Future perspectives of emerging novel drug targets and immunotherapies to control drug addiction.

Substance Use Disorder (SUD) is one of the major mental illnesses that is terrifically intensifying worldwide. It is becoming overwhelming due to limited options for treatment. The complexity of addiction disorders is the main impediment to understanding the pathophysiology of the illness. Hence, unveiling the complexity of the brain through basic research, identification of novel signaling pathways, the discovery of new drug targets, and advancement in cutting-edge technologies will help control this disorder. Additionally, there is a great hope of controlling the SUDs through immunotherapeutic measures like therapeutic antibodies and vaccines. Vaccines have played a cardinal role in eliminating many diseases like polio, measles, and smallpox. Further, vaccines have controlled many diseases like cholera, dengue, diphtheria, Haemophilus influenza type b (Hib), human papillomavirus, influenza, Japanese encephalitis, etc. Recently, COVID-19 was controlled in many countries by vaccination. Currently, continuous effort is done to develop vaccines against nicotine, cocaine, morphine, methamphetamine, and heroin. Antibody therapy against SUDs is another important area where serious attention is required. Antibodies have contributed substantially against many serious diseases like diphtheria, rabies, Crohn's disease, asthma, rheumatoid arthritis, and bladder cancer. Antibody therapy is gaining immense momentum due to its success rate in cancer treatment. Furthermore, enormous advancement has been made in antibody therapy due to the generation of high-efficiency humanized antibodies with a long half-life. The advantage of antibody therapy is its instant outcome. This article's main highlight is discussing the drug targets of SUDs and their associated mechanisms. Importantly, we have also discussed the scope of prophylactic measures to eliminate drug dependence.

Risk mitigation guidance and safer supply prescribing among young people who use drugs in the context of COVID-19 and overdose emergencies.

Across North America, overlapping overdose and COVID-19 emergencies have had a substantial impact on young people who use drugs (YPWUD). New risk mitigation guidance (RMG) prescribing practices were introduced in British Columbia, Canada, in 2020 to allow people to decrease risk of overdose and withdrawal and better self-isolate. We examined how the prescribing of hydromorphone tablets specifically impacted YPWUD's substance use and care trajectories. Between April 2020 and July 2021, we conducted virtual interviews with 30 YPWUD who had accessed an RMG prescription of hydromorphone in the previous six months and 10 addiction medicine physicians working in Vancouver. A thematic analysis was conducted. YPWUD participants highlighted a disjuncture between RMG prescriptions and the safe supply of unadulterated substances such as fentanyl, underscoring that having access to the latter is critical to reducing their reliance on street-based drug markets and overdose-related risks. They described re-appropriating these prescriptions to meet their needs, stockpiling hydromorphone so that it could be used as an "emergency backup" when they were unable to procure unregulated, illicit opioids. In the context of entrenched poverty, hydromorphone was also used to generate income for the purchase of drugs and various necessities. For some YPWUD, hydromorphone prescriptions could be used alongside opioid agonist therapy (OAT) to reduce withdrawal and cravings and improve adherence to OAT. However, some physicians were wary of prescribing hydromorphone due to the lack of evidence for this new approach. Our findings underscore the importance of providing YPWUD with a safe supply of the substances they are actively using alongside a continuum of substance use treatment and care, and the need for both medical and community-based safe and safer supply models.

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.

The Impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Substance Use in the United States.

The SARS-CoV-2 pandemic has been associated with dramatic increases in substance use, as marked by increased alcohol, nicotine, and cannabis sales. Lethal opioid overdoses also increased dramatically, especially during the initial phases of the epidemic when lockdowns and social isolation combined with increasing fentanyl contamination of the illicit drug supply resulted in more overdoses and fewer opportunities for rescue. Substance use, and especially inhalational drug use, increases the likelihood of both transmission and severe infection. Youth are especially vulnerable to substance use and have increased risk of long-term problems. These outcomes highlight the need for greater access to substance use treatment. Virtual treatment, which emerged as a promising format during the pandemic, may reduce access barriers. This article reviews trends in substance use during the pandemic, explores root causes of increased use and overdose, and examines the potential to increase treatment through virtual care, especially during future periods of disruption.

Trazodone Prolonged-Release Monotherapy in Cannabis Dependent Patients during Lockdown Due to COVID-19 Pandemic: A Case Series.

(1) Background: During the SARS-CoV-2 (COVID-19) pandemic, cannabis use increased relative to pre-pandemic levels, while forced home confinement frequently caused sleep/wake cycle disruptions, psychological distress, and maladaptive coping strategies with the consequent appearance of anxiety symptoms and their potential impact on substance use problems. (2) Aim: Long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. The present work aims to investigate the effectiveness of trazodone in optimizing the condition of people with cannabis dependence under pandemic conditions. (3) Methods: All cases with cannabis use disorder were uniformly treated with long-acting trazodone 150 mg or 300 mg/day; their craving and clinical status were monitored through appropriate psychometric scales. Side effects were recorded as they were reported by patients. We described the cases of three young patients-one man and two women-who were affected by chronic cannabis use disorder and who experienced lockdown-related psychological distress and sought psychiatric help. (4) Results: The described cases highlight that the once-a-day formulation of trazodone seems to have a therapeutic role in patients with cannabis use disorder and to guarantee tolerability and efficacy over time. No significant side effects emerged. (5) Conclusions: The use of long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. Trazodone deserves to be studied in terms of its efficacy for cannabis use disorder.

