Ingestion of Illicit Substances by Young Children Before and During the COVID-19 Pandemic.

Importance: Information about the trend in illicit substance ingestions among young children during the pandemic is limited. Objectives: To assess immediate and sustained changes in overall illicit substance ingestion rates among children younger than 6 years before and during the COVID-19 pandemic and to examine changes by substance type (amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids) while controlling for differing statewide medicinal and recreational cannabis legalization policies. Design, Setting, and Participants: Retrospective cross-sectional study using an interrupted time series at 46 tertiary care children's hospitals within the Pediatric Health Information System (PHIS). Participants were children younger than 6 years who presented to a PHIS hospital for an illicit substance(s) ingestion between January 1, 2017, and December 31, 2021. Data were analyzed in February 2023. Exposure: Absence or presence of the COVID-19 pandemic. Main Outcome(s) and Measure(s): The primary outcome was the monthly rate of encounters for illicit substance ingestions among children younger than 6 years defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code(s) for poisoning by amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids. The secondary outcomes were the monthly rate of encounters for individual substances. Results: Among 7659 children presenting with ingestions, the mean (SD) age was 2.2 (1.3) years and 5825 (76.0%) were Medicaid insured/self-pay. There was a 25.6% (95% CI, 13.2%-39.4%) immediate increase in overall ingestions at the onset of the pandemic compared with the prepandemic period, which was attributed to cannabis, opioid, and ethanol ingestions. There was a 1.8% (95% CI, 1.1%-2.4%) sustained monthly relative increase compared with prepandemic trends in overall ingestions which was due to opioids. There was no association between medicinal or recreational cannabis legalization and the rate of cannabis ingestion encounters. Conclusions and Relevance: In this study of illicit substance ingestions in young children before and during the COVID-19 pandemic, there was an immediate and sustained increase in illicit substance ingestions during the pandemic. Additional studies are needed to contextualize these findings in the setting of pandemic-related stress and to identify interventions to prevent ingestions in face of such stress, such as improved parental mental health and substance treatment services, accessible childcare, and increased substance storage education.

Definitive urine drug test findings in patients prescribed opioids for pain from a large national database.

OBJECTIVE: Clinicians and policymakers have been wrestling with the appropriateness and safety of opioid therapy during the opioid crisis. Policy and clinical decisions have often been made without much current data on trends in drug use in patients with pain. Thus, we evaluated definitive urine drug test (UDT) results in patients being treated for pain to see if those taking their prescribed opioids were less likely to be positive for the primary illicit drugs currently driving overdose deaths: cocaine, heroin, fentanyl, and methamphetamine. DESIGN, SETTING, AND PATIENTS: A cross-sectional study of UDT results from January 1, 2015 to September 30, 2021, from 600,000 patient specimens submitted for testing by pain management specialists. INTERVENTIONS: UDT by liquid chromatography-tandem mass spectrometry as ordered by the treating clinician. MAIN OUTCOME MEASURES: Presence of other substances stratified by whether a patient's prescribed opioid was found. RESULTS: The presence of cocaine, heroin, fentanyl, and methamphetamine for the total population was low (<5 percent). Of the 347,092 patients prescribed opioids, 76 percent (n = 264,961) were positive on UDT for their prescribed opioid ("consistent"). Compared to patients without their prescribed opioid present ("inconsistent"), patients consistent with therapy were 54 percent (incidence rate ratio (IRR) 1.54, 95 percent confidence interval (CI) 1.47-1.59) less likely to be positive for cocaine, 47 percent [IRR 1.47, 95 percent CI 1.34-1.57] less likely to be positive for heroin, and 35 percent [IRR 1.35, 95 percent CI 1.24-1.45] less likely to be positive for methamphetamine, p < 0.001. Differences between the groups for fentanyl were not significant. CONCLUSIONS: Overall positivity rates for cocaine, heroin, fentanyl, and methamphetamine were low. Patients with prescribed opioid present were less likely to be positive for cocaine, heroin, or methamphetamine. Patterns of substance use within this pain management population should be used to inform ongoing policy decisions.

