Rates of stimulant use, including misuse of prescription stimulants and use of cocaine and methamphetamine, are rising rapidly among adolescents and young adults ("youth"). Stimulant misuse is associated with overdose, polysubstance use, substance use disorders, and other medical harms. Substance use is often initiated during adolescence and young adulthood, and interventions during these crucial years have the potential to impact the lifetime risk of stimulant use disorder and associated harms. In this narrative review, we review recent data on prescription and illicit stimulant use in youth. We describe the rising contribution of stimulants to polysubstance use involving opioids and other substances and to overdose, as well as ways to minimize harm. We also discuss prescription stimulant misuse, which is especially prevalent among youth relative to other age groups, and the limited evidence on potential pathways from prescription stimulant use to illicit stimulant use. Last, we assess potential strategies for the prevention and treatment of stimulant use disorder in youth.

The COVID-19 pandemic has consistently raised the number of drug seizures, in United States as in Europe. The COVID-19 pandemic has also changed the typology of seizures from "more traditional" drugs to New Psychoactive Substances (NPSs), depending on geographical area. In Europe, the most frequent NPSs are synthetic cannabinoids (SCs) and cathinones, nonetheless synthetic opioids and phenethylamines are widely used. The aim of the study is the detection of NPS and other substances of abuse available in the black market, by quali/quantitative methods in LC-MS/MS and GC-MS. From 2018 to 2021, 268 seizures occurred in total and were analyzed by the Forensic Toxicology Laboratory (FTL) of Naples (Italy). The distribution of analyzed seizures over the years is the following: 53 in 2018, 61 in 2019, 89 in 2020 and 65 during the first semester of 2021. Cannabis was the most detected drug both in hashish and marijuana seizures, followed by cocaine > heroine > prescribed drugs > ketamine-amphetamine MDMA. No NPSs were seized until June 2021, when NPSs were found in two different seizures: Case #1 showed a bar of Cannabis resin containing a low level of Δ9THC = 0.57% associated to SC AB-FUBINACA in 4.5%; Case #2 showed a vegetal resinous substance (Δ9THC = 0.27%) with SC 5F-APINACA (4.1%) associated with methadone (1.0%). The detection of NPSs is alarming evidence that can lead to an increase in the risk of overdose or other negative and unpredictable consequences, such as violent or self-harming behavior in unaware users of cannabis derivatives considered of "natural" origin.

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.

Background: Fentanyl-related deaths continue to increase in the United States; however, most national studies focus on fatal overdose. More research, including data on nonfatal overdose, is needed.Objective: We examined trends in characteristics of fatal and nonfatal fentanyl-related poisonings ("exposures") in the US.Methods: National Poison Control data were examined to estimate trends in characteristics of reported exposures between 2015 and 2021 (N = 15,391; 38.7% female). We also delineated correlates of experiencing a major adverse effect or death.Results: The proportion of exposures increased among all age groups between ages 13 and 39 (ps < .05) with the largest increase among those age 13-19 (a 127.8% increase). With respect to reasons for use, the proportion of cases involving fentanyl "abuse" increased by 63.8% (p < .001). The proportion involving fentanyl inhalation increased 427.6% from 5.7% to 29.9% and injection increased from 6.7% to 9.6%, a 42.3% increase (ps < .01). The proportion also increased for co-use of methamphetamine (by 669.0%), cocaine (by 374.0%), and heroin (by 159.5%). The proportion of major adverse effects increased from 15.5% to 39.6% (p < .001). In the multivariable model, "abuse", suspected suicide attempts, and use via inhalation were risk factors for experiencing a major effect or death, and misuse, ingestion, dermal use, and co-use of methamphetamine were associated with lower risk.Conclusion: Poison Control data suggest that characteristics of individuals exposed to fentanyl continue to shift, with use via inhalation increasing and medical outcomes of nonfatal poisonings becoming more severe. These results complement mortality data and inform prevention and harm reduction efforts.

Stimulant use disorders present an enduring public health concern. Chronic stimulant use is associated with a range of health problems, with notable increases in stimulant overdose that disproportionately affect marginalized populations. With these persistent problems, it is important to understand the behavioral and pharmacological factors that contribute to stimulant use in humans. The purpose of this chapter is to provide an update and narrative review on recent human laboratory research that has evaluated the behavioral pharmacology of stimulant drugs. We focus on two prototypic stimulants: cocaine as a prototype monoamine reuptake inhibitor and d-amphetamine as a prototype monoamine releaser. As such, placebo controlled human laboratory studies that involved administration of doses of cocaine or d-amphetamine and were published in peer reviewed journals within the last 10 years (i.e., since 2011) are reviewed. Primary outcomes from these studies are subjective effects, reinforcing effects, cognitive/behavioral effects, and discriminative stimulus effects. Both cocaine and d-amphetamine produce classical stimulant-like behavioral effects (e.g., increase positive subjective effects, function as reinforcers), but there are notable gaps in the literature including understanding sex differences in response to stimulant drugs, cognitive-behavioral effects of stimulants, and influence of use history (e.g., relatively drug naïve vs drug experienced) on stimulant effects.

