Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity

The use of low sub-hallucinogenic doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies limits our knowledge of microdosing and its effects. Moreover, research conducted in laboratory settings might fail to capture the motivation of individuals engaged in microdosing protocols. We recruited 34 individuals planning to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled design, we investigated the effects of 0.5 g dried mushrooms on subjective experience, behavior, creativity, perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, which could be explained by unblinding. For the other measurements, we observed either null effects or a trend towards cognitive impairment and, in the case of EEG, towards reduced theta band spectral power. Our findings support the possibility that expectation effects underlie at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

Great Expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials

Rationale: Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research.Objective: In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research.Results: We found that although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants’ expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies concern study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy.Conclusion: Incorporating these design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increase the ability to discern treatment-specific effects of psychedelic therapy

Effects of the Covid-19 pandemic on maternity staff in 2020 – a scoping review

In the spring of 2020, the SARS-CoV-2 virus caused the Covid-19 pandemic, bringing with it drastic changes and challenges for health systems and medical staff. Among the affected were obstetricians and midwives, whose close physical contact with pregnant women, women who recently gave birth, and their children was indispensable. In the obstetric setting, births cannot be postponed, and maternity staff had to adapt to assure obstetric safety while balancing evidence-based standards with the new challenges posed by the pandemic. This scoping review gives a comprehensive overview of the effecs the Covid-19 pandemic had on maternity staff. We followed the evidence-based approach described by Arksey & O’Malley: we searched several databases for English and German articles published between January 2020 and January 2021 that discussed or touched upon the effects the pandemic had on maternity staff in OECD countries and China. We found that structural challenges caused by the crisis and its subjective effects on maternity staff fell into two main topic areas. Structural challenges (the first main topic) were divided into five subtopics: staff shortages and restructuring; personal protective equipment and tests; switching to virtual communication; handling women with a positive SARS-CoV-2 infection; and excluding accompanying persons. The pandemic also strongly affected the staff’s mental health (the second main topic.) Attempting to meet challenges posed by the pandemic while afraid of contamination, suffering overwork and exhaustion, and struggling to resolve ethical-moral dilemmas had severe negative subjective effects. Several studies indicated increased depression, anxiety, stress levels, and risk of post-traumatic stress symptoms, although the crisis also generated strong occupational solidarity. Care for pregnant, birthing, and breast-feeding women cannot be interrupted, even during a pandemic crisis that requires social distancing. Maternity staff sometimes had to abandon normal standards of obstetric care and were confronted with enormous challenges and structural adjustments that did not leave them unscathed: their mental health suffered considerably. Researchers should study maternity staff’s experiences during the pandemic to prepare recommendations that will protect staff during future epidemics.

«One prick and then it´s done»: a mixed-methods exploratory study on intramuscular injection in heroin-assisted treatment

Background Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients’ views and opinions on the topic and the underlying reasons for this practice. Methods The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. Results Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. Conclusion As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment.

A Randomised, Crossover, Clinical Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the BIDI Stick ENDS Compared with Combustible Cigarettes and a Comparator ENDS in Adult Smokers

Background: Nicotine pharmacokinetic assessments of electronic nicotine delivery systems (ENDS) are crucial to understand their ability to provide an alternative to cigarette smoking. Subjective effects data also strongly contribute to this understanding. The BIDI® Stick is a disposable ENDS product which contains 6% nicotine benzoate salt and various flavours. Methods: In this study we assessed nicotine pharmacokinetic and subjective effects of BIDI® Stick ENDS in adult smokers, compared to cigarettes and a comparator ENDS product. During each of eight (8) study visits, volunteer smoker subjects randomly used one of either their usual brand (UB) of cigarette, a BIDI® Stick ENDS, or a comparator ENDS (JUUL 5% with Virginia Tobacco flavour), during both defined (10 puffs, 30 seconds apart) and ad libitum puffing sessions. Blood samples were collected at various time points and subjective effects questionnaires were administered. Results: Plasma nicotine Cmax 0-120 was not significantly different between BIDI® Stick ENDS with any flavour (range 15.3 (9.90) ng/ml for BIDI® Stick Winter to 17.6 (9.00) ng/ml for BIDI® Stick Classic) and UB cigarettes [16.2 (9.17) ng/ml]. AUC0-120 and Tmax 0-120 values were also not significantly different between BIDI® Stick ENDS and UB cigarettes, while subjective effects measures were also similar between BIDI® Stick ENDS and UB cigarettes. Conclusions: BIDI® Stick ENDS delivered nicotine to users comparably to their UB combustible cigarette and also elicited similar subjective effects such as satisfaction and relief. Thus, the BIDI® Stick ENDS may be a satisfying alternative to cigarettes among current smokers and may support their transitioning away from cigarette smoking. Trial registration: ClinicalTrials.gov (identifier number NCT05072925).

