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The Journal of Pharmacology and... Jun 2024Endocannabinoids, which are present throughout the central nervous system (CNS), can activate CB1 and CB2 receptors. CB1 and CB2 agonists exhibit broad...
Endocannabinoids, which are present throughout the central nervous system (CNS), can activate CB1 and CB2 receptors. CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases. However, careful evaluation of abuse potential is necessary. This study evaluated the abuse potential of lenabasum, a selective CB2 receptor agonist in participants (n=56) endorsing recreational cannabis use. Three doses of lenabasum (20, 60, and 120mg) were compared to placebo, and nabilone (3 and 6mg). The primary endpoint was the peak effect (Emax) on a bipolar Drug Liking visual analog scale (VAS). Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. : Lenabasum was safe and well tolerated. Compared to placebo, a 20mg dose of lenabasum did not increase ratings of Drug Liking and had no distinguishable effect on other VAS endpoints. Dose-dependent increases in ratings of Drug Liking were observed with 60 and 120mg lenabasum. Drug Liking and all other VAS outcomes were greatest for nabilone 3mg and 6mg, which is a currently FDA-approved medication. : At a target therapeutic dose (20mg), lenabasum did not elicit subjective ratings of Drug Liking. However, supratherapeutic doses of lenabasum (60 and 120mg) did elicit subjective ratings of Drug Liking compared to placebo. Although both doses of lenabasum were associated with lower ratings of Drug Liking compared to 3mg and 6mg of nabilone, suggesting that lenabasum does have abuse potential and should be used cautiously in clinical settings. This work provides evidence that in people with a history of recreational cannabis use, lenabasum was safe and well-tolerated, although it did demonstrate abuse potential. This work supports further development of lenabasum for potential therapeutic indications.
PubMed: 38936978
DOI: 10.1124/jpet.124.002129 -
The British Journal of General Practice... Jul 2024
Topics: Humans; General Practice; Alcoholics Anonymous; Alcoholism; United Kingdom; Practice Patterns, Physicians'
PubMed: 38936861
DOI: 10.3399/bjgp24X738549 -
Brain Research Jun 2024Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects...
Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.
PubMed: 38936532
DOI: 10.1016/j.brainres.2024.149096 -
Hepatology (Baltimore, Md.) Jun 2024The public health impact of alcohol-associated liver disease (ALD), a serious consequence of problematic alcohol use, and alcohol use disorder (AUD) is growing, with ALD...
The public health impact of alcohol-associated liver disease (ALD), a serious consequence of problematic alcohol use, and alcohol use disorder (AUD) is growing, with ALD becoming a major cause of alcohol-related death overall and the leading indication for liver transplantation in the United States. Comprehensive care for ALD often requires treatment of AUD. Although there is a growing body of evidence showing that AUD treatment is associated with reductions in liver-related morbidity and mortality, only a minority of patients with ALD and AUD receive this care. Integrated and collaborative models that streamline both ALD and AUD care for patients with ALD and AUD are promising approaches to bridge this treatment gap and rely on multidisciplinary and interprofessional teams and partnerships. Here, we review the role of AUD care in ALD treatment, the effects of AUD treatment on liver-related outcomes, the impact of comorbid conditions such as other substance use disorders, obesity, and metabolic syndrome, the current landscape of integrated and collaborative care for ALD and AUD in various treatment settings. We further review knowledge gaps and unmet needs that remain, including the role of precision medicine, the application of harm reduction approaches, the impact of health disparities, the need for additional AUD treatment options as well as further efforts to support implementation and dissemination.
PubMed: 38935926
DOI: 10.1097/HEP.0000000000000996 -
JAMA Jun 2024
PubMed: 38935607
DOI: 10.1001/jama.2024.11977 -
MMWR. Morbidity and Mortality Weekly... Jun 2024In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year. Medications for opioid use disorder (OUD),...
