Cocaine Use Research Articles

Predictors of retention in heroin-assisted treatment in Denmark 2010–2018 – A record-linkage study

IntroductionWhile randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care. MethodsThis retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment. ResultsThe one-year retention rate was 69.63 % (95 % CI 65.06 %–73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83–3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT. ConclusionsThis observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Demographic and Clinical Profile of Persons with Substance Abuse Disorder Attending Happy Life Psychological Services Islamabad, Pakistan

Substance Abuse Disorder is a treatable mental health disorder that influences persons’ brains and behavior. It leads to an inability to control drug use, resulting in moderate to severe addiction. The research aims to study the demographic and clinical profile of persons with substance abuse disorders attending Happy Life Psychological Services (HLPS). A sample of 156 persons with substance abuse disorder was selected who were admitted to HLPS in the past two years. The study showed that 78.8% of persons with substance abuse disorder were males admitted at HLPS. In the reported cases, smoking, tobacco, opioids, cannabis, amphetamines, sedatives, hallucinogens, alcohol, and cocaine use was significantly higher in males, but inhalant use was higher in females. Middle adults were the age group where drug addiction was higher and mental health problems were most evident. Even medical comorbidities and suicidal intentions seem higher in this specific age group. In addition, married persons experienced more personality, anxiety, depression, and psychotic disorders than unmarried persons. The study outcomes can be used at the broader level to control the use of drugs in developing countries like Pakistan. Everyone is responsible for controlling the easy accessibility of drugs within the country especially, the Anti-Narcotics Agency should perform a pivotal role in this regard.

Differential effects of deep brain stimulation on reinstatement of cocaine seeking in male and female rats

There are currently no FDA-approved treatments for cocaine use disorder. Recent preclinical and clinical studies showed that deep brain stimulation (DBS) in limbic regions reduced drug seeking behavior. Our previous work indicated that DBS of the nucleus accumbens shell attenuated reinstatement of cocaine seeking, a model of relapse, in male rats. The current experiments were designed to evaluate the effect of electrical DBS on cocaine reinstatement in female rats across the estrous cycle. Rats were allowed to self-administer cocaine and lever responding was subsequently extinguished. Cocaine seeking was reinstated by an acute injection of experimenter-delivered cocaine. The effect of nucleus accumbens shell DBS vs. sham stimulation on cocaine-primed reinstatement was evaluated in female and male rats using a within-subjects counterbalanced design. Consistent with previous work, accumbens shell DBS suppressed cocaine seeking in male rats. In sharp contrast, accumbens shell DBS had no effect on cocaine reinstatement in female rats evaluated in either the estrus or non-estrus phases. These results suggest that changes across the estrous cycle are not responsible for the differences in the effect of DBS on cocaine reinstatement between female and male rats.

Virtual reality cue-exposure therapy in reducing cocaine craving: the Promoting Innovative COgnitive behavioral therapy for Cocaine use disorder (PICOC) study protocol for a randomized controlled trial

BackgroundCocaine craving is a central symptom of cocaine use disorders (CUD). Virtual reality cue-exposure therapy for craving (VRCET) allows more immersive, realistic, and controllable exposure than traditional non-VR cue-exposure therapy (CET), whose efficacy is limited in treating substance use disorders. The purpose of this study is to evaluate the efficacy and acceptability of VRCET, as a stand-alone and add-on intervention (i.e., combined with cognitive therapy), compared to a picture-based CET (PCET), in reducing self-reported cocaine craving in inpatients hospitalized for CUD.MethodsFifty-four inpatients hospitalized for CUD will be randomized in one of two intensive 3-week treatment arms: 10 meetings/2-week treatment of VRCET plus 5 meetings/1-week treatment of memory-focused cognitive therapy (MFCT; experimental arm), or 15 meetings/3-week treatment of PCET (active control arm). The Craving Experience Questionnaire (CEQ – F & S) will be used to assess the primary outcome, i.e., the post-treatment decrease of self-reported cocaine craving frequency (within the past 2 weeks) and intensity scores (in VR exposure to cocaine cues). Secondary endpoints include urinary, physiological, and self-reported cocaine use-related measures. Assessments are scheduled at pretreatment, after 2 weeks of treatment (i.e., VRCET vs. PCET), post-treatment (3 weeks, i.e., VRCET + MFCT vs. PCET), and at 1-month follow-up. Acceptability will be evaluated via (i) the Spatial Presence for Immersive Environments – Cybersickness along VRCET and (ii) the Client Satisfaction Questionnaires after 2 weeks of treatment and post-treatment.DiscussionThis study will be the first to evaluate the acceptability and efficacy of VRCET for CUD, as a psychotherapeutic add-on, to reduce both cocaine craving frequency and intensity. Additionally, this study will provide evidence about the specific interest of VRCET, compared to a non-VR-based CET, as a cue reactivity and exposure paradigm for treating substance use disorders.Trial registrationNCT05833529 [clinicaltrials.gov]. Prospectively registered on April 17, 2023.

