Older adults in psychedelic-assisted therapy trials: A systematic review.

BACKGROUND: Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder. AIMS: The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. METHODS: A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE. RESULTS: 4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. CONCLUSIONS: While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder.

Background: MDMA-assisted psychotherapy (MDMA-AP) is a combined psychotherapeutic and pharmacologic intervention that shows promise in the treatment of posttraumatic stress disorder (PTSD). Although therapeutic alliance has been established as a key predictor across psychotherapies and is emphasised within MDMA-AP treatment manuals, research has not yet examined the relationship between therapeutic alliance and MDMA-AP treatment outcomes.Objective: Examine whether therapeutic alliance predicts changes in PTSD symptoms following MDMA-AP.Method: Twenty-three individuals with chronic PTSD participated in a MDMA-AP clinical trial that included a randomised (MDMA vs. placebo) and open-label phase. The present analyses focused on participants who were administered MDMA over the course of the randomised and open-label phases (n = 22). Therapeutic alliance was assessed using the Working Alliance Inventory at sessions baseline (pre-session 3) and sessions 4 and 9. PTSD symptoms were assessed using the Clinician Administered PTSD Scale and the Impact of Events Scale-Revised.Results: Controlling for baseline clinician-assessed PTSD severity, therapeutic alliance at sessions 4 and 9 (but not baseline) significantly predicted post-MDMA-AP clinician-assessed PTSD severity. Controlling for baseline self-reported PTSD severity, therapeutic alliance at baseline (although this did not survive correction for multiple comparisons) and sessions 4 and 9 predicted post-MDMA-AP self-reported PTSD severity.Conclusions: The present results provide the first preliminary evidence for the relationship between the therapeutic alliance and treatment outcomes within MDMA-AP for PTSD. These findings highlight the important role of psychotherapy, and common psychotherapeutic factors, within MDMA-AP. Replication in studies with larger and more diverse clinical samples remain necessary.Trial registration: ClinicalTrials.gov identifier: NCT00090064.

Among individuals with chronic posttraumatic stress disorder, therapeutic alliance predicted changes in posttraumatic stress disorder severity following MDMA-assisted psychotherapy.Therapeutic alliance may play a key role in facilitating therapeutic improvement within MDMA-assisted psychotherapy.Further research remains necessary to confirm these preliminary findings and the role of therapeutic alliance in MDMA-assisted psychotherapy.

The Effect of Organic Trace Mineral Supplementation in the Form of Proteinates on Performance and Sustainability Parameters in Laying Hens: A Meta-Analysis.

The effect of supplementing organic trace minerals (OTM), in the form of mineral proteinates (Bioplex® Cu, Fe, Mn, and Zn, Alltech Inc., Nicholasville, KY, USA), in the diets of laying hens was examined using Comprehensive Meta-Analysis (CMA) statistical software. The impact on production performance, egg quality traits, and sustainability parameters related to the carbon footprint of egg production was assessed. Data were obtained from 32 global studies, comprising 107 dietary assessments of 30,992 laying hens. Overall pooled effect size (raw mean difference) of production performance when dietary organic trace minerals were supplemented either in basal diets, partial replacement of inorganic trace minerals (ITM), or total replacement of ITM, indicated that use of Bioplex minerals resulted in 2.07% higher hen-day production (HDP), whilst feed conversion ratio (FCR) was lower by 51.28 g feed/kg egg and 22.82 g feed/dozen eggs, respectively. For egg quality traits, daily egg mass was 0.50 g/hen/day higher and egg weight was 0.48 g per egg greater when Bioplex minerals were incorporated in the diet. The mean difference in egg loss was -0.62%. Eggshell thickness was greater by 0.01 mm, and a higher eggshell strength of 0.14 kgf was observed. Eggshell weight was heavier by 0.20 g, eggshell percentage was higher by 0.15%, and Haugh unit was 1 point higher (0.89). We also carried out a meta-regression of the effects of the study factors (location, year of study, hen breed/strain, age of hens, number of hens, and study duration) on the overall pooled effect size of the production performance and egg quality traits in response to supplementary OTM inclusion, and it indicated that certain factors had a significant (p < 0.05) impact on the results. Finally, a life cycle assessment (LCA) model was selected to evaluate the impact of feeding organic trace mineral proteinates on the carbon footprint (feed and total emission intensities) of the egg production using the data generated from the meta-analysis. Results showed that the inclusion of OTM proteinates resulted in an average drop in feed and total emission intensities per kg eggs of 2.40% and 2.50%, respectively, for a low-global-warming-potential (GWP) diet and a drop of 2.40% and 2.48% for feed and total emissions, respectively, based on high-GWP diet. Based on the overall results, the inclusion of organic trace mineral proteinates in layer diets can benefit production performance and egg quality traits while contributing to a lower carbon footprint.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences.