Trends in drug use among nightclub and festival attendees in New York City, 2017-2022.

BACKGROUND: Drug use is prevalent among people who attend electronic dance music (EDM) parties at nightclubs or festivals. This population can serve as a sentinel population to monitor trends in use of party drugs and new psychoactive substances (NPS) that may diffuse through larger segments of the population. METHODS: We surveyed adults entering randomly selected EDM parties at nightclubs and dance festivals in New York City about their drug use in 2017 (n=954), 2018 (n=1,029), 2019 (n=606), 2021 (n=229), and 2022 (n=419). We estimated trends in past-year and past-month use of 22 drugs or drug classes based on self-report from 2017-2022 and examined whether there were shifts pre- vs. post-COVID (2017-2019 vs. 2021-2022). RESULTS: Between 2017 and 2022, there were increases in past-year and past-month use of shrooms (psilocybin), ketamine, poppers (amyl/butyl nitrites), synthetic cathinones ("bath salts"), and novel psychedelics (lysergamides and DOx series), increases in past-year cannabis use, and increases in past-month use of 2C series drugs. Between 2017 and 2022, there were decreases in past-year heroin use and decreases in past-month cocaine use, novel stimulant use, and nonmedical benzodiazepine use. The odds of use of shrooms, poppers, and 2C series drugs significantly increased after COVID, and the odds of use of cocaine, ecstasy, heroin, methamphetamine, novel stimulants, and prescription opioids (nonmedical use) decreased post-COVID. CONCLUSIONS: We estimate shifts in prevalence of various drugs among this sentinel population, which can inform ongoing surveillance efforts and public health response in this and the general populations.

Long-term wastewater-based surveillance and impacts of the COVID-19 pandemic on drug use trends in a U.S. Northeast rural town.

Herein we discuss the findings of a two-year wastewater-based drug use surveillance from September 2018 to August 2020 and present objective evidence on the impacts of the COVID-19 pandemic on drug use in a rural community. 24-h composite wastewater samples were collected twice each month from a university town in Northeastern United States and were analyzed for ten priority opioids and stimulants: morphine, codeine, hydrocodone, methadone, fentanyl cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA). All target drugs were detected at 100 % frequency in wastewater samples. On a mass basis, the average estimated per capita drug consumption were highest for cocaine, morphine, and amphetamine, and lowest for MDMA, MDEA, and hydrocodone. Furthermore, the estimated per capita consumption of fentanyl was higher than previous reports from rural and university settings in the U.S. Generally, drug consumption was higher during the spring semesters, with year-on-year semester increases also noted over the 2-y study period. Except for methadone and cocaine, the estimated average per capita consumption of drugs increased over the pandemic period, with the highest increase noted for MDMA (286 % increase compared to baseline, p = 0.016). Estimated average consumption of methadone and cocaine decreased slightly by 6 % and 7 %, respectively. These results demonstrate the utility and strength of wastewater-based approaches in capturing long-term and evolving trends in drug use within communities. Our study findings reflect the regionwide problem with opioid-related overdoses and increasing stimulant prescription rates. Our findings also provide objective data and insights for health policymakers on the effects of the pandemic period on community drug use in a rural U.S. town.

Disruption to Australian heroin, methamphetamine, cocaine and ecstasy markets with the COVID-19 pandemic and associated restrictions.

