Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

The present paper discusses the current literature with regard to substance-assisted psychotherapy with Methylenedioxymethamphetamine (MDMA) for posttraumatic stress disorder (PTSD). The aim of the paper is to give a comprehensive overview of the development from MDMA's early application in psychotherapy to its present and future role in the treatment of PTSD. It is further attempted to increase the attention for MDMA's therapeutic potential by providing a thorough depiction of the scientific evidence regarding its theorized mechanism of action and potential harms of its application in the clinical setting (e.g., misattribution of therapeutic gains to medication instead of psychological changes). Empirical support for the use of MDMA-assisted psychotherapy, including the randomized, double-blind, placebo-controlled trails that have been conducted since 2008, is discussed. Thus far, an overall remission rate of 66.2% and low rates of adverse effects have been found in the six phase two trials conducted in clinical settings with 105 blinded subjects with chronic PTSD. The results seem to support MDMA's safe and effective use as an adjunct to psychotherapy. Even though preliminary studies may look promising, more studies of its application in a psychotherapeutic context are needed in order to establish MDMA as a potential adjunct to therapy

The link between childhood trauma and dissociation in frequent users of classic psychedelics and dissociatives

Background: Childhood trauma severity is associated with the level of subsequent substance use as well as with the self-reported severity of dissociation. Classic psychedelics and dissociatives target neurotransmitter systems thought to be involved in the onset of dissociative symptoms and may evoke severe and long-lasting symptoms of depersonalization in some users. However, it is currently unclear whether drug use puts people with a history of childhood trauma at higher risk of developing dissociative symptoms. Objectives: The current study investigates whether the one-year prevalence of substance use significantly moderates the link between childhood trauma and the severity of depersonalization. Methods: Participants (n = 297, of which 80.2% were active users) filled out an online self-report questionnaire including the Childhood Trauma Questionnaire (CTQ), the Cambridge Depersonalisation Scale (CDS), and information about their substance use. Results: Results indicate that childhood trauma and substance use are significant individual predictors of dissociation scores in this sample, but no moderation of substance use on the link between childhood trauma and depersonalization was established. Conclusions: It is hypothesized that the quality (particularly the context) of the experience of substance use rather than the sheer quantity may be responsible for the manifestation of depersonalization

Psychedelic forum member preferences for carer experience and consumption behavior: Can “Trip Sitters” Help Inform Psychedelic Harm Reduction Services?

Background: There is limited research on the provision of harm reduction services to people who use psychedelics. Little is known about provision of care to people consuming psychedelics outside of clinical trials. Methods: We investigated how people who used psychedelics discussed their preferences for care (or “trip sitting”) on two online forums: The Shroomery and DMT Nexus. A thematic analysis of the discussion was conducted to better understand consumer preferences for harm reduction services and resources. Results: We identified two key themes: experience and remote sitting. Forum participants valued trip sitters who had experienced psychedelic and other non-ordinary states of consciousness, who had knowledge of the health and medical industry, psychedelic literature and/or had previously cared for other psychedelic consumers. Forum participants also identified the value of consuming a psychedelic without somebody who was in their physical proximity, through communicating their plans to a remote trip sitter. The use of online tools was identified as a way to maximize the benefit of privacy while retaining carer benefits. Conclusion: Demand for trip sitters with lived psychedelic experience is likely influenced by stigma and empathy. Trip sitters who could relate to the effects of psychedelics assisted consumers in avoiding stigma while vulnerable under the effects of psychedelics. As such, psychedelic harm reduction services should be delivered by peers to ensure care maximizes the benefits of empathy. Psychedelic harm reduction services should consider how remote workers could be employed. There is a clear demand for remote psychedelic care services and to our knowledge this has not yet been explored

Sober sitter or coconsumer? Psychedelics, online forums and preferences for interpersonal interactions

Contemporary clinical research into the psychotherapeutic administration of psychedelics has primarily emphasized the importance of therapeutic interpersonal interactions to assist clients prepare for and integrate the acute effects of psychedelics. Alternative therapeutic frameworks have encouraged active talk therapy between therapists and clients during the administration phase. We used data gathered from forums to investigate consumer preferences concerning interpersonal interactions during their psychedelic-occasioned experience. Google was used to locate relevant posts on the psychedelic forums The Shroomery and The DMT Nexus. We analyzed these posts using thematic analysis, in which two researchers independently categorized posts in accordance with emergent themes. These themes were then refined through iterative reflexivity. We then identified four themes pertaining to psychedelic consumer interpersonal interaction preferences: nonintrusive; boundary setting; help; and sober sitter or coconsumer. Further analysis revealed parallels between consumer preferences and clinical guidelines for psychedelic-assisted psychotherapy, including the emphasis of carer acceptance; minimal involvement; nondirection; hazard management and emotional stability. However, there was also disparity between consumer preferences and guidelines, specifically concerning desires for consumer agency; for psychedelic consumption alongside other consumers, and for carers who had consumed psychedelics themselves. These findings have clinical implications and thus may aid the development of future guidelines

Therapeutic (Sub)stance: Current practice and therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A systematized review

Background: Clinical trials are currently investigating the potential of substance-assisted psychotherapy (SAPT) as treatment for several psychiatric conditions. The potential therapeutic effects of SAPT may be influenced by contextual factors including preparation prior to and integration after the substance-assisted therapy sessions. Aims: This systematized review outlines recommendations for current practice in preparatory sessions in SAPT including safety measures and screening procedures, preparation of set and setting, session contents, methods, and roles, prerequisites, and appropriate conduct of therapists. Methods: A systematized review of the literature was conducted based on PRISMA guidelines. MEDLINE (OVID), PsycINFO (OVID), and Cochrane Library were searched and clinical trials, treatment manuals, study protocols, case studies, qualitative studies, descriptive studies, theoretical papers, reviews, book chapters, and conference proceedings published until February 1, 2022 were retrieved. Results: The final synthesis included k = 83 sources. Information about safety measures including screening of participants, set and setting, contextual-, physiological-, and psychological preparation, roles, competencies, prerequisites, and characteristics of the therapists, and the establishment of a therapeutic relationship were summarized and discussed. Conclusion: It is concluded that there is a consensus in the literature about the importance of adequate preparation before the administration of psychoactive substances in SAPT. However, the extent and approaches for these sessions vary across different models and there is a need for timelier and more rigorous qualitative and quantitative investigations assessing different approaches and techniques for the optimal preparation of clients in SAPT

Staging of neurofibrillary pathology in Alzheimer's disease: A study of the BrainNet Europe consortium

It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and β-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-μm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers. © 2008 The Authors

Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome. © 2014, Springer-Verlag Wien

Assessment of β-amyloid deposits in human brain: A study of the BrainNet Europe Consortium

β-Amyloid (Aβ) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as 1 and α synuclein related lesions, also Aβ related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of Aβ, i.e. phase 1 = deposition of Aβ exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of Aβ phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of Aβ-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the Aβ phase in AD is feasible even in large scale retrospective studies. © Springer-Verlag 2009

Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity