Bernhard Luscher, Mengyang Feng, Sarah J Jefferson
There has been much recent progress in understanding of the mechanism of ketamine's rapid and enduring antidepressant effects. Here we review recent insights from clinical and preclinical studies, with special emphasis of ketamine-induced changes in GABAergic synaptic transmission that are considered essential for its antidepressant therapeutic effects. Subanesthetic ketamine is now understood to exert its initial action by selectively blocking a subset of NMDA receptors on GABAergic interneurons, which results in disinhibition of glutamatergic target neurons, a surge in extracellular glutamate and correspondingly elevated glutamatergic synaptic transmission...
2020: Advances in Pharmacology
Joao P De Aquino, José M Flores, Victor J Avila-Quintero, Peggy Compton, Mehmet Sofuoglu
The clinical features and neurobiology of pain and opioid use disorder (OUD) are inextricably linked. Despite emerging evidence supporting the negative impact of ongoing pain in the treatment of OUD, the pharmacological management of pain in the presence of OUD has received limited attention. We sought to systematically review the studies investigating pharmacotherapies for pain among persons with OUD. Eligible studies had participants with OUD and outcomes including evoked or spontaneous pain. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase...
September 24, 2020: Addiction Biology
Jiajie Chen, Fan Wang, Jia Zhu, Yongbin Li, Wei Liu, Jiuhua Xue, Hong Shi, Wei Li, Qiang Li, Wei Wang
Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts...
November 3, 2020: Addiction Biology
Michael B Gatch, Ritu A Shetty, Nathalie Sumien, Michael J Forster
A new generation of novel cathinone compounds has been developed as stimulant substitutes to avoid drug control laws and detection of use by blood tests. Dipentylone, N-ethylhexedrone, 4-chloroethcathinone (4-CEC), and 4'-methyl-α-pyrrolidinohexiophenone (MPHP) were tested for in vivo psychostimulant-like effects to assess their abuse liability. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice to screen for locomotor stimulant effects and to identify behaviorally-active dose ranges, times of peak effect, and durations of action...
November 5, 2020: Addiction Biology
Scott A Langenecker, Leah R Kling, Natania A Crane, Stephanie M Gorka, Robin Nusslock, Katherine S F Damme, Jessica Weafer, Harriet de Wit, K Luan Phan
BACKGROUND: Drug addiction and dependence continue as an unresolved source of morbidity and mortality. Two approaches to identifying risk for abuse and addiction are psychopharmacological challenge studies and neuroimaging experiments. The present study combined these two approaches by examining associations between self-reported euphoria or liking after a dose of d-amphetamine and neural-based responses to anticipation of a monetary reward. METHODS: Healthy young adults (N = 73) aged 19 and 26, without any history of alcohol/substance dependence completed four laboratory sessions in which they received oral d-amphetamine (20 mg) or placebo, and completed drug effect questionnaires...
January 1, 2020: Drug and Alcohol Dependence
Steven C Eastlack, Elyse M Cornett, Alan D Kaye
Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers...
June 2020: Pain and Therapy
Shannon Inglet, Bradly Winter, Sarah E Yost, Sophia Entringer, Anh Lian, Meryl Biksacky, Renee D Pitt, Whitney Mortensen
OBJECTIVE: To compile and synthesize the available literature describing medical cannabis use across various disease states. DATA SOURCES: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English...
November 2020: Annals of Pharmacotherapy
Min-Ho Nam, Woojin Won, Kyung-Seok Han, C Justin Lee
μ-opioid receptor (MOR) is a class of opioid receptors that is critical for analgesia, reward, and euphoria. MOR is distributed in various brain regions, including the hippocampus, where traditionally, it is believed to be localized mainly at the presynaptic terminals of the GABAergic inhibitory interneurons to exert a strong disinhibitory effect on excitatory pyramidal neurons. However, recent intensive research has uncovered the existence of MOR in hippocampal astrocytes, shedding light on how astrocytic MOR participates in opioid signaling via glia-neuron interaction in the hippocampus...
