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Elizabeth KC Schwartz,1,2 Noah R Wolkowicz,1,2 Joao P De Aquino,1,2 R Ross MacLean,1,2 Mehmet Sofuoglu1,2 1Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 2Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USACorrespondence: Elizabeth KC Schwartz, Tel +1-203-932-5711, Fax +1-203-937-3472, Email Elizabeth.schwartz@yale.eduAbstract: Cocaine use disorder (CUD) is a devastating disorder, impacting both individuals and society. Individuals with CUD face many barriers in accessing treatment for CUD, and most individuals with CUD never receive treatment. In this review, we provide an overview of CUD, including risk factors for CUD, common co-occurring disorders, acute and chronic effects of cocaine use, and currently available pharmacological and behavioral treatments. There are no FDA-approved pharmacological treatments for CUD. Future studies with larger sample sizes and testing treatment combinations are warranted. However, individuals with CUD and co-occurring disorders (eg, a mood or anxiety disorder) may benefit from medication treatments. There are behavioral interventions that have demonstrated efficacy in treating CUD – contingency management (CM) and cognitive-behavioral therapy for substance use disorders (CBT-SUD) in particular – however many barriers remain in delivering these treatments to patients. Following the discussion of current treatments, we highlight some promising emerging treatments, as well as offer a framework that can be used in building a treatment plan for individuals with CUD.Keywords: cocaine, cocaine use disorder, treatment, pharmacotherapy, behavioral interventions

Background and Objectives: Amidst increasing opioid-related overdoses in the USA, opioid use disorder (OUD) treatment has seen few novel treatments emerge. High-potency synthetic opioids (HPSOs) have altered clinical approaches, prompting evaluation of existing medications for opioid use disorder (MOUD) and interest in slow-release oral morphine (SROM) as another therapeutic option. Here we survey addiction specialists on the influence of HPSOs on clinical practice, views on current MOUD regulations, and openness to novel therapies such as SROM., Methods: Anonymous, online survey conducted at a national conference of addiction specialists (N = 91). Pearson χ 2 tests and Fisher's exact tests to compare respondent characteristics., Results: Approximately 89% of respondents (N = 91) acknowledge that HPSOs shifted addiction treatment in recent years, with 86% modifying their MOUD prescribing accordingly. Moreover, 84% report having patients who could benefit from other full opioid agonists beyond methadone for OUD management. Many report off-label prescribing of full agonist opioids other than methadone for withdrawal symptoms or initiating MOUD. Eighty percent reported being in favor of incorporating SROM as a third-line monotherapy for OUD., Discussion and Conclusion: This sample of addiction specialists supports innovative alternatives for MOUD in the USA to combat the challenges posed by fentanyl and related HPSOs. Future work should further addiction specialists' opinions on barriers to OUD treatment and exploration of these international strategies in the USA., Scientific Significance: This appears to be the first study exploring addiction specialists' perspectives on regulatory barriers to OUD treatment and their willingness to uptake internationally adopted strategies such as SROM., (© 2024 The Author(s). The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry (AAAP).)