A Semantic Scale Network analysis of the revised Mystical Experiences Questionnaire: A call for collaboration

Background and aims Multiple laboratories have proposed measures of subjective effects of psychedelics as potential mediators of their therapeutic impact. Other work has identified individual differences that covary with subjective responses in informative ways. The range of potential measures of responses, traits, and outcomes is vast. Ideas for new measures are likely numerous. The field will progress efficiently if proposed new scales can add incremental validity. Semantic Scale Network analyses identify conceptual overlap among scales based on items (rather than participant ratings), which could help laboratories avoid putting effort into measures that are unlikely to account for unique variance. Semantic Scale Network analyses can also reveal links to constructs from disparate research literatures, potentially helping investigators generate novel hypotheses and explain connections among disparate findings. The results of Semantic Scale Network analyses have the potential to improve as more investigators enter their scales into the corpus. Method Example analyses using the revised Mystical Experiences Questionnaire (MEQ) underscore the uniqueness and discriminant validity of the MEQ subscales. Results Findings dovetail with published theorizing and suggest potentially novel links with different therapeutic effects. The MEQ total or subscales overlap with measures of awe, inspiration, regret, dissatisfaction, transcendence, depression, fatigue, and spirituality. Links with measures of stress, alexithymia, and gender identity suggest lines of further work. Conclusions This analytic approach might suggest unique applications for psychedelic-assisted treatments and provide perspectives on phenomena outside the field. As psychedelic researchers enter their scales to the corpus for Semantic Scale Network analyses, the field will benefit.

Abuse and dependence potential of sphingosine-1-phosphate (S1P) receptor modulators used in the treatment of multiple sclerosis: a review of literature and public data

Abuse and misuse of prescription drugs remains an ongoing concern in the USA and worldwide; thus, all centrally active new drugs must be assessed for abuse and dependence potential. Sphingosine-1-phosphate (S1P) receptor modulators are used primarily in the treatment of multiple sclerosis. Among the new S1P receptor modulators, siponimod, ozanimod, and ponesimod have recently been approved in the USA, European Union (EU), and other countries. This review of literature and other public data has been undertaken to assess the potential for abuse of S1P receptor modulators, including ozanimod, siponimod, ponesimod, and fingolimod, as well as several similar compounds in development. The S1P receptor modulators have not shown chemical or pharmacological similarity to known drugs of abuse; have not shown abuse or dependence potential in animal models for subjective effects, reinforcement, or physical dependence; and do not have adverse event profiles demonstrating effects of interest to individuals who abuse drugs (such as sedative, stimulant, mood-elevating, or hallucinogenic effects). In addition, no reports of actual abuse, misuse, or dependence were identified in the scientific literature for fingolimod, which has been on the market since 2010 (USA) and 2011 (EU). Overall, the data suggest that S1P receptor modulators are not associated with significant potential for abuse or dependence, consistent with their unscheduled status in the USA and internationally.

Natural Language as a Window into the Subjective Effects and Neurochemistry of Psychedelic Drugs

Psychedelics are drugs capable of eliciting profound alterations in the subjective experience of the users, sometimes with long-lasting consequences. Because of this, psychedelic research tends to focus on human subjects, given their capacity to construct detailed narratives about the contents of their consciousness experiences. In spite of its relevance, the interaction between serotonergic psychedelics and language production is comparatively understudied in the recent literature. This review is focused on two aspects of this interaction: how the acute effects of psychedelic drugs impact on speech organization regardless of its semantic content, and how to characterize the subjective effects of psychedelic drugs by analyzing the semantic content of written retrospective reports. We show that the computational characterization of language production is an emergent powerful tool to predict the therapeutic outcome of individual experiences, relate the effects elicited by psychedelics with those associated with other altered states of consciousness, draw comparisons between the psychedelic state and the symptomatology of certain psychiatric disorders, and investigate the neurochemical profile and mechanism of action of different psychedelic drugs. We conclude that researchers studying psychedelics can considerably expand the range of their potential scientific conclusions by analyzing brief interviews obtained before, during and after the acute effects. Finally, we list a series of questions and open problems that should be addressed to further consolidate this approach.