Synthetic Drugs of Addiction

Drugs of abuse activate neuroimmune signaling in addiction-related regions of the brain, including the prefrontal cortex (PFC) which mediates executive control, attention, and behavioral inhibition. Traditional psychostimulants including methamphetamine and cocaine are known to induce PFC inflammation, yet the effects of synthetic cathinone derivatives are largely unexplored. In this study, we examined the ability of repeated binge-like intake of the pyrovalerone cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) to alter cytokine profiles in the PFC...

BACKGROUND: The comprehensive monitoring of licit and illicit drug consumption plays a crucial role in understanding the complexities of patient conditions and designing effective treatment strategies. In this study, the prevalence of psychoactive prescription drugs, classical illicit drugs, and new psychoactive substances (NPS) were objectively assessed in individuals diagnosed with drug-related psychiatric disorders or episodes. METHODS: Blood, urine, and hair samples were collected from psychiatric patients admitted to the Mental Health Department and Drug Addiction Service of the North Rome Local Health Authority with declared or suspected psychoactive drug use...

Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure-activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [3 H]DAMGO, [3 H]Ile5,6 -deltorphin II and [3 H]HS665, respectively...

Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis...

The rise of novel synthetic drugs, such as cathinones in "bath salts" and synthetic cannabinoids, poses serious health risks due to their severe side effects and unpredictable interactions with other substances, and their evasion of routine drug screenings poses additional challenges in managing opioid agonist treatments. We present a case of an Indian male in his thirties with a history of opiate dependence who was treated with buprenorphine/naloxone. Six months into the treatment, he presented with symptoms of sedation, agitation, and paranoia...

Treatment of opioid use disorder (OUD) with buprenorphine has evolved considerably in the last decade as the scale of the OUD epidemic has increased along with the emergence of high-potency synthetic opioids (HPSOs) and stimulants in the drug supply. These changes have outpaced the development of prospective research, so a clinical consideration document based on expert consensus is needed to address pressing clinical questions. This clinical considerations document is based on a narrative literature review and expert consensus and will specifically address considerations for changes to the clinical practice of treatment of OUD with buprenorphine for individuals using HPSO...

In the last decade, the U.S. opioid overdose crisis has magnified, particularly since the introduction of synthetic opioids, including fentanyl. Despite the benefits of medications for opioid use disorder (MOUD), only about a fifth of people with opioid use disorder (OUD) in the U.S. receive MOUD. The ubiquity of pharmacists, along with their extensive education and training, represents great potential for expansion of MOUD services, particularly in community pharmacies. The National Institute on Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) convened a working group to develop a research agenda to expand OUD treatment in the community pharmacy sector to support improved access to MOUD and patient outcomes...

BACKGROUND: The US Food and Drug Administration (FDA) requires a warning label on nicotine e-cigarettes and pouches: 'This product contains nicotine. Nicotine is an addictive chemical'. Some brands marketing synthetic nicotine products have modified the warning ('This product contains tobacco-free nicotine (TFN)…'). The public health impact of altering the warning is unknown, so we examined its impact on risk perceptions and use intentions. METHODS: 1000 participants completed an anonymous online survey...

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses...

Eutylone is a cathinone-derived synthetic amphetamine scheduled by the World Health Organization and European Monitoring Centre for Drugs and Drug Addiction since 2022 due to its growing consumption. We report here an eutylone intoxication involving a 38-year-old man and a 29-year-old woman in a chemsex context. A bag containing a white crystalline powder labelled as a research product was found in their vehicle. Nuclear magnetic resonance and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analyses identified the powder as eutylone and confirmed purity superior to 99%...

Introduction: Despite their inclination to induce tolerance, addictive states, and respiratory depression, synthetic opioids are among the most effective clinically administered drugs to treat severe acute/chronic pain and induce surgical anesthesia. Current medical interventions for opioid-induced respiratory depression (OIRD), wooden chest syndrome, and opioid use disorder (OUD) show limited efficacy and are marked by low success in the face of highly potent synthetic opioids such as fentanyl. D-Cysteine ethylester (D-CYSee) prevents OIRD and post-treatment withdrawal in male/female rats and mice with minimal effect on analgesic status...