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.

The 3' Untranslated Regions of Ebola Virus mRNAs Contain AU-Rich Elements Involved in Posttranscriptional Stabilization and Decay.

The 3' untranslated regions (UTRs) of Ebola virus (EBOV) mRNAs are enriched in their AU content and therefore represent potential targets for RNA binding proteins targeting AU-rich elements (ARE-BPs). ARE-BPs are known to fine-tune RNA turnover and translational activity. We identified putative AREs within EBOV mRNA 3' UTRs and assessed whether they might modulate mRNA stability. Using mammalian and zebrafish embryo reporter assays, we show a conserved, ARE-BP-mediated stabilizing effect and increased reporter activity with the tested EBOV 3' UTRs. When coexpressed with the prototypic ARE-BP tristetraprolin (TTP, ZFP36) that mainly destabilizes its target mRNAs, the EBOV nucleoprotein (NP) 3' UTR resulted in decreased reporter gene activity. Coexpression of NP with TTP led to reduced NP protein expression and diminished EBOV minigenome activity. In conclusion, the enrichment of AU residues in EBOV 3' UTRs makes them possible targets for cellular ARE-BPs, leading to modulation of RNA stability and translational activity.

Art of the Kill: Designing and Testing Viral Inactivation Procedures for Highly Pathogenic Negative Sense RNA Viruses.

The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the inactivation procedures, which comes with an array of challenges for each method. This includes the use of cytotoxic reagents for chemical inactivation and defining the precise inactivation parameters for physical inactivation. Here, we provide a workflow for various inactivation methods using Ebola, Nipah, and Lassa viruses as our examples. We choose three distinct inactivation methods (TRIzol/TRIzol LS, aldehyde fixation using different fixatives, and heat) to highlight the challenges of each method and provide possible solutions. We show that, whereas published chemical inactivation methods are highly reliable, the parameters for heat inactivation must be clearly defined to ensure complete inactivation. In addition to the inactivation data, we also provide examples and templates for the documentation required for approval and use of inactivation SOPs, including an inactivation report, the procedure sections of developed SOPs, and an electronic inactivation certificate that accompanies inactivated samples. The provided information can be used as a roadmap for similar studies at high and maximum containment laboratories.

Quantum monodromy in NCNCS - direct experimental confirmation.

Since the first confirmation of quantum monodromy in NCNCS (B. P. Winnewisser et al., Report No. TH07 in 60th International Symposium on Molecular Spectroscopy, Columbus, OH, (2005) and B. P. Winnewisser et al., Phys. Rev. Lett., 2005, 95, 243002) we have continued to explore its implications for the quantum structure of molecules. To confirm quantum monodromy bending-vibrational + axial-rotational quantum energy level information is needed. This was not directly available from the pure a-type rotational transitions available in 2005. The confirmation of quantum monodromy therefore had to be based on the fitting of the Generalised SemiRigid Bender (GSRB) model to the experimental rotational data. The GSRB is a physically motivated model and was able to extract the required information based on the changes of the rotational energy level structure upon excitation of the bending vibration and of the axial rotation. These results were, in some sense, predictions. Our goal here was to obtain a fully experimental and unambigous confirmation of quantum monodromy in NCNCS. This involved a series of experimental campaigns at the Canadian Light Source (CLS) synchrotron. To coax the required information out of the masses of spectral data that had been obtained a variety of techniques had to be used. The result is that we can now confirm, without recourse to a theoretical model, the existence of quantum monodromy in the ν7 bending mode of NCNCS. As a side benefit we also confirm the power of the GSRB model to extract the required information from the previously available data. The predictions previously provided by the GSRB were surprisingly accurate. Only a slight augmentation of the model was required to allow us to refit it including the new data, while maintaining the quality of the fitting for that data previously available. We also present a very basic introduction to the idea of monodromy and to how the GSRB was used.

Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. Methods: We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. Results: PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials.

Are psychedelic medicines the reset for chronic pain? Preliminary findings and research needs.

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

A Systematic Approach to Standardizing Drinking Outcomes From Timeline Followback Data.

