The revival of the psychedelic experience scale: Revealing its extended-mystical, visual, and distressing experiential spectrum with LSD and psilocybin studies.

BACKGROUND: Research with the Psychedelic Experience Questionnaire/Scale (PES) focuses on questions relating to mystical experience (Mystical Experience Questionnaire (MEQ)). The psychometric potential of the non-MEQ items of the PES remains largely unexplored. AIMS: We investigated whether the PES also yields subscales besides the MEQ30 subscales. METHODS: Data from 239 PES measurements (140 healthy participants) from six studies with moderate to high doses of lysergic acid diethylamide and/or psilocybin were included. New subscales (with items other than MEQ30) were created and validated as follows: (1) theoretical derivation of candidate items; (2) removal of items with rare experiences; (3) exploratory factor analysis; and (4) confirmatory factor analysis. Correlations of subscales within the PES and between the PES and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) were performed. In addition, a cluster analysis using all items (except rare experiences) was performed. RESULTS: The reliability of the four original factors of the MEQ30 was confirmed and four additional factors for the non-MEQ items were revealed: paradoxicality, connectedness, visual experience, and distressing experience. The first two additional factors were strongly correlated with the MEQ30 mystical subscale. Adding the new subscales to the MEQ30 subscales increased the explained variance with the 5D-ASC. The cluster analysis confirmed our main results and provided additional insights for future psychedelic psychometrics. CONCLUSION: The study yields a new validated 6-factor structure for extended mystical experience (MEQ40: MEQ30 + Paradoxicality + Connectedness) and covers psychedelic experience as a whole more comprehensively than has hitherto been possible within a single questionnaire (PES48). The entire PES (PES100) can also be used for further future psychedelic-psychometric research.

Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration.

BACKGROUND: While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. METHODS: We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions. RESULTS: Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity. CONCLUSIONS: The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.

Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants.

There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly positive, negative subjective effects, including anxiety, may occur. The induction of overall positive acute subjective effects is desired in psychedelic-assisted therapy because positive acute experiences are associated with greater therapeutic long-term benefits. 3,4-Methylenedioxymethamphetamine (MDMA) produces marked positive subjective effects and is used recreationally with LSD, known as "candyflipping." The present study investigated whether the co-administration of MDMA can be used to augment acute subjective effects of LSD. We used a double-blind, randomized, placebo-controlled, crossover design with 24 healthy subjects (12 women, 12 men) to compare the co-administration of MDMA (100 mg) and LSD (100 µg) with MDMA and LSD administration alone and placebo. Outcome measures included subjective, autonomic, and endocrine effects and pharmacokinetics. MDMA co-administration with LSD did not change the quality of acute subjective effects compared with LSD alone. However, acute subjective effects lasted longer after LSD + MDMA co-administration compared with LSD and MDMA alone, consistent with higher plasma concentrations of LSD (Cmax and area under the curve) and a longer plasma elimination half-life of LSD when MDMA was co-administered. The LSD + MDMA combination increased blood pressure, heart rate, and pupil size more than LSD alone. Both MDMA alone and the LSD + MDMA combination increased oxytocin levels more than LSD alone. Overall, the co-administration of MDMA (100 mg) did not improve acute effects or the safety profile of LSD (100 µg). The combined use of MDMA and LSD is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy. Trial registration: ClinicalTrials.gov identifier: NCT04516902.

Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants.