In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year. Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality. However, only a small proportion of persons with OUD receive these medications. Data from the 2022 National Survey on Drug Use and Health were applied to a cascade of care framework to estimate and characterize U.S. adult populations who need OUD treatment, receive any OUD treatment, and receive medications for OUD. In 2022, 3.7% of U.S. adults aged ≥18 years needed OUD treatment. Among these, only 25.1% received medications for OUD. Most adults who needed OUD treatment either did not perceive that they needed it (42.7%) or received OUD treatment without medications for OUD (30.0%). Compared with non-Hispanic Black or African American and Hispanic or Latino adults, higher percentages of non-Hispanic White adults received any OUD treatment. Higher percentages of men and adults aged 35-49 years received medications for OUD than did women and younger or older adults. Expanded communication about the effectiveness of medications for OUD is needed. Increased efforts to engage persons with OUD in treatment that includes medications are essential. Clinicians and other treatment providers should offer or arrange evidence-based treatment, including medications, for patients with OUD. Pharmacists and payors can work to make these medications available without delays.
Topics: Humans; United States; Adult; Middle Aged; Male; Female; Opioid-Related Disorders; Young Adult; Adolescent; Buprenorphine; Aged; Opiate Substitution Treatment; Methadone
PubMed: 38935567
DOI: 10.15585/mmwr.mm7325a1 -
European Journal of Psychotraumatology 2024Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is...
Types of childhood maltreatment as predictors of posttraumatic stress disorder severity and complex posttraumatic stress disorder in patients with substance use disorders.
Childhood maltreatment (CM) can be divided into: emotional abuse (EA), physical abuse (PA), sexual abuse (SA), emotional neglect (EN), and physical neglect (PN). CM is associated with (Complex)Posttraumatic stress disorder (PTSD/CPTSD) and substance use disorder (SUD). This cross-sectional study examined the relationships between CM-subtypes with PTSD-severity and CPTSD in patients with SUD-PTSD. Participants ( = 209) were treatment-seeking SUD-PTSD patients who completed the Childhood Trauma Questionnaire-short form, the Clinician-Administered PTSD Scale for DSM-5 and the International Trauma Questionnaire. Regression analyses and a model selection procedure to select an optimal model were used to examine CM-subtypes as predictors of (C)PTSD, adjusted for sex and age. Total CM and all CM-types significantly predicted PTSD-severity in the univariate regression analysis, with EA begin the strongest predictor. In the multiple regression only SA predicted PTSD-severity. Subsequently, model selection indicated that the optimal model to predict PTSD-severity included EA and SA. In the univariate analyses total CM, EA, and PN significantly predicted CPTSD-classification, and total CM and all CM-types significantly predicted CPTSD-severity. In the multiple regression for CPTSD-classification only EA and PA were significant predictors and for CPTSD-severity EA, PA and SA were significant predictors. In post-hoc multiple regression analyses, only EA was a significant predictor of CPTSD-classification and CPTSD-severity. Finally, in the model selection the most parsimonious model only included EA for both CPTSD-classification and CPTSD-severity. Sex was not a moderator in the relationship between CM and PTSD, nor in CM and CPTSD. These findings indicate that for SUD-PTSD patients, several CM-types have predictive value for (C)PTSD-severity, however SA and especially EA appear to contribute to these complaints. Since EA does not constitute an A-criterion, it is generally more overlooked in PTSD treatment. Its impact should therefore be underlined, and clinicians should be attentive to EA in their treatment.
Topics: Humans; Stress Disorders, Post-Traumatic; Male; Female; Substance-Related Disorders; Cross-Sectional Studies; Adult; Surveys and Questionnaires; Child Abuse; Adult Survivors of Child Abuse; Middle Aged; Severity of Illness Index; Child
PubMed: 38934350
DOI: 10.1080/20008066.2024.2367179 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence...
BACKGROUND
Acute intoxication is a common chief complaint in emergency medicine, but there is a lack of up-to-date studies from the emergency departments in Norway on the incidence and prevalence of various toxic substances. The aim of this study was to survey acute intoxications at the emergency department of St Olav's Hospital, Trondheim.