July 15, 2020: Cellular and Molecular Life Sciences: CMLS
Hiromitsu Imai, Misaki Morita, Hajime Morita, Tetsuji Ohyama, Shimako Tanaka, Shinya Uchida, Noriyuki Namiki, Naoto Uemura, Kyoichi Ohashi
AIMS: Opioids are commonly used analgesics for moderate to severe pain, but levels of drug effect vary among individuals. As for the mechanisms underlying these individual differences, there have been reports suggesting effects of polymorphisms in the gene encoding μ-opioid receptor ( OPRM1 ). However, whether these polymorphisms affect the actions of μ-opioid receptor partial agonists has yet to be determined. This study aimed to assess differences in the pharmacological actions of buprenorphine, a μ-opioid receptor partial agonist, due to a polymorphism (A118G, rs1799971) in the OPRM1 gene in humans...
September 1, 2020: International Journal of Clinical Pharmacology and Therapeutics
Mauro Pettorruso, Luisa De Risio, Giovanni Martinotti, Marco Di Nicola, Filippo Ruggeri, Gianluigi Conte, Massimo Di Giannantonio, Luigi Janiri
Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria...
2014: BioMed Research International
Wei-Ning Jiang, Xiao Jing, Man Li, Hong Deng, Tao Jiang, Ke-Zhao Xiong, Ying Chen, Xiao-Fei Wang, Quan-Jun Wang
Corydalis is a Chinese herb that has been used in China for hundreds of years for analgesic and other purposes. Corydaline and l-tetrahydropalmatine (l-THP) are the main active ingredients of Corydalis. This study was aimed to study the potential utility of corydaline and l-THP in the treatment of opioid abuse and addiction and explore the possible mechanisms underlying their pharmacological actions. Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine and Western-blot immunoreactive assays were used to evaluate morphine-induced changes in dopamine D2 receptor and GluA1 AMPA receptor and GluA2 AMPA receptor expression in the brain of rats...
July 25, 2020: European Journal of Pharmacology
Ze-Xu Wei, Qi Wu, Qing-Shan Liu, Yong Cheng
Drug dependence may affect the neurotransmitter system levels in the human body. This study recruited 113 healthy control subjects, 118 heroin-dependent patients and 118 methamphetamine-dependent patients and examined the serum 5-HT, dopamine, glutamate and norepinephrine levels in the 349 volunteers. ELISA assays demonstrated that the serum 5-HT levels were significantly reduced in the drug-dependent patients, whereas the serum dopamine and glutamate levels were both significantly increased in the drug-dependent patients when compared with control subjects...
August 17, 2020: Journal of Neural Transmission
Erin N Bobeck, QiLiang Chen, Michael M Morgan, Susan L Ingram
Opioid inhibition of presynaptic GABA release in the ventrolateral periaqueductal gray (vlPAG) activates the descending antinociception pathway. Tolerance to repeated opioid administration is associated with upregulation of adenylyl cyclase activity. The objective of these studies was to test the hypothesis that adenylyl cyclase contributes to opioid tolerance by modulating GABA neurotransmission. Repeated microinjections of morphine or the adenylyl cyclase activator NKH477 into the vlPAG decreased morphine antinociception as would be expected with the development of tolerance...
August 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Hanna Viisanen-Kuopila, Tuomas O Lilius, Boriss Sagalajev, Pekka Rauhala, Eija Kalso, Antti Pertovaara
Descending facilitatory circuitry that involves the rostroventromedial medulla (RVM) exerts a significant role in the development of antinociceptive tolerance and hyperalgesia following chronic morphine treatment. The role of the RVM in the development of antinociceptive tolerance to oxycodone, another clinically used strong opioid, is not yet known. Ketamine, an NMDA receptor antagonist, attenuates opioid antinociceptive tolerance, but its effect on RVM cell discharge in opioid tolerant animals is not known...