Mescaline, lysergic acid diethylamide (LSD), and psilocybin are classic serotonergic psychedelics. A valid, direct comparison of the effects of these substances is lacking. The main goal of the present study was to investigate potential pharmacological, physiological and phenomenological differences at psychoactive-equivalent doses of mescaline, LSD, and psilocybin. The present study used a randomized, double-blind, placebo-controlled, cross-over design to compare the acute subjective effects, autonomic effects, and pharmacokinetics of typically used, moderate to high doses of mescaline (300 and 500 mg), LSD (100 µg), and psilocybin (20 mg) in 32 healthy participants. A mescaline dose of 300 mg was used in the first 16 participants and 500 mg was used in the subsequent 16 participants. Acute subjective effects of 500 mg mescaline, LSD, and psilocybin were comparable across various psychometric scales. Autonomic effects of 500 mg mescaline, LSD, and psilocybin were moderate, with psilocybin causing a higher increase in diastolic blood pressure compared with LSD, and LSD showing a trend toward an increase in heart rate compared with psilocybin. The tolerability of mescaline, LSD, and psilocybin was comparable, with mescaline at both doses inducing slightly more subacute adverse effects (12-24 h) than LSD and psilocybin. Clear distinctions were seen in the duration of action between the three substances. Mescaline had the longest effect duration (mean: 11.1 h), followed by LSD (mean: 8.2 h), and psilocybin (mean: 4.9 h). Plasma elimination half-lives of mescaline and LSD were similar (approximately 3.5 h). The longer effect duration of mescaline compared with LSD was due to the longer time to reach maximal plasma concentrations and related peak effects. Mescaline and LSD, but not psilocybin, enhanced circulating oxytocin. None of the substances altered plasma brain-derived neurotrophic factor concentrations. In conclusion, the present study found no evidence of qualitative differences in altered states of consciousness that were induced by equally strong doses of mescaline, LSD, and psilocybin. The results indicate that any differences in the pharmacological profiles of mescaline, LSD, and psilocybin do not translate into relevant differences in the subjective experience. ClinicalTrials.gov identifier: NCT04227756.

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity.

Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 µg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.

Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants.

N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test different intravenous DMT administration regimens: placebo, low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus + low infusion (15 mg + 0.6 mg/min), and high bolus + high infusion (25 mg + 1 mg/min). Study sessions lasted for 5 h and were separated by at least 1 week. Participant's lifetime use of psychedelics was ≤20 times. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics of DMT, and plasma levels of brain-derived neurotropic factor (BDNF) and oxytocin. Low (15 mg) and high (25 mg) DMT bolus doses rapidly induced very intense psychedelic effects that peaked within 2 min. DMT infusions (0.6 or 1 mg/min) without a bolus induced slowly increasing and dose-dependent psychedelic effects that reached plateaus after 30 min. Both bolus doses produced more negative subjective effects and anxiety than infusions. After stopping the infusion, all drug effects rapidly decreased and completely subsided within 15 min, consistent with a short early plasma elimination half-life (t1/2α) of 5.0-5.8 min, followed by longer late elimination (t1/2ß = 14-16 min) after 15-20 min. Subjective effects of DMT were stable from 30 to 90 min, despite further increasing plasma concentrations, thus indicating acute tolerance to continuous DMT administration. Intravenous DMT, particularly when administered as an infusion, is a promising tool for the controlled induction of a psychedelic state that can be tailored to the specific needs of patients and therapeutic sessions.Trial registration: ClinicalTrials.gov identifier: NCT04353024.

Brazilian instrument for assessing of eating disorders in children and adolescents.

OBJECTIVE: This study aimed to develop the Brazilian instrument for assessing eating disorders in children and adolescents and test its psychometric quality using item response theory (IRT). DESIGN: Cross-sectional study. PARTICIPANTS: Participants aged between five and twelve years old of both sexes. MAIN MEASURES: IRT logistic model of two parameters was used to evaluate the item's severity and discrimination and test information curve of symptoms of eating disorders' latent trait symptoms. Content validity and reliability were also assessed. The IRT evaluation suggested that the instrument contained items that performed differently concerning severity, discrimination, and test information curve presented good accuracy. RESULTS: There was agreement on the clarity of language (83.3%) and theoretical relevance (91.7%), indicating good content validity. The value of the Cronbach's Alpha was 0.63 (95% confidence interval), and the result of the Spearman-Brown test was 0.65. CONCLUSION: These results indicate good performance of the screening tool in assessing the level of eating disorders in children and adolescents.

Prevalence of self-reported lifetime medical diagnosis of depression in Brazil: analysis of data from the 2019 Brazilian National Health Survey.

