Understanding Stimulant Use and Use Disorders in a New Era.

Extending from the triple wave epidemic of opioid-related overdose deaths, a fourth wave of high mortality involving methamphetamine and cocaine use has been gathering force. This article provides a review of the published literature on stimulants including epidemiology, pharmacology, neurobiology, medical and psychiatric consequences, withdrawal management, and medical and behavioral treatments.

Health consequences of cocaine use in France: data from the French Addictovigilance Network.

As the number and severity of complications related to cocaine use reported to the French Addictovigilance Network have increased, the French health authorities requested a national epidemiologic study of the data collected by this network from 2010 to 2016. For this purpose, the spontaneous reports (SRs) linked to cocaine notified by health professionals were analyzed as well as the data from the pharmacoepidemiological surveys OPPIDUM (observation of illegal drugs and misuse of psychotropic medications) and DRAMES (deaths related to the abuse of licit and illicit psychoactive substances). In total, 1 265 SRs were analyzed (510% increase from 2010 to 2016). Users were mainly men (952/1 261; 75%), with a median age of 35.0 years [IQ25-75 : 28-42]. Cocaine was consumed through the intranasal route by 52% of users (416/797), followed by intravenous administration (32%, 253/797) and inhalation (24%, 190/797). The use of cocaine powder and crack cocaine was reported in 70% (475/674) and 23% (154/674) of SRs, respectively. Cocaine was consumed with other psychoactive substances and alcohol in 47% (603/1265) and 60% (387/649) of cases, respectively. The main cocaine-related complications were psychiatric complications (29%), neurologic complications (24%) and cardiovascular complications (23%). Analysis of the OPPIDUM survey data showed that in 2016, 15.9 and 2.4% of the included subjects consumed cocaine or crack cocaine the week preceding the survey, the highest rate for the 2006-2016 period. The DRAMES survey indicated that cocaine-related deaths increased by threefold from 2014 to 2016. These data confirm that cocaine use in France is worrying with an increase in the number of severe complications and deaths.

Suicide mortality risk in a cohort of individuals treated for alcohol, heroin or cocaine abuse: Results of a follow-up study.

Cohort study. This follow-up study (from 1975 to 2016) was aimed to estimate the mortality risk for suicide in a cohort of patients presenting to a public treatment centre for addiction (SERD) with Alcohol Use Disorder (AUD), Heroin Use Disorder - HUD or Cocaine Use Disorder (CUD), also relating to their access to a Mental Heath Service. Crude Mortality Rates for suicide were higher for patients with AUDs, for men and subjects 45-64 years old. Hanging was the main cause of suicide death. We highlight an increase in mortality in the period 2009-2012, which coincides with the economic recession, and in the year of first contact with a SERD. The Standardized Mortality Ratios (SMRs) were 4.9, higher among females than males. From the multivariate analysis, a higher risk for patients that were separated or divorced was observed. The results of our study provide some guidance on the features of subjects at greatest risk of death from suicide, which may be useful in reducing and preventing suicide and gaining a better clinical management of patients with SUDs.

Cocaine use and overdose mortality in the United States: Evidence from two national data sources, 2002-2018.

BACKGROUND: Cocaine-involved overdose mortality has recently risen in the United States (US), yet it is unclear to what extent patterns in cocaine-involved overdose mortality parallel patterns in cocaine use. This study: examined time trends (2002-2018) in past-year cocaine use and cocaine-involved overdose mortality in the US; and compared demographics and drug involvement of adults who reported past-year cocaine use versus adults who died of a cocaine-involved overdose. METHODS: Data from two sources were utilized: (1) the National Survey on Drug Use and Health (n = 1,334 adults self-reporting cocaine use in 2018); and (2) the Multiple Cause of Death dataset of the National Center for Health Statistics (N = 14,630 adults who died of a cocaine-involved overdose in 2018). The study examined prevalence of past-year cocaine use, mortality rates for cocaine-involved overdose, 2002-2018 trends, demographic characteristics, and involvement of other drugs. RESULTS: Results of Joinpoint Regression indicated that the prevalence of past-year cocaine use increased after 2011, with an annual percent change of 5.13, while age-adjusted cocaine-involved overdose mortality rates escalated after 2012, with an annual percent change of 26.54. In 2018, prevalence of past-year cocaine use did not significantly differ (p = 0.09) by racial/ethnic group, yet Non-Hispanic Blacks had an age-adjusted cocaine-involved overdose mortality rate more than double the rate in Non-Hispanic Whites and significantly higher (p < 0.001) than in any other group. CONCLUSIONS: While the prevalence of cocaine use has increased modestly, cocaine-involved overdose mortality has risen dramatically. Cocaine-involved overdose mortality is disproportionately affecting individuals who are Black, older, or with lower educational attainment.