BACKGROUND: Changes to drug markets can affect drug use and related harms. We aimed to describe market trends of heroin, methamphetamine, cocaine and ecstasy in Australia following the introduction of COVID-19 pandemic-associated restrictions. METHODS: Australians residing in capital cities who regularly inject drugs (n ∼= 900 each year) or regularly use ecstasy and/or other illicit stimulants (n ∼= 800 each year) participated in annual interviews 2014-2022. We used self-reported market indicators (price, availability, and purity) for heroin, crystal methamphetamine, cocaine, and ecstasy crystal to estimate generalised additive models. Observations from the 2014-2019 surveys were used to establish the pre-pandemic trend; 2020, 2021 and 2022 observations were considered immediate, short-term and longer-term changes since the introduction of pandemic restrictions. RESULTS: Immediate impacts on market indicators were observed for heroin and methamphetamine in 2020 relative to the 2014-2019 trend; price per cap/point increased (ß: A$9.69, 95% confidence interval [CI]: 2.25-17.1 and ß: A$40.3, 95% CI: 33.1-47.5, respectively), while perceived availability (adjusted odds ratio [aOR] for 'easy'/'very easy' to obtain: 0.38, 95% CI: 0.24-0.59 and aOR: 0.08, 95% CI: 0.03-0.25, respectively) and perceived purity (aOR for 'high' purity: 0.36, 95% CI: 0.23-0.54 and aOR: 0.33, 95% CI: 0.20-0.54, respectively) decreased. There was no longer evidence for change in 2021 or 2022 relative to the 2014-2019 trend. Changes to ecstasy and cocaine markets were most evident in 2022 relative to the pre-pandemic trend: price per gram increased (ß: A$92.8, 95% CI: 61.6-124 and ß: A$24.3, 95% CI: 7.93-40.6, respectively) and perceived purity decreased (aOR for 'high purity': 0.18, 95% CI: 0.09-0.35 and 0.57, 95% CI: 0.36-0.90, respectively), while ecstasy was also perceived as less easy to obtain (aOR: 0.18, 95% CI: 0.09-0.35). CONCLUSION: There were distinct disruptions to illicit drug markets in Australia after the COVID-19 pandemic began; the timing and magnitude varied by drug.

Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US.

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

The United Kingdom's first unsanctioned overdose prevention site; A proof-of-concept evaluation.

BACKGROUND: The United Kingdom (UK) is currently experiencing a public health crisis of drug-related deaths. The government has rejected recommendations to open overdose prevention services, under the Misuse of Drugs Act 1971. To report on the operation and use of an unsanctioned overdose prevention service which operated in Glasgow city centre from September 2020 to May 2021. METHODS: Description of the service, with analysis of data collected on its use. RESULTS: The service operated for nine months without permission or funding from official sources. We report on the 894 injections supervised and recorded, and nine successful interventions with overdose events (seven opioid/two cocaine). Powder cocaine injection predominated either alone (60.6%) or with heroin (22.1%). Injection was mostly in the groin (68.0%) or arm (16.8%). More injections were recorded by males (70.1%). Around 65% of injection events featured an individual who was on a buprenorphine/methadone prescription. CONCLUSION: It is feasible for an overdose prevention service to operate successfully in the UK without being shut down by the police or with negative consequences for the community. Future sites in the UK must tailor to the substances used by their potential clients, international trends (e.g. for fentanyl use) did not apply here. There is an urgent need and demand for these services in the UK to reduce harm, prevent and intervene during overdose, and provide vital psychosocial support for health and wellbeing in a highly marginalised population.

Impact of Cannabis Use, Substance Use Disorders, and Psychiatric Diagnoses on COVID-19 Outcomes: A Retrospective Cohort Study.