Rationale: Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the acute response to oral tetrahydrocannabinol (THC) in humans., Methods: 56 healthy men and women with prior exposure to cannabis but no history of CUD participated in a randomized, placebo-controlled, human laboratory study where they received a single 10 mg dose of oral THC (dronabinol). Subjective psychoactive effects were assessed by the visual analog scale of "high", psychotomimetic effects by the Clinician-Administered Dissociative Symptoms Scale and Psychotomimetic States Inventory, verbal learning and memory by Rey Auditory Verbal Learning Test (RAVLT), and physiological effects by heart rate. Outcomes were regularly measured on the test day, except for the RAVLT, which was assessed once. Peak differences from baseline were analyzed using a nonparametric method for repeated measures., Results: Oral THC (10 mg) demonstrated significant dose-related effects in psychotomimetic and physiological domains, but not in RAVLT outcomes. A notable interaction between THC dose and sex emerged concerning the subjective "high" scores, with women reporting heightened sensations (p = 0.05). No other significant effects of sex and THC dose interaction were observed., Conclusion: Oral THC (10 mg) yields similar acute psychotomimetic and physiological effects across sexes, but women may experience a pronounced subjective psychoactive effect. Further research is needed to identify individual vulnerabilities and facilitate tailored interventions addressing CUD., Clinicaltrials: GOV REGISTRATION: https://clinicaltrials.gov/study/NCT02781519?term=Ranganathan&intr=THC&rank=3 ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The clinical implications of high potency synthetic opioids (HPSO) on medications for opioid use disorder (MOUDs) are not well understood. Although pharmacological interactions are plausible, the clinical significance of such interaction has not been systematically elucidated. This scoping review investigates the relationship between HPSO exposure and various MOUD treatment outcomes., Methods: We followed PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews) for scoping reviews with extensive a priori search strategy of databases: MEDLINE, EMBASE, PsycINFO, Web of Science, CINAHL, and Cochrane., Results: From 9149 studies, 34 fulfilled the inclusion criteria. Synthesized data reveal several critical insights: First, there is a variable but high occurrence (38%-80%) of HPSO usage among individuals with MOUDs. Second, MOUDs are linked to a decreased risk of overdoses and deaths associated with HPSO. Third, HPSO consumption is correlated with the risk of precipitated withdrawal when starting buprenorphine. Fourth, low-dose buprenorphine is being recognized as one method to avoid moderate withdrawal symptoms prior to treatment. Lastly, significant gaps exist in human experimental data concerning the effects of HPSO on key factors critical for treating OUD-craving, withdrawal symptoms, and pain., Conclusions: Current evidence supports MOUD safety and effectiveness in reducing nonmedical opioid use. Further research is needed to explore HPSO's influence on the acute factors preceding nonmedical opioid use, such as cravings, withdrawal symptoms, and pain. This research could inform the optimization of MOUD dosing strategies. Achieving consensus and harmonizing data across clinical and research protocols could diminish variability, enhancing our understanding of HPSOs effect on MOUD treatment outcomes., Competing Interests: J.P.D. is supported by grants K23DA052682, R21DA057240, and R01DA060066 from the National Institute on Drug Abuse. J.P.D. has been supported in clinical trials by Jazz Pharmaceuticals, specifically through medication provisions. Additionally, J.P.D. has been a compensated consultant for Boehringer Ingelheim. S.B.M. reported consulting for Alkermes previously. I.P. reports the following: in kind (medications) support for research studies from Alkermes and BioXcel Therapeutics; coeditor for Journal of Addiction Medicine; has received textbook royalties from McGraw/Hill; Patents and Inventions: (1) Arias A, Petrakis I, Krystal JH. Composition and methods to treat addiction. Provisional Use Patent application no. 61/973/961. April 2, 2014. Filed by Yale University Office of Cooperative Research, (2) Gihyun, Yoon, Petrakis I, Krystal JH. Compounds, Compositions and Methods for Treating or Preventing Depression and Other Diseases. US Provisional Patent application no. 62/444,552, filed on January10, 2017, by Yale University Office of Cooperative Research OCR 7088 US01. O.J., C.H., E.C., and M.C.F. report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Introduction: Attentional bias (AB) is believed to be an important factor in the development and maintenance of both opioid use disorder (OUD) and chronic pain. Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), produce analgesic effects via processes that are potentially relevant to AB and is commonly used by persons with OUD. This exploratory study investigated if THC influences AB towards pain and opioid cues individuals with OUD., Methods: Using a within-subject, crossover design, 27 adults receiving methadone were randomly assigned to receive single doses of oral THC (10 mg, 20 mg administered as dronabinol) or placebo across three, 5-h sessions. During each session, a visual probe task was used to measure AB to pain and opioid cues at baseline and 120 min post-THC administration., Results: Mixed-effects models examined main effects of THC dose, time, and their interaction across all participants; findings were then stratified by methadone dose (low dose <90 mg/day and high dose ≥90 mg/day). Among individuals receiving high doses of methadone, a significant interaction was observed such that AB towards opioids increased following 10 mg THC administration and decreased following 20 mg THC administration. Additionally, participants receiving low doses of methadone showed significant increases in the variability of opioid-related AB post THC administration., Conclusion: We provide preliminary evidence showing that THC may cause dose-dependent effects on selective attention for opioid cues among methadone patients. These results underscore the need for further clinical investigation into the effects of cannabinoids and other substances with potential analgesic and addictive properties among persons with OUD., Competing Interests: Declaration of competing interest None. Funding Statement This work was supported by the Robert E. Leet and Clara Guthrie Patterson Mentored Clinical Research Award and by the VISN-1 Mental Illness Research, Education, and Clinical Center (MIRECC) Pilot Award Program. Joao P. De Aquino is supported by Grants K23DA052682 and R21DA057240 from the National Institute on Drug Abuse (NIDA). R. Ross MacLean is supported by a Development Career Development Award 1IK2CX002286 from VA Clinical Science Research and Development (CSR&D). Other than providing funding, the Patterson Trust, the VA and NIDA had no role in the conception and conduction of this project or in the interpretation or reporting of its findings., (Published by Elsevier Ltd.)

In recent years, Black people in the U.S. have had one of the highest increases in opioid overdose mortality rates, despite being less likely to be prescribed opioids for pain. This population is also less likely to receive medications for opioid use disorder (MOUD). Chronic pain is a central factor in understanding this crisis, as minoritized people are more likely to live with undertreated pain, a major risk factor for developing opioid use disorder (OUD). Current practices fail to effectively treat pain among persons with OUD, a missed opportunity that is worse in minoritized populations and further producing disparities. In this perspective, we discuss how racism-related stress and disparities in addiction treatments may impact the pain experience, diagnosis, treatment, contribute to developing OUD, and perpetuate stigma. This high-level perspective invites clinicians and researchers to reflect on the biopsychosocial burden imposed upon historically minoritized people with pain and OUD. To address such complex issues, multidisciplinary efforts and methodological improvements are required, imbued by antiracist values. Collaboration across disciplines is necessary toward the common goal of improving pain management and mitigating opioid mortality among minoritized populations. As antiracist perspectives inform research practices and cultural humility principles guide care, we will be better equipped to close current gaps in knowledge and address widening healthcare disparities.