OBJECTIVES: To assess the prevalence of and factors associated with the lifetime medical diagnosis of depression in Brazil. DESIGN: Population-based, cross-sectional study. SETTING: Analysis of data from the 2019 Brazilian National Health Survey. PARTICIPANTS: 90 846 individuals aged ≥15 years were included. OUTCOME MEASURE: The self-reported medical diagnosis of depression at some point in one's life was the main outcome. Prevalence ratios (PRs) with 95% CIs were calculated by Poisson regression with robust variance. The independent variables included the geographical area of residence, sociodemographic characteristics, current smoking status, alcohol abuse, daily screen time, and the presence of physical disorders and mental health comorbidities. RESULTS: The self-reported lifetime prevalence of medical diagnosis of depression was 9.9% (95% CI 9.5% to 10.2%). The probability of having received a medical diagnosis of depression was higher among urban residents (PR 1.23; 95% CI 1.12 to 1.35); females (2.75; 2.52 to 2.99); those aged 20-29 years (1.17; 0.91 to 1.51), 30-39 years (1.73; 1.36 to 2.19), 40-49 years (2.30; 1.81 to 2.91), 50-59 years (2.32; 1.84 to 2.93) and 60-69 years (2.27; 1.78 to 2.90) compared with those under 20 years; white-skinned people (0.69 (0.61 to 0.78) for black-skinned people and 0.74 (0.69 to 0.80) for indigenous, yellow and brown-skinned people compared with white-skinned people); those with fewer years of education (1.33(1.12 to 1.58) among those with 9-11 years, 1.14 (0.96 to 1.34) among those with 1-8 years and 1.29 (1.11 to 1.50) among those with 0 years compared with those with ≥12 years of education); those who were separated/divorced (1.43; 1.29 to 1.59), widowed (1.06; 0.95 to 1.19) and single (1.01; 0.93 to 1.10) compared with married people; smokers (1.26; 1.14 to 1.38); heavy screen users (1.31; 1.16 to 1.48) compared with those whose usage was <6 hours/day; those with a medical diagnosis of a physical disorder (1.80; 1.67 to 1.97); and individuals with a medical diagnosis of a mental health comorbidity (5.05; 4.68 to 5.46). CONCLUSION: This nationwide population-based study of self-reported lifetime medical diagnosis of depression in Brazil showed that the prevalence was almost 10%. Considering the current Brazilian population, this prevalence corresponds to more than 2 million people who have been diagnosed with depression at some point in their lives.

Liquid chromatography-tandem mass spectrometry method for the bioanalysis of N,N-dimethyltryptamine (DMT) and its metabolites DMT-N-oxide and indole-3-acetic acid in human plasma.

The indole alkaloid N,N-dimethyltryptamine (DMT) induces psychedelic effects in humans. In addition to ceremonial and recreational use, DMT is subject to clinical investigations. Sensitive bioanalytical methods are required to assess the pharmacokinetics of DMT and its metabolites in human plasma. Here, a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of DMT and its major metabolites indole-3-acetic acid (IAA) and DMT-N-oxide (DMT-NO) was developed and validated. As IAA is an endogenous component of human plasma, 13C6-IAA was used to determine IAA concentrations. After simple protein precipitation with methanol, analytes were separated on a pentafluorophenyl column. A gradient consisting of 0.1% (v/v) formic acid in a methanol-water mixture was applied for analyte separation. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range of the assay was 0.25-250 ng/mL for DMT, 0.1-100 ng/mL for DMT-NO, and 25-25,000 ng/mL for 13C6-IAA. The intra- and inter-assay accuracy was 93-113% for all analytes at all quality control levels, with coefficient of variation ≤ 11%. All analytes were stable under storage conditions relevant for the analysis of large batches of study samples. The validated method was capable of assessing pharmacokinetic (PK) parameters of DMT and its metabolites in study participants intravenously perfused with 1 mg/min DMT for 90 min. Overall, the developed method is easy-to-use, has a short run time, and qualifies for PK and metabolism studies of DMT in clinical settings.

Development and validation of an LC-MS/MS method for the quantification of mescaline and major metabolites in human plasma.

Mescaline is a psychedelic phenethylamine found in different species of cacti. Currently, mescaline's acute subjective effects and pharmacokinetics are investigated in several modern clinical studies. Therefore, we developed a bioanalytical method for the rapid quantification of mescaline and its metabolites in human plasma. Mescaline and its metabolites 3,4,5-trimethoxyphenylacetic acid (TMPAA), N-acetyl mescaline (NAM), and 3,5-dimethoxy-4-hydroxyphenethylamine (4-desmethyl mescaline) were simultaneously analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Optimal chromatographic separation was achieved with an Acquity Premier HSS T3 C18 column. The analytes were detected in positive ionization mode using scheduled multiple reaction monitoring. A single step extraction method was implemented to enable fast and automatable plasma sample preparation. An intra-assay accuracy between 84.9% and 106% and a precision of ≤ 7.33% was observed in three validation runs. Plasma was extracted by simple protein precipitation, resulting in a complete recovery (≥ 98.3%) and minor matrix effects (≤ 7.58%). No interference with endogenous matrix components could be detected in human plasma samples (n = 7). Importantly, method sensitivity sufficed for assessing pharmacokinetic parameters of mescaline in clinical study samples with lower limits of quantification of 12.5, 12.5, and 1.25 ng/mL for mescaline, TMPAA, and NAM, respectively. Nonetheless, 4-desmethyl mescaline could not be selectively quantified in pharmacokinetic samples due to interference with another mescaline metabolite. Overall, we developed and validated a reliable and very easy-to-use method for forensic applications as well as investigating the clinical pharmacokinetics of mescaline.