Objective: While psychiatric disorders have been recognized as a risk factor for COVID-19 outcomes, the impact of substance use disorders (SUD) on COVID-19 outcomes has not, to date, been examined in a systematic manner. We examined the association between SUD (cannabis, cocaine, alcohol, opioid, and benzodiazepine) as well as psychiatric diagnoses (schizophrenia, mood disorders, anxiety disorders) and COVID-19 outcomes in a large, retrospective cohort study.Methods: COVID-19-positive patients admitted to a large health care system in the US between January and December 2020 were included in this study. SUD and psychiatric diagnoses were identified from urine toxicology reports and ICD-10 diagnosis codes in the electronic medical record, respectively. Multivariable logistic regression was performed controlling for potential confounders such as age, race, sex, smoking status, and medical comorbidities. COVID-19-relevant outcomes included mortality, need for intensive care unit (ICU) admission, need for ventilatory support, length of hospitalization, and number of hospitalizations.Results: Among COVID-19 patients (N = 6,291), those with SUD were more likely to require ICU admission (adjusted odds ratio [AOR] = 1.46, P = .003) and ventilatory support (AOR = 1.49, P = .01). The association between SUD and ICU admission was driven by alcohol use disorder (AUD), whereas that between SUD and ventilatory support was driven by both AUD and opioid use disorder (OUD). Patients with SUD were more likely to have a longer mean maximum length of hospitalization (11.32 vs 8.62 days, P < .0001) and a greater mean number of hospital admissions in 2020 (2.96 vs 2.33, P < .0001). These associations were significant for cannabis use disorder, AUD, OUD, and benzodiazepine use disorder. The association with greater number of admissions was also significant for cocaine use disorder. Patients with psychiatric diagnoses were also more likely to have a greater maximum length of hospitalization (11.93 vs 8.39 days, P < .0001) and hospital admissions (2.72 vs 2.31, P < .0001). These associations were significant for schizophrenia, mood disorders, and anxiety disorders.Conclusions: COVID-19 patients with SUD had greater likelihood of requiring critical interventions, such as ICU admission and ventilatory support. SUD and psychiatric diagnoses were also associated with a longer duration of hospitalization and greater number of hospital admissions. These findings identify COVID-19 patients with SUD and psychiatric comorbidities as a high-risk group.

Development of a Graphene-Oxide-Deposited Carbon Electrode for the Rapid and Low-Level Detection of Fentanyl and Derivatives.

The opioid overdose crisis in North America worsened during the COVID-19 pandemic, with multiple jurisdictions reporting more deaths per day due to the fentanyl-contaminated drug supply than COVID-19. The rapid quantitative detection of fentanyl in the illicit opioid drug supply or in bodily fluids at biologically relevant concentrations (i.e., <80 nM) remains a significant challenge. Electroanalytical techniques are inexpensive and can be used to rapidly detect fentanyl, but detection limits need to be improved. Herein, we detail the development of an electrochemical-based fentanyl analytical detection strategy that used a glassy carbon electrode modified with electrochemically reduced graphene oxide (ERGO) via electrophoretic deposition. The resulting surface was further electrochemically reduced in the presence of fentanyl to enhance the sensitivity. Multiple ERGO thicknesses were prepared in order to prove the versatility and ability to fine-tune the layer to the desired response. Fentanyl was detected at <10 ppb (<30 nM) with a limit of detection of 2 ppb and a calibration curve that covered 4 orders of concentration (from 1 ppb to 10 ppm). This method was sensitive to fentanyl analogues such as carfentanil. Interference from the presence of 100-fold excess of other opioids (heroin, cocaine) or substances typically found in illicit drug samples (e.g. caffeine and sucrose) was not significant.

Test-retest reliability of a new assessment to detect detailed temporal patterns of polysubstance use.

OBJECTIVE: While polysubstance use is highly prevalent among people who use drugs, the field lacks a reliable assessment that can detect detailed temporal patterns of polysubstance use. This study assessed the test-retest reliability of the newly developed Polysubstance Use-Temporal Patterns Section (PSU-TPS). METHODS: Participants who used cocaine plus alcohol and/or marijuana at least once in the past 30 days (n = 48) were interviewed at baseline and approximately 7 days later (retest) using the Substance Abuse Module and the PSU-TPS. Reliability of PSU-TPS measures of quantity, frequency, and duration of polysubstance use was examined using intra-class correlation coefficients (ICCs) and kappa tests. RESULTS: Excellent reliability was observed for frequencies of concurrent polysubstance use patterns in the past 30 days (ICC range: 0.90-0.94) and quantity of alcohol use (ICC = 0.83), and fair to good reliability was observed for duration of substance use (ICC range: 0.52-0.73). CONCLUSION: Detailed information regarding cocaine, alcohol, and marijuana polysubstance use in the past 30 days can be reliably measured with the PSU-TPS. Data on the order and timing of polysubstance use at the hourly level will improve our understanding of the implications of sequential and simultaneous use patterns, which can help inform treatment and prevention efforts.

Early-Onset Cardiovascular Disease From Cocaine, Amphetamines, Alcohol, and Marijuana.