MATERIAL AND METHOD
In this review of patient records, we used data from the emergency department at St Olav's Hospital in Trondheim in the period 1 January 2019-31 December 2020. All cases with 'acute intoxication' as the reason for the emergency department visit were included.
RESULTS
In a patient population of 836 unique patients, there were a total of 1423 intoxications, of which 168/836 patients (20.0 %) had more than one intoxication episode in the period. The median age was 31 years (interquartile range 22-47), and 395/836 (47.2 %) of the patients were women. Combined drug intoxication constituted 666/1423 (46.8 %) of the cases, and the most frequent intoxications were from ethanol: 802/1423 (56.4 %); benzodiazepines 314/1423 (24.0 %); and opioids 243/1423 (17.1 %). Altogether, 1146/1423 (80.5 %) incidents resulted in hospital admission. There were no deaths during their hospital stay.
INTERPRETATION
Emergency departments must be prepared to manage patients who have taken various poisoning agents. The antidotes must be available, and it must be possible to perform interventions.
Topics: Humans; Norway; Emergency Service, Hospital; Adult; Female; Male; Hospitals, University; Middle Aged; Young Adult; Poisoning; Benzodiazepines; Alcoholic Intoxication; Retrospective Studies; Incidence; Adolescent; Drug Overdose
PubMed: 38934322
DOI: 10.4045/tidsskr.23.0417 -
Neuro-ophthalmology (Aeolus Press) 2024Nitrous oxide is used as an anaesthetic and analgesic agent in the medical setting and is known to cause raised intracranial pressure. The use of nitrous oxide...
Nitrous oxide is used as an anaesthetic and analgesic agent in the medical setting and is known to cause raised intracranial pressure. The use of nitrous oxide recreationally for the drug's euphoric and relaxant properties has been linked to multiple neurological and psychiatric sequelae including neuropathy, myelopathy, and psychosis. We describe a case of a young person who declared heavy nitrous oxide use resulting in vision-threatening papilloedema secondary to raised intracranial pressure. He underwent emergency lumbar drainage alongside high-dose acetazolamide and parenteral vitamin B injections. To our knowledge, there have yet to be other reports of cases where heavy nitrous oxide use has caused secondary pseudotumor cerebri syndrome.
PubMed: 38933749
DOI: 10.1080/01658107.2023.2301359 -
China CDC Weekly Jun 2024This study aims to perform a systematic review and meta-analysis on the global prevalence of cannabis use to inform drug prevention strategies, policy-making, and...
This study aims to perform a systematic review and meta-analysis on the global prevalence of cannabis use to inform drug prevention strategies, policy-making, and resource allocation. This study initially screened 177,843 studies published between January 1, 2000, and January 15, 2024, using peer-reviewed databases including Web of Science, PubMed, Scopus, Embase, and Cochrane Library. Ultimately, 595 studies were identified for data extraction, and 39 of these were selected as country-representative studies. Heterogeneity among the selected studies was assessed using the chi-squared test and I statistic, while sensitivity analysis was conducted to evaluate the robustness of the results. The prevalence of cannabis use varied between 0.42% and 43.90% across 33 European countries, 1.40% to 38.12% across 15 North and South American countries, 0.30% to 19.10% across 16 Asian countries, and 1.30% to 48.70% across 18 Oceania and African countries. The pooled prevalence of cannabis use was 12.0% [95% confidence interval (): 10.0, 14.3] in countries where cannabis is legalized, compared to 5.4% (95% : 4.3, 6.9) in non-legalized countries. Our findings indicate that the prevalence of cannabis use has disproportionately increased in most countries with the implementation of medical or recreational cannabis legalization policies and relevant geographic proximity. Increased efforts are needed to monitor newly cannabis-legalized countries and prevent initial use.
PubMed: 38933041
DOI: 10.46234/ccdcw2024.116