Shared functional connectome fingerprints following ritualistic ayahuasca intake.

The knowledge that brain functional connectomes are unique and reliable has enabled behaviourally relevant inferences at a subject level. However, whether such "fingerprints" persist under altered states of consciousness is unknown. Ayahuasca is a potent serotonergic psychedelic which produces a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its shared use may highlight relevant novel interactions between mental state and functional connectome (FC) idiosyncrasy. Using 7T fMRI, we assessed resting-state static and dynamic FCs for 21 Santo Daime members after collective ayahuasca intake in an acute, within-subject study. Here, connectome fingerprinting revealed FCs showed reduced idiosyncrasy, accompanied by a spatiotemporal reallocation of keypoint edges. Importantly, we show that interindividual differences in higher-order FC motifs are relevant to experiential phenotypes, given that they can predict perceptual drug effects. Collectively, our findings offer an example of how individualised connectivity markers can be used to trace a subject's FC across altered states of consciousness.

Cortical structural differences following repeated ayahuasca use hold molecular signatures.

Introduction: Serotonergic psychedelics such as ayahuasca are reported to promote both structural and functional neural plasticity via partial 5-HT2A agonism. However, little is known about how these molecular mechanisms may extend to repeated psychedelic administration in humans, let alone neuroanatomy. While early evidence suggests localised changes to cortical thickness in long-term ayahuasca users, it is unknown how such findings may be reflected by large-scale anatomical brain networks comprising cytoarchitecturally complex regions. Methods: Here, we examined the relationship between cortical gene expression markers of psychedelic action and brain morphometric change following repeated ayahuasca usage, using high-field 7 Tesla neuroimaging data derived from 24 members of an ayahuasca-using church (Santo Daime) and case-matched controls. Results: Using a morphometric similarity network (MSN) analysis, repeated ayahuasca use was associated with a spatially distributed cortical patterning of both structural differentiation in sensorimotor areas and de-differentiation in transmodal areas. Cortical MSN remodelling was found to be spatially correlated with dysregulation of 5-HT2A gene expression as well as a broader set of genes encoding target receptors pertinent to ayahuasca's effects. Furthermore, these associations were similarly interrelated with altered gene expression of specific transcriptional factors and immediate early genes previously identified in preclinical assays as relevant to psychedelic-induced neuroplasticity. Conclusion: Taken together, these findings provide preliminary evidence that the molecular mechanisms of psychedelic action may scale up to a macroscale level of brain organisation in vivo. Closer attention to the role of cortical transcriptomics in structural-functional coupling may help account for the behavioural differences observed in experienced psychedelic users.

Altered State of Consciousness and Mental Imagery as a Function of N, N-dimethyltryptamine Concentration in Ritualistic Ayahuasca Users.

Consumption of the psychedelic brew ayahuasca is a central ritualistic aspect of the Santo Daime religion. The current observational, baseline controlled study was designed to assess whether members (n = 24) of the Santo Daime church would show enhanced capacity for mental imagery during an ayahuasca experience. In addition, this study assessed whether the effects of ayahuasca on consciousness and mental imagery were related to peak serum concentration of N, N-dimethyltryptamine (DMT), the main psychoactive component. Measures of altered states of consciousness (5-Dimensional Altered States of Consciousness Questionnaire) and ego dissolution (Ego Dissolution Inventory [EDI]) as well as measures of mental imagery (visual perspective shifting, vividness of visual imagery, cognitive flexibility, associative thinking) were taken on two subsequent days on which members of Santo Daime were sober or drank a self-selected volume of ayahuasca. Measures of altered states of consciousness revealed that feelings of oceanic boundlessness, visual restructuralization, and EDI increased most prominently after drinking and shared a positive correlation with peak DMT concentration. Measures of mental imagery did not noticeably differ between the baseline and ayahuasca condition, although subjective ratings of cognitive flexibility were lower under ayahuasca. Two measures related to mental imagery, that is, perspective shifts and cognitive flexibility, were significantly correlated to peak DMT concentrations. Peak concentrations of DMT and other alkaloids did not correlate with ayahuasca dose. These findings confirm previous notions that the primary phenomenological characteristics of ayahuasca are driven by DMT. Compensatory or neuroadaptive effects associated with long-term ayahuasca intake may have mitigated the acute impact of ayahuasca in Santo Daime members on mental imagery.