Cardiovascular disease (CVD), a disease typically associated with aging and the definitive leading cause of death worldwide, now threatens young and middle-aged populations. Recreational abuse of alcohol, marijuana, cocaine, and amphetamine-type stimulants has been an escalating public health problem for decades, but now use of these substances has become a significant contributor to early-onset CVD. While this remains a global phenomenon, the epicentre of substance abuse is rooted in North America, where it has been exacerbated by the response to the COVID-19 pandemic. For the first time in history, the United States crossed 100,000 overdose-related deaths in a calendar year. Sadly, Canada's recreational drug abuse problem closely mirrors that of the US. This is indicative of the larger public health crisis, as we now know that these substances are cardiotoxic and are contributing to the rising levels of premature chronic CVD, including hypertension, arrhythmias, heart failure, stroke, myocardial infarction, arterial dissection, sudden cardiac death, and early mortality.

Long-term monitoring of drug consumption patterns during the COVID-19 pandemic in a small-sized community in Brazil through wastewater-based epidemiology.

The abuse of legal and illegal drugs is a global public health problem, also affecting the social and economic well-being of the population. Thus, there is a significant interest in monitoring drug consumption. Relevant epidemiological information on lifestyle habits can be obtained from the chemical analysis of urban wastewater. In this work, passive sampling using polar organic chemical integrative samplers (POCIS) was used to quantify licit and illicit drugs biomarkers in wastewater for the application of wastewater-based epidemiology (WBE). In this WBE study, a small urban community of approximately 1179 inhabitants was monitored from 18 March 2020 to 3 March 2021, covering the mobility restriction and flexibilization periods of the COVID-19 pandemic in Brazil. Consumption was estimated for amphetamine, caffeine, cocaine, MDMA, methamphetamine, nicotine, and THC. The highest estimated consumption among illicit drugs was for THC (2369 ± 1037 mg day-1 1000 inh-1) followed by cocaine (353 ± 192 mg day-1 1000 inh-1). There was a negative correlation between consumption of caffeine, cocaine, MDMA, nicotine, and THC with human mobility, expressed by cellular phone mobility reports (P-value = 0.0094, 0.0019, 0.0080, 0.0009, and 0.0133, respectively). Our study is the first long-term drug consumption evaluation during the COVID-19 pandemic, with continuous sampling for almost a whole year. The observed reduction in consumption of both licit and illicit drugs is probably associated with stay-at-home orders and reduced access, which can be due to the closure of commercial facilities during some time of the evaluated period, smaller drug supply, and reduced income of the population due to the shutdown of companies and unemployment. The assay described in this study can be used as a complementary and cost-effective tool to the long-term monitoring of drug use biomarkers in wastewater, a relevant epidemiological strategy currently limited to short collection times.

Use of laboratory data for illicit drug use surveillance and identification of socioeconomic risk factors.

BACKGROUND: Drug overdose is the leading cause of death among people 25-44 years of age in the United States. Existing drug surveillance methods are important for prevention and directing treatment, but are limited by delayed reporting and lack of geographic granularity. METHODS: Laboratory urine drug screen and complete metabolic panel data from patients presenting to the emergency department was used to observe long-term and short-term temporal and geospatial changes at the zip code-level in St. Louis. Multivariate linear regression was performed to investigate associations between zip code-level socioeconomic factors and drug screening positivity rates. RESULTS: An increase in the fentanyl positive drug screens was seen during the initial COVID-19 shutdown period in the spring of 2020. A decrease in cocaine positivity was seen in the fall and winter of 2020, with a return to baseline coinciding with the second major COVID-19 shutdown in the summer of 2021. These changes appeared to be independent of changes in emergency department utilization as measured by complete metabolic panels ordered. Significant short-term changes in fentanyl and cocaine positivity rates between specific time periods were able to be localized to individual zip codes. Zip code-level multivariate analysis demonstrated independent associations between socioeconomic/demographic factors and fentanyl/cocaine positivity rates as determined by laboratory drug screening data. CONCLUSIONS: Analyzing clinical laboratory drug screening data can enable a more temporally and geographically granular view of population-level drug use surveillance. Additionally, laboratory data can be utilized to find population-level socioeconomic associations with illicit drug use, presenting a potential avenue for the use of this data to guide public health and healthcare policy decisions.

