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Background: In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of CBD and explore the impact of different factors on PK outcomes. Materials and Methods: This systematic review and meta-regression analysis was preregistered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsycInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including T max , C max , AUC 0-t , AUC 0-inf , and T 1/2 , in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Before-After Studies with no Control Group was used. Random-effects multivariable meta-regression analysis was conducted. Results: A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech ( n =14), oil-based ( n =21), alcohol-based ( n =10), water-based ( n =12), Sativex ( n =17), and Epidiolex ® ( n =22). For single-dose studies, CBD doses ranged between 2 and 100 mg in inhalation, 5-50 mg in oromucosal, and 0.42-6000 mg in oral administration. Sixty-six trial arms had only male participants or a higher number of male than female participants. The duration of the PK session was between 4 and 164 h. A higher CBD dose was associated with higher C max , AUC 0-t , and AUC 0-inf . Compared with oral administration, oromucosal administration was associated with lower C max , AUC 0-t , and AUC 0-inf . Fed status was associated with higher C max and AUC 0-t when compared with the fasting status. A higher ratio of female participants was associated with lower T max in oral administration and higher C max . Conclusion: As expected, CBD dose, route of administration, and diet were major determinants of CBD PK with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Although CBD appeared to have a faster onset and longer duration in women, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.

Background: Cannabidiol (CBD) is a widely available cannabis product with many claims as to potential health benefits including alleviating symptoms related to opioid use disorder (OUD). However, little is known as to how individuals with OUD perceive CBD, to what extent they may already be using CBD, and for what purposes., Methods: A survey was conducted among individuals receiving treatment for OUD at the Addiction Institute of Mount Sinai in New York City from July 2021 to August 2023. The survey consisted of demographic questions, questions about opioid use, CBD use, and perceptions regarding CBD. Statistical analysis using ordinal logistic regression was employed to compare perceptions between CBD users and non-users while adjusting for age and race., Results: Among 587 respondents, 550 completed the survey. Among all survey completers, 129 (23%) reported a history of using CBD for a variety of reasons including: anxiety (81, 62.8%), pain (65, 50.4%), sleep (63, 48.8%), depression (62, 48.1%), recreational purposes (32, 24.8%), or for other reasons (8, 6.2%). Of note, 22 (17.1%) respondents reported using CBD to control their addiction and 54 (41.9%) reported using CBD to ease opioid withdrawal symptoms. CBD users demonstrated more positive perceptions regarding its legality (β = 0.673, OR = 1.960, 95% CI [1.211, 3.176], p = .006), social acceptance (β = 0.718, OR = 2.051, 95% CI [1.257, 3.341], p = .004), and therapeutic potential compared to non-users. CBD users also had a more positive view of its potential future role in managing addiction (β = 0.613, OR = 1.846, 95% CI [1.181, 2.887], p = .007)., Conclusions: This study highlights a significant association between CBD usage and progressive views regarding CBD among individuals with OUD, suggesting a growing interest in CBD as a potential adjunctive therapy for individuals in substance use treatment. Some patients are already using CBD for anxiety, pain, sleep, depression, or as a harm reduction intervention to control their addiction or for opioid withdrawal symptoms. These findings underscore the importance of integrating patient perspectives into future research and treatment strategies involving CBD in the context of OUD., (© 2024. The Author(s).)

Potential of natural language processing (NLP) in extracting patient's information from clinical notes of opioid treatment programs (OTP) and leveraging it in development of predictive models has not been fully explored. The goal of this study was to assess potential of NLP in identifying legal, social, mental, medical and family environment-based determinants of distress from clinical narratives of patients with opioid addiction, and then using this information in predicting OTP outcomes. Around 63% of patients reported improvements after completing OTP. We compared the results of logistics regression and random forest for predictive modeling. Random forest model performed slightly better than logistic regression (75% F1 score) with 74% accuracy. Clinical Relevance- Psychiatric and medical disorders, social, legal and family-based distress are important determinants of distress in patients enrolled in OTP. These information are often recorded in clinical notes. Extraction of this information and their utilization as features in machine learning models will lead to the enhancement of the performance of the OTP outcome predictive models.