Cocaine in Hospital Admissions for Diseases of the Circulatory System and as the Underlying Cause of Death: Analysis and Discussion.

Cocaine is a cardiotoxic drug which has been associated with morbi-mortality due to cardiovascular diseases (CVD). This study aims to: (1) analyze the hospitalizations due to cardiovascular processes and the presence of cocaine among the toxic habits of patients; and (2) discuss the forensic difficulties in sudden cardiac death (SCD) in the presence of cocaine. Hospital discharges due to CVD reporting cocaine consumption as a secondary diagnosis between 2003 and 2013 in Spain were analyzed. Subsequently, a review of judicial autopsies (SCD in cocaine users) was carried out to illustrate the forensic difficulties in the determination of the manner and underlying cause of death when cocaine use is involved. The average CVD morbidity rate was 1104.4 per 100,000 population. The most common main diagnoses of which cocaine use was recorded as a secondary diagnosis were rheumatic fever, ischemic heart disease and cerebrovascular disease in male patients between 15 and 44 years. The cardiovascular findings in the autopsies of cocaine users vary, and determining the mechanism that triggered the death in forensic practice is a challenge. The presence of cocaine among the toxic habits of young patients admitted for CVD in Spain is increasing. In our opinion, criteria must be unified to establish the manner and underlying cause of death in SCD and toxicological analysis can be a key part in the process.

Mortality Risk among Cocaine Users before and after the Economic Recession: Results of a Longitudinal Study.

BACKGROUND: Studies have highlighted 2 different groups of cocaine users (CUs): "socially integrated" (stable living conditions, regular employment, use cocaine alone or in combination with other psychoactive substances) and "socially marginalized" (socioeconomic and health problems, former or current heroin users, many injecting cocaine). These differences are also found in the elevated mortality risk for CUs, higher among subjects with cocaine and heroin use. This study targeted residents in Northern Italy who turned to a public treatment center for drug addiction following problems caused by primary cocaine use between 1982 and 2016. OBJECTIVES: To estimate mortality risk for subjects who have never used heroin (CUs) compared to that of subjects who have used heroin (HCUs). METHOD: Retrospective cohort study. We selected 1,993 subjects; 18,015 Person Years (PY). RESULTS: Over time, the quota of subjects injecting cocaine and using heroin decreased, while patients not using heroin increased. Both new patients and crude mortality rates (CMR) decreased during the years 2009-2012 and increased in the following period. CMRs were 5.55 per 1,000 PY, higher for HCUs, men and subjects aged over 44 years. Standardized mortality rates were 3.49, higher for women, injecting cocaine and HCUS. Among CUs, most of the deaths were from injury excluding drug related and tumors; among HCUs, from drug-related causes and diseases of the cardiovascular system. CONCLUSION: The study results show a change in the characteristics of SERD clients being treated for primary cocaine use, which are reflected both in mortality risk and causes of death. After a long period of a decrease, mortality risk increased in the period after the economic recession. Aspects concerning the effects of the economic recession on the problematic consumption of cocaine and on the risk of death are discussed.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Unintentional drug overdose deaths involving cocaine among middle-aged and older adults in New York City.

BACKGROUND: Cocaine is commonly involved in unintentional drug poisoning (overdose) deaths, accounting for 46% of overdose deaths in New York City (NYC) in 2016. However, little research exists regarding cocaine use by middle-aged and older adults, who are more likely than younger individuals to have underlying cardiovascular disease (CVD) and therefore, may be at increased risk for the adverse health consequences of cocaine. METHODS: We conducted a retrospective analysis of unintentional drug overdose deaths of middle-aged and older NYC residents age 45-84 from 2000 to 2016 using two linked sources, NYC death certificates and toxicology results from the Office of the Chief Medical Examiner. RESULTS: From 2000 to 2016, there were 6061 unintentional drug overdose deaths among New Yorkers age 45-84. Of those, cocaine was involved in 53% (n = 3183). Co-occurring opioid involvement (fentanyl, heroin, methadone, or opioid analgesics) among deaths involving cocaine was common (58%). Compared to decedents of non-cocaine involved overdose, decedents of cocaine-involved overdose were more likely to be male and non-Latino Black. Multivariable analysis showed that adults age 45-54 (adjusted odds ratio [AOR] = 1.34, 95% 1.05, 1.70), males (AOR = 1.30, 95% CI 1.15, 1.46), Bronx residence (AOR = 1.29, 95% CI 1.08, 1.54), and non-Latino black race/ethnicity (AOR = 2.37, 95% CI 2.07, 2.72) were independently associated with cocaine-involved overdose. CONCLUSION: Characteristics of decedents of cocaine-involved overdose overlap with populations with high CVD burden in NYC. Studies are needed to better understand the risks of cocaine among adults with underlying CVD.

Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: comparison between powder cocaine and crack cocaine cases.

Objective: To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C1 group) and crack (C2 group) consumers. Methods: Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C1 and C2 patients were performed adjusting for alcohol and other drug co-ingestion. Results: We included 3002 cases (C1: 2600; C2: 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C1>C2) and other drugs (56.8%, C2>C1), the most frequent amphetamine (19.4%, C1>C2) and opioids (18.9%, C2>C1). C2 patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% (n = 12) died. Conclusion: Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.

Effect of ß-blocker Therapy on Hospital Readmission and Mortality in Heart Failure Patients With Concurrent Cocaine Use.

BACKGROUND: ß-Blockers are first-line agents for reduction in symptoms, hospitalization, and mortality in patients with heart failure having reduced ejection fraction (HFrEF). However, the safety and efficacy of continuous ß-blocker therapy (BBT) in patients who actively use cocaine remain controversial, and available literature is limited. We aimed to evaluate the effect of BBT on hospital readmission and mortality in patients having HFrEF with concurrent cocaine use. METHODS: We conducted a retrospective study of patients with a diagnosis of HFrEF between 2011 and 2014 based on International Classification of Diseases 9-Clinical Modification codes. We included patients aged 18 and older who tested positive for cocaine on a urine toxicology test obtained at the time of index admission. Patients were followed for 1 year. Multivariate logistic regression was used to assess the effect of BBT on the 30-day, all-cause and heart failure-related readmissions. RESULTS: The 30-day readmission rates for BBT versus no BBT groups were 20% versus 41% (odds ratio [OR]: 0.17, 95% confidence interval [CI] = 0.05-0.56, P = .004) for heart failure-related readmissions and 25% versus 46% (OR: 0.19, 95% CI = 0.06-0.64, P = .007) for all-cause readmissions. CONCLUSION: The BBT reduced 30-day, all-cause and heart failure-related readmission rate but not 1-year mortality in patients having HFrEF with concurrent cocaine use.

The implications of cocaine use and associated behaviors on adverse cardiovascular outcomes among veterans: Insights from the VA Clinical Assessment, Reporting, and Tracking (CART) Program.

BACKGROUND: Cocaine use has been associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). It is unclear whether this is due to direct effects of cocaine or other factors. HYPOTHESIS: Cocaine use is associated with worse outcomes in patients undergoing cardiac catheterization METHODS: We used the Veterans Affairs database to identify veterans undergoing coronary catheterization between 2007 and 2014. We analyzed association between cocaine use and 1-year all-cause mortality, myocardial infarction (MI), and cerebrovascular accident (CVA) among veterans with obstructive CAD (N = 122 035). To explore factors contributing to these associations, we sequentially adjusted for cardiac risk factors, risky behaviors, and clinical conditions directly affected by cocaine. RESULTS: 3082 (2.5%) veterans were cocaine users. Cocaine users were younger (median 58.2 vs 65.3 years; P < 0.001), more likely to be African American (58.9% vs 10.6%; P < 0.001), and had fewer traditional cardiac risk factors. After adjustment for cardiac risk factors, cocaine was associated with increased risk of mortality (HR: 1.23, 95% CI: 1.08-1.39), MI (HR: 1.40, 95% CI: 1.07-1.83), and CVA (HR: 1.88, 95% CI: 1.38-2.57). With continued adjustment, increased CVA risk remained significantly associated with cocaine use, whereas MI risk was mediated by risky behaviors and mortality was fully explained by conditions directly affected by cocaine. CONCLUSIONS: Cocaine use is associated with adverse cardiac events in veterans with CAD. Contributors to this association are multifaceted and specific to individual cardiovascular outcomes, including associated risky behaviors and direct effects of cocaine. Effective intervention programs to reduce cardiac events in this population will require multiple components addressing these factors.

Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction.

BACKGROUND: Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited. OBJECTIVES: The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes. METHODS: The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death. RESULTS: A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates. CONCLUSIONS: Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events.

Cross-sectional cause of death comparisons for stimulant and opioid mortality in San Francisco, 2005-2015.