Use of illicit drugs, alcohol and tobacco in Spain and Portugal during the COVID-19 crisis in 2020 as measured by wastewater-based epidemiology.

The COVID-19 pandemic spread rapidly worldwide in the year 2020, which was initially restrained by drastic mobility restrictions. In this work, we investigated the use of illicit drugs (amphetamine, methamphetamine, ecstasy, cocaine and cannabis), and licit substances of abuse (alcohol and tobacco) during the earlier months (March-July 2020) of the pandemic restrictions in four Spanish (Bilbao and its metropolitan area, Vitoria-Gasteiz, Castellón and Santiago de Compostela) and two Portuguese (Porto and Vila do Conde) locations by wastewater-based epidemiology (WBE). The results show that no methamphetamine was detected in any of the locations monitored, while amphetamine use was only detectable in the two locations from the Basque Country (Bilbao and its metropolitan area and Vitoria-Gasteiz), with high estimated average usage rates (700-930 mg day-1 1000 inhabitant-1). The remaining substances were detected in all the investigated catchment areas. In general, no remarkable changes were found in population normalized loads compared to former years, except for cocaine (i.e. its main metabolite, benzoylecgonine). For this drug, a notable decrease in use was discernible in Castellón, while its usage in Porto and Santiago de Compostela seemed to continue in a rising trend, already initiated in former years. Furthermore, two events of ecstasy (3,4-methylenedioxymethamphetamine, MDMA) dumping in the sewage network were confirmed by enantiomeric analysis, one in Santiago de Compostela just prior the lockdown and the second one in the Bilbao and its metropolitan area in July after relieving the more stringent measures. The latter could also be associated with a police intervention. The comparison of WBE with (web) survey data, which do not provide information at a local level, points towards contradictory conclusions for some of the substances, thereby highlighting the need for stable WBE networks capable of near real-time monitoring drug use.

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern.

Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or 'crack' cocaine, the free base. While the first is commonly administered by insufflation ('snorting') or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine's prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

Substance use disorders and COVID-19: An analysis of nation-wide Veterans Health Administration electronic health records.

BACKGROUND: Substance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality. METHODS: Veterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+). Outcomes were COVID-19+ by 11/01/20, hospitalization, ICU admission, or death within 60 days of a positive test. Main predictors were any ICD-10-CM SUDs, with substance-specific SUDs (cannabis, cocaine, opioid, stimulant, sedative) explored individually. Logistic regression produced unadjusted and covariate-adjusted odds ratios (OR; aOR). RESULTS: Among COVID-19+ patients, 19.25% were hospitalized, 7.71% admitted to ICU, and 5.84% died. In unadjusted models, any SUD and all substance-specific SUDs except cannabis use disorder were associated with COVID-19+(ORs=1.06-1.85); adjusted models produced similar results. Any SUD and all substance-specific SUDs were associated with hospitalization (aORs: 1.24-1.91). Any SUD, cocaine and opioid disorder were associated with ICU admission in unadjusted but not adjusted models. Any SUD, cannabis, cocaine, and stimulant disorders were inversely associated with mortality in unadjusted models (OR=0.27-0.46). After adjustment, associations with mortality were no longer significant. In ad hoc analyses, adjusted odds of mortality were lower among the 49.9% of COVID-19+ patients with SUD who had SUD treatment in 2019, but not among those without such treatment. CONCLUSIONS: In VHA patients, SUDs are associated with COVID-19 hospitalization but not COVID-19 mortality. SUD treatment may provide closer monitoring of care, ensuring that these patients received needed medical attention, enabling them to ultimately survive serious illness.

Temporal monitoring of stimulants during the COVID-19 pandemic in Belgium through the analysis of influent wastewater.

