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UNASSIGNED: The use of psychoactive substances to increase cognitive performance while studying has been termed \'pharmacological cognitive enhancement\' (PCE). In previous years, several large-scale national surveys have focused on their use by students at university, including drug types, prevalence rates, and predictive factors. The recent coronavirus pandemic brought about widespread structural changes for UK universities, as students were forced to adapt to home-based learning and in many cases reduced academic support. No study has yet focused primarily on the impact of pandemic social restrictions on PCE in students and academic staff, and whether personality and demographic factors reveal user profiles that predict use during the pandemic period.
UNASSIGNED: A convenience sample of 736 UK students and staff aged 18-54 (M = 22.2, SD = 5.2) completed a cross-sectional survey assessing PCE prevalence rates, polydrug use, perceived effects, academic self-efficacy and personality during the first year of social restrictions (March 2020 - February 2021) compared with the previous year (March 2019 - February 2020).
UNASSIGNED: There was a significant self-reported rise in the use of all drug types (all ps < 0.001) during social restrictions, particularly with Modafinil (+42%), nutraceuticals (+30.2%) and microdose LSD (+22.2%). Respondents also indicated stronger PCE effects for all substances, except alcohol, in comparison to the previous year. Polydrug use with modafinil and other prescription stimulants increased the most during social restrictions. Personality factors and gender identity reliably predicted PCE use and lower agreeableness was often the strongest predictor, followed by identifying as male and lower conscientiousness. Academic self-efficacy and student/academic staff status were not consistent predictors.
UNASSIGNED: This is the first survey of UK students to investigate PCE during coronavirus social restrictions and to assess predictive factors. Findings reveal a rise in PCE use and polydrug use which we suggest is because of increased pressures on students created by the lockdown and reduced access to university resources.

Buprenorphine is an effective medication for both opioid use disorder (OUD) and chronic pain (CP), but transitioning from full opioid agonists to buprenorphine, a partial opioid agonist, can be challenging. Preliminary studies suggest that low-dose buprenorphine initiation can overcome some challenges in starting treatment, but no randomized controlled trials have compared low-dose and standard buprenorphine initiation approaches regarding effectiveness and safety or examined implementation in hospital settings. In a pragmatic open-label hybrid type I effectiveness-implementation trial based in a single urban health system, 270 hospitalized patients with (a) CP and (b) OUD or opioid misuse are being randomized to buprenorphine treatment initiation using 5-day low-dose or standard initiation protocols. Outcomes include buprenorphine treatment uptake (primary), defined as receiving buprenorphine treatment 7 days after enrollment, and other OUD and pain outcomes at 1-, 3-, and 6-month follow-up (secondary). Data collection will also include safety measures, implementation of low-dose initiation protocols, patient acceptability, and cost-effectiveness. Comparing strategies in a randomized clinical trial will provide the most definitive data to date regarding the effectiveness and safety of low-dose buprenorphine initiation. The study will also provide important data on treating CP at a time that clinical guidelines are evolving to center buprenorphine as a preferred opioid for CP.

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

Background: Buprenorphine initiation in opioid-tolerant patients usually requires decreasing the total opioid intake per day due to its potential for precipitating withdrawal. However, this strategy may not be tolerated in patients who require higher amounts of opioids, such as those with cancer pain. Case Presentation: We utilized a buprenorphine microdosing strategy for a postoperative cancer patient who was previously taking buprenorphine-naloxone for chronic noncancer pain, then initiated on methadone for uncontrolled cancer-related pain. He had a planned cancer resection in the hospital. He subsequently underwent a successful transition from methadone to buprenorphine-naloxone through microdosing in one week with close monitoring in the inpatient setting. Conclusions: Using a microdosing strategy to transition from methadone to buprenorphine-naloxone in a span of days was achieved in this case report. More research regarding the feasibility and tolerability of microinductions is needed, especially in the setting of chronic pain or cancer-related pain.

Background and aim: In the present study, we focus on the relationship between state authenticity - the experience of being true to oneself in a particular moment - and microdosing - a practice that implies repeatedly ingesting very small doses of psychedelics that do not reach the threshold for perceptual alterations. We propose that microdosing could increase state authenticity through influencing people\'s mood and the number and satisfaction with daily activities. Methods: We used self-assessments of state authenticity collected from 18 microdosers in the Netherlands across the period of 1 month for a total of 192 observations. Results: We found that on the microdosing day and the day thereafter, state authenticity was significantly higher. Furthermore, the number of activities and the satisfaction with them were higher on the day when participants microdosed, while the following day only the number of activities was higher. Both the number or activities and the satisfaction with them were positively related to state authenticity. Conclusion: We propose that feeling and behaving authentically could have a central role in explaining the positive effects of microdosing on health and wellbeing that are reported by current research.