Objective: Substance-use is a prevalent presentation to the emergency department (ED); however, the clinical characterization of patients who are treated and discharged without admission for further treatment is under-investigated. The study aims to define and characterize the clinical profiles of this patient population., Methods: Patients' presentations were examined by clinical data mining (chart review) of ED records of substance use-related events of individuals discharged without admission for further treatment. Records (N = 199) from three major hospitals in New York City from March and June 2017 were randomly sampled with primary diagnosis of alcohol, opioid-related and other psychoactive substance-use presentations. Qualitative thematic coding of clinical presentation with inter-rater reliability was performed. Quantitative distinctive validity tested independence through Pearson's chi-squared and analysis of variance using Fisher's F-test., Results: Six distinct clinical profiles were identified, including, High Utilizers (chronically intoxicated with comorbid health conditions) (36.7%), Single Episode (20.1%), Service Request (14.1%), Altered Mental Status (13.6%), Overdose (9.0%), and Withdrawal (7.5%). The profiles differed (p < 0.05) in age, housing status, payor, mode of arrival, referral source, index visit time, prescribed treatment, triage acuity level, psychiatric history, and medical history. Differences (p < 0.05) between groups across clinical profiles in age and pain level at triage were observed., Conclusions: The identified clinical profiles represent the broad spectrum and complex nature of substance use-related ED utilization, highlighting critical factors of psychosocial and mental-health comorbidities. These findings provide a preliminary foundation to support person-centered interventions to decrease substance use-related ED utilization and to increase engagement/linkage of patients to addiction treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Psychiatric and medical disorders, social and family environment, and legal distress are important determinants of distress that impact the effectiveness of the treatment in opioid treatment program (OTP). This information is not routinely captured in electronic health record, but may be found in clinical notes. This study aims to explore the feasibility and effectiveness of natural language processing (NLP) strategy for identifying legal, social, mental and medical determinates of distress along with emotional pain rooted in family environment from clinical narratives of patients with opioid addiction, and then using this information to find its impact on OTP outcomes. Analysis in this study showed that mental and legal distress significantly impact the result of the treatment in OTP.

The goal of this paper is to apply unsupervised machine learning techniques in order to discover latent clusters in patients who have opioid misuse and also undergone COVID-19 testing. Target dataset has been constructed based on COVID-19 testing results at Mount Sinai Health System and opioid treatment program (OTP) information from New York State Office of Addiction Service and Support (OASAS). The dataset was preprocessed using factor analysis for mixed data (FAMD) method and then K-means algorithm along with elbow method were used to determine the number of optimal clusters. Four patient clusters were identified among which the fourth cluster constituted the maximum percentage of positive COVID-19 test results (20%). Compared to the other clusters, this cluster has the highest percentage of African Americans. This cluster has also the highest mortality rate (16.52%), hospitalization rate after receiving the COVID-19 test result (72.17%, use of ventilator (7.83%) and ICU admission rate (47.83%). In addition, this cluster has the highest percentage of patients with at least one chronic disease (99.13%) and age-adjusted comorbidity score more than 1 (83.48%). Longer participation in OTP was associated with the highest morbidity and mortality from COVID-19.

