstrate therapeutic effects for anxiety and depression associated with life-threatening illnesses. Ayahuasca has been proposed as a possible therapeutic agent in the treatment of psychiatric disorders. Preliminary studies suggest that ayahuasca could promote therapeutic effects for people with physical illnesses. The aim of this study was to explore how the ritual use of ayahuasca during the treatment of severe physical illnesses (SPI) may influence the way people understand and relate to their illness, using qualitative methods to assess the participants' perspectives. Participants who consumed ayahuasca ritualistically during the period of treatment for SPI were purposely chosen. Data were obtained through semi-structured interviews. A thematic analysis was performed with 14 individuals. The ritual experience with ayahuasca acted on the participants' illness understanding through multiple psychological mechanisms, including introspection, self-analysis, emotional processing and catharsis, recall of autobiographical memories subjectively related to illness origin, illness resignification, and perspective changes. This study suggests that the experience with ayahuasca may facilitate illness acceptance through an influence on the meanings of the illness, life, and death. These changes may favor a more balanced relationship with illness and treatment.