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At least 19 recordsLinked to original sources

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride↗

Dynamic Alterations in the Blood Transcriptome Characterize Drug Use Behavior and Co-Morbidities in Cocaine Use Disorder: A Preliminary Study.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse that can benefit from multimodal treatment monitoring. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome are not only limited but also computationally complex. Therefore, we developed an analytical pipeline to investigate the connection between drug use behaviors during abstinence and change in the blood transcriptome. We conducted a longitudinal study with CUD (n = 12 subjects) and collected behavioral metrics and blood RNA-seq at baseline, 3, 6, and 9 months. Our analytical pipeline of the high-dimensional data encompasses hierarchical k-means clustering to classify subjects to responder groups based on behavioral scores and abstinence duration, in silico cell deconvolution, differential analysis with correlated multivariate testing over time, gene set enrichment analysis, and gene co-expression with time splines and RNA-seq data. The pipeline captured dynamic changes in behavioral scores and abstinence duration in responder groups. Genes showing differential transcript-level expression were enriched in substance use and cardiovascular disease-associated genetic risk loci in responder groups. Lastly, time-dependent gene co-expression revealed dynamic changes related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. This is a preliminary investigation, providing an innovative and scalable pipeline for blood-based longitudinal RNA-seq studies in CUD, potentially applicable to other substance use disorders. It outlines a data-driven approach for analyzing composite longitudinal drug use behavioral phenotypes with blood-based transcriptomics. We also demonstrate changes in drug use behaviors and the blood transcriptome during drug abstinence.

Humans↗

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine + UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4 mg/day, 16 mg/day) for 8 weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC + UDS and cocaine + UDS during treatment. RESULTS: Participants (n = 301) averaged 46 (SD = 8.64) years of age, were majority male (78.41 %), non-Hispanic (89.70 %), and African American (66.45 %). GEE results indicated that patients who submitted THC + UDS had significantly higher odds of submitting cocaine + UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR = 1.47, 95 % CI = 1.21-1.79, p = 0.00). Time (OR = 0.9998, 95 % CI: 0.9997, 0.9999, p = 0.018) and the covariate of sex assigned at birth (OR = 1.77, 95 % CI = 1.13-2.77, p = 0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine + UDS over time for all patients and 77 % higher odds of submitting cocaine + UDS for females. CONCLUSION: THC + UDS was associated with increased odds of submitting a cocaine + UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans↗

Low dose desipramine treatment of cocaine-related panic attacks.

Thirteen patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia that started during or shortly after cocaine exposure were treated in the UCLA Anxiety Disorders Program (Los Angeles, CA). Low starting doses (ranging from 2.5 to 10 mg/day) of desipramine were used. Doses were then slowly increased to an average daily dose of 25 mg. Eleven patients who were able to tolerate an initial increase in panic anxiety responded to this treatment strategy with almost full resolution of panic attacks. The authors discuss the possible value and mechanisms of low dose treatment of cocaine-related panic attacks.

Adult↗

Neurologic complications of drugs. Tardive dyskinesias, neuroleptic malignant syndrome, and cocaine-related syndromes.

Drugs, either self-administered or prescribed by physicians, can result in substantial neurologic disability in psychiatric patients. It is clear that the use of neuroleptic agents to treat psychiatric illness may result in a variety of tardive movement disorders. Most commonly, these take the form of orobuccal dyskinesias, but choreic movements of the trunk and extremities, dystonic postures, myoclonus, tics, parkinsonism, and akathisic syndromes also may occur. The choreic tardive syndromes are thought to occur more commonly in the elderly female population, but tardive variants may affect a different population. The neuroleptic malignant syndrome carries a significant mortality and remains a diagnostic and therapeutic challenge. Early detection and vigorous treatment reduces the morbidity and mortality from this condition. Stroke, seizures, and various movement disorders may complicate the illicit use of cocaine and complicate the rehabilitation of those patients dependent on its use. The unsatisfactory treatment of tardive syndromes, neuroleptic malignant syndrome, and cocaine-induced neurologic disease underscores our incomplete understanding of the neurochemistry of dopamine, the function of newly discovered dopamine receptors, and the role they play in maintaining normal emotional and motoric function. For now, awareness of the varied neurologic syndromes related to neurotransmitter-modulating agents should provide the impetus for careful use of these agents and for the continued development of improved drugs for the treatment of psychiatric disease.

Age Factors↗

Grand mal seizures temporally related to cocaine use: clinical and diagnostic features.