Background: Drug addiction is a complex brain disorder that is characterized by craving, withdrawal, and relapse, which can be perpetuated by social stress. Stemming from an acute life event, chronic stress, or trauma in a social context, social stress has a major role in the initiation and trajectory of substance use. Preclinical literature shows that early life stress exposure and social isolation facilitate and enhance drug self-administration. Epidemiological evidence links childhood adversity to increased risk for drug use and demonstrates that cumulative stress experiences are predictive of substance use severity in a dose-dependent manner. Stress and drug use induce overlapping brain alterations leading to downregulation or deficits in brain reward circuitry, thereby resulting in greater sensitization to the rewarding properties of drugs. Though stress in the context of addiction has been studied at the neural level, a gap in our understanding of the neural underpinnings of social stress in humans remains., Methods: We conducted a systematic review of in vivo structural and functional neuroimaging studies to evaluate the neural processes associated with social stress in individuals with substance use disorder. Results were considered in relation to participants' history of social stress and with regard to the effects of social stress induced during the neuroimaging paradigm., Results: An exhaustive search yielded 21 studies that matched inclusion criteria. Social stress induces broad structural and functional neural effects in individuals with substance use disorder throughout their lifespan and across drug classes. A few patterns emerged across studies: (1) many of the brain regions altered in individuals who were exposed to chronic social stress and during acute stress induction have been implicated in addiction networks (including the prefrontal cortex, insula, hippocampus, and amygdala); (2) individuals with childhood maltreatment and substance use history had decreased gray matter or activation in regions of executive functioning (including the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex), the hippocampal complex, and the supplementary motor area; and (3) during stress-induction paradigms, activation in the anterior cingulate cortex, caudate, and amygdala was most commonly observed., Conclusions/implications: A distinct overlap is shown between social stress-related circuitry and addiction circuitry, particularly in brain regions implicated in drug-seeking, craving, and relapse. Given the few studies that have thoroughly investigated social stress, the evidence accumulated to date needs to be replicated and extended, particularly using research designs and methods that disentangle the effects of substance use from social stress. Future clinical studies can leverage this information to evaluate the impact of exposure to trauma or adverse life events within substance use research. Expanding knowledge in this emerging field could help clarify neural mechanisms underlying addiction risk and progression to guide causal-experimental inquiry and novel prevention and treatment strategies., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Potential of big data analytics in analyzing outcomes of opioid treatment programs (OTP) has not been fully explored. The goal of this study was to assess potential of big data in predicting OTP outcomes based on the initial intake forms which includes demographics, social and health history. The analytical sample comprised over 30,000 people admitted in OTP. Around 66% of patients reported improvements after completing OTP. We compared the results of Logistics Regression, Random Forest, and XGBoost for predictive modeling. XGBoost with sampling and threshold tuning performed the best (44% F1 score) with over 60% accuracy. Further big data exploration of OTP is warranted.

Background: Multiple psychopathologies feature impaired clinical insight. Emerging evidence suggests that insight problems may similarly characterize addiction, perhaps due to aberrant functioning of self-referential brain circuitry, including the rostral anterior cingulate and ventromedial prefrontal cortices (rACC/vmPFC). We developed a new fMRI task to probe whether rACC/vmPFC abnormalities in cocaine use disorder (CUD) constitute neural correlates of readiness to change, one facet of insight., Methods: Eighteen individuals with current CUD and 15 healthy controls responded about their own need to change their drug use and eating behavior (control condition) and the need for a named acquaintance to do the same (two additional control conditions). Measures of simulated drug-choice behavior, addiction severity, and neuropsychological function were collected outside the scanner., Results: CUD participants perceived a greater need for behavior change than controls (as expected, given their diagnosis), but fell short of "agreeing" to a need for change; in CUD, lower perceived need correlated with higher simulated drug-choice behavior, a proxy measure of drug-seeking. During drug-related insight judgments, CUD participants had higher activation than controls in an anatomically-defined region of interest (ROI) in the medial orbitofrontal cortex, part of the rACC/vmPFC. Although not showing group differences, activation in an anatomically-defined ACC ROI correlated with insight-related task behavior (in all participants) and memory performance (in CUD)., Conclusions: As a group, individuals with current CUD appear to show mild insight problems and rACC/vmPFC abnormalities vis-à-vis readiness to change behavior. With replication and extension of these results, insight-related circuitry may emerge as a novel therapeutic target., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: High blood pressure (BP) is associated independently with cocaine use and lead exposure. It is not known whether cocaine use and lead exposure act jointly to disrupt cardiovascular health., Objective: To determine whether cocaine use modifies the association between cumulative lead levels and elevated BP., Materials and Methods: We measured cumulative tibia lead levels in 35 adults: 20 with cocaine use disorder (CUD) and 15 non-CUD controls using in vivo K-shell X-ray fluorescence. Generalized estimating equation regression determined associations between log 2 -transformed lead and BP (systolic, diastolic, and mean arterial pressure) and assessed the modifying association of cocaine use (as addiction severity) on the lead-BP relationship, adjusting for age, sex, smoking, and education. Sensitivity analyses included correction for potential selection bias., Results: Cases and controls differed by sex (%male: 90% vs. 67%), age (50.7 vs. 39.9 years), education (12.8 vs. 14.4 years), and tibia lead (3.50 vs. 2.35 μg/g). Lead was positively associated with systolic ( P = 0.01) and diastolic BP ( P = 0.01). We observed an interaction between lead and addiction severity on BP ( P values for systolic BP: 0.01, diastolic BP: 0.003, and mean arterial BP: <0.0001); the association was stronger among individuals with more severe cocaine addiction: Systolic BP: Est.: 17.89, 95% confidence interval (CI): 9.52; 26.26, diastolic BP Est.: 17.89, 95% CI: 7.33; 13.79, mean arterial BP: Est.: 13.09, 95% CI: 10.34; 15.83., Conclusions: Lead was adversely associated with BP. This association was strongest among individuals with more severe cocaine addiction. The results from this small pilot study suggest that the interaction between lead and cocaine should be considered in studies of substance abuse-related health outcomes., Competing Interests: Conflicts of interest There are no conflicts of interest.