Chronic pain and opioid use disorder (OUD) are major public health problems, with rising opioid-related overdose deaths linked to increased opioid prescriptions for pain management. Novel treatment approaches for these commonly comorbid disorders are needed. Growing evidence supports a role for glial activation for both chronic pain and substance use disorders, including OUD. This review provides an overview of glial modulators as a novel treatment approach for comorbid pain and OUD. We aim to synthesize clinical studies investigating the efficacy of glial modulators in treating these comorbid disorders. We conducted a literature search of PubMed and Google Scholar databases in October 2023 to identify relevant clinical trials. The included studies varied in terms of patient population, study methodology and outcomes assessed, and were often limited by small sample sizes and other methodological issues. Additionally, several glial modulators have yet to be studied for chronic pain and OUD. Despite these limitations, these studies yielded positive signals that merit further investigation. Both chronic pain and OUD remain significant public health problems, with many treatment challenges. Glial modulators continue to hold promise as novel therapeutics for comorbid pain and OUD, given positive indications that they can improve pain measures, and reduce addiction-related outcomes. As our understanding of the mechanisms underlying the contributions of glial modulators to pain and addiction behaviours deepens, we will be better equipped to identify more specific therapeutic targets for chronic pain and OUD., (© 2024 British Pharmacological Society.)

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance., Competing Interests: Dr. De Aquino has received in-kind medication support for clinical trials from Jazz Pharmaceuticals and has served as a consultant for Boehringer Ingelheim. Dr. Petrakis has received in-kind medication support for research studies from Alkermes and BioXcel Therapeutics and is co-editor of the Journal of Addiction Medicine. Dr. Petrakis has received royalties from McGraw Hill and is named on provisional patent applications for methods to treat addiction (U.S. 61/973/961) and for methods for treating or preventing depression and other diseases (U.S. 62/444,552). The other authors report no financial relationships with commercial interests.

Background and Objectives: Childhood trauma (CT) increases addiction vulnerability. We examined CT's impact on delta-9-tetrahydrocannabinol (THC) effects., Methods: This is a post-hoc analysis of a randomized, placebo-controlled, crossover trial investigating the effects of oral THC (10, 20 mg) among 25 persons receiving methadone for opioid use disorder (OUD)., Results: Greater CT was associated with lower aversive effects from higher THC doses (20 mg) (p = .006)., Discussion and Conclusions: CT may reduce the subjective aversive effects of THC, potentially leading to greater cannabis use in individuals with OUD., Scientific Significance: These findings offer insights into THC's risks versus benefits in OUD subgroups and emphasize assessing CT in OUD treatment and research., (© 2023 The American Academy of Addiction Psychiatry (AAAP).)

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis., (© 2024 British Pharmacological Society.)

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, because ongoing opioid use brings changes in pain responses and most pain assessment tools have not been validated for this population. In this narrative review, we discuss the fundamentals of pain assessment for populations with OUD. First, we describe the biological, psychological and social aspects of the pain experience among people with OUD, as well as how opioid-related phenomena may contribute to the pain experience in this population. We then review methods to assess pain, including (1) traditional self-reported methods, such visual analogue scales and structured questionnaires; (2) behavioural observations and physiological indicators; (3) and laboratory-based approaches, such as quantitative sensory testing. These methods are considered from a perspective that encompasses both pain and OUD. Finally, we discuss strategies for improving pain assessment in persons with OUD and implications for future research, including educational strategies for multidisciplinary teams. We highlight the substantial gaps that persist in this literature, particularly regarding the applicability of current pain assessment methods to persons with OUD, as well as the generalizability of the existing results from adjacent populations on chronic opioid therapy but without OUD. As research linking pain and OUD evolves, considering the needs of diverse populations with complex psychosocial backgrounds, clinicians will be better equipped to reduce these gaps., (© 2024 British Pharmacological Society.)

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear. Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD. Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality. Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p  = .98). There is evidence of moderate heterogeneity and publication bias. Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

France is experiencing exceptionally high closures of hospital geriatric beds, which increases the difficulties of access to geriatric care for the oldest and most frail French citizens. The French Society of Geriatrics and Gerontology (SFGG) conducted a national survey in January 2023 among French geriatricians and gerontologists with the aim of drawing up an inventory of the closure of hospital geriatric beds in France and the reasons for these closures. The online survey was carried out among the 1,600 members of the SFGG between January 8 and 22, 2023. The results showed that 34.7% of geriatric units were affected by bed closures in January 2023, with 25.7% of beds closed on average. All levels of hospital geriatric sectors were affected by bed closures, but rehabilitation units were the most affected ones. The most frequent reason for bed closures was the lack of nurses, then the lack of physicians, and finally the lack of nursing aids. Reopening dates were not defined in more than 90% of cases. Resolving this crisis will imply recognizing and revaluing geriatric caregivers, both financially and in terms of more appropriate caregiver/patient ratios. These measures are necessary to avoid the bankruptcy of hospitals and to preserve decent, respectful and dignified care for our seniors.