Social context and drug cues modulate inhibitory control in cocaine addiction: involvement of the STN evidenced through functional MRI.

Addictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no neurobiological study investigating this mediation in humans. This study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI "Social" Stop-Signal Task (SSST) in the presence or absence of an observer while being exposed to cocaine-related (vs. neutral) cues eliciting craving in drug users. The results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. During inhibition (Stop Correct vs Stop Incorrect), activity in the right STN, right inferior frontal gyrus (IFG), and bilateral orbitofrontal cortex (OFC) varied according to the type of cue. Notably, the presence of an observer reversed this effect in most areas for CUD participants. These findings highlight the impact of social context and drug cues on inhibitory control in CUD and the mediation of these effects by the right STN and bilateral OFC, emphasizing the importance of considering the social context in addiction research. They also comfort the STN as a potential addiction treatment target.

Naloxone Use During Pregnancy-Data from 26 US Jurisdictions, 2019-2020.

We aimed to determine the prevalence of self-reported naloxone use during pregnancy among people in the United States with a recent live birth. A secondary objective was to characterize people at increased risk of overdose who did and did not use naloxone. We analyzed data from the Pregnancy Risk Assessment Monitoring System from 26 US jurisdictions that conducted an opioid supplement survey from 2019 to 2020. Respondents with increased risk of experiencing an opioid overdose were identified based on self-reported use of illicit amphetamines, heroin, cocaine, or receiving medication for opioid use disorder (MOUD) during pregnancy. Weighted prevalence estimates and 95% confidence intervals were calculated for reported naloxone use at any point during pregnancy among people with an increased risk of overdose. Naloxone use during pregnancy was reported by <1% of the overall study population (unweighted N = 88/34,528). Prevalence of naloxone use was 5.0% (95% CI: 0.0-10.6) among respondents who reported illicit amphetamine use, 15.2% (1.8-28.6) among those who reported heroin use, and 17.6% (0.0-38.1) among those who reported cocaine use. Naloxone use was 14.5% (8.4-20.6) among those who reported taking MOUD. Among people with increased risk of overdose, no significant differences in naloxone use were observed by age, race/ethnicity, education level, residential metropolitan status, or insurance status. Prevalence of naloxone use among people with an increased risk of overdose during pregnancy ranged from 5.0% to 17.6%. Access to naloxone, overdose prevention education, and treatment for substance use disorders may help reduce morbidity and mortality.

Rare and novel complications of botulinum neurotoxin type A and dermal filler injections

Botulinum neurotoxin type A (BoNTA) and filler injection procedures usually provide predicted outcomes with a low incidence of complications. Most of the complications after these procedures have been extensively discussed. In this study, we report on these injectables’ less well-known, recently reported, and novel complications and attempt to clarify the underlying mechanisms. Counterfeit or mishandled BoNTA has been associated with botulism. BoNTA has been linked to uncommon complications, including morphea-like lesions, nontuberculous mycobacterial infections, vascular occlusion, and pseudoaneurysm of the superficial temporal artery. Unusual complications from filler injection include nonscarring alopecia, intraoral necrosis, nontuberculous mycobacterial infections, xanthelasma-like reactions, intracranial perforation, and pneumosinus dilatans. Post-BoNTA injection nodules and filler infection from bone destruction due to cocaine use are new complications. These complications pose a challenge for diagnosis and treatment. This publication aims to assist in promptly identifying and managing these rare and novel complications when necessary.