The number of people who suffer from a substance abuse disorder has continued to rise over the last decade; particularly, the number of drug-related overdose deaths has sharply increased during the COVID-19 pandemic. Converging lines of clinical observations, supported by imaging and neuropsychological performance testing, have demonstrated that substance abuse-induced dysregulation of neurotransmissions in the brain is critical for development and expression of the addictive properties of abused substances. Recent scientific advances have allowed for better understanding of the neurobiological processes that mediates drugs of abuse and addiction. This chapter presents the past classic concepts and the recent advances in our knowledge about how cocaine, amphetamines, opioids, alcohol, and nicotine alter multiple neurotransmitter systems, which contribute to the behaviors associated with each drug. Additionally, we discuss the interactive effects of HIV-1 or COVID-19 and substance abuse on neurotransmission and neurobiological pathways. Finally, we introduce therapeutic strategies for development of pharmacotherapies for substance abuse disorders.

Opioid abuse continues to be a significant public health challenge, with rates of opioid-related overdose deaths increasing continuously over the last two decades. There also has been a sharp increase in overdose deaths involving stimulant drugs, primarily cocaine and methamphetamine. Recent estimates indicate a high prevalence of co-use of opioids and stimulants, which is a particularly complex problem. Behavioral pharmacology research over the last few decades has characterized interactions between opioids and stimulants as well as evaluated potential treatments. This chapter describes interactions between opioids and stimulants, with a focus on pre-clinical studies of abuse-related behavioral effects using self-administration, reinstatement, drug discrimination, place conditioning, and intracranial self-stimulation paradigms in laboratory animals. In general, the literature provides substantial evidence of mutual enhancement between opioids and stimulants for abuse-related effects, although such results are not ubiquitous. Enhanced abuse-related effects could manifest in many ways including engaging in drug seeking and taking behaviors with greater persistence, effort, and motivation and/or increased likelihood of relapse. Moreover, studies on opioid/stimulant combinations set the stage for evaluating potential treatments for polysubstance use. Behavioral pharmacology research has proven invaluable for elucidating these relationships using rigorous experimental designs and quantitative analyses of pharmacological and behavioral data.

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.

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.

Little is known about patients' addiction severity, substance use, or mental health symptoms upon entering integrated treatment. This is the first study to compare baseline characteristics among cohorts of patients with co-occurring disorders entering a private integrated residential treatment program in 2013 and 2017; a period when severe and persistent mental illness diagnoses, mental health service use, and overdose deaths increased. Our sample includes 3400 patients entering private, integrated residential treatment during 2013 (n = 1535) and 2017 (n = 1865). Trained staff completed admission interviews of all participants that included the Addiction Severity Index (ASI), a semi-structured interview to evaluate the past 30-day functioning of the following domains: medical, employment, alcohol, drug, legal, family or social support systems, and psychiatric. We used a p-value of 0.05 to assess significance. With the exception of the drug composite score, the 2017 cohort scored higher than the 2013 cohort on all other composite scores. Compared to the 2013 cohort, the 2017 cohort reported more days using alcohol, cocaine, amphetamines, and engaging in polysubstance use. Conversely, the 2017 cohort reported fewer days using other prescription opioids and sedatives than the 2013 cohort. After controlling for age, the 2017 cohort reported more days of marijuana use than the 2013 cohort. The 2017 cohort reported higher rates of the following symptoms: depression, anxiety, hallucinations, and suicidal ideation. Findings underscore differences among integrated treatment patient cohorts for baseline addiction severity, substance use, or mental health symptoms.

Overdose death rates caused by psychostimulants have increased by 22.3% annually from 2008 to 2017. Cue-evoked drug craving progressively increases and contributes to perpetual relapse. Preclinical models have determined that glutamate receptor plasticity within the nucleus accumbens (NAc) drives amplified cue-evoked drug seeking after prolonged abstinence (>40 days). Isolated condition (IC) rearing increases cocaine and amphetamine (AMP) self-administration and cue-induced reinstatement. We tested the hypothesis that housing in the IC will augment AMP seeking after short and prolonged abstinence from AMP self-administration when compared with rats reared in the enrichment condition (EC). EC and IC male rats acquired stable AMP or SAL self-administration and were tested in a cue-induced AMP-seeking test after 1 and 40 days of abstinence. After the seeking test, the whole NAc was extracted and prepared for western blot analysis. Results indicate that IC rats had more active lever presses during a brief extinction interval and during the cue-induced seeking test. After 40 days of abstinence, IC rats had more active lever presses than EC rats during the cue-induced seeking test. Western blots indicated that the expression ratio between GluA1:mGlur5 was reduced only in IC-AMP-trained rats and the ratio between GluA1:mGlur1 was positively correlated with AMP seeking after prolonged abstinence in IC-AMP rats. These results indicate that IC housing engenders a vulnerable phenotype prone to persistent AMP seeking. The behavioural momentum of this vulnerable phenotype is further revealed when AMP-associated cues are presented following prolonged abstinence.

A 47-year-old female with attention-deficit/hyperactivity disorder on prescription Adderall presented to the hospital with worsening dyspnea for the one-month duration. She was admitted to the medical intensive care unit with respiratory failure requiring non-invasive positive pressure ventilation. Cardiac catheterization confirmed the diagnosis of non-cardiogenic pulmonary edema. With the discontinuation of Adderall, use of BiPAP, and aggressive diuresis with loop diuretics, there was evidence of symptomatic, laboratory, and radiological improvement. Her symptoms were attributed to Adderall use as a diagnosis of exclusion. To our knowledge, this paper reports the first case of Adderall-induced non-cardiogenic pulmonary edema leading to respiratory failure. Although case reports of abuse or overdose of other stimulants such as amphetamine and cocaine leading to a plethora of cardiac and pulmonary complications such as acute respiratory distress syndrome (ARDS), cardiogenic pulmonary edema, and non-cardiogenic pulmonary edema exist, there are no reports that using Adderall at routine prescription doses can lead to these problems.