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Kratom, a plant that produces opioid-like effects, has gained popularity in the U.S. for self-treating symptoms of chronic pain, mood disorders, and substance-use disorders (SUDs). Most data on kratom are from surveys into which current kratom-using adults could self-select; such surveys may underrepresent people who have used kratom and chosen to stop. Available data also do not adequately assess important psychosocial factors surrounding kratom use. In this study, U.S. adults who reported past 6-month alcohol, opioid, and/or stimulant use (N = 1,670) were recruited via Amazon Mechanical Turk between September and December 2020. Of the 1,510 evaluable respondents, 202 (13.4%) reported lifetime kratom use. Kratom-using adults, relative to others, were typically younger, male, unpartnered, without children, and had lower income. They had higher rates of chronic pain (31.7% vs. 21.9%, p = .003), childhood adversity, anxiety, and depression (p < .001), and lower perceived social rank (d = .19, .02-.22) and socioeconomic status (d = .37 .16-.26). They also reported higher use rates for most substances (except alcohol); this included medically supervised and unsupervised use of prescription opioids and diverted opioid agonist therapy (OAT) medications. Most (83.2%) met diagnostic criteria for any past-year SUD. Those reporting kratom use were less likely to reside in an urban/suburban area. The strongest predictors of kratom use were use of other drugs: cannabidiol (OR = 3.73), psychedelics (OR = 3.39), and nonmedical prescription opioids (OR = 1.72). Another strong predictor was lifetime OAT utilization (OR = 2.31). Despite seemingly poorer psychosocial functioning and health among respondents reporting lifetime kratom use, use of other substances may be the strongest indicators of kratom use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

An international ban on psychedelics initiated by the United Nations' Convention on Psychotropic Substances in 1971 restricted the clinical use of these ancient psychoactive substances. Yet, in an era marked by rising mental health concerns and a growing "Deaths of Despair" epidemic (i.e., excess mortality and morbidity from suicide, drug overdose, and alcoholism), the structured psychedelic use that has long been a part of ritual healing experiences for human societies is slowly regaining credibility in Western medicine for its potential to treat various mental health conditions. We use a historical lens to examine the use of psychedelic therapies over time, translate ancient lessons to contemporary clinical and research practice, and interrogate the practical and ethical questions researchers must grapple with before they can enter mainstream medicine. Given the COVID-19 pandemic and its contributions to the global mental health burden, we also reflect on how psychedelic therapy might serve as a tool for medicine in the aftermath of collective trauma. Ultimately, it is argued that a "psychedelic renaissance" anchored in the lessons of antiquity can potentially help shift healthcare systems-and perhaps the broader society-towards practices that are more humane, attentive to underlying causes of distress, and supportive of human flourishing.

It is increasingly accepted that higher levels of excellence and innovation in research can be achieved by organizations that promote equity, diversity, and inclusion across several domains including ethnicity and gender. The purpose of this commentary is to provide an overview of the methods used to increase diversity within ACNP, as well as recommendations for accelerating progress. Annual membership surveys confirm increases in female membership and leadership positions, slower but encouraging signals for “Asian” and “Hispanic” members, and less progress for African American and other ethnic populations. Meetings have become visibly more diverse, due in part to ethnic minority travel awards and apparently increasing diversity among guest attendees. Evidence of increasing inclusion includes well-attended networking events and minority-relevant programming, active communications about diversity-related events and resources, and strong statements by ACNP leadership that embrace diversity as a core value and support collaboration among key committees and task forces to identify and implement pro-inclusion and diversity-enhancing efforts. We believe ACNP can accelerate progress with more scientifically valid approaches to assessing diversity and inclusion. The current membership survey includes five outmoded ethnic options and postmeeting surveys that are not designed to assess inclusion efforts and consequences. Measures should be developed that better characterize diversity and assess efforts to reduce the barriers that exist for potential non-White populations (e.g., annual membership and meeting attendance costs). Increased collaboration with NIH and other organizations that are committed to these same goals may also contribute to acceleration of progress by ACNP and other scientific organizations.