Application of European Society of Cardiology guidelines for evaluating acute coronary syndrome risk in low-risk patients with cocaine-associated chest pain: Findings from the RISK study – An observational analysis

BackgroundCocaine was the drug of choice in 4.7 % of all recreational drug-related emergency department visits. Of these patients, 40 % present with cocaine-associated chest pain, of whom 4.7 % develop an acute coronary syndrome. The American Heart Association recommends a 12-hour observation period for these patients. ObjectiveThis study primarily aimed to ascertain whether the European Society of Cardiology non-ST-elevation myocardial infarction guidelines can be safely applied to rule-out acute coronary syndrome in low-risk patients with cocaine-associated chest pain. MethodsFor this prospective observational cohort study, patients, aged 18–45 years old, who presented with cocaine-associated chest pain and were risk stratified as low risk according to the European Society of Cardiology non-ST-elevation myocardial infarction guidelines and therefore discharged home without prolonged observation period, were included. They were followed to assess major adverse cardiac events four weeks after presentation to the emergency department or chest pain unit. Cocaine use was confirmed with urine toxicology screening. ResultsA total of 107 patients were included and analysed. The accuracy of the self-reported history of recent cocaine use was 94 %. Post-discharge cocaine use persisted among 32 % of patients. None of the included 107 patients died and major adverse cardiac event within four weeks did not occur among 97 patients with available data regarding MACE. ConclusionRuling out an acute coronary syndrome using the European Society of Cardiology non-ST-elevation myocardial infarction guidelines is likely to be safe for patients with cocaine-associated chest pain, however this study was underpowered to reach definitive conclusions.

Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters

HIV-associated neurological disorder (HAND) is a serious complication of HIV infection marked by neurotoxicity induced by viral proteins like Tat. Substance abuse exacerbates neurocognitive impairment in people living with HIV. There is an urgent need for therapeutic strategies to combat HAND comorbid with Cocaine Use Disorder (CUD). Our analysis of HIV and cocaine-induced transcriptomes in primary cortical cultures revealed significant overexpression of the macrophage-specific gene aconitate decarboxylase 1 (Acod1). The ACOD1 protein converts the tricarboxylic acid intermediate cis-aconitate into itaconate during the activation of inflammation. Itaconate then facilitates cytokine production and activates anti-inflammatory transcription factors, shielding macrophages from infection-induced cell death. However, the immunometabolic function of itaconate was unexplored in HIV and cocaine-exposed microglia. We assessed the potential of 4-octyl-itaconate (4OI), a cell-penetrable ester form of itaconate known for its anti-inflammatory properties. When primary cortical cultures exposed to Tat and cocaine were treated with 4OI, microglial cell number increased and the morphological altercations induced by Tat and cocaine were reversed. Microglial cells also appeared more ramified, resembling the quiescent microglia. 4OI treatment inhibited secretion of the proinflammatory cytokines IL-1α, IL-1β, IL-6, and MIP1-α induced by Tat and cocaine. Transcriptome profiling determined that Nrf2 target genes were significantly activated in Tat and 4OI treated cultures relative to Tat alone. Further, genes associated with cytoskeleton dynamics in inflammatory microglia were downregulated by 4OI treatment. Together, the results strongly suggest 4-octyl-itaconate holds promise as a potential candidate for therapeutic development to treat HAND coupled with CUD comorbidities.Graphical Model of 4OI-mediated neuroprotection against Tat-Cocaine toxicity. Tat and Tat-Cocaine treatment induce neuronal damage, which is mitigated by 4OI through microglia cells. This cartoon shows the reduction of harmful effects such as pro-inflammatory cytokine release, upregulation of P2R, PDE, and Acod1 by the presence of 4OI. This ester modified itaconate triggers anti-inflammatory responses and activates antioxidant pathways

Disrupted dynamic brain functional connectivity in male cocaine use disorder: Hyperconnectivity, strongly-connected state tendency, and links to impulsivity and borderline traits