The opioid and cannabinoid receptor systems are inextricably linked-overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta-9-tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within-subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5-h test sessions. Measures of experimental and self-reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed-effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low-dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk-benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis., (© 2023 Society for the Study of Addiction.)

Objectives: To assess the knowledge and the use in clinical practice of the "French National Authority for Health" (HAS) 2021 recommendations on the diagnosis of malnutrition in older adults aged 70 years and above., Methods: An online survey was developed by the working Group on Geriatrics and Nutrition (GEGN) of the "Société Française de Gériatrie et de Gérontologie (SFGG)" and conducted among members of the SFGG. A self-administered questionnaire composed of 21 closed questions was used., Results: A total of 132 (10.2 %) members of the SFGG responded to the survey. The respondents were aged 43.4 ± 9.94 years old and 97 (73.5 %) were women. Almost half of them were medical doctors (n = 53 ; 40.2 %). Of the respondents, 81 % had already heard of the HAS 2021 recommendations. This percentage is higher for doctors (96 %) than for other professions (74 %). French respondents were more likely to have heard of these -recommendations (84 %) than respondents from other countries (42.9 %). However, only 41.6 % of the respondents believe they know these recommendations in detail. On a visual analogue scale from 0 (never) to 100 (always), respondents use these recommendations in their professional practice at 76.8 ± 20.2 %. However, on a scale from 0 (never difficult) to 100 (always difficult), some barriers to their use in clinical practice were highlighted. These mainly concerned the measurement of muscle mass (84.4 ± 17.2 %) and muscle strength (79.5 ± 19.9 %) in patients., Conclusion: Although the majority of respondents use the HAS 2021 recommendations in their professional practice, they often have difficulties in measuring muscle strength and muscle mass of their patients. The assessment of sarcopenia still needs to be implemented in clinical routine. Until then, better communication about simple alternatives that do not require special equipment is needed.

The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment.

Background: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects., Methods: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality., Results: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline., Conclusions: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics., Competing Interests: Conflict of Interest No conflicts declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials., Objectives: we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies., Study Eligibility Criteria, Participants, and Interventions: we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving., Study Appraisal and Synthesis Methods: Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes., Results: Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes., Limitations: Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy., Conclusions: There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.

Rationale: Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions., Objectives: To determine the feasibility of a pulsed-nicotine infusion model in smokers., Methods: Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session., Results: Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test., Conclusions: These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Cannabis use (CU) is common among persons with bipolar disorder (BD). Evidence suggests that CU is associated with poorer outcomes among persons with BD; however, these findings remain inconsistent. The present exploratory study aims to examine clinical, functional, and cognitive correlates of CU among persons with BD. Methods: U.S. veterans with BD type I who participated in a large-scale, nationwide study were categorized into four groups: current CU, past CU, past other drug use, and no drug use. Bivariate analyses, univariate analyses of covariance, and Levene's Test for Equality of Variance were used to compare groups on clinical, cognitive, and functional measures. Results: Of 254 (84.6% male) veterans with BD type I included in the analyses, 13 (5.1%) had current CU, 37 (14.5%) past CU, 77 (30.3%) past other drug use, and 127 (50%) reported no drug use. BD with CU was associated with post-traumatic stress disorder (PTSD) and experiencing lifetime suicidal ideation. Notably, current CU was associated with higher working memory performance, compared to both past CU and no drug use. Likewise, current CU was associated with higher functional capacity, compared to past CU as well as no drug use. Conclusions: These findings contribute to the growing literature on the complex effects of cannabis on BD. As the commercialization and legalization of cannabis increases, further research in this area is warranted to quantify posed risks to this population, and thereby guide clinical decision-making.