Objectives: Investigation into parental decision-making processes involving ketamine is of high priority, given the necessary role of parents in consenting to treatment. In this study, we examined parental attitudes toward the emerging use of ketamine in adolescent mood disorders and suicidality. Methods: Two hundred eighty-three English-speaking parents completed an online survey using Amazon Mechanical Turk on psychiatric use of ketamine, acceptability of treatment, and their perceptions of ketamine treatment. Data quality control measures were used to mitigate invalid reporting. Results: Parents reported high acceptability toward use of ketamine for suicidality, major depressive disorder, and bipolar disorder in adolescents. Primary concerns around ketamine involved its potential side effects and lack of United States Food and Drug Administration (FDA) approval. Responses indicated a preference for short-term applications and less invasive routes of administration for ketamine. Parent history of mental illness, familiarity with psychological treatments, and comfort using other mental health interventions in their children predicted greater acceptability of ketamine. Conclusion: Although ketamine is not currently approved by the FDA for psychiatric use in children nor recommended outside of research protocols, these findings suggest that parents have interest in the application of ketamine as a treatment for pediatric mood disorders and point to future directions for research and clinical orientation.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

Background: Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure of administering a fixed dose. Aims: The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose. Methods: We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N = 288) in which psilocybin was administered in the range 20 to 30 mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg ( n = 120), participants receiving 30 mg/70 kg ( n = 182), and participants whose weight-adjusted dose was about 25 mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) ( n = 103). Results: In the 20 mg/70 kg and 30 mg/70 kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113 kg) the present results showed no evidence that body weight affected subjective effects of psilocybin. Conclusions: These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.

Serotonin 2A receptor (5-HT2AR) agonist “classic psychedelics” are drawing increasing interest as potential mental health treatments. Recent work suggests psychedelics can exert persisting anxiolytic and antidepressant effects lasting up to several months after a single administration. Data indicate acute subjective drug effects as important psychological factors involved in observed therapeutic benefits. Additionally, animal models have shown an important role for 5-HT2AR agonists in modulating learning and memory function with relevance for Alzheimer’s Disease (AD) and related dementias. A number of biological mechanisms of action are under investigation to elucidate 5-HT2AR agonists’ therapeutic potential, including enhanced neuroplasticity, anti-inflammatory effects, and alterations in brain functional connectivity. These diverse lines of research are reviewed here along with a discussion of AD pathophysiology and neuropsychiatric symptoms to highlight classic psychedelics as potential novel pharmacotherapies for patients with AD. Human clinical research suggests a possible role for high-dose psychedelic administration in symptomatic treatment of depressed mood and anxiety in early-stage AD. Preclinical data indicate a potential for low- or high-dose psychedelic treatment regimens to slow or reverse brain atrophy, enhance cognitive function, and slow progression of AD. In conclusion, rationale and potential approaches for preliminary research with psychedelics in patients with AD are presented, and ramifications of this line of investigation for development of novel AD treatments are discussed.