Cocaine use is a major public health problem with serious negative consequences at both the individual and societal levels. Cocaine use disorder (CUD) is associated with cognitive and emotional impairments, often manifesting as alterations in brain functional connectivity (FC). This study employed resting-state functional magnetic resonance imaging (rs-fMRI) to examine dynamic FC in 38 male participants with CUD and 31 matched healthy controls. Using group spatial independent component analysis (group ICA) combined with sliding window approach, we identified two recurring distinct connectivity states: the strongly-connected state (state 1) and weakly-connected state (state 2). CUD patients exhibited significant increased mean dwell and fraction time in state 1, and increased transitions from state 2 to state 1, demonstrated significant strongly-connected state tendency. Our analysis revealed abnormal FC patterns that are state-dependent and state-shared in CUD patients. This study observed hyperconnectivity within the default mode network (DMN) and between DMN and other networks, which varied depending on the state. Furthermore, after adjustment for multiple comparisons, we found significant correlations between these altered dynamic FCs and clinical measures of impulsivity and borderline personality disorder. The disrupted FC and repetitive effects of precuneus and angular gyrus across correlations suggested that they might be the important hub of neural circuits related behaviorally and mentally in CUD. In summary, our study highlighted the potential of these disrupted FC as neuroimaging biomarkers and therapeutic targets, and provided new insights into the understanding of the neurophysiologic mechanisms of CUD.

A novel delta opioid receptor specific peptide reduces craving in an animal model of cocaine seeking

Substance use disorder, and particularly cocaine use disorder, is a complex disease that affects societal, economic, and psychological factors. Endogenous β-endorphin released after prolonged cocaine withdrawal has been reported to activate the accumbal delta-opioid receptor (DOR), leading to attenuated cocaine seeking. However, using DOR β-endorphin activation to treat cocaine use disorder is impractical since β-endorphin does not cross the blood-brain barrier. Also, only activation of the sub-group DOR1 efficiently attenuates craving, as activation of DOR2 yields an opposite effect. Here, we isolated a specific peptide, PEP1, from a phage display peptide library with similar biological properties to β–endorphin, demonstrating specificity for DOR1 and functioning as full receptor agonists. Our pharmacodynamic results showed fast trafficking incorporation of DOR into the cell membrane, interpreted as superior rehabilitation of the receptor and its bioavailability compared to commercial agonists. We administered PEP1, either intrabrain or intranasal, to rats trained to self-administer cocaine. PEP1 induced a significant decrease in cocaine-craving behavior and reinstatement in three different animal models of addiction. Also, PEP1 did not exhibit rewarding properties and did not interfere with the natural reward system. ICP-OES analysis revealed that at least one hour post-administration, PEP1 was retained in the brain rather than in peripheral organs. These findings render PEP1 a potential novel regulator of cocaine craving, especially for being non-addictive. Hence, PEP1 should be further examined as a possible new therapy for substance use disorder.

Structural brain changes associated with cocaine use and digital cognitive behavioral therapy in cocaine use disorder treatment

BackgroundFew studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization. MethodsIn this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo). ResultsIrrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV. ConclusionsThese results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.

Response-contingent cocaine increases the reinforcing effectiveness of social contact.

Epidemiological studies report a high concordance rate of drug use within groups, suggesting an interplay between drug reinforcement and social cohesion. Preclinical studies reveal that (a) contingent access to a social partner increases cocaine intake and (b) experimenter-delivered cocaine increases the reinforcing effects of social contact. The purpose of this study was to determine if response-contingent cocaine increases the reinforcing effectiveness of social contact. Male rats were implanted with intravenous catheters and trained on a fixed ratio (FR1) schedule for 30-s access to a social partner. The reinforcing effectiveness of social contact was then determined using a progressive ratio (PR) schedule. After the PR test, rats were divided into two groups in which each response on an FR1 schedule produced social access and either response-contingent cocaine (0.5 mg/kg/infusion) or saline. After 9 days, the reinforcing effectiveness of social contact in the absence of infusions was determined again on the PR schedule. The cocaine and saline reinforcers were then switched between groups and the latter procedures were repeated. Recent exposure to response-contingent cocaine increased the reinforcing effectiveness of social contact on the PR schedule. This effect was transient, and the reinforcing effectiveness of social contact returned to baseline levels once response-contingent cocaine was replaced with saline. These data indicate that recent exposure to response-contingent cocaine transiently increases the reinforcing effectiveness of social contact and suggest that cocaine use may strengthen social cohesion by increasing the reinforcing effects of social contact with other individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Substance Use Disorder and Violence Among People with Severe Mental Illness in the United States.

