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Synthetic Drugs of Addiction

Nora D Volkow, Emily B Jones, Emily B Einstein, Eric M Wargo
Importance: More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. Observations: Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality...
December 5, 2018: JAMA Psychiatry
Dicky Struik, Fabrizio Sanna, Liana Fattore
Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is being increasing legalized. In addition, use of synthetic cannabinoid drugs is gaining considerable popularity and is associated with mass poisonings and occasional deaths. Delineating factors involved in cannabis use and addiction therefore becomes increasingly important. Similarly to other drugs of abuse, the prevalence of cannabis use and addiction differs remarkably between males and females, suggesting that sex plays a role in regulating cannabinoid sensitivity...
2018: Frontiers in Behavioral Neuroscience
Andrea R Terrell, Vipin Adhlakha, Poluru Reddy
Buprenorphine, a synthetic opioid possessing both analgesic and opioid receptor antagonist properties, has proven to be an effective therapeutic aid for opioid dependency and chronic pain management. The downside, as with all opioids, natural or synthetic, is its potential for misuse and abuse. The euphoria induced by buprenorphine leads to abuse. Additionally, individuals with an active addiction to short-acting opioids such as heroin may use buprenorphine between doses of their drug of choice to stave off withdrawal symptoms...
2019: Methods in Molecular Biology
Bruce E Blough, Ann M Decker, Antonio Landavazo, Ojas A Namjoshi, John S Partilla, Michael H Baumann, Richard B Rothman
RATIONALE: Novel synthetic "bath salt" cathinones continue to appear on the street as abused and addictive drugs. The range of subjective experiences produced by different cathinones suggests that some compounds have primarily dopaminergic activity (possible stimulants) while others have primarily serotonergic activity (possible empathogenics). An understanding of the structure activity relationships (SARs) of these compounds will help in assessing the likely behavioral effects of future novel structures, and to define potential therapeutic strategies to reverse any reinforcing effects...
October 20, 2018: Psychopharmacology
Alan D Kaye, Elyse M Cornett, Shilpa S Patil, Sonja A Gennuso, Matthew M Colontonio, Dustin R Latimer, Aaron J Kaye, Richard D Urman, Nalini Vadivelu
There has been significant research to develop an ideal synthetic opioid. Opioids with variable properties possessing efficacy and with reduced side effects have been synthesized when compared to previously used agents. An opioid modulator is a drug that can produce both agonistic and antagonistic effects by binding to different opioid receptors and therefore cannot be classified as one or the other alone. These compounds can differ in their structures while still possessing opioid-mediated actions. This review will discuss TRV130 receptor modulators and other novel opioid receptor modulators, including Mitragyna "Kratom," Ignavine, Salvinorin-A, DPI-289, UFP-505, LP1, SKF-10,047, Cebranopadol, Naltrexone-14-O-sulfate, and Naloxegol...
June 2018: Best Practice & Research. Clinical Anaesthesiology
Stephane Thobois, Christine Brefel-Courbon, Didier Le Bars, Véronique Sgambato-Faure
Opioid receptors are localized throughout peripheral and central nervous system and interact with endogenous opioid peptides and drugs including heroin, synthetic opioids, and pain relievers (codeine, morphine). If several opioid PET tracers exist for preclinical studies, only a few have been used in human. Some tracers are selective for one subtype of opioid receptors (e.g., [11 C]CAF (carfentanil) for μ receptor) while others are not ([11 C]DPN (diprenorphine)). As shown by imaging studies, the opioid system is involved in pain processing, but also in addiction, neuropsychiatric manifestations (harm avoidance, sadness, novelty seeking behavior), feeding and food disorders and, finally, movement disorders and levodopa-induced dyskinesias...