BACKGROUND: Opioids and stimulants (e.g., cocaine or methamphetamine/amphetamine [MAMP]) are major contributors to acute substance toxicity deaths. Causes of stimulant death have received little attention. We sought to characterize and compare causes of death and significant contributing conditions among persons who died from acute opioid, cocaine, or MAMP toxicity. METHODS: We identified all opioid, cocaine, or MAMP deaths in San Francisco from 2005 to 2015 through the California Electronic Death Reporting System. Multivariable logistic regression analyses were used to estimate associations between acute substance toxicity deaths (opioid versus stimulant; cocaine versus MAMP), additional reported causes of death, and significant contributing conditions most often linked to opioid and stimulant use. RESULTS: From 2005-2015, there were 1252 opioid deaths and 749 stimulant deaths. Cocaine accounted for most stimulant deaths. Decedents with cardiac or cerebral hemorrhage deaths had higher adjusted odds of death due to acute stimulant toxicity versus acute opioid toxicity (aOR = 4.79, 95%CI = 2.88-7.96, p < 0.01; aOR = 58.58, 95%CI = 21.06-162.91, p < 0.01, respectively); no statistically significant associations were found for cocaine compared to MAMP deaths. Significant contributing cardiac conditions were associated with higher adjusted odds of stimulant compared to opioid (aOR = 1.46, 95%CI = 1.19-1.79, p < 0.01) and cocaine compared to MAMP death (aOR = 1.66, 95%CI = 1.13-2.45, p = .01). CONCLUSIONS: Stimulant compared to opioid deaths tended to involve cardiac or cerebrovascular causes of death, and cocaine deaths were more likely than MAMP deaths to involve significant contributing cardiac conditions. Mounting evidence suggests that stimulant use be considered a cardio/cerebrovascular risk factor and clinical care be adjusted to address this heightened risk.

Mortality Trends among Cocaine Users Treated between 1989 and 2013 in Northern Italy: Results of a Longitudinal Study.

A total of 852 participants attending 11 centers for addiction treatment in north Italy following problems due to cocaine abuse between 1989 and 2013 were recruited. Two typologies were created: cocaine users (never heroin) (CU) and heroin and cocaine users (HCU). During the 38-year follow-up period, 4.8% of the whole cohort died. Over the whole period, tumors were the main causes of death; starting in 2010, suicide deaths became the first cause of death. Among CUs, most deaths were due to road accidents and suicide; among HCUs, most of the deaths were from opiate overdose and from cardio-circulatory system diseases. The excess mortality observed for all causes in either sex was 6.24; higher in females (15.03) as compared in males (6.23), higher in HCUs (9.06) as compared in CUs (5.21). The directly age-sex standardized mortality rates were 5.31 per 100, higher for females, declining after 2009 for all patients and after 2004 for HCUs. Multivariate analysis confirms the decreasing trend in the risk of death and shows a higher mortality risk for participants in the under-25 age group. Among cocaine users, special attention should be paid to the prevention of suicide deaths.

Mortality risk in a sample of emergency department patients who use cocaine with alcohol and/or cannabis.

BACKGROUND: Illicit drug use is common among emergency department (ED) patients, yet the association between drug use and subsequent mortality is not well understood. This study examines 36-month mortality rates for a sample of ED patients based on reported use of alcohol, cannabis, and cocaine, both individually and in combination. METHODS: Patients (N = 1669) from 2 urban EDs were surveyed at the time of the visit. The patient survey included the Alcohol Smoking and Substance Involvement Screening Test (ASSIST) and information on physical and mental health, health care utilization, and risk factors associated with substance use. ASSIST scores were used to categorize patients into drug risk groups. Mortality information from the National Death Index was used to calculate mortality rates from 2009 to 2012. A Cox regression model identified associations between drug risk groups and mortality while controlling for patient demographics. RESULTS: The use of cocaine and cannabis both individually and in combination was associated with significantly higher mortality risk compared with other ED patients. CONCLUSIONS: ED patients who use cannabis and cocaine have higher mortality risks than other patients. Further research is necessary to determine whether this result is stable across racial/ethnic groups.

Effect of ageing and time since first heroin and cocaine use on mortality from external and natural causes in a Spanish cohort of drug users.