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.

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience.

There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids. Plasma samples of 23 individuals were collected both before and after ayahuasca consumption. Samples were analysed through targeted metabolomics and further integrated with subjective ratings of the ayahuasca experience (i.e., using the 5-Dimension Altered States of Consciousness Rating Scale [ASC]), and plasma ayahuasca-alkaloids using integrated network analysis. Metabolic pathways enrichment analysis using diffusion algorithms for specific KEGG modules was performed on the metabolic output. Compared to baseline, the consumption of ayahuasca increased N-acyl-ethanolamine endocannabinoids, decreased 2-acyl-glycerol endocannabinoids, and altered several large-neutral amino acids (LNAAs). Integrated network results indicated that most of the LNAAs were inversely associated with 9 out of the 11 subscales of the ASC, except for tryptophan which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with the ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in several pathways involved in neurotransmission such as serotonin and dopamine synthesis. In conclusion, a crosstalk between the circulating LNAAs and the subjective effects is suggested, which is independent of the alkaloid concentrations and provides insights into the specific metabolic fingerprint and mechanism of action underlying ayahuasca experiences.

Therapeutic effect of an ayahuasca analogue in clinically depressed patients: a longitudinal observational study.

RATIONALE: Studies have suggested mental health improvements following the use of the psychotropic plant concoction ayahuasca in non-clinical and clinical samples. OBJECTIVES: The present observational study assessed depressive symptomatology in 20 clinically depressed patients (symptom score > 13 on the Beck's Depression Inventory) before attendance of an ayahuasca ceremony and 1 month and 1 year after. Secondary measures included ratings of altered states of consciousness and ego dissolution during the ayahuasca ceremony as well as global measures of mindfulness, satisfaction with life, depression, anxiety, and stress. RESULTS: Twenty participants completed baseline and 1-day follow-up, 19 completed measures at 1-month follow-up, and 17 completed measures at 1-year follow-up. BDI scores reduced from baseline (M = 22.7) to all post-ceremony measures (Ms 11.45, 12.89, and 8.88, for 1-day, 1-month, and 1-year follow-up, respectively). After 1 day, 12/20 participants were in remission (BDI < 13). Remission rates after 1 month and 1 year were 13/19 and 12/17, respectively. Three participants remained mildly depressed (BDI 14-19) at the 1-month and 1-year follow-up. Two participants did not respond and remained at a moderate/severe level of depression at 1-year follow-up. Reductions on the secondary mental health measures and increases in mindfulness and satisfaction with life were found up to 1 year post-ceremony. Improvements in clinical depression and mental health correlated with levels of experienced ego dissolution and oceanic boundlessness during the ceremony up to 1 month after the ceremony. Engagement in additional mental health treatments or use of another psychedelic during study participation may have contributed to improved mental health ratings at 1-year follow-up. CONCLUSION: Ayahuasca produces long-term mental health improvements in clinically depressed patients, which highlights its therapeutic potential.

Persisting Effects of Ayahuasca on Empathy, Creative Thinking, Decentering, Personality, and Well-Being.

Background: Naturalistic and placebo-controlled studies have suggested that ayahuasca, a traditional Amazonian beverage, could be helpful in the treatment of psychopathologies like depression and anxiety disorders by changing otherwise disturbed cognitive and emotional processes. To better understand its full therapeutic potential, one way is to study the effects on processes like flexible thinking, empathy, and well-being, which are normally compromised in stress-related psychopathologies. Materials and Methods: Volunteers attending ayahuasca ceremonies were asked to complete a test battery at three separate occasions: baseline, the morning after, and 1 week after the ceremony. We included the constructs of creative thinking (measured by Picture Concept Test), empathy (Multifaceted Empathy Test), satisfaction with life (Satisfaction with Life Scale), decentering (Experiences Questionnaire), and personality (Big Five Inventory) into the test battery. Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire, the Ego Dissolution Scale, and Visual Analogue Scales. Results: In total, 43 attendees (males = 22; females = 21) completed parts of the baseline assessment, 20 (males = 12; females = 8) completed assessments in the morning after the ceremony, and 19 (males = 14; females = 5) completed assessments at the 1-week follow-up. At one and 7 days post-ceremony, cognitive empathy, satisfaction with life, and decentering increased, while divergent thinking (Fluency corrected for Originality) decreased, when compared to baseline. Implicit emotional empathy increased at 1-week follow-up, whereas ratings of the trait neuroticism decreased. Conclusion: The study suggests that a single ingestion of ayahuasca in a social setting is associated with enhancement of subjective well-being, an enhanced ability to take an objective and non-judging stance towards the self (decentering), and the ability to correctly recognize emotions in others, compared to baseline, lasting up to 1 week post-ceremony. To understand the therapeutic potential related to these effects, further research with clinical populations is needed in which these effects can be assessed, including its link with therapeutic outcomes. Together, this will increase our understanding of the effectiveness and breadth of future therapeutic options.