Public Health Implications of Cannabis Legalization: An Exploration of Adolescent Use and Evidence-Based Interventions.

This article examines the relaxation of state marijuana laws, changes in adolescent use of marijuana, and implications for drug education. Under federal law, use of marijuana remains illegal. In spite of this federal legislation, as of 1 June 2021, 36 states, four territories and the District of Columbia have enacted medical marijuana laws. There are 17 states, two territories and the District of Columbia that have also passed recreational marijuana laws. One of the concerns regarding the enactment of legislation that has increased access to marijuana is the possibility of increased adolescent use of marijuana. While there are documented benefits of marijuana use for certain medical conditions, we know that marijuana use by young people can interfere with brain development, so increased marijuana use by adolescents raises legitimate health concerns. A review of results from national survey data, including CDC's YRBS, Monitoring the Future, and the National Household Survey on Drug Use, allows us to document changes in marijuana use over time. Increased legal access to marijuana also has implications for educational programming. A "Reefer Madness" type educational approach no longer works (if it ever did). We explore various strategies, including prevention programs for education about marijuana, and make recommendations for health educators.

Substance abuse and neurotransmission.

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.

Advantages and disadvantages of disulfiram coadministered with popular addictive substances.

Disulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesirable effects. To date, there is still limited data regarding the detailed safety profile of DSF as a concomitant drug. In this review article, we outline the current state of knowledge about DSF, its broad pharmacological action, as well as therapeutic effects, with a particular emphasis on the molecular understanding of its potential pharmacodynamic interactions with common addictive substances (e.g., alcohol, cocaine, cannabinoids, opioids) supported by relevant examples.

Impacts of the COVID-19 pandemic on healthcare access among patients receiving medication for opioid use disorder.

BACKGROUND: The COVID-19 pandemic significantly altered treatment delivery for opioid treatment programs (OTPs) dispensing medications for opioid use disorder (MOUD). We aimed to identify patterns of substance use among MOUD patients and examine whether COVID-19-related impacts on access to healthcare varied across subgroups. METHODS: This analysis was embedded within a type 3 hybrid trial that enrolled patients across eight OTPs at the start of the pandemic. Enrolled patients reported on past-30 day use of multiple substances during their baseline assessment. Participants re-contacted in May-July 2020 completed a survey about COVID-19-related impacts on various life domains. Using latent class analysis we identified patient subgroups, and then examined group differences on a set of negative and positive COVID-19 impacts related to healthcare access. RESULTS: Of the 188 trial participants, 135 (72 %) completed the survey. Latent class analysis identified three MOUD patient subgroups: minimal use (class probability: 0.25); opioid use (class probability: 0.34); and polysubstance use (class probability: 0.41). Compared to the minimal use group, the polysubstance use group reported increased substance use and difficulty accessing sterile needles, naloxone, and preferred substance. The opioid use group reported increased substance use and difficulty accessing their preferred substance. There were no significant group differences related to accessing routine or specialized healthcare or medication; or paying attention to their health. CONCLUSIONS: During COVID-19, many MOUD patients reported challenges accessing care, particularly harm reduction services for patients with polysubstance use. Additional efforts, like providing wraparound support, may be necessary to serve the needs of MOUD patients.

COVID-19 innovations in medication for addiction treatment at a Skid Row syringe exchange.

Syringe exchange patients in Los Angeles' Skid Row endure conditions such as deep poverty, polysubstance use, underlying health problems, and living on the streets or in homeless encampments/shelters that make them uniquely vulnerable to acquiring and dying from COVID-19. In this commentary, we discuss two essential changes that Homeless Health Care Los Angeles (HHCLA) made to modify existing medication for addiction treatment (MAT) services to address the specific treatment needs of this high-risk population during COVID-19. First, HHCLA implemented a novel "telephone booth" model that allowed socially distanced on-site "face-to-face" treatment of syringe exchange patients; this model helped us to overcome the inherent challenges of using traditional telemedicine approaches (e.g., video, mobile telephone) with this disadvantaged patient population. Second, HHCLA transitioned from on-site direct dispensing of MAT medications in our providers' offices to a less contact- and time-intensive "coordinated pharmacy" model that allowed patients the freedom to obtain MAT medications off-site from participating pharmacies. Our data indicate that implementing these COVID-19-related changes effectively maintained patient enrollment and engagement in MAT-illuminating new, potentially effective models for delivering MAT that meet the critical health and safety needs of syringe exchange patients following COVID-19.