Background: Although Alcohol Use Disorder (AUD) is highly prevalent worldwide, treating this condition remains challenging. Further, potential treatments for AUD do not fully address alcohol-induced neuroadaptive changes. Understanding the effects of pharmacotherapies for AUD on the human brain may lead to tailored, more effective treatments, and improved individual clinical outcomes., Objectives: We systematically reviewed the literature for studies investigating pharmacotherapies for AUD that included neuroimaging-based treatment outcomes. We searched the PubMed, Scielo, and PsycINFO databases up to January 2021., Study Eligibility Criteria, Participants, and Interventions: Eligible studies included those investigating pharmacotherapies for AUD and employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and/or proton magnetic resonance spectroscopy (H-MRS)., Study Appraisal and Synthesis Methods: Two independent reviewers screened studies' titles and abstracts for inclusion. Data extraction forms were shared among all the authors to standardize data collection. We gathered information on the following variables: sample size; mean age; sociodemographic and clinical characteristics; alcohol use status; study design and methodology; main neuroimaging findings and brain-regions of interest (i.e., brain areas activated by alcohol use and possible pharmacological interactions); and limitations of each study., Results: Out of 177 studies selected, 20 studies provided relevant data for the research topic. Findings indicate that: (1) Acamprosate and gabapentin may selectively modulate limbic regions and the anterior cingulate cortex; (2) Naltrexone and disulfiram effects may involve prefrontal, premotor, and cerebellar regions; (3) Pharmacotherapies acting on glutamate and GABA neurotransmission involve primarily areas underpinning reward and negative affective states, and; (4) Pharmacotherapies acting on opioid and dopamine systems may affect areas responsible for the cognitive and motor factors of AUD., Limitations: Most of the studies were focused on naltrexone. A small number of studies investigated the action of disulfiram and gabapentin, and no neuroimaging studies investigated topiramate. In addition, the time between medication and neuroimaging scans varied widely across studies., Conclusions: We identified key-brain regions modulated by treatments available for AUD. Some of the regions modulated by naltrexone are not specific to the brain reward system, such as the parahippocampal gyrus (temporal lobe), parietal and occipital lobes. Other treatments also modulate not specific regions of the reward system, but play a role in the addictive behaviors, including the insula and dorsolateral prefrontal cortex. The role of these brain regions in mediating the AUD pharmacotherapy response warrants investigation in future research studies.

Faster delivery rate enhances the abuse potential of drugs of abuse, yet systematic studies on the impact of delivery rate on the acute effects of nicotine in humans are lacking. Using an intravenous (IV) nicotine infusion procedure that allows precise control of rate of delivery, we examined the impact of nicotine delivery rate on the positive subjective drug effects, smoking urges, withdrawal, heart rate, blood pressure and attention function in smokers. Twenty-four male and female (ages 21-35) dependent smokers attended five experimental sessions, following overnight abstinence from smoking. Using a crossover design, participants attended five sessions, where they were assigned to a random sequence of saline infusion or 1 mg nicotine delivered over 1, 2.5, 5 or 10 min at rates of 1, 0.4, 0.2 or 0.1 mg/min, respectively. The positive subjective effects of nicotine were most robust under the two faster delivery rate conditions, 1- and 0.4-mg nicotine/min. In contrast, all nicotine delivery rates were equally more effective than saline in alleviating urges to smoke. Likewise, nicotine-induced heart rate increases did not vary with the rate of nicotine delivery. Lastly, the cognitive enhancing effects of nicotine were observed only under the two slowest delivery rate conditions-0.1- and 0.2-mg nicotine/min. Collectively, these findings support the critical role of delivery rate in optimizing nicotine's abuse potential versus potential therapeutic effects and have timely implications for developing novel therapeutics for nicotine dependence, as well as for tobacco regulatory science., (© 2022 Society for the Study of Addiction.)

Purpose of Review: This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse liability., Recent Findings: Pharmacological treatments for substance use disorders may include gabapentinoids, baclofen, modafinil, ketamine, cannabinoids, gamma-hydroxybutyrate, and psychedelics. Gabapentinoids may decrease negative subjective effects of withdrawal in alcohol and cannabis use disorders. Cannabinoids similarly appear to decrease use and withdrawal symptoms in cannabis use disorder, while research shows stimulant medications may reduce cravings and increase abstinence in cocaine use disorder. Ketamine and psychedelics may help treat multiple substance use disorders. Ketamine may reduce withdrawal symptoms, promote abstinence, and diminish cravings in alcohol and cocaine use disorders and psychedelics may promote remission, decrease use, and reduce cravings in alcohol and opioid use disorders., Summary: Regardless of current regulatory approval statuses and potentials for abuse, multiple agents should not be dismissed prematurely as possible treatments for substance use disorders. However, further clinical research is needed before effective implementation can begin in practice., Supplementary Information: The online version contains supplementary material available at 10.1007/s40429-022-00432-9., Competing Interests: Competing interestsThe authors declare no conflicts of interest. Dr. Potenza has consulted for Opiant Therapeutics, Game Day Data, Baria-Tek, the Addiction Policy Forum, AXA and Idorsia Pharmaceuticals; has been involved in a patent application with Yale University and Novartis; has received research support from Mohegan Sun Casino and the National Center for Responsible Gaming; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse-control disorders or other health topics; has consulted for and/or advised gambling and legal entities on issues related to impulse-control/addictive disorders; has provided clinical care in a problem gambling services program; has performed grant reviews for research-funding agencies; has edited journals and journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. The other authors do not report disclosures., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The French Society of Geriatrics and Gerontology (SFGG) stands against ageism and strives to combat it in all its forms. The SFGG has warned about the persistence of age discrimination and the emergence of new forms of ageism alongside traditional stereotypes. The SFGG took a position on the occasion of the 70 th anniversary of the Universal Declaration of Human Rights in December 2018. In September 2020, the SFGG again raised the alarm, on the 20 th anniversary of the inclusion of the Rights of the Elderly in the European Charter. It has organised a wide-reaching communication campaign against ageism, involving learned societies of geriatrics and gerontology as well as all the major international institutions working to defend the rights of older adults.