The effects of yoga on functionality appreciation and additional facets of positive body image.

This study investigated the effects of yoga on functionality appreciation, and the potential mechanisms that could explain the impact of yoga on additional facets of positive body image. Young adult women (N = 114; Mage = 22.19) were randomised to a 10-week Hatha yoga programme or waitlist control group. Participants completed measures of functionality appreciation, body appreciation, body compassion, appearance evaluation, self-objectification, and embodiment at Pretest, Midtest, Posttest, and 1-month Follow-Up. Follow-up data could not be analysed due to high levels of attrition. The remaining data showed that, compared to the control group, women in the yoga programme experienced lower self-objectification at Midtest and greater embodiment over time. Further, all participants experienced improvements in body appreciation, body compassion, and appearance evaluation over time, regardless of their assigned group. Lower self-objectification contributed to improvements in body appreciation and body compassion. In addition, greater embodiment contributed to improvements in body appreciation, body compassion, and appearance evaluation. Contrary to our expectations, yoga did not lead to increased functionality appreciation, nor was functionality appreciation a mediator of the impact of yoga on positive body image. Instead, lower self-objectification, and greater embodiment, drove improvements in positive body image.

Mindfulness-Based Intervention for People With Dementia and Their Partners: Results of a Mixed-Methods Study.

OBJECTIVE: Studies have shown preliminary support for mindfulness-based interventions benefitting people with dementia and their caregivers. However, most studies focus on these two groups separately. This study examined whether it would be possible and beneficial for people with dementia and their caregiver to jointly undergo an adjusted Mindfulness-Based Stress Reduction (MBSR) training, named TANDEM. METHODS: The 8-week MBSR training was adjusted based on a literature review and interviews with experts (clinicians and mindfulness trainers). Seven couples (a person with early-stage dementia and their caregiver) participated together in the 8-week TANDEM program. Semi-structured qualitative interviews were conducted after completion. Questionnaires (administered before and after the intervention) assessed the primary outcomes of quality of life and psychological distress (stress, anxiety and depressive symptoms). Secondary outcomes were mindfulness, self-compassion, positive mental health, worrying, and perceived burden (for caregivers). RESULTS: All participants completed the program and reported beneficial effects (relaxation, awareness, acceptance, and resilience). Most managed to integrate exercises into their daily lives and planned to continue their practice. Participating in a group was considered valuable and supportive. Furthermore, it was appreciated that participants could follow the training together (as a couple). The quantitative results showed a small effect on increased quality of life for caregivers. No substantial decrease in psychological distress was apparent. Caregivers displayed a large increase in mindfulness. CONCLUSION: The results of this mixed-methods study suggest that an adjusted mindfulness program is feasible and well-received among couples of persons with early-stage dementia and their caregiver, warranting further research in this area.

Retrieval-Induced Forgetting in the Feigning Amnesia for a Crime Paradigm.

Previous studies demonstrated that, when asked to honestly provide information about a mock crime, former feigners performed worse than those who were requested to confess to this event. Thus, feigning amnesia for a mock crime undermined genuine memory for the same experience. In the present study, we examined whether retrieval-induced forgetting (RIF) underlies this memory-undermining effect. After watching a mock crime, participants had to feign amnesia or confess to having committed that crime. Feigners were given retrieval practice instructions (i.e., retrieval-practice group) or no further instructions (i.e., control group). Immediately and 1 day later, all participants had to genuinely report what they remembered about the crime. Although simulators in the retrieval-practice group recalled the largest amount of information as a positive consequence of retrieval, the ratio for crucial crime-related details was lower than that exhibited by both simulators who were given no instructions and confessors. These findings suggest that RIF might play a role in forgetting critical information in claims of crime-related amnesia. Theoretical and practical implications will be discussed.