BACKGROUND AND AIMS: Wastewater-based epidemiology (WBE) is a complementary epidemiological data source to monitor stimulant consumption. The aims were to: (i) study intra- and inter-year temporal changes in stimulant use in Belgium during the first wave of the COVID-19 pandemic; and (ii) evaluate the effect of COVID-19 restrictive measures on stimulant consumption. METHODS: The study population corresponded to the catchments of four wastewater treatment plants corresponding with four Belgian cities (i.e., Antwerp-Zuid, Boom, Brussels, Leuven). Daily 24-h composite influent wastewater samples collected over one week in September 2019 and March through June 2020 during the first wave of the COVID-19 pandemic were analyzed for biomarkers of amphetamine, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Measured concentrations were converted to population-normalized mass loads by considering the daily flow rate and the catchment population size. Mobile network data was used to accurately capture population movements in the different catchment areas. Temporal changes were assessed with multiple linear regression models, and the effect of the COVID-19 interventions on stimulant consumption were investigated. RESULTS: An increase in amphetamine use was observed in three cities during governmental restrictions, with highest consumption predominantly during lockdown. Similarly, cocaine consumption was higher after the pandemic started, with highest consumption noted during the lockdown period in Boom and Leuven. Consumption of MDMA was similar in Antwerp-Zuid, Brussels and Leuven throughout the entire sampled period. In Boom, the highest consumption was observed during the full lockdown period. CONCLUSIONS: The present study shows the potential of WBE to assess the impact of stringent lockdown measures on stimulant use in Belgium. This paper shows that strong restrictive measures did not have a profound effect on stimulant consumption.

A Multicenter Study on the Impact of Gender, Age, and Dual Diagnosis on Substance Consumption and Mental Health Status in Outpatients Treated for Substance Use Disorders During COVID-19 Lockdown.

Objective COVID-19 and lockdown measures impacted mental health globally and had a particular impact on patients with substance use disorders (SUD). However, the impact of gender, age, and dual diagnosis on consumption patterns and mental health during COVID-19 lockdown among patients with SUD has not been analyzed in depth. Therefore, this study aimed to examine substance use and mental health status during COVID-19 lockdown considering gender, age, and previous dual diagnosis in patients with SUD treated in different outpatient addiction clinics in Catalonia. Methods: Thirteen clinics participated and 588 patients were enrolled in the study, of whom 70.7% were men and 29.3% were women. The mean age was 48 ± 11.3 years, and 63.2% had dual diagnoses. Results: Men reported significantly more frequent alcohol and cocaine consumption during lockdown, while women experienced more anxiety and depressive symptoms. Younger patients more frequently reported consuming cocaine and cannabis, breaking the lockdown rule, worsened family relationships, and reduced incomes. Older patients more frequently reported maintaining abstinence. Previous dual diagnosis was more often associated with benzodiazepine use disorder, less active working during lockdown, and more anxiety and depressive symptoms than not having previous dual diagnosis. Conclusions: Both new psychiatric symptoms and general worsening of existing symptoms were frequent during the lockdown. Differences based on the gender, age, and dual diagnosis of outpatients treated for substance use disorders should be considered in the planning of protection measures such as home confinement.

Substance use during the COVID-19 pandemic: What is really happening?