2018: International Review of Neurobiology
Paul J Jannetto, Anders Helander, Uttam Garg, Gregory C Janis, Bruce Goldberger, Hemamalini Ketha
BACKGROUND: Since 2013, an unprecedented surge in fentanyl overdose deaths has been caused by heroin laced with illicitly produced fentanyl and/or fentanyl analogs (FAs) sold as heroin. The US Drug Enforcement Agency's National Forensic Laboratory Information System reported a >300% increase in fentanyl encounters from 4697 in 2014 to 14440 in 2015. In 2015, the CDC reported 9580 deaths caused by synthetic opioids, primarily fentanyl, a 72% increase from 2014. The European Monitoring Centre for Drugs and Drug Addiction has also encountered several new FAs in the heroin supply...
October 10, 2018: Clinical Chemistry
Laura B Ferguson, Lingling Zhang, Shi Wang, Courtney Bridges, R Adron Harris, Igor Ponomarev
Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that act as transcription factors in response to endogenous lipid messengers. The fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also improve symptoms of several other diseases. Transposable elements (TEs), repetitive sequences in mammalian genomes, are implicated in many of the same conditions for which PPAR agonists are therapeutic, including neurodegeneration, schizophrenia, and drug addiction...
2018: Frontiers in Molecular Neuroscience
Ismail Altintop, Cigdem Karakukcu
The chameleon can disguise itself in nature by taking on different colors and forms. As synthetic cannabinoids (SC) have clinically similar effects to those of several psychoactive agents, they are one of the most difficult intoxications to diagnose. The reasons for this are due to clinical variations throughout the world and the differences in symptoms having not been determined due to their similarity to the intoxication of several other drugs. The aim of this study was to obtain prospective data of patients presenting at the Emergency Department (ED) with suspected SC intoxication, and as a result of prospective examination of samples, to determine a new generation of SC use, SC types, clinical findings, and treatments...
September 22, 2018: Behavioral Sciences
Monika Židková, Rachel Horsley, Ondřej Hloch, Tomáš Hložek
Recreational use of the potent synthetic opioid 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700) is rising, accompanied by increasingly frequent cases of serious intoxication. This article reports a case of near-fatal U-47700 intoxication. A man was found unconscious (with drug powder residues). After 40 h in hospital (including 12 h of supported ventilation), he recovered and was discharged. Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used to detect and quantify substances in powders, serum and urine...
September 19, 2018: Journal of Forensic Sciences
Laurent Karila, Maude Marillier, Boris Chaumette, Joel Billieux, Nicolas Franchitto, Amine Benyamina
Synthetic opioids (SO) are a major risk for public health across the world. These drugs can be divided into 2 categories, pharmaceutical and non-pharmaceutical fentanyls. A new generation of SO has emerged on the drug market since 2010. North America is currently facing an opioid epidemic of morbi-mortality, caused by over-prescription of opioids, illegally diverted prescribed medicines, the increasing use of heroin and the emergence of SO. Furthermore, this opioid crisis is also seen in Europe. SO are new psychoactive substances characterized by different feature such as easy availability on the Internet, low price, purity, legality, and lack of detection in laboratory tests...
September 12, 2018: Neuroscience and Biobehavioral Reviews
Ann E Klega, Jennifer Tickal Keehbauch
Approximately 10% of the U.S. population 12 years and older reported using illicit substances in 2015. This article reviews the clinical effects and treatment of persons who use cocaine, methamphetamines, 3,4-methylenedioxymethamphetamine (MDMA), synthetic cannabinoids, and synthetic cathinones ("bath salts"). Cocaine blocks the reuptake of the monoamine transporters dopamine, norepinephrine, and serotonin. Immediate clinical effects include increased energy and euphoria, as well as hypertension and arrhythmias...
July 15, 2018: American Family Physician
Michael Evans-Brown, Roumen Sedefov
New psychoactive substances (NPS) are drugs that are not controlled by the United Nations international drug control conventions of 1961 and 1971 but that may pose similar threats to public health. Many of them are traded as "legal" replacements to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine, amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by globalization, there has been a large increase in the availability and, subsequently, harms caused by these substances over the last decade in Europe...