STUDY OBJECTIVES: To determine the appropriate diagnostic workup of the emergency department patient with an uncomplicated cocaine-related grand mal seizure. DESIGN SETTING: Retrospective analysis. A city and county ED with 45,000 selected visits per year. TYPE OF PARTICIPANTS: Thirty-seven patients with acute grand mal seizure after cocaine exposure were studied. All had historical or laboratory evidence of cocaine use and no history of prior seizure disorder. INTERVENTIONS: The diagnostic workup varied among patients. Most received computed head tomography (35), whereas fewer received-ECG (18), EEG (16), and lumbar puncture (six). MEASUREMENTS AND MAIN RESULTS: Thirty-three patients with an uncomplicated cocaine-related seizure had an unremarkable series of diagnostic tests. The four patients with remarkable neurologic manifestations were compared with the remainder of patients who were without neurologic abnormalities. Comparison of groups by route of cocaine intake revealed no significant difference in the time interval to seizure (P = .761). CONCLUSION: Diagnostic workup probably is not indicated for the patient experiencing a cocaine-related generalized seizure who will recover promptly and have a normal postictal examination.

Adolescent↗

Cocaine problems in the coca-growing countries of South America.

The problems of cocaine present a rather particular profile in the Central Andes region from which this drug originates. On the one hand there is a relatively harmless pattern of use (coca leaf chewing) in the countries concerned which minimizes the drug's most hazardous properties. On the other hand the region suffers from some of the most severe cocaine-related problems to be observed anywhere: (a) easy access to the newer, highly toxic preparations of the drug (such as coca paste) and a rapid growth in the number of new users; (b) the abandonment of certain traditional and essential agricultural activities in favour of the more profitable coca leaf production; (c) the severe ecological damage being caused in the coca growing areas; and (d) the establishment of a powerful coca trade economy which is subverting the very fabric of society and is creating corruption, lawless violence and political anarchy.

Coca↗

Cocaine: the newest risk factor for cardiovascular disease.

Cocaine-related cardiovascular events escalated during the 1980s as cocaine became purer, cheaper, and easier to obtain. Cocaine abuse is a risk factor for myocardial ischemia and/or infarction, cardiac arrhythmias, pulmonary edema, ruptured aortic aneurysm, cerebral infarction, infective endocarditis, vascular thrombosis, myocarditis, and dilated cardiomyopathy. As medical and social complications of cocaine have become evident, and with the growing negative image of cocaine, the number of first-time users has begun to decline. Cocaine abuse is seen on all levels of our society and has emerged as an issue of significant medical and public health importance. All routes and forms of cocaine abuse are potentially cardiotoxic and can be lethal. Fatal cardiac complications can occur in a first-time user. All physicians should be alert for cocaine abuse when confronted with unexplained cardiac symptoms. Cocaine is the newest and sometimes unrecognized risk factor for cardiovascular disease in young individuals otherwise free of cardiovascular risk factors.

Cardiovascular Diseases↗

Cardiovascular complications of cocaine abuse.

Cardiovascular complications are among the most common and dangerous complications of cocaine abuse, ranging from episodic arrhythmias to myocardial infarction, strokes, cardiomyopathy, and sudden death. The central nervous system-mediated action of cocaine triggers an increase in circulating catecholamines, resulting in arterial vasoconstriction, increase in myocardial oxygen demand, myocardial ischemia, tachycardia, and other arrhythmias. The peripheral cardiovascular action of cocaine involves the inhibition of reuptake of catecholamines at adrenergic nerve terminals, with local release of epinephrine, direct stimulation and vasospasm of the coronary arteries, coronary intimal hyperplasia, inhibition of baroreceptors, interference with the electrical conduction through the myocardium, and direct myocardial toxicity. The cardiovascular complications of cocaine include cardiac dysrhythmias and hypertension, acute myocardial infarction, myocarditis, infectious endocarditis, ventricular dysfunction, dilated cardiomyopathy, hypotensive shock, and cerebral strokes. Cocaine-related vascular changes in the pregnant woman and fetus have been related to an increased incidence of abortion, abruptio placentae, and congenital anomalies of the fetus.

Cardiovascular Diseases↗

Emergency room evaluation of cocaine-associated neuropsychiatric disorders.

The widespread abuse of cocaine has produced an alarming number of cocaine-related emergency room visits in the last several years. The authors discuss the various issues involved in emergency rom evaluation of patients who abuse cocaine and manifest signs and symptoms suggesting neuropsychiatric disease. Appropriate triage is emphasized, and a discussion of impediments to the accurate assessment of these patients ensues. The unique features of cocaine-induced mood, psychotic, and organic disorders are then detailed and contrasted with other functional and organic disorders. Strategies for the emergency room treatment of patients exhibiting symptomatology consistent with cocaine intoxication and withdrawal are outlined. The issues of psychiatric comorbidity and dual diagnosis in the cocaine-abusing population are examined. In addition, the neurological complications associated with the use of cocaine are reviewed. Finally, emerging data from single photon emission computerized tomography (SPECT) analysis of cocaine abusers is reported.

Brain Damage, Chronic↗

Conditioned responses to cocaine-related stimuli in cocaine abuse patients.

Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine-related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.

Adult↗

Introduction to the forensic pathology of cocaine.