The COVID-19 pandemic is associated with increased levels of anxiety, fear, sadness, difficulty adjusting, symptoms of post-traumatic stress disorder and suicidality, both in the general population and specific subgroups. The presence of this type of psychopathology increases the risk of involvement with or worsens the use of addictive substances and alcohol as a maladaptive coping strategy.1 According to these data, people with substance use disorders are a population at high risk for COVID-19 infection and serious illness. Α large controlled retrospective case study in the US found that people with substance use disorders are significantly more vulnerable to COVID-19 and its complications (primarily those with opioid use disorder OR = 10.21 and with tobacco use disorder OR = 8.25), and that the course and outcome of the disease (hospitalization, death) was worse than in non-dependent individuals. The main culprits are increased physical co-morbidity (frequent respiratory and cardiovascular problems), poor health and living conditions, marginalization and difficulties in accessing health services. 2,3 Ιnternational epidemiological data during the first months of the pandemic regarding the use of addictive substances do not lead to safe conclusions. A cross-sectional online epidemiological study conducted on a sample of 36,538 adults from 21 European countries between April and July 2020 found an overall decrease in alcohol use, which was mainly attributed to the reduction of heavy episodic consumption, while at the same time an increase in alcohol consumption among people with severe alcohol use was recorded. Τhe use of cannabis and nicotine showed increasing trends, as well as the use of cocaine, but to a lesser extent, while the use of MDMA (ecstasy) showed a decrease.4 In a review of 45 cross-sectional studies conducted between December 2019 and November 2020, alcohol use was on the rise overall, despite geographical variations, as was the use of other addictive substances, cannabis in particular.5 It should be noted that those who increased alcohol use during quarantine were those exhibiting higher levels of negative emotionality mechanisms.6 In Greece, an online cross-sectional survey in April 2020 in the general population during the first lockdown showed a reduction in alcohol use (43.7% of alcohol users reduced or quit), a reduction in cannabis (67.3% quit), while 33.3% increased nicotine use. These changes were attributed to the limitation of alcohol availability, social distancing, changes in daily routine and income reduction.7,8 Also, wastewater samples from Athens, analyzed by the Laboratory of Analytical Chemistry of EKPA, showed a significant increase in the use of cocaine (67%), amphetamine (350%) and methamphetamine (37%), and a decrease in the use of MDMA (- 38%) during the first lockdown, compared to the corresponding period of the previous year.9 Analysis of wastewater samples from other European cities "suggest that levels of use of most drugs appear generally lower during the initial lockdowns, but then appear to bounce back once lockdown was lifted. A comparison with 2019 appears to suggest similar overall consumption of most drugs, and in several cities possibly even higher levels, based on this data source. Exceptions here appear to be MDMA and methamphetamine, two drugs for which the levels observed in 2020 appear lower in most of the participating cities".10,11 There were also changes in the locations of use of the substances, as with the periodic restrictions the use was transferred mainly at home and in open public spaces; in some cases, it was associated with increased intravenous use and cases of intoxication. Finally, intermittent difficulties in drug availability and trafficking have led users to search for other substances, increase experimentation and multidrug use, and make online purchases. In addition, there is concern about the increasing abuse of benzodiazepines, which are either diverted from therapeutic use or appear on the illicit market, often as new benzodiazepines.10,12 According to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), "the drug market has been remarkably resilient to disruption caused by the pandemic" … Drug trafficking has adapted to the new conditions with changes in routes and methods of trafficking, and by further enhancing the digital presence of the drug market… "Any reductions in drug consumption seen during the initial lockdowns rapidly disappeared as social distancing measures were eased. In general terms, there appears to have been less consumer interest in drugs usually associated with recreational events, such as MDMA, and greater interest in drugs linked with home use. However, the easing of restrictions … during the summer was associated with a rebound in the levels of use". Also, "survey data suggest that those using drugs occasionally prior to COVID-19 may have reduced or even ceased their use during the pandemic, but more-regular users may have increased their drug consumption".10 Measures taken to control the pandemic have reduced and modified the mental health and addiction treatment services provided. Although services have been adequately restored, there has initially been a 60% reduction in the availability and provision of detoxification services in Europe.13 Live contact, mainly at group level, was significantly reduced or stopped altogether for a long period, as well as the frequency of individual appointments. Therapeutic programs sought to respond to the new conditions using technology and telemedicine, providing online group support and psychotherapy. Substitution treatment programs have become more flexible by providing long-term pharmaceutical substitutes (take home) to prevent users from moving. There have also been facilitations in prescribing by treating physicians. Thus, the addicts' contact with the treatment process was maintained, but it was insufficient to meet their increased needs during this period. In conclusion, it should be noted that substance use appears to have an autonomous dynamism in relation to the pandemic and the consequent psychopathology, being in a "loose" causal relationship with it. Therefore, hasty and untimely generalizations should be avoided, and easy conclusions should not be drawn through extrapolations from previous socio-economic crises of different types or through partial spatiotemporal understandings, which are usually presented by the media in the form of negative alarming information.

The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis.

PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.