Mitragyna speciosa ('kratom') contains mu opioid partial agonists. It is widely available, and occasionally used as a home remedy for opioid use disorder. The Drug Enforcement Agency considers kratom a drug of concern; however, prevalence of use and role in drug misuse are unknown. This study aimed to characterize kratom use in the United States.Cross-sectional Survey of Non-Medical Use of Prescription Drugs (NMURx) Program, 2018 third quarter and 2019 first quarter.A validated non-probability online survey in the United States.A total of 59 714 respondents aged 18 years or older, weighted to represent the adult US population (n = 252 063 800).In addition to prevalence of past-year kratom and other drug use, behavior proportions were estimated. The Drug Abuse Screening Test (DAST-10) estimated consequences of drug abuse.The estimated prevalence of past-year kratom use in the adult US population was 0.8% [95% confidence interval (CI) = 0.7-0.9], representing 2 031 803 adults. Life-time prevalence was 1.3% (95% CI = 1.2-1.4), representing 3 353 624 adults. Kratom users were younger (mean 35 years, P 0.001), with higher proportions of males (61.0 versus 48.6%, P 0.001), students (14.1 versus 7.5%, P 0.001) and health-care professionals (9.7 versus 4.5%, P 0.001) and fewer bachelor's/advanced degree graduates (33.4 versus 42.6%, P 0.001) compared with non-users. Results were inconclusive on whether there was a difference in kratom use by race, household income or employment status. Among those with past-year kratom use, 36.7% (95% CI = 32.1-41.3) non-medically used prescription opioids, 21.7% (95% CI = 18.0-25.5) used illicit opioids, 54.4% (95% CI = 49.5-59.3) used another illicit drug and 67.1% (95% CI = 62.5-71.8) used cannabis. The DAST-10 profile was more often substantial/severe in kratom users (21 versus 1%, P 0.001) compared with non-users.Estimated United States past-year prevalence of kratom use is 0.8%, and kratom users tend to have more serious substance abuse profiles than non-users or users of cannabis, alcohol or cigarettes. To our knowledge, this is the first description of kratom use at the national level.

Background Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD). Aims The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use. Methods An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings. Results Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption. Conclusions While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Background Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as a potential substance of abuse, with limited data on its use and effects. This study characterized kratom user demographics, use patterns, and perceived drug effects. Methods A cross-sectional, anonymous online survey was conducted between January and December 2017. Results 2,798 kratom users – mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %) – completed the survey. Kratom was primarily taken orally in doses of 1−3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting >1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100. Conclusion Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic.

Background:Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.Aims:To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.Methods:An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.Results:343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.Conclusions:Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. (PsycINFO Database Record

Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. Aims: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Methods: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. Results: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. Conclusions: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse.

Background: Opioid overdose (OD) rates in the United States have reached unprecedented levels. Current OD prevention strategies largely consist of distribution of naloxone and in-person trainings, which face obstacles to expedient, widespread dissemination. Web-based interventions have increased opioid OD response knowledge in patients with opioid use disorders; however, these interventions have not been tested in the larger population of individuals that are prescribed opioid analgesics. This study assessed a web-based intervention providing education across three knowledge domains: opioid effects, opioid OD symptoms, and opioid OD response. Methods: Participants (N=197) were adults recruited on Amazon Mechanical Turk from May to June 2017, who were prescribed an opioid medication for pain. Participants were randomly assigned to a Presentation (n=97) intervention communicating relevant facts in each knowledge domain, or a Presentation + Mastery (n=100) intervention including the same facts but requiring that participants respond correctly to >80% of embedded questions in each module before advancing. Participants completed the Brief Opioid Overdose Knowledge (BOOK) measure before and after the interventions, and provided feedback on acceptability. Results: Both versions of the intervention resulted in significant pre- to post-intervention increases in BOOK scores across all knowledge domains (p

dose ranging trial ofmodafinil inmethamphetamine (MA) dependence. Methods: Eighteen MA dependent outpatients received modafinil (100, 400, or 600mg per day) for four weeks. Subjects receivedweeklyMotivational Interviewing andwere assessed twice per week. The first subject was randomly assigned to 100mg per day. Subsequent subjects were assigned to different dose groups using Eff Tox, a Bayesian dose finding computer program. Dose assignment was based on the results of prior subjects with respect to efficacy (defined as two or more MA-negative urine samples) and toxicity (defined as any adverse effect requiring discontinuation of modafinil). Results: Two subjects were assigned to the 100mg dose condition, 2 to the 400mg condition, and 14 to the 600mg condition. The next subject would have been assigned to the 600mg condition. Conclusions: Subsequent trials ofmodafinil forMAdependence should utilize a 600mgdose ofmodafinil. Bayesian dose finding is a novel, rational method for selecting doses to be used in outpatient trials. Financial support: Supported by NIH R01 DA23567.