Feigning Amnesia Moderately Impairs Memory for a Mock Crime Video.

Previous studies showed that feigning amnesia for a crime impairs actual memory for the target event. Lack of rehearsal has been proposed as an explanation for this memory-undermining effect of feigning. The aim of the present study was to replicate and extend previous research adopting a mock crime video instead of a narrative story. We showed participants a video of a violent crime. Next, they were requested to imagine that they had committed this offense and to either feign amnesia or confess the crime. A third condition was included: Participants in the delayed test-only control condition did not receive any instruction. On subsequent recall tests, participants in all three conditions were instructed to report as much information as possible about the offense. On the free recall test, feigning amnesia impaired memory for the video clip, but participants who were asked to feign crime-related amnesia outperformed controls. However, no differences between simulators and confessors were found on both correct cued recollection or on distortion and commission rates. We also explored whether inner speech might modulate memory for the crime. Inner speech traits were not found to be related to the simulating amnesia effect. Theoretical and practical implications of our results are discussed.

Can implicit measures detect source information in crime-related amnesia?

Participants who are asked to simulate amnesia for a mock crime have a weaker memory for this event when they have to give up their role as a feigner, than those who are not asked to feign memory loss. According to the source monitoring framework (SMF), this memory-undermining effect of simulating amnesia for a crime would be due to misattribution of the right source of information. However, we know that the content of self-generated information (e.g., feigned version of the crime) might be preserved and recognised over time as a result of elaborative cognitive processing. In the present study, we aimed to contrast these two explanations. We showed participants a mock crime video and we instructed them to either feign amnesia (simulators) or confess the mock crime (confessors). Next, a free recall memory test was administered. After one week, participants were asked to perform a personalised source monitoring task using the autobiographical Implicit Association Test (aIAT). As predicted, we found that simulators were able to discriminate the content of their self-generated feigned story of the crime from the original version. Moreover, simulators were quicker than confessors at the aIAT task. Practical and theoretical implications of our results are discussed.

In vino veritas? Alcohol, response inhibition and lying.

AIMS: Despite the widespread belief that alcohol makes the truth come out more easily, we know very little on how alcohol impacts deception. Given that alcohol impairs response inhibition, and that response inhibition may be critically involved in deception, we expected that alcohol intake would hamper lying. METHODS: In total, 104 volunteers were tested at a science festival, where they had the opportunity to drink alcohol. Stop-Signal Reaction Times (SSRTs) served as operationalization of response inhibition. Differences in error rates and reaction times (RTs) between lying and truth telling served as indicators of the cognitive cost of lying. RESULTS: Higher blood alcohol concentration was related to longer SSRTs, but unrelated to the cognitive costs of lying. CONCLUSION: This study validates previous laboratory research on alcohol and response inhibition in a realistic drinking environment, yet failed to find an effect of alcohol on lying. Implications of these findings and for the role of response inhibition in lying are discussed.

Let's use those tests! Evaluations of crime-related amnesia claims.

Suspects awaiting trial often claim that they cannot remember important parts of their violent crimes. It is not unusual that forensic experts readily accept such claims and interpret them in terms of dissociative amnesia or, more specifically, a "red-out". This interpretation hinges on the assumption that heightened levels of stress implicated in violent crimes interfere with memory. We argue that the notion of red-out is a priori not plausible and that alternative interpretations-primarily malingering and substance-induced organic amnesia-should be considered and ruled out first before concluding that memory loss is dissociative in nature. We illustrate our point with four cases that superficially have the contours of red-out tragedies. We believe that, in such cases, neuropsychological tests and/or psychopharmacological information on dose-response relationships can assist forensic experts to exclude malingering or substance-induced amnesia. There is no reason for not using tests and tools from neuropsychology and psychopharmacology.

The origin of children's implanted false memories: memory traces or compliance?