September 8, 2018: Handbook of Experimental Pharmacology
Julie A Marusich, Elaine A Gay, Bruce E Blough
RATIONALE: Synthetic cathinones are used as stimulants of abuse. Different stimulants may induce distinct rates of disease progression, yielding neurochemical changes that may vary across brain regions or neurotransmitter systems. OBJECTIVES: This research sought to behaviorally and chemically differentiate stages of synthetic cathinone abuse through rodent self-administration and measurement of the neurotransmitter profile in multiple brain regions. METHODS: Male rats were trained to self-administer α-PVP, mephedrone (4MMC), or saline...
September 6, 2018: Psychopharmacology
Maria Antonietta De Luca, Liana Fattore
Cannabis sativa has a long history of use for medical purposes despite marijuana's addictive potential. The discovery of the endogenous cannabinoid system as a neuromodulatory system composed of receptors, endogenous ligands (endocannabinoids), and enzymes responsible for their synthesis and degradation, together with recent advancements in the elucidation of cannabinoid pharmacology, has renewed interest in medicines acting on the endocannabinoid system. Synthetic cannabinoid agonists have been developed and used for treatment of different human pathologic conditions, and promising potent cannabinoid antagonists are currently under clinical evaluation...
September 2018: Clinical Therapeutics
Jie Chen, Xiao Lin, Kyoung Jin Park, Kang Ro Lee, Hyun-Ju Park
The protein lysine methyltransferase G9a, which controls gene expression by epigenetic regulation of H3K9 methylation, is related to various human diseases, including cancer, drug addiction, and mental retardation. In recent years, genetic, biological, and physiological evidence has established G9a inhibitors as potential chemotherapeutic agents for cancer treatment. In this study, we identified protoberberine alkaloid pseudodehydrocorydaline (CT13) as a novel G9a inhibitor, by structure-based virtual screening of in-house library containing natural product compounds...
September 2018: Journal of Computer-aided Molecular Design
Jørgen G Bramness, Geert Dom, Antoni Gual, Karl Mann, Friedrich Martin Wurst
AIM: This study was aimed at investigating the availability and prescription of different medicinal variants of cannabis and their status in European countries. METHODS: A -web-based survey was sent to all member societies of the -European Federation of Addiction Societies (EUFAS) in 2 waves during the summer of 2017. All 34 member societies in 19 different European countries were invited to participate. RESULTS: We received 28 responses from 17 European countries...
2018: European Addiction Research
Piotr Adamowicz, Piotr Hydzik
INTRODUCTION: The second largest group of new drugs monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is synthetic cathinones. Substances that are controlled by the law are immediately replaced by new uncontrolled derivatives that cause constant and dynamic changes on the drug market. Some of the most recent synthetic cathinones that have appeared on the "legal highs" market are 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) and α-pyrrolidinohexanophenone (α-PHP)...
August 17, 2018: Clinical Toxicology
Carl R Lupica, Alexander F Hoffman
The increasing use of cannabis, its derivatives, and synthetic cannabinoids for medicinal and recreational purposes has led to burgeoning interest in understanding the addictive potential of this class of molecules. It is estimated that ∼10% of marijuana users will eventually show signs of dependence on the drug, and the diagnosis of cannabis use disorder (CUD) is increasing in the United States. The molecule that sustains the use of cannabis is Δ9 -tetrahydrocannabinol (Δ9 -THC), and our knowledge of its effects, and those of other cannabinoids on brain function has expanded rapidly in the past two decades...
September 2018: Learning & Memory
S Creagh, D Warden, M A Latif, A Paydar
Synthetic drugs contain substances that are pharmacologically similar to those found in traditional illicit drugs. Some of the most commonly abused synthetic drugs include synthetic marijuana, bath salts, ecstasy, N-bomb, methamphetamine and anabolic steroids. Many of them share the same chemical properties and physiologic responses with the drugs they mimic and may exaggerate the pathologic response in the brain leading to addiction. These drugs have detrimental (and often irreversible) effects on the brain and primarily affect the central nervous system by two mechanisms: 1) Neural hyper stimulation via increasing activation of certain neurotransmitters (norepinephrine, dopamine, and serotonin), 2) Cause significant reduction in CNS neural connectivity affecting various brain regions such as the basal ganglia, hippocampus, cerebellum, parietal lobe, and globus pallidus...
2018: Clinical radiology & imaging journal
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