Background: Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects., Methods: We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by previously established validity measures., Results: Nine studies were identified, with a total of 225 participants, of whom 63% were male, and 37% were female. Six studies included methadone-maintained persons with OUD; four studies included buprenorphine-maintained persons with OUD; and three studies included healthy persons as comparison groups. Either additional doses of OAT or other opioids - morphine, oxycodone, hydromorphone, or remifentanil - were administered. In seven studies, persons with OUD on OAT did not experience analgesia, despite receiving opioid doses up to 20 times greater than those clinically used to treat severe pain among the opioid naïve. Conversely, in two studies, high-potency opioids did produce analgesia, albeit with greater abuse potential. Notably, persons with OUD on OAT remained vulnerable to respiratory depression., Conclusions: Although persons with OUD on OAT can derive analgesic effects from opioids, high-potency compounds may be required to achieve clinically significant pain relief. Further, persons with OUD on OAT may remain vulnerable to opioid-induced abuse potential and respiratory depression. Together, these finding have clinical, methodological, and mechanistic implications for the treatment of acute pain in the context of OAT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The clinical features and neurobiology of pain and opioid use disorder (OUD) are inextricably linked. Despite emerging evidence supporting the negative impact of ongoing pain in the treatment of OUD, the pharmacological management of pain in the presence of OUD has received limited attention. We sought to systematically review the studies investigating pharmacotherapies for pain among persons with OUD. Eligible studies had participants with OUD and outcomes including evoked or spontaneous pain. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Out of 1,097 studies that met the search criteria, 12 studies provided data relevant to the research question-five laboratory studies and seven clinical trials. Random effects pooled estimates suggested no significant difference between groups at baseline but a response favoring the active treatment group over placebo, with nonsignificant heterogeneity between studies. Findings from these studies provide preliminary evidence for analgesic and antihyperalgesic effects of gabapentin, GABA agonists, and NMDA antagonists among persons with OUD. To establish the tradeoffs between the analgesic effects and abuse liability of these compounds, further well-controlled clinical trials are required among persons with OUD. This review also underscores the need for methodological enhancement in drug development for pain in OUD. Future research should address the clinical and neurobiological overlap between pain- and addiction-related phenomena. Transdisciplinary approaches may identify biomarkers of these shared phenomena and their neural substrates. The development of novel therapeutics for pain in OUD may be accelerated by such integration of pain and addiction research., (© 2020 Society for the Study of Addiction.)

Although expanding the availability of buprenorphine-a first-line pharmacotherapy for opioid-use disorder (OUD)-has increased the capacity of healthcare systems to offer treatment, starting this medication is fraught with significant barriers. Standard induction regimens require persons with OUD to taper and discontinue full opioid agonists and experience opioid withdrawal prior to the first dose of buprenorphine. Further, emerging evidence indicates that precipitated withdrawal during induction may impact long-term treatment outcomes. Microinduction is a novel approach that, by harnessing buprenorphine's unique pharmacological profile, may allow circumventing the needed for prolonged opioid tapers, and reduce the risk of precipitated withdrawal-holding promise to enhance treatment access. In this review, we examine the pharmacological basis for microinduction and appraise the evidence of this approach to improve clinical outcomes among persons with OUD. First, we highlight the potential dose-dependent effects of buprenorphine on two key neuroadaptations at the mu-opioid receptor (MOR)-resensitization and upregulation. We then focus on how microinduction may reverse these chronic MOR neuroadaptations, allowing the maintenance of an adequate opioid tone, and thereby potentially circumventing opioid withdrawal. Second, we describe the clinical evidence available, derived from observational reports and open-label studies, examining the potential efficacy of microinduction. Despite significant heterogeneity-exemplified by variable buprenorphine formulations, daily doses, and schedules of administration-these data provide preliminary support for the feasibility of microinduction. Finally, we provide new mechanistic, methodological, and clinical insights to guide future translational research, as well as randomized, placebo-controlled clinical trials in this compelling agenda of pharmacotherapy development.

The SFGG (French Society of geriatrics and gerontology) stands up against ageism and fights it in all its forms of expression. The SFGG warns about the persistence of age discrimination and the emergence of new forms of ageism alongside traditional stereotypes. The SFGG has taken a position on the occasion of the 70th anniversary of the Universal Declaration of Human Rights in December 2018. In September 2020, the SFGG is again raising the alarm on the 20th anniversary of the inclusion of the Rights of the Elderly in the European Charter. It is organising a wide communication campaign against ageism, involving all the learned societies of geriatrics and gerontology as well as all the major international institutions that defend the rights of older adults.

