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Synthetic Drugs of Addiction

Ayesha Murtuza, Ajaz Bulbul, John Paul Shen, Parissa Keshavarzian, Brian D Woodward, Fernando J Lopez-Diaz, Scott M Lippman, Hatim Husain
EGFR-activating mutations are observed in approximately 15% to 20% of patients with non-small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. The compound has received additional FDA approval as first-line therapy with improvement in progression-free survival by suppressing the activating mutation and preventing the rise of the dominant resistance clone...
February 4, 2019: Cancer Research
Roberto Colangeli, Roberto Di Maio, Massimo Pierucci, Gabriele Deidda, Maurizio Casarrubea, Giuseppe Di Giovanni
Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE)...
February 1, 2019: Neurobiology of Disease
Luisa Alessandra Atehortua-Martinez, Cyriaque Masniere, Patrizia Campolongo, Stéphanie Chasseigneaux, Jacques Callebert, Clemens Zwergel, Antonello Mai, Jean-Louis Laplanche, Huixiong Chen, Mélanie Etheve-Quelquejeu, Bruno Mégarbane, Nadia Benturquia
BACKGROUND: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability. AIMS: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties. METHODS: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated...
January 15, 2019: Journal of Psychopharmacology
Barbara Lovrecic, Mercedes Lovrecic, Branko Gabrovec, Marco Carli, Matteo Pacini, Angelo G I Maremmani, Icro Maremmani
Background : In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim : To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use...
January 9, 2019: International Journal of Environmental Research and Public Health
S A Baechler, V M Factor, I Dalla Rosa, A Ravji, D Becker, S Khiati, L M Miller Jenkins, M Lang, C Sourbier, S A Michaels, L M Neckers, H L Zhang, A Spinazzola, S N Huang, J U Marquardt, Y Pommier
Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment...
January 8, 2019: Nature Communications
Ricardo Jorge Dinis-Oliveira
Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers...
February 2019: Journal of Forensic and Legal Medicine
Takayuki Harada, Hiroshi Tsutomi, Rintaro Mori, David B Wilson
BACKGROUND: Amphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related substances. ATS are highly addictive and prolonged use may result in a series of mental and physical symptoms including anxiety, confusion, insomnia, mood disturbances, cognitive impairments, paranoia, hallucinations and delusion.Currently there is no widely accepted treatment for ATS-use disorder. However, cognitive-behavioural treatment (CBT) is the first-choice treatment...
December 22, 2018: Cochrane Database of Systematic Reviews
Na Ye, Bang Li, Qi Mao, Eric A Wold, Sheng Tian, John A Allen, Jia Zhou
While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction...
December 12, 2018: ACS Chemical Neuroscience
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
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