BACKGROUND: We aimed to assess the effect of ageing and time since first heroin/cocaine use on cause-specific mortality risk and age disparities in excess mortality among heroin (HUs) and cocaine users (CUs) in Spain. METHODS: A cohort of 15,305 HUs and 11,905 CUs aged 15-49 starting drug treatment during 1997-2007 in Madrid and Barcelona was followed until December 2008. Effects of ageing and time since first heroin/cocaine use were estimated using a competing risk Cox model and the relative and absolute excess mortality compared to the general population through directly age-sex standardized rate ratios (SRRs) and differences (SRDs), respectively. RESULTS: Mortality risk from natural causes increased with time since first heroin use, whereas that from overdose declined after having peaked in the first quinquennium. Significant effects of time since first cocaine use were not identified, although fatal overdose risk seemed higher in CUs after five years. Mortality risk from natural causes (HUs and CUs), injuries (HUs), and overdoses (CUs) increased with age, the latter without reaching statistical significance. Crude mortality rates from overdoses and injuries remained very high at age 40-59 among both HUs (595 and 217 deaths/100,000 person-years, respectively) and CUs (191 and 88 deaths/100,000 person-years). SRDs from all and natural causes were much higher at age 40-59 than 15-29 in both HUs (2134 vs. 834 deaths/100,000 person-years) and CUs (927 vs. 221 deaths/100,000 person-years), while the opposite occurred with SRRs. CONCLUSION: The high mortality risk among HUs and CUs at all ages from both external and natural causes, and increased SRDs with ageing, suggest that high-level healthcare and harm reduction services should be established early and maintained throughout the lifetime of these populations.

An exploratory study of information sources and key findings on UK cocaine-related deaths.

Cocaine-related deaths have increased since the early 1990s in Europe, including the UK. Being multi-factorial, they are difficult to define, detect and record. The European Monitoring Centre for Drugs and Drug Addiction commissioned research to: describe trends reported to Special Mortality Registries and General Mortality Registers; provide demographic and drug-use characteristic information of cases; and establish how deaths are identified and classified. A questionnaire was developed and piloted amongst all European Monitoring Centre for Drugs and Drug Addiction Focal Point experts/Special Mortality Registries: 19 (63%) responded; nine countries provided aggregated data. UK General Mortality Registers use cause of death and toxicology to identify cocaine-related deaths. Categorisation is based on International Classification of Diseases codes. Special Mortality Registries use toxicology, autopsy, evidence and cause of death. The cocaine metabolites commonly screened for are: benzoylecgonine, ecgonine methyl ester, cocaethylene and ecgonine. The 2000s saw a generally accelerating upward trend in cases, followed by a decline in 2009. The UK recorded 2700-2900 deaths during 1998-2012. UK Special Mortality Registry data (2005-2009) indicate: 25-44 year-olds account for 74% of deaths; mean age=34 (range 15-81) years; 84% male. Cocaine overdoses account for two-thirds of cases; cocaine alone being mentioned/implicated in 23% in the UK. Opioids are involved in most (58%) cocaine overdose cases.

Vascular disease in cocaine addiction.

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 ß-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.

Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence.

BACKGROUND: The health burden of cannabis use in patients with other substance dependencies is not fully understood. OBJECTIVE: To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders. PARTICIPANTS: Patients with opiate, cocaine, or alcohol dependence admitted to detoxification from 2001 to 2010 at a teaching hospital in Badalona, Spain. MAIN MEASUREMENTS: Sociodemographic characteristics, drug use, medical comorbidities, and urine drug screens were obtained at admission. Deaths were ascertained through clinical records and a death registry. Mortality rates and Cox regression models were used to analyze the association between urinary cannabis and mortality. RESULTS: A total of 474 patients (20% women) were admitted with a median age of 38 years (interquartile range: 32-44 years). The main substances that motivated admissions were opiates (27%), cocaine (24%), and alcohol (49%). Positive urinary cannabis was detected in 168 patients (35%). Prevalence of cannabis use among patients with opiate, cocaine, or alcohol dependence was 46.5%, 42.9%, and 25.5%, respectively. At admission, 110 (23.7%) patients had human immunodeficiency virus infection and 217 (46.5%) had hepatitis C virus infection. Patients were studied for a median of 5.6 years (interquartile range: 2.6-7.7 years) (2454.7 person-years), and at the end of the study, 50 patients (10.5%) had died, yielding a mortality rate of 2.04 × 100 patient-years (95% confidence interval: 1.53-2.66). There was no association between cannabis detection and overall mortality in the adjusted regression models [hazard ratio (95% confidence interval): 1.12 (0.60-2.00), P = 0.73], but acquired immune deficiency syndrome-related deaths were more frequent in those positive for cannabis (26% vs 2%, P = 0.03). CONCLUSION: Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.