August 5, 2020: Journal of Neurophysiology
Liyana Hazwani Mohd Adnan, Nor Hidayah Abu Bakar, Nordin Simbak, Nasir Mohamad, Rusli Ismail, Nor Zidah Ahmad, Nor Suliana Mustafa, Nurul Farah Aina Md Fauzi
Opioids, amphetamines, and other types of substances have been widely abused around the world. Opioid dependence and tolerance are two distinct phenomena that have been associated with substance abuse issues. The management of its adverse consequences is becoming more challenging. More and more people are treated in Methadone Maintenance Therapy (MMT) program yet the issues are still unresolved. Researchers are continuing to study the best formulation in treating opioid dependent people starting with modern and alternative drug therapies...
July 2020: Iranian Journal of Basic Medical Sciences
Reda M Chalhoub, Peter W Kalivas
Opioid use disorder (OUD) represents a major public health problem that affects millions of people in the USA and worldwide. The relapsing and recurring aspect of OUD, driven by lasting neurobiological adaptations at different reward centres in the brain, represents a major obstacle towards successful long-term remission from opioid use. Currently, three drugs that modulate the function of the opioidergic receptors, methadone, buprenorphine and naltrexone have been approved by the US Food and Drug Administration (FDA) to treat OUD...
October 2020: Drugs
Kaushal Shah, Billy Stout, Hunter Caskey
The increase in the prescription of opioid medications has resulted in a wildfire of misuse of opioids, both for medical and non-medical reasons, with over 1.7 million people in the United States (US) suffering from distinct disorders owing to opioid use. While various medications, such as methadone, buprenorphine, and naloxone, among others, have been used in treating opioid withdrawal symptoms, concerns of the potential abuse of these drugs, the cost of procurement, legislations, and prescription policies have risen...
July 11, 2020: Curēus
Enrico Marinelli, Renata Beck, Antonio Malvasi, Alfredo Fabrizio Lo Faro, Simona Zaami
Gamma-hydroxybutyrate (GHB) is a central nervous system depressant primarily used as a recreational drug of abuse, but also for the treatment of narcolepsy with cataplexy in adult patients and as an adjuvant for control of alcohol withdrawal syndrome. The main aim of this review is to summarise updated knowledge about GHB pharmacokinetics and pharmacodynamics, acute poisoning, and clinical features of GHB withdrawal syndrome, its diagnosis and medical treatment. The most common clinical signs and symptoms of acute poisoning include sleepiness to deep coma, bradycardia, hypotension, and respiratory failure...
March 1, 2020: Arhiv za Higijenu Rada i Toksikologiju
Shaoming Jin, Xiao Ning, Jin Cao, Yaonan Wang
γ -Hydroxybutyrate (GHB) is a neurotransmitter, which exhibits a strong central nervous system depressant effect. The abuse of GHB or its precursor substances ( γ -butyrolactone (GBL) and 1,4-butanediol (1,4-BD)) may cause serious problems. This study developed a fast and effective UHPLC-MS/MS method for the simultaneous quantification of GHB, GBL, and 1,4-BD in four popular beverages, including carbonated drinks, tea, apple cider vinegar, and coffee. The established method overcomes the influence of the in-source collision-induced dissociation of unstable compounds during quantification...
2020: International Journal of Analytical Chemistry
Rana El Rawas, Inês M Amaral, Alex Hofer
Drug addiction is a multifactorial disorder resulting from the complex interaction between biological, environmental and drug-induced effects. Generally, stress is a well-known risk factor for the development of drug addiction and relapse. While most of the research focuses on risk factors that increase the vulnerability to drugs of abuse, recent studies are focusing on the areas of strength/positive coping approaches that can increase resistance to drugs of abuse. In this review, we concentrate on resilience, seen as a dynamic process, which can allow individuals to positively adapt within the context of a specific risk for psychiatric illness...
August 2020: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
2020-08-27 05:01:42
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