In studying substance use disorder (SUD) and violence in severe mental illness (SMI), researchers account for presence of SUD or addictions to specific substances. However these studies fail to comprehensively capture solitary drug use versus specific combinations in a single exhaustive variable with more nuance (e.g., opioids only, alcohol only, both alcohol and opioids only, and so on). Using logistic regression to predict past-year violence, this study compared conventional SUD measurement (Model I: presence versus absence of SUD or specific SUDS) to a newer and more holistic approach (Model II: a single exhaustive variable with both solitary addictions [e.g., opioids only] and specific combinations of addictions [e.g., both opioids and alcohol only]) among 10,551 people with SMI in the National Survey of Drug Use and Health (20,015 - 2019). After adjusting for a wide variety of factors in Model II, people with (1) alcohol use disorders only were 2.24 times more likely to be violent (CI = 1.46-3.45, p <.001); (2) opioid use disorders only were 3.45 times more likely (CI-1.48-8.05, p,>01); (3) both alcohol and cocaine use disorders or cocaine only were 5.85 times more likely (CI = 2.63-13.05, p <.001); and (4) both alcohol and opioid use disorders only were 4.28 times more likely (CI = 1.34-13.71, p <.05). These more nuanced findings in Model II differed substantially from those using conventional SUD assessment in Model I, and the newer and more holistic approach can better reflect the complexity of addiction in relation to violence in SMI. Therefore studies, practices, and policies that address SUD and violence in SMI could be beneficially revisited with this greater comprehensiveness and detail.

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats.

Relapse to drug use after abstinence is a major challenge in treating substance use disorder. Exposure to drug-associated cues during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective pharmacological intervention is available. We discovered that a nutritional supplement we developed as part of a nutritional approach for managing patients with substance use disorder reduced patient reports of drug craving and relapse. The goal of this study was to determine the efficacy of this supplement, SMAASH-C, at reducing drug-craving/relapse vulnerability in males and females in rat models with cocaine. Effects were determined following extended-access cocaine self-administration (24-hr/day for 10 days) and a two-week treatment regimen at a moderate and moderate-to-high dose (0.4 and 0.8 g/kg/day) as well as a 6-week regimen at a moderate dose (0.4 g/kg/day; Experiment 2). We also determined its efficacy to offset serum markers of organ toxicity in response to chronic cocaine self-administration and abstinence (aspartate transaminase, alanine transaminase, amylase; urea nitrogen). In females, both the 2- and 6-week SMAASH-C treatment regimens reduced cocaine-seeking (extinction or cue-induced reinstatement), particularly when drug-seeking was heightened (e.g., during estrus). Despite a lack of efficacy to reduce drug-seeking in males, SMAASH-C treatment normalized cocaine/abstinence-induced increases in serum levels of aspartate transaminase and amylase, which are markers of liver and pancreatic toxicity respectively. Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.

Effects of self- and experimenter-administered cocaine on subsequent ethanol drinking in rhesus monkeys

BackgroundOne possible reason for the lack of FDA-approved pharmacotherapies to treat cocaine use disorder (CUD) is that, although cocaine is typically used in combination with alcohol, it is studied in isolation in preclinical studies. A better understanding of the cocaine-alcohol interactions that promote polysubstance use (PSU) will improve animal models of CUD and hasten pharmacotherapy development. We used a rhesus monkey model of cocaine-alcohol PSU to investigate one possible mechanism: that alcohol is used to mitigate negative effects associated with termination of cocaine use. MethodsIn 6 adult male rhesus monkeys, the relationship between self-administered cocaine intake and oral ethanol intake 2hours later was examined during self-administration of cocaine (0.0003–0.3mg/kg per injection, i.v.) under a fixed-ratio 30 schedule (FR30) or a progressive-ratio (PR) schedule. Next, ethanol consumption was measured 0–120minutes after experimenter-administered cocaine (0.3–1.7mg/kg, i.v.). ResultsSelf-administered cocaine intake under both FR30 and PR schedules was unrelated to oral ethanol intakes 2hours later. When cocaine was administered non-contingently, cocaine decreased ethanol intake as well as intake of a non-alcoholic solution in monkeys who never consumed ethanol (n=4) in a time- and dose-dependent manner. ConclusionsTaken together, the results do not provide evidence for cocaine-induced increases in ethanol consumption. By extension, the results do not support the hypothesis that cocaine users drink alcohol to counteract negative effects that occur after terminating use. This finding implies either that such effects do not exist or that such effects exist but are unaffected by ethanol.