The objective of this national French survey was to determine the coronavirus disease 2019 (COVID-19) semiology in seniors (n = 353; mean, 84.7 ± 7.0 years). A total of 57.8% of patients exhibited ≤3 symptoms, including thermal dysregulation (83.6%), cough (58.9%), asthenia (52.7%), polypnea (39.9%), and gastrointestinal signs (24.4%). Patients ≥80 years exhibited falls (P = .002) and asthenia (P = .002). Patients with neurocognitive disorders exhibited delirium (P < .001) and altered consciousness (P = .001). Clinical peculiarities of COVID-19 were reported in seniors., Clinical Trials Registration: NCT04343781., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: As the United States faces a national opioid crisis, opioid overdose deaths have significantly risen over the past decade. Patients with opioid use disorder, particularly those who use high-potency synthetic opioids, are at an increased risk of fatal opioid overdose. Alternative dosing strategies for the treatment of opioid use disorder must be considered in high-risk patients to prevent opioid overdose. Case : One patient with opioid use disorder at high risk for overdose was treated with extended-release (XR) intramuscular (IM) naltrexone initially every 28 days, but was frequently reporting increased cravings during the week prior to the next injection being due. This patient's dose of XR IM naltrexone was then given at an increased dosing frequency of every 21-24 days for three months. Opioid craving suppression was achieved without clinical or laboratory evidence of side effects or hepatotoxicity. Discussion : In patients with especially high risk of opioid overdose, consideration of novel dosing strategies for continuation of opioid abstinence is necessary. This is the first report demonstrating the short-term safety and efficacy of more frequent dosing of XR IM naltrexone. This case demonstrates that in select high-risk patients, more frequent dosing of XR IM naltrexone may be an effective strategy to reduce opioid cravings. Informed Consent : The case was reviewed with the Intuition's Privacy Officer who informed the authors that informed consent could not be obtained by the patient's family members due to 38 U.S.C 7332 restrictions on protected information. This manuscript was de-identified and approved by the institution's local privacy officer for publication in accordance with institution policy.

Competing Interests: "Tous les auteurs répondent à tous les critères suivants : contribution à la conception ou à l’analyse et à l’interprétation des données ; rédaction de l’article ou révision critique et apport intellectuel important ; approbation de la version finale à publier."

Background: Multiple states have authorized cannabis as an opioid substitution agent and as a treatment for posttraumatic stress disorder (PTSD)., Objectives: This study sought to investigate the relationship between cannabis use, non-medical opioid use, and PTSD symptoms among U.S. veterans., Methods: From 1992-2011, veterans admitted to specialized intensive PTSD treatment participated in a national evaluation with assessments at intake and four months after discharge. Participants with non-medical opioid use ≥ 7 days during the 30 days preceding admission were divided into two groups: those with cannabis use ≥ 7 days, and those without cannabis use. These two groups were compared on measures of substance use and PTSD symptoms at baseline and 4-months outpatient follow-up. We hypothesized that, at both assessments, the group with baseline cannabis use would show less non-medical opioid use and less severe PTSD symptoms., Results: Of 1,413 veterans with current non-medical opioid use, 438 (30.3%) also used cannabis, and 985 (69.7%) did not. At baseline, veterans with concurrent non-medical opioid and cannabis use had slightly fewer days of non-medical opioid use ( p < .005; d = -0.16), greater use of other substances ( p < .0001) and more PTSD symptoms ( p = .003; d = 0.16), compared to veterans who used non-medical opioids but not cannabis. At follow-up, substance use or PTSD symptoms did not significantly differ., Conclusion: Cannabis use was not associated with a substantial reduction of non-medical opioid use, or either improvement or worsening of PTSD symptoms in this population. Hence, these data do not encourage cannabis use to treat either non-medical opioid use or PTSD.

Conception and construction of nursing homes focuses mostly on architectural design. The cost of gardens and amount of work they require is usually underestimated. This often results in inaccessible, unfit and poorly designed outdoor spaces. This article describes a partnership between three French institutions established in response to the needs of people with cognitive disabilities. This partnership led to three different approaches (scientific, pedagogical and practical) with a common objective to provide dementia-friendly outdoor spaces.

Objectives: Alternative transition protocols from methadone to buprenorphine in the treatment of opioid use disorder (OUD) are needed to reduce the risk of precipitated withdrawal and opioid use during induction., Methods: Case report (n = 1)., Results: One patient with OUD underwent a rapid microinduction outpatient protocol that did not cause precipitated withdrawal or require preceding taper before cessation of methadone. The induction was carried out safely in the outpatient setting., Conclusions: This report provides a patient-centered approach demonstrating feasibility and cost-effectiveness of rapid transition to buprenorphine in the US outpatient psychiatry setting. Barriers to adherence to opioid agonist therapy may be reduced using this protocol.

The COVID-19 epidemic that started in November in China became a national epidemic from March 16, 2020 with the declaration of population containment in order to reduce the spread of the virus in France. From March 17 to March 27, 2020, the monitoring unit of the French society of geriatrics and gerontology decided to conduct a survey to analyze the implementation of the mobilization of geriatric units, given that this epidemic had shown that it resulted in excess mortality mainly among the elderly. The survey was able to bring together the response of 34 services, nine of which were located in a high epidemic cluster zone. Dedicated acute geriatric units for patients infected with COVID-19 were present in eight facilities, only outside the cluster zones. Nine geriatric follow-up and rehabilitation services were dedicated, an additional telemedicine activity concerned 35% of the facilities, and family listening and tablet communication facilities concerned 36% of the facilities. This survey is a snapshot of an initial moment in the epidemic. It provides an opportunity to describe the context in which this epidemic occurred in terms of geriatric policy, and to assess the responsiveness and inventiveness of these services in meeting the needs of the elderly.