Objective: The timeline followback (TLFB) interview is the gold standard for the quantitative assessment of alcohol use. However, self-reported "drinks" can vary in alcohol content. If this variability is not accounted for, it can compromise the reliability and validity of TLFB data. To improve the precision of the TLFB data, we developed a detailed standard operating procedure (SOP) to calculate standard drinks more accurately from participant reports. Method: For the new SOP, the volume and alcohol content by volume (ABV) of distinct types of alcoholic beverages were determined based on product websites and other reliable sources. Recipes for specific cocktails were constructed based on recipes from bartending education websites. One standard drink was defined as 0.6 oz (14 g) of absolute alcohol. Standard drink totals were contrasted for the new SOP approach and the standard procedure, which generally assumed that one self-reported drink was equivalent to one standard drink. Results: Relative to the standard TLFB procedure, higher numbers of standard drinks were reported after implementing the TLFB SOP. Conclusions: Variability in procedures for conversion of self-reported alcohol consumption to standard drinks can confound the interpretation of TLFB data. The use and reporting of a detailed SOP can significantly reduce the potential for such inconsistencies. Detailed and consistent procedures for calculation of standard drinks can enhance the quality of TLFB drinking data.

Chimpanzees (Pan troglodytes) in U.S. Zoos, Sanctuaries, and Research Facilities: A Survey-Based Comparison of Species-Typical Behaviors.

A survey was sent to zoos, research facilities, and sanctuaries which housed chimpanzees. Data collected included information about 1122 chimpanzees' age, sex, social group-size, rearing history, and enclosure. Respondents were also asked to indicate if certain behaviors had been observed in each chimpanzee over the prior two years. Species- typical behaviors (STBs) were queried, including copulation, tool-use, nest-building, and social grooming. Tool-use was reported present for 94.3% of the sample (n = 982), active social grooming for 85.7% (n = 1121), copulation for 68.3% (n = 863) and nest-building for 58.9% (n = 982). Of the subjects for whom we had data regarding all four STBs (n = 860), 45.6% were reported to engage in all four. Logistic regression analyses using forward Wald criteria were conducted to determine the best model for each STB based on the predictors of age, sex, rearing history, group-size, facility-type, and a sex-by-rearing interaction. The best model for copulation (χ2(6) = 124.62, p < 0.001) included rearing, group-size, facility-type, and the sex-by-rearing interaction. Chimpanzees were more likely to copulate if they were mother-reared, in larger groups, living in research facilities, and, if not mother-reared (NOTMR), more likely to copulate if they were female. The best model for tool-use retained the predictors of age category, facility-type, and sex-by-rearing (χ2(5) = 55.78, p < 0.001). Chimpanzees were more likely to use tools if they were adult, living in research facilities, and if NOTMR, were female. The best model for nest-building included facility-type and rearing (χ2(3) = 205.71, p < 0.001). Chimpanzees were more likely to build nests if they were MR and if they were living in zoos or in sanctuaries. The best model for active social grooming retained the predictors of age, sex, rearing, and type of facility (χ2(6) = 102.15, p < 0.001). Chimpanzees were more likely to engage in active social grooming if they were immature, female, mother-reared, and living in zoos. This research provides a basic behavioral profile for many chimpanzees living under human care in the United States and allows us to determine potential methods for improving the welfare of these and future chimpanzees in this population.

Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial.

Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.

A 25-Year Retrospective Review of Mortality in Chimpanzees (Pan troglodytes) in Accredited U.S. Zoos from a Management and Welfare Perspective.

Understanding causes of death allows adjustment of health management strategies for animals in managed care. From 224 documented chimpanzee deaths occurring from 1995 to 2019 in 42 accredited U.S. zoos, post-mortem records and necropsy reports were analyzed for the primary cause of death, which were available for 214 individuals. In total, 37 cases of stillbirth and neonatal deaths were assessed (16.5%); however, the focus was otherwise placed on the remaining 177 cases in which the death occurred in individuals aged greater than 1 month. There were no sex-related differences in etiology; however, age variation in the cause of death was statistically significant (p < 0.001). Elderly (35 years and older) chimpanzees tended to die of intrinsic, often degenerative, etiologies, whereas infants, juveniles, and adolescents (less than 15 years) were more likely to be involved in fatal trauma. Overall, there were 27 deaths (15.3% of all post-neonatal deaths) related to trauma and 13 of these were directly or indirectly related to conspecific aggression. Understanding causes of mortality and the interrelation with management can benefit managed populations of chimpanzees.