During the last several years, a clearer understanding of cocaine's effects on the body has emerged. Metabolism and tissue distribution are better understood. A diverse group of cocaine-related illnesses have been reported, but many appear to share the underlying mechanism of catecholamine toxicity. Knowledge of cocaine's metabolism makes possible certain conclusions about route of ingestion, time of use, and patterns of abuse in general. Knowledge of the histologic alterations known to be associated with cocaine use can pinpoint cocaine as the cause of death, even in cases where there are negligible blood levels. What follows is a brief review of recent observations that bear on the forensic aspects of cocaine abuse.

Cocaine↗

Neurovascular complications of cocaine abuse.

A 3-year prospective study of 31,081 admissions to an inner-city, emergency trauma hospital revealed 33 patients less than or equal to 45 years of age who had a total of 35 acute neurovascular events (infarction or hemorrhage) related to cocaine abuse (3% of the total 979 cocaine-related admissions). Fifty-four percent of the events were ischemic, and 46% were hemorrhagic. Six patients died. The majority (63%) of ischemic events were hemispheric and subcortical in distribution. Eleven of 13 angiograms were abnormal (five aneurysms and two arteriovenous malformations were identified). No case of "vasculitis" was seen. Seventy percent of the patients exclusively abused crack cocaine, and 94% of the neurovascular events were related to its use. No first-time cocaine users were identified. During the last year of the study, 29% of the 558 cocaine-related admissions were psychiatric admissions, and most (58%) were for treatment of depressive illness (34 patients were admitted for attempted suicide).

Adult↗

Brain, lung, and cardiovascular interactions with cocaine and cocaine-induced catecholamine effects.

The pathophysiologic effects of cocaine on neuronal, pulmonary, and cardiovascular tissue are related to the drug's interaction with select catecholamine and neuroendocrine systems. Cocaine has been shown to alter circulating levels of the neurotransmitters, dopamine, norepinephrine, epinephrine, as well as the hypothalamic-pituitary-adrenal axis hormones corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Furthermore, brain and lung tissue have been identified as primary sites of cocaine sequestration and metabolism. This paper reviews evidence suggesting that steroid-potentiated actions of catecholamines on vascular tissues contributes to the etiology of cocaine-related medical complications, including ischemic stroke, coronary ischemia, and ischemia-based renal failure.

Adrenal Cortex Hormones↗

Progression of dependence in male cocaine addicts.

We studied the self-reported temporal sequence of cocaine-related problems in 45 male predominantly Black (85%), lower SES cocaine addicts undergoing inpatient treatment at a large urban VA psychiatric hospital. Subjects reported recent average use of 2.5 g of cocaine per day for 14 days each month and experiencing a mean of 14 cocaine-related problems. The temporal sequence of cocaine-related problems was roughly consistent with the sequence of alcohol-related problems reported for alcoholics, with the earliest problems being interpersonal (e.g., arguments with others) and the most recent problems the severest (e.g., job loss, marital separation). The cocaine addicts showed a faster progression from first cocaine use to first cocaine-related problems (mean of 3.75 years) than that reported for alcoholics from first drink to first heavy drinking (8-10 years). Cocaine smokers had a faster course (3.4 years) than intranasal users (5.3 years).

Adult↗

Cocaine abuse: an expanding healthcare problem for the 1990s.

Cocaine, the most addictive recreational drug available, has increased in popularity and widespread use in the past decade. Crack, a new form of cocaine that is smoked, is purer and more rapidly absorbed into the vascular system, greatly increasing the risk of overdose. Cocaine produces many physiologic effects on the body systems. This case report focuses on two cardiovascular responses related to cocaine use: cardiomyopathy and coronary vasospasm. Cocaine abusers may present with complaints of chest pain or other nonspecific symptoms that require diligent assessment skills to be recognized as cocaine-related. Therefore, it is essential that nurses be knowledgeable about the effects of cocaine and the symptoms of cocaine abuse.

Adult↗

A longitudinal analysis of factors associated with morbidity in cocaine abusers with psychiatric illness.

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary-care hospital emergency department, we identified a sample of 80 patients with a cocaine-related presentation who came to the emergency department and were referred to the psychiatric facility. Forty-six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute-care psychiatric unit. Sixty-two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy-four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p less than 0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job-related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leading to relapse.

Adult↗

New perspectives in the legal psychiatry of cocaine-related crimes.

The legal criteria for the insanity defense as it applies to cocaine-related crimes remains elusive because of cocaine's unique spectrum of effects on human thought and action. This paper discusses the literature relevant to cocaine and forensic psychiatry/psychology, and summarizes the results of a survey of forensic psychiatrists on the topic of drug-induced psychosis. A conceptual framework is posited for the expert witness to distinguish the separable effects of cocaine on human behavior and to clarify their relationship to criminal responsibility.

Cocaine↗