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IntroductionSerotonergic 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.MethodsHere, 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.ResultsUsing 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.ConclusionTaken 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.

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.

ObjectiveStudies 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.MethodsThe 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).ResultsAll 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.ConclusionThe 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.

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.

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.