UNASSIGNED: Buprenorphine may provide superior analgesia to full opioid agonist therapy and reverse the effects of opioid-induced hyperalgesia, while having a favorable safety profile and fewer adverse effects, in chronic non-cancer pain treatment. Low-dose initiation of buprenorphine is a useful strategy for patients on long-term opioid therapy because it avoids the need for moderate opioid withdrawal required for traditional buprenorphine initiations. However, there are few published reports of low-dose initiation regimens in the setting of chronic pain.
UNASSIGNED: The aim of the study was to describe a case series of individuals living with chronic pain who were transitioned from long-term full opioid agonist therapy onto sublingual buprenorphine/naloxone using low-dose initiation regimens.
UNASSIGNED: This study is a retrospective case series that included all patients who received care at an outpatient chronic pain clinic and were scheduled for low-dose initiation of buprenorphine/naloxone between March 2020 and December 2022. Data were collected through a retrospective review of electronic medical records and results were analyzed using descriptive statistics.
UNASSIGNED: Eighteen patients underwent transitions from their baseline opioids onto buprenorphine/naloxone using a low-dose initiation regimen. Of those patients, 17 successfully completed the initiation (94.44%), 12 experienced adverse effects during the initiation (66.67%), with only one patient requiring treatment discontinuation, and all adverse effects resolved once maintenance doses of buprenorphine/naloxone were established. The mean Clinical Global Impression-Improvement score after initiation was 2 (1-5).
UNASSIGNED: Low-dose initiation is an effective approach to transition patients with chronic non-cancer pain from long-term opioid therapy to buprenorphine/naloxone without major complications or worsening pain.
Contexte: La buprénorphine peut offrir une analgésie supérieure à celle d’un traitement par agonistes opioïdes complet et inverser les effets de l’hyperalgésie induite par les opioïdes, tout en présentant un profil d’innocuité favorable et moins d’effets indésirables dans le traitement de la douleur chronique non cancéreuse. L’initiation à faible dose de la buprénorphine est une stratégie utile pour les patients sous traitement opioïde à long terme, car elle évite le besoin de sevrage des opioïdes modéré nécessaire pour les traitements traditionnels à base de buprénorphine. Cependant, il existe peu de rapports publiés sur les régimes d’initiation à faible dose dans le cadre de la douleur chronique.Objectifs: L’objectif de cette étude était de décrire une série de cas d’individus vivant avec une douleur chronique qui sont passés d’un traitement opioïde complet à long terme à un traitement par buprénorphine sublinguale/naloxone en ayant recours à des régimes d’initiation à faible dose.Méthodes: Cette étude est une série de cas rétrospective incluant tous les patients pris en charge dans une clinique externe de traitement de la douleur chronique et pour lesquels un schéma d’initiation à faible dose de buprénorphine/naloxone a été programmé entre mars 2020 et décembre 2022. Les données ont été collectées par le biais d’un examen rétrospectif des dossiers médicaux électroniques et les résultats ont été analysés à l’aide de statistiques descriptives.Résultats: Dix-huit patients ont fait la transition des opioïdes de base à la buprénorphine/naloxone en utilisant un régime d’initiation à faible dose. Parmi ces patients, 17 ont terminé l’initiation avec succès (94,44 %), 12 ont présenté des effets indésirables pendant l’initiation (66,67 %) et un seul patient a dû interrompre son traitement. Tous les effets indésirables ont disparu une fois les doses d’entretien de buprénorphine/naloxone établies. Le score d’impression clinique globale-amélioration moyen après le début du traitement était de 2 (1-5).Conclusion: L’initiation à faible dose est une approche efficace pour faire passer les patients souffrant de douleur chronique non cancéreuse d’un traitement opioïde à long terme à la buprénorphine/naloxone sans complications majeures ni aggravation de la douleur.

Phase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products. In our experience, Phase 0 microdose studies have not been fully embraced by the pharmaceutical industry. This notion is based on the number of Phase 0 studies that we have been involved in. Thus, we conducted at least 17 Phase 0 microdose studies in the Zero\'s (on average, two per year), but in the years beyond this, it was only 15 studies (1.4 per year); in these latter years, we did conduct a total of 23 studies which employed an intravenous (i.v.) microdose for absolute bioavailability (ABA) assessments (two per year on average), which are the most used and potentially informative type of clinical study using a microdose, albeit they are formally not microdose studies. In the current review, we summarize the past use of and experience with Phase 0 microdose designs in early clinical development, including intravenous 14C microdose ABA studies, and assess what is needed to increase the adoption of useful applications of Phase 0/microdose studies in the near future.

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BACKGROUND: This case series records a cohort of patients treated with transdermal buprenorphine patches as part of a buprenorphine microdose induction protocol to transition from methadone to buprenorphine in a community setting. This has historically been a difficult process to manage in community settings and this case series explored a method to gradually manage this in an outpatient setting.
METHODS: A retrospective file audit was conducted of the electronic medical records of cohealth Innerspace patients who had undergone buprenorphine microdose induction using transdermal patches. A total of 32 patients were identified.
RESULTS: In this case series 23 of the 32 patients successfully transitioned from methadone to sublingual or long-acting injectable depot buprenorphine preparations utilising the transdermal buprenorphine microdosing technique. All patients in this case series regardless of the success of the transition were retained in treatment.
CONCLUSIONS: A fixed-dose transdermal buprenorphine patch regimen enabled 23 of 32 patients in this case series transition from methadone to buprenorphine in an outpatient setting. Given the small sample size further research is required to demonstrate the effectiveness of this technique.