Rationale: The catechol-O-methyl transferase (COMT) enzyme has been implicated in determining dopaminergic tone and the effects of delta-9-tetrahydrocannabinol (THC) in the human brain., Objective: This study was designed to evaluate the effect of (1) a functional polymorphism and (2) acute pharmacological inhibition of COMT on the acute response to THC in humans., Methods: Sub-study I: The effect of intravenous (IV) THC (0.05 mg/kg) was investigated in 74 healthy subjects genotyped for the COMT rs4680 (Val/Met) polymorphism in a 2-test-day double-blind, randomized, placebo-controlled study. Sub-study II: COMT rs4680 homozygous subjects (Val/Val and Met/Met) from sub-study I received the COMT enzyme inhibitor tolcapone (200 mg) followed by IV THC or placebo on two additional test days. Subjective, behavioral, and cognitive data were obtained periodically on each test day., Results: Sub-study I: Val/Val individuals were most sensitive to THC-induced attention and working memory deficits. In contrast, the psychotomimetic and subjective effects of THC were not influenced by COMT genotype. Sub-study II: Tolcapone reduced THC-induced working memory deficits, but not THC's psychotomimetic effects. Tolcapone and COMT genotype (met/met) were associated with an increased report of feeling "mellow.", Conclusions: The interaction between COMT rs4680 polymorphisms and tolcapone on the cognitive, but not on the psychotomimetic and overall subjective effects of THC, suggests that modulation of dopaminergic signaling may selectively influence specific cannabinoid effects in healthy individuals. The role of dopaminergic signaling in the cognitive effects of cannabinoids should be considered in drug development efforts targeting these effects. CLINICALTRIALS.GOV REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00678730?term=NCT00678730&rank=1 ClinicalTrials.gov Identifier: NCT00678730.

Rationale: Δ-9-Tetrahydrocannabinol (Δ-9-THC) produces psychotomimetic effects in humans. However, the role of dopamine signaling in producing such effects is unclear. We hypothesized that dopaminergic antagonism would reduce the psychotomimetic effect of Δ-9-THC., Objective: The objective of this study was to evaluate whether pre-treatment with haloperidol would alter the psychotomimetic and perceptual-altering effects of Δ-9-THC, measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinician-Administered Dissociative Symptom Scale (CADSS) in humans., Methods: In a two-test-day double-blind study, 28 healthy individuals were administered with active (0.057 mg/kg) or placebo oral haloperidol, followed 90 and 215 min later by intravenous administration of active (0.0286 mg/kg) Δ-9-THC and placebo, respectively. This secondary analysis was conducted because of the observation in other studies and in our data that a significant proportion of individuals may not have an adequate response to THC (floor effect), thus limiting the ability to test an interaction. Therefore, this analysis was performed including only responders to THC (n = 10), defined as individuals who had an increase of at least one point on the PANSS positive scale, consistent with prior human laboratory studies., Results: In the 10 responders, Δ-9-THC-induced increases in PANSS positive scores were significantly lower in the haloperidol condition (1.1 + 0.35) compared with the placebo condition (2.9 + 0.92)., Conclusion: This responder analysis showed that haloperidol did reduce the psychotomimetic effect of Δ-9-THC, supporting the hypothesis that dopaminergic signaling may participate in the psychosis-like effects of cannabinoids.

Objectives: Dance interventions are pleasant social activities that are often offered to people with dementia in care settings. Effectiveness of dance as a psychosocial intervention for people with dementia has been studied to some extent, but several methodological issues remain unexplored. This review aimed to analyze studies on dance interventions for people with dementia and to identify practice recommendations for the development of these interventions., Methods: An electronic database search was run in December 2017 to identify records of dance interventions for people with dementia. We included all studies regardless of experimental design. Selected records were analyzed according to five criteria: study design and intentions of interventions; profile of participants and in/exclusion criteria; treatment indications and contraindications; description and performance of the interventions; and involved physical, cognitive, psychological, and social processes in dance., Results: Fourteen records were included in which various study designs were observed. Description and performance of the interventions were well documented. Nine practice recommendations for implementing dance interventions were identified according to primary intentions of the intervention (therapeutic or recreational): indications; contra-indications; participant profile; dosage; session sequencing; setting of intervention; observance/attendance; contributors and facilitators;and assessments., Conclusions: Dance is a holistic intervention that can be implemented with a therapeutic or a leisure intention. Practice recommendations about dance interventions remain incomplete and insufficiently studied. Such recommendations could be helpful for clinicians to implement dance interventions in facilities where they work to better target people who could benefit from them, and for researchers to develop research in this field.