Characterizing Thalamocortical (Dys)connectivity Following D-Amphetamine, LSD, and MDMA Administration.

BACKGROUND: Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging. Specifically, thalamic intrinsic functional connectivity is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal limbic cortices (hypoconnectivity). Psychedelics such as lysergic acid diethlyamide (LSD) elicit similar thalamocortical hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical hypoconnectivity with prefrontal limbic cortices, because current findings are equivocal. Thalamocortical hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic-induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics. METHODS: We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic intrinsic functional connectivity with 2 brain networks (auditory-sensorimotor and salience networks, corresponding to sensorimotor and prefrontal limbic cortices, respectively), using a double-blind, placebo-controlled, crossover design. RESULTS: All active substances elicited auditory-sensorimotor-thalamic hyperconnectivity compared with placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with the salience network, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns. CONCLUSIONS: Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects.

Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744.

Validation of the Family Health Behavior Scale for the Brazilian population

Abstract Objective: To validate the Family Health Behavior Scale (FHBS) for Brazilian families. Methods: The sample included 272 children aged 5 to 12 years old. Caregivers and their healthy answered the FHBS and questions about physical activity. In addition, anthropometric measurements of the children's weight and height were performed, as well as the bioimpedance exam. The scale was translated and the following validities were assessed: content (qualitative analysis and content validity index), construct (factor analysis) and concurrent validity (difference between domains and the total score with the categories of BMI, fat percentage and physical activity). Reliability (Cronbach's alpha, ceiling-floor effect, two-half test, intraclass correlation and Bland - Altman) was also assessed. Results: FHBS instrument performed well with regard to the psychometric properties in the Brazilian population. The content validity index was 0.987. Fit indices of the factor analysis were considered satisfactory, according to Bartlett's sphericity test (χ 2 = 1927, df = 351; p < 0.001) and the Kaiser-Meyer-Olkin index (KMO = 0.789). Concurrent validity, the differences between the mean of the domains and the total score between the categories of BMI (p = 0.011), percentage of fat (0.004) and physical activity (p < 0.001) were all significant. The reliability results were Cronbach's alpha internal consistency = 0.83, adequate ceiling-floor effect, 0.8105 (0.09 SD) two-half test, 0.626 intraclass correlation (95% CI: 0.406 to 0.777) and Bland - Altman -0.840 (-22.76 to 21.07). Conclusion: The FHBS adapted for the Brazilian population showed evidence of adequate psychometric performance.

Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants.

BACKGROUND: LSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is called hallucinogen-persisting perception disorder (HPPD). Data on both conditions is very limited. OBJECTIVE: This study aims to provide descriptive data on reoccurring drug-like experiences after the administration of LSD and psilocybin in controlled studies with healthy participants. METHODS AND MATERIALS: Data from 142 healthy subjects enrolled in six double-blinded, placebo-controlled, randomized cross-over studies were analyzed. In total, 60 subjects received LSD; 27 subjects received LSD, MDMA, and D-amphetamine; 31 subjects received LSD and psilocybin; and 25 subjects received psilocybin and escitalopram. At the end-of-study visit (mean 39.8 days after last study session, SD 37.2), subjects were asked for any reoccurring drug effects since the initial substance effects had worn off. Those reporting reoccurring perception changes more than 24 h after administration were contacted for follow-up (mean follow-up duration: 31.2 months, SD 28.6). RESULTS: Thirteen out of 142 subjects reported reoccurring drug-like experiences (LSD: seven, psilocybin: two, both: four). The reported phenomena were predominantly mild and perceived as neutral to pleasant. Flashbacks were mostly of visual nature, lasted for seconds to minutes, and occurred within a week after the last drug administration. Two subjects reported distressing experiences that subsided spontaneously. One subject reported brief and pleasant visual perception changes which reoccurred for 7 months. None of the subjects reported impairment in their daily lives. None of the cases met DSM-V criteria for HPPD. CONCLUSION: Reoccurring drug-like experiences after the administration of LSD and psilocybin are a common phenomenon occurring in up to 9.2% of healthy subjects (7.8% for LSD, 8.3% for psilocybin and 14.3% if both substances are administered). Additionally, our work suggests that flashback phenomena are not a clinically relevant problem in controlled studies with healthy participants.