Improving Access to Tertiary Movement Disorders Subspecialty Care: A Team Model Born From the COVID-19 Crisis.

Patient demand continues to outpace growth of the neurology workforce, especially in its subspecialties such as movement disorders. Various strategies have been deployed to address this. The coronavirus disease 2019 pandemic accentuated the mismatch by propelling telemedicine and access demands to the forefront. Previously, we reported improving general neurology access using a physician-advanced practice provider team model. Here, we share our experiences of piloting a similar model in subspecialty care (movement disorders) between September 1 and December 17, 2020. Before the pilot, the wait time to be seen by movement disorders subspecialists exceeded 4 months. Our data show marked improvement in new patient access (23.8% improvement and 214% increase in the number of new patients seen) with excellent patient acceptance. Our approach and the lessons learned may be useful to address access for other neurology subspecialties.

Correction: Recombinant Lloviu virus as a tool to study viral replication and host responses.

[This corrects the article DOI: 10.1371/journal.ppat.1010268.].

Diagnosing Prescription Opioid Use Disorder in Patients Using Prescribed Opioids for Chronic Pain.

OBJECTIVE: The diagnostic criteria for opioid use disorder, originally developed for heroin, did not anticipate the surge in prescription opioid use and the resulting complexities in diagnosing prescription opioid use disorder (POUD), including differentiation of pain relief (therapeutic intent) from more common drug use motives, such as to get high or to cope with negative affect. The authors examined the validity of the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 opioid version, an instrument designed to make this differentiation. METHODS: Patients (N=606) from pain clinics and inpatient substance treatment who ever received a ≥30-day opioid prescription for chronic pain were evaluated for DSM-5 POUD (i.e., withdrawal and tolerance were not considered positive if patients used opioids only as prescribed, per DSM-5 guidelines) and pain-adjusted POUD (behavioral/subjective criteria were not considered positive if pain relief [therapeutic intent] was the sole motive). Bivariate correlated-outcome regression models indicated associations of 10 validators with DSM-5 and pain-adjusted POUD measures, using mean ratios for dimensional measures and odds ratios for binary measures. RESULTS: The prevalences of DSM-5 and pain-adjusted POUD, respectively, were 44.4% and 30.4% at the ≥2-criteria threshold and 29.5% and 25.3% at the ≥4-criteria threshold. Pain adjustment had little effect on prevalence among substance treatment patients but resulted in substantially lower prevalence among pain treatment patients. All validators had significantly stronger associations with pain-adjusted than with DSM-5 dimensional POUD measures (ratios of mean ratios, 1.22-2.31). For most validators, pain-adjusted binary POUD had larger odds ratios than DSM-5 measures. CONCLUSIONS: Adapting POUD measures for pain relief (therapeutic intent) improved validity. Studies should investigate the clinical utility of differentiating between therapeutic and nontherapeutic intent in evaluating POUD diagnostic criteria.

A randomized clinical trial of the effects of brief versus extended opioid overdose education on naloxone utilization outcomes by individuals with opioid use disorder.

BACKGROUND: Overdose education and naloxone distribution (OEND) trains people who use opioids (PWUO) in how to intervene in cases of opioid overdose but best practices have not been assessed empirically. METHODS: PWUO along with a significant other (SO) were randomized to one of three training conditions. In the Treatment-as-Usual (TAU) condition, participants were randomized to receive minimal overdose-related education. In the extended training (ET) condition, PWUO received an extended training, while their SO received no overdose training. In the final condition, both the participant and SO received the extended overdose training (ETwSO). Outcome measures were naloxone use and overdose knowledge and competency assessed immediately before and after training, and at 1-, 3-, 6-, and 12-month timepoints following training. RESULTS: Three hundred and twenty-one PWUO (w/ a SO) were randomized. All intensities of OD training were associated with sustained increases in OD knowledge/ competency (versus pre-training baseline p's < 0.01). PWUO intervened in 166 ODs. The 12-month incidence of naloxone use did not significantly differ between groups. Extended training (ET + ETwSO) compared to TAU resulted in significantly greater naloxone utilization by: 30 days (10.1% vs 4.1%, p = 0.041), 60 days (16.4% vs 5.2%, p<0.001) and 90 days (17.9% vs 9.5%, p = 0.039). CONCLUSIONS: All intensities of OD training were associated with sustained increases in OD knowledge and competency, and equivalent rates of successful naloxone use. More extensive training increased naloxone utilization during the first 3 months. However, the benefits of more comprehensive training should be balanced against feasibility.