A longstanding question in false memory research is whether children's implanted false memories represent actual memory traces or merely result from compliance. The current study examined this question using a response latency based deception task. Forty-five 8-year-old children received narratives about a true (first day at school) and false event (hot air balloon ride). Across two interviews, 58/32% of the participants developed a partial/full false memory. Interestingly, these children also showed higher false recall on an unrelated DRM paradigm compared to children without a false memory. The crucial finding, however, was that the results of the deception task revealed that children with partial and full false memories were faster to confirm than to deny statements relating to the false event. This indicates that children's implanted false memories reflect actual memory traces, and are unlikely to be explained by mere compliance.

Skin conductance and memory fragmentation after exposure to an emotional film clip in depersonalization disorder.

It is often assumed that when confronted with an emotional event, patients with DPD inhibit information processing. It is also thought that this fosters memory fragmentation. This hypothesis has not been tested in chronic depersonalization. The aim of this study was to investigate the temporal pattern of autonomic responding to emotional material in depersonalization disorder, along with concomitant deficits in subjective and objective memory formation (i.e., difficulties to form a coherent narrative consisting of an ordered sequence of events). Participants with depersonalization disorder (n=14) and healthy control participants (n=14) viewed an emotional video clip while their skin conductance (SC) levels were measured. Peritraumatic dissociation was measured before and after the clip, and memory performance was measured 35 min after viewing. Compared to controls, depersonalized participants exhibited a distinctly different temporal pattern of autonomic responding, characterized by an earlier peak and subsequent flattening of SCLs. Maximum SCLs did not differ between the two groups. Moreover, unlike the control group, depersonalized participants showed no SC recovery after clip offset. In terms of memory performance, patients exhibited objective memory fragmentation, which they also reported subjectively. However, they did not differ from controls in free recall performance. Apparently, emotional responding in DPD is characterized by a shortened latency to peak with subsequent flattening and is accompanied by memory fragmentation in the light of otherwise unremarkable memory functioning.

Expectancies and memory for an emotional film fragment: a placebo study.

This study investigated whether positive ("memory-enhancing") and negative ("memory-impairing") placebos may enhance and undermine, respectively, memory of a film fragment. After watching an emotional film fragment, participants were assigned to a "memory-enhancing" placebo group (n = 30), control group (n = 30), or "memory-impairing" placebo group (n = 30). Only participants who believed in the placebo effect were included in the analyses. In the positive placebo group, memory for the film fragment was better than that of participants who received negative placebos or control participants. Participants in the negative placebo group made more distortion errors than participants in the positive placebo or control group. Our findings show that people's expectancies about their memory may affect their memory performance. These results may have implications for both clinical practice and the legal domain.

Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat.

One manner to study the role of serotonin (5-HT) in behavioral functions is through nutritional manipulation of its precursor tryptophan (TRP). By means of the method of acute TRP depletion, plasma TRP levels can be reduced in a reversible way in both humans and rats. In the present study a TRP-free protein-carbohydrate mixture was used to investigate the behavioral effects of lowering TRP and 5-HT concentrations in adult male rats. These animals were tested in models of anxiety (open field, home cage emergence test), depression (forced swimming test) and cognition (object recognition test and Morris water escape test). The TRP-free protein-carbohydrate mixture substantially reduced the ratio TRP/SigmaLNAA within 2 and 4 h by 75 and 60%, respectively. It was found that 4 h after administration, the treatment did not affect anxiety-related behavior nor did it cause depressive-like behavior. Also, no treatment effect was found on spatial learning performance in a Morris water escape test. On the other hand, performance in an object recognition test was clearly impaired after TRP depletion. Taken together, these data suggest that acute lowered central 5-HT levels are not associated with changes in affective behavior (i.e. anxiety and depression), but do impair object memory in adult rats.

Alcoholic blackout for criminally relevant behavior.

Some criminal suspects claim to have had an alcohol-induced blackout during crimes they have committed. Are alcoholic blackouts a frequently occurring phenomenon, or are they merely used as an excuse to minimize responsibility? Frequency and type of blackout were surveyed retrospectively in two healthy samples (n = 256 and n = 100). Also, a comparison of blood alcohol concentrations was made between people who did and those who did not claim a blackout when stopped in a traffic-control study (n = 100). In the two survey studies, blackouts were reported frequently by the person himself (or herself) and others (67% and 76%, respectively) in contrast to the traffic-control study (14%), in which blackouts were reported only when persons were involved in an accident. These results indicate that although blackouts during serious misbehavior are reported outside the court, both the denial and the claim of alcoholic blackout may serve a strategic function.