Opioids play an outsized role in America's drug problems, but they also play a critically important role in medicine. Thus, they deserve special attention. Illegally manufactured opioids (such as fentanyl) are involved in a majority of U.S. drug overdoses, but the problems are broader and deeper than drug fatalities. Depending on the drugs involved, there can be myriad physical and mental health consequences associated with having a substance use disorder. And it is not just those using drugs who suffer. Substance use and related behaviors can significantly affect individuals' families, friends, employers, and wider communities...

BACKGROUND: Co-use of benzodiazepines and opioids significantly increases fatal overdose risk, yet few studies have examined co-use of these drugs when obtained both with and without a prescription. We examined associations of daily co-use of prescribed benzodiazepines/tranquilizers (BZD/TRQ) and prescribed and nonprescribed opioids among people who use street opioids (PWUO). METHODS: PWUO (N = 417) were recruited from Baltimore City and neighboring Anne Arundel County, Maryland, and surveyed on sociodemographic characteristics, structural vulnerabilities, healthcare access and utilization, substance use, and overdose experiences...

BACKGROUND AND OBJECTIVES: Synthetic cannabinoids (SCs) may function as a marijuana alternative for soldiers subject to frequent drug screens, yet no study has interviewed past military users of SCs. METHODS: Veterans participating in eight US veterans treatment courts were interviewed (n = 318; response rate = 54.9%). Thematic analyses were completed. RESULTS: Sixty-five veterans (21.3%) reported SC use. Three major themes were identified: SCs were not a suitable marijuana replacement, the experience was unpleasant/problematic, and curiosity, sometimes paired with the perception of safely eluding drug screens, facilitated use...

BACKGROUND: Opioid overdose deaths in 2021 were the highest ever, driven by fentanyl and polysubstance use. OBJECTIVE: The aim of the study was to characterize drug use, assessed by urine drug screens (UDSs), in patients with untreated opioid use disorder (OUD) presenting to 28 emergency departments (EDs) nationally and by region. METHODS: We analyzed UDSs from patients enrolled in the CTN-0099 ED-INNOVATION (Emergency Department-Initiated Buprenorphine Validation) trial between July 12, 2020 and March 9, 2022...

For the first time in history, the United States surpassed 100,000 overdose-related deaths in a 12-month period, driven by synthetic opioids such as fentanyl. Also for the first time, potential chemical weapons are readily available on the streets and the dark web. Opioids represent a rare trifecta, used for licit pain management, as an illicit drug of abuse, and with potential use as a weapon of terror. Community-based Response to Drug Overdose (CReDO) is an initiative to unite agencies, disciplines, government and private partners in one coordinated opioid emergencies response plan under nationwide standards, and can be integrated into the Disaster Medicine discipline due to the risk of mass casualty incidents involving fentanyl or its derivatives...

AIMS: To characterize polysubstance death in the United States during the transition to the fourth wave of the drug overdose crisis. To characterize co-involved substances in fatal overdose involving synthetic opioids (mainly illicitly manufactured fentanyl analogues) by year, state, and intersectional sociodemographic groups. DESIGN: Population-based study of national death records. SETTING: United States. PARTICIPANTS/CASES: All people who died from drug overdose in the United States between 2010 and 2021...

Morphine addiction is closely associated with dysbiosis of the gut microbiota. miRNAs play a crucial role in regulating intestinal bacterial growth and are involved in the development of disease. Ginsenoside Rg1 exhibits an anti-addiction effect and significantly improves intestinal microbiota disorders. In pseudo-germfree mice, supplementation with Bacteroides vulgatus ( B. vulgatus ) synergistically enhanced Rg1 to alleviate morphine addiction. However, it is currently unknown the relationship between fecal miRNAs in morphine-exposed mice and their potential modulation of gut microbiome, as well as their role in mediating the resistance of ginsenoside Rg1 to drug addiction...

Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59...

BACKGROUND: New psychoactive substances (NPS) have become a global phenomenon, with over 134 countries and territories from all world regions reporting them. Since December 2021, governments, laboratories, and partner agencies have confirmed to the UNODC Early Warning Advisory (EWA) on NPS over 1124 substances. It is agreed that NPS control is one of the most challenging tasks for developing countries. Identifying the present and future threads of NPS is the most challenging task for law enforcement officials...