Impulse control disorders due to cocaine and synthetic stimulants use: a systematic review

The introduction of ICD-11 has opened up new horizons in understanding the impact of modern narcotic substances on mental health, in particular, it has increased the list of possible mental disorders associated with drug use. The purpose of the work is to conduct a systematic review of the literature and describe the features of the pathogenesis, clinical picture, and effectiveness of various types of therapy for impulse control disorders associated with use of cocaine and synthetic stimulants. A systematic analysis of scientific publications was performed in the eLibrary, PubMed, CNKI, and Google Scholar databases according to PRISMA recommendations. 41 publications were selected from the initially found 4,953 articles. The pathogenesis of induced impulse control disorders is associated with the direct effect of stimulant drugs on the brain and consists in the activation of D3 and 5‑HT1A receptors, as well as activation of limbic brain regions and a lack of inhibitory effects of the frontal lobe. Increased impulsivity in users of cocaine and synthetic stimulants has been proven in a large number of neurophysiological and neuroimaging studies. The frequency of occurrence, clinical features, and approaches to therapy of impulse control disorders resulting from the use of drugs with dopaminergic action (drugs for the treatment of Parkinson's disease and hyperprolactinemia, third-generation antipsychotics, and venlafaxine in high doses) have been described in details. At the same time, there is indirect evidence that cocaine and synthetic stimulants should cause impulse control disorders, since they have similar neurotransmitter activity. In addition, there are descriptions of the predominance of individual symptoms of impulse control disorders in this group of drug users. However, at the time of the review, no detailed description of these drug-induced disorders has been found. These are the prospects for further research. The use of fluoxetine and oxcarbazepine (for intermittent explosive disorder) and naltrexone (for kleptomania), as well as comprehensive prevention of drug use relapse and psychotherapy, has the highest degree of evidence as a therapy for impulse control disorders.

Brain alterations in Cocaine Use Disorder: Does the route of use matter and does it relate to the treatment outcome?

AimsCocaine Use Disorder (CUD) is an important health issue, associated with structural brain abnormalities. However, the impact of the route of administration and their predictive value for relapse remain unknown. Methods: We conducted an anatomical MRI study in 55 CUD patients (26 CUD-Crack and 29 CUD-Hydro) entering inpatient detoxification, and 38 matched healthy controls. In patients, a 3-months outpatient follow-up was carried out to specify the treatment outcome status (relapser when cocaine was consumed once or more during the past month). A Voxel-Based Morphometry approach was used. ResultsCompared with controls, CUD patients had widespread gray matter alterations, mostly in frontal and temporal cortices, but also in the cerebellum and several sub-cortical structures. We then compared CUD-Crack with CUD-Hydro patients and found that crack-cocaine use was associated with lower volume in the right inferior and middle temporal gyri, and the right fusiform gyrus. Cerebellar vermis was smaller during detoxification in subsequent relapsers compared to three-months abstainers. ConclusionsPatients with CUD display widespread cortical and subcortical brain shrinkage. Patients with preferential crack-cocaine use and subsequent relapsers showed specific gray matter volume deficits, suggesting that different patterns of cocaine use and different clinical outcome are associated with different brain macrostructure.

Machine Learning-Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention.

A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication. This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects. The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02-7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53-0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score ( P < 0.001), used cocaine on more days over the prior 30 days than other quartiles ( P < 0.001), and had highest proportions with alcohol and cocaine use disorder ( P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference ( P = 0.02) and all experiencing homelessness ( P < 0.001). Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.

Absence of Evidence for Sustained Effects of Daily Cannabidiol Administration on Anandamide Plasma Concentration in Individuals with Cocaine Use Disorder: Exploratory Findings from a Randomized Controlled Trial.

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD's effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).