Background: Chronic cocaine use is associated with stroke, coronary artery disease and myocardial infarction, resulting in severe impairments or sudden mortality. In the absence of clear cardiovascular symptoms, individuals with cocaine use disorder (iCUD) seeking addiction treatment receive mostly psychotherapy and psychiatric pharmacotherapy, with no attention to vascular disease ( i.e ., atherosclerosis). Little is known about the pre-clinical signs of cardiovascular risk in iCUD and early signs of vascular disease are undetected in this underserved population., Aim: To assess inflammation, plaque burden and plaque composition in iCUD aiming to detect markers of atherosclerosis and vascular disease., Methods: The bilateral carotid arteries were imaged with positron emission tomography/magnetic resonance imaging (PET/MRI) in iCUD asymptomatic for cardiovascular disease, healthy controls, and individuals with cardiovascular risk. PET with 18F-fluorodeoxyglucose ( 18 F-FDG) evaluated vascular inflammation and 3-D dark-blood MRI assessed plaque burden including wall area and thickness. Drug use and severity of addiction were assessed with standardized instruments., Results: The majority of iCUD and controls had carotid FDG-PET signal greater than 1.6 but lower than 3, indicating the presence of mild to moderate inflammation. However, the MRI measure of wall structure was thicker in iCUD as compared to the controls and cardiovascular risk group, indicating greater carotid plaque burden. iCUD had larger wall area as compared to the healthy controls but not as compared to the cardiovascular risk group, indicating structural wall similarities between the non-control study groups. In iCUD, wall area correlated with greater cocaine withdrawal and craving., Conclusion: These preliminary results show markers of carotid artery disease burden in cardiovascular disease-asymptomatic iCUD. Broader trials are warranted to develop protocols for early detection of cardiovascular risk and preventive intervention in iCUD., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest.

One of the main foci of addiction research is the delineation of markers that track the propensity of relapse. Speech analysis can provide an unbiased assessment that can be deployed outside the lab, enabling objective measurements and relapse susceptibility tracking. This work is the first attempt to study unscripted speech markers in cocaine users. We analyzed 23 subjects performing two tasks: describing the positive consequences (PC) of abstinence and the negative consequences (NC) of using cocaine. We perform two main experiments: first, we analyzed whether acoustic and semantic features can infer clinical variables such as the Cocaine Selective Severity Assessment; then, we analyzed the main problem of interest: to see if these features are powerful enough to infer if the subjects remains abstinent. Our results show that speech features have potential to be used as a proxy to monitor cocaine users under treatment to recover from their addiction.