Validation of the Family Health Behavior Scale for the Brazilian population.

OBJECTIVE: To validate the Family Health Behavior Scale (FHBS) for Brazilian families. METHODS: The sample included 272 children aged 5 to 12 years old. Caregivers and their healthy answered the FHBS and questions about physical activity. In addition, anthropometric measurements of the children's weight and height were performed, as well as the bioimpedance exam. The scale was translated and the following validities were assessed: content (qualitative analysis and content validity index), construct (factor analysis) and concurrent validity (difference between domains and the total score with the categories of BMI, fat percentage and physical activity). Reliability (Cronbach's alpha, ceiling-floor effect, two-half test, intraclass correlation and Bland - Altman) was also assessed. RESULTS: FHBS instrument performed well with regard to the psychometric properties in the Brazilian population. The content validity index was 0.987. Fit indices of the factor analysis were considered satisfactory, according to Bartlett's sphericity test (χ 2 = 1927, df = 351; p < 0.001) and the Kaiser-Meyer-Olkin index (KMO = 0.789). Concurrent validity, the differences between the mean of the domains and the total score between the categories of BMI (p = 0.011), percentage of fat (0.004) and physical activity (p < 0.001) were all significant. The reliability results were Cronbach's alpha internal consistency = 0.83, adequate ceiling-floor effect, 0.8105 (0.09 SD) two-half test, 0.626 intraclass correlation (95% CI: 0.406 to 0.777) and Bland - Altman -0.840 (-22.76 to 21.07). CONCLUSION: The FHBS adapted for the Brazilian population showed evidence of adequate psychometric performance.

Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is used both recreationally and therapeutically. Little is known about the factors influencing inter- and intra-individual differences in the acute response to MDMA. Effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood state before intake. METHODS: We pooled data from 10 randomized, double-blind, placebo-controlled, cross-over studies performed in the same laboratory in 194 healthy subjects receiving doses of 75 or 125mg of MDMA. We investigated the influence of drug dose, body weight, sex, age, drug pre-experience, genetics, personality and mental state before drug intake on the acute physiological and psychological response to MDMA. RESULTS: In univariable analyses, the MDMA plasma concentration was the strongest predictor for most outcome variables. When adjusting for dose per body weight, we found that (a) a higher activity of the enzyme CYP2D6 predicted lower MDMA plasma concentration, (b) a higher score in the personality trait "openness to experience" predicted more perceived "closeness", a stronger decrease in "general inactivation", and higher scores in the 5D-ASC (5 Dimensions of Altered States of Consciousness Questionnaire) scales "oceanic boundlessness" and "visionary restructuralization", and (c) subjects with high "neuroticism" or trait anxiety were more likely to have unpleasant and/or anxious reactions. CONCLUSIONS: Although MDMA plasma concentration was the strongest predictor, several personality traits and mood state variables additionally explained variance in the response to MDMA. The results confirm that both pharmacological and non-pharmacological variables influence the response to MDMA. These findings may be relevant for the therapeutic use of MDMA.

Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects.

Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25-200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose-response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.

MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens.

It has been reported that serotonergic hallucinogens like lysergic acid diethylamide (LSD) induce decreases in functional connectivity within various resting-state networks. These alterations were seen as reflecting specific neuronal effects of hallucinogens and it was speculated that these shifts in connectivity underlie the characteristic subjective drug effects. In this study, we test the hypothesis that these alterations are not specific for hallucinogens but that they can be induced by monoaminergic stimulation using the non-hallucinogenic serotonin-norepinephrine-dopamine releasing agent 3,4-methylenedioxymethamphetamine (MDMA). In a randomized, placebo-controlled, double-blind, crossover design, 45 healthy participants underwent functional magnetic resonance imaging (fMRI) following oral administration of 125 mg MDMA. The networks under question were identified using independent component analysis (ICA) and were tested with regard to within-network connectivity. Results revealed decreased connectivity within two visual networks, the default mode network (DMN), and the sensorimotor network. These findings were almost identical to the results previously reported for hallucinogenic drugs. Therefore, our results suggest that monoaminergic substances can induce widespread changes in within-network connectivity in the absence of marked subjective drug effects. This contradicts the notion that these alterations can be regarded as specific for serotonergic hallucinogens. However, changes within the DMN might explain antidepressants effects of some of these substances.

Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

Unscheduled Emergency Visits after Cardiac Devices Implantation: Comparison between Cardioverter Defibrillators and Cardiac Resynchronization Therapy Devices in less than one year of Follow Up / Consultas Não Programadas em Emergência após Implante de Dispositivos Cardíacos: Comparativo entre Cardiodesfibriladores e Ressincronizadores em Seguimento Inferior a 1 Ano

Abstract Background: The use of Cardiovascular Implantable Electronic Devices (CIED), such as the Implantable Cardioverter Defibrillator (ICD) and Cardiac Resynchronization Therapy (CRT), is increasing. The number of leads may vary according to the device. Lead placement in the left ventricle increases surgical time and may be associated with greater morbidity after hospital discharge, an event that is often confused with the underlying disease severity. Objective: To evaluate the rate of unscheduled emergency hospitalizations and death after implantable device surgery stratified by the type of device. Methods: Prospective cohort study of 199 patients submitted to cardiac device implantation. The groups were stratified according to the type of device: ICD group (n = 124) and CRT group (n = 75). Probability estimates were analyzed by the Kaplan-Meier method according to the outcome. A value of p < 0.05 was considered significant in the statistical analyses. Results: Most of the sample comprised male patients (71.9%), with a mean age of 61.1 ± 14.2. Left ventricular ejection fraction was similar between the groups (CRT 37.4 ± 18.1 vs. ICD 39.1 ± 17.0, p = 0.532). The rate of unscheduled visits to the emergency unit related to the device was 4.8% in the ICD group and 10.6% in the CRT group (p = 0.20). The probability of device-related survival of the variable "death" was different between the groups (p = 0.008). Conclusions: Patients after CRT implantation show a higher probability of mortality after surgery at a follow-up of less than 1 year. The rate of unscheduled hospital visits, related or not to the implant, does not differ between the groups.

Resumo Fundamento: O uso de dispositivos cardíacos eletrônicos implantáveis (DCEI) como o cardiodesfibrilador (CDI) e terapia de ressincronização cardíaca (TRC) - é cada vez maior. O número de eletrodos de estimulação e desfibrilação varia de acordo com o dispositivo. A colocação do eletrodo no ventrículo esquerdo aumenta o tempo cirúrgico podendo associar-se a maior morbidade no acompanhamento após alta hospitalar, evento muitas vezes confundível com a gravidade da patologia base. Objetivo: Avaliar a taxa de internação não programada na emergência e óbito após cirurgia de dispositivos implantáveis estratificados pelo tipo de aparelho. Métodos: Estudo de coorte prospectivo analisando 199 pacientes submetidos à implante de dispositivos cardíacos. Os grupos foram divididos de acordo com o tipo de dispositivo: CDI (n = 124) e TRC (n = 75). Estimativas de probabilidades foram analisadas pelo método de Kaplan-Meier de acordo com o desfecho. Valor de p < 0,05 foi considerado significativo nas análises estatísticas. Resultados: A maioria da amostra era do sexo masculino (71,9%) - idade média de 61,1 ± 14,2. A fração de ejeção do ventrículo esquerdo foi similar entre os grupos (TRC 37,4 ± 18,1 vs. CDI 39,1 ± 17,0; p = 0,532). A taxa de visita não programada na emergência relacionada ao dispositivo foi de 4,8% no grupo CDI e de 10,6% no grupo TRC (p = 0,20). A probabilidade de sobrevida relacionada ao dispositivo da variável "óbito" mostrou-se diferente entre os grupos (p = 0,008). Conclusões: Paciente após o implante de TRC apresenta maior probabilidade de mortalidade após o procedimento cirúrgico no seguimento menor que 1 ano. A taxa de visita hospitalar não programada, relacionadas ou não ao implante, não difere entre os grupos.