Background: The choice for drugs over alternative reinforcers is a translational hallmark feature of drug addiction. The neural basis of such drug-biased choice is not well understood, particularly in individuals with protracted drug abstinence who cannot ethically participate in studies that offer drug-using opportunities., Methods: We developed a functional magnetic resonance imaging drug-choice task to examine the choice for viewing drug-related images, rather than for actually consuming a drug. Actively using (n = 18) and abstaining (n = 19) individuals with a history of cocaine use disorder (CUD: dependence or abuse) and matched healthy control subjects (n = 26) participated., Results: Individuals with CUD, especially those actively using cocaine outside the laboratory, made more choices than control subjects to view images depicting cocaine (especially when directly compared against images depicting an alternative appetitive reinforcer [food]). Functional magnetic resonance imaging data revealed that in individuals with CUD, the act of making drug-related choices engaged brain regions implicated in choice difficulty or ambivalence (i.e., dorsal anterior cingulate cortex, which was higher in all individuals with CUD than control subjects). Drug-related choices in CUD also engaged brain regions implicated in reward (e.g., midbrain/ventral tegmental area, which was most activated in active users, although this region was not hypothesized a priori)., Conclusions: These results help clarify the neural mechanisms underlying drug-biased choice in human addiction, which, beyond mechanisms involved in value assignment or reward, may critically involve mechanisms that contribute to resolving difficult decisions. Future studies are needed to validate these behavioral and neural abnormalities as markers of drug seeking and relapse in treatment contexts., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Anger is considered a unique high-arousal and approach-related negative emotion. The influence of individual differences in trait anger on the processing of visual stimuli is relevant to questions about emotional processing and remains to be explored. Using functional magnetic resonance imaging (fMRI), we explored the neural responses to standardized images, selected based on valence and arousal ratings in a group of men with high trait anger compared to those with normative to low anger scores (controls). Results show increased activation in the left-lateralized ventral fronto-parietal attention network to unpleasant images by individuals with high trait anger. There was also a group by arousal interaction in the left thalamus/pulvinar such that individuals with high trait anger had increased pulvinar activation to the high-arousal (versus low arousal) unpleasant images as compared to controls. Thus, individual differences in trait anger in men are associated with brain regions subserving executive attentional and sensory integration during the processing of unpleasant emotional stimuli, particularly to high arousal images.

Background : Childhood trauma affects neurodevelopment and promotes vulnerability to impaired constraint, depression, and addiction. Reduced gray matter concentration (GMC) in the mesocorticolimbic regions implicated in reward processing and cognitive control may be an underlying substrate, as documented separately in addiction and for childhood trauma. The purpose of this study was to understand the contribution of childhood maltreatment to GMC effects in individuals with cocaine use disorder. Methods : Individuals with cocaine use disorder were partitioned into groups of low vs. high childhood trauma based on median split of the total score of the Childhood Trauma Questionnaire (CTQ; CUD-L, N = 23; CUD-H, N = 24) and compared with age, race, and gender matched healthy controls with low trauma ( N = 29). GMC was obtained using voxel-based morphometry applied to T1-weighted MRI scans. Drug use, depression and constraint were assessed with standardized instruments. Results : Whole-brain group comparisons showed reduced GMC in the right lateral orbitofrontal cortex (OFC) in CUD-H as compared with controls (cluster-level p FWE-corr < 0.001) and CUD-L (cluster-level p FWE-corr = 0.035); there were no significant differences between CUD-L and controls. A hierarchical regression analysis across both CUD groups revealed that childhood trauma, but not demographics and drug use, and beyond constraint and depression, accounted for 37.7% of the variance in the GMC in the right lateral OFC ( p < 0.001). Conclusions : Beyond other contributing factors, childhood trauma predicted GMC reductions in the OFC in individuals with cocaine use disorder. These findings underscore a link between premorbid environmental stress and morphological integrity of a brain region central for behaviors underlying drug addiction. These results further highlight the importance of accounting for childhood trauma, potentially as a factor predisposing to addiction, when examining and interpreting neural alterations in cocaine addicted individuals.

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality., Competing Interests: statement Nothing declared.

This article describes the theoretical-conceptual frame of equine-facilitated psychotherapy (EFP) for adolescents at-risk, the unique components of this intervention, and its implementation in an evaluation study. The study was conducted at a residential treatment facility for adolescents at-risk. We examined the outcomes of EFP on self-image, self-control, trust and general life satisfaction. Fourteen resident adolescents comprised the treatment group, and were compared with a matched group of 15 residents who did not receive EFP (control). The treatment comprised a weekly individual EFP session over a period of seven months. The study found a trend of positive change in all four research parameters within the treatment group. Additional indications of the intervention's positive influence were also found and are discussed.