Abstract：
:The α1 -adrenergic antagonist, doxazosin, has improved cocaine use disorder (CUD) presumably by blocking norepinephrine (NE) stimulation and reward from cocaine-induced NE increases. If the NE levels for release were lower, then doxazosin might more readily block this NE stimulation and be more effective. The NE available for release can be lower through a genetic polymorphism in dopamine β-hydroxylase (DBH) (C-1021T, rs1611115), which reduces DβH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DβH levels. This 12-week, double-blind, randomized, placebo-controlled trial included 76 CUD patients: 49 with higher DβH levels from the DBH CC genotype and 27 with lower DβH levels from T-allele carriers (CT or TT). Patients were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29) and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy. Cocaine use was reduced at a higher rate among patients in the doxazosin than in the placebo arm. We found significantly lower cocaine use rates among patients carrying the T-allele (CT/TT) than the CC genotype. The percentage of cocaine positive urines was reduced by 41 percent from baseline in the CT/TT group with low DβH and NE levels, as compared with no net reduction in the CC genotype group with normal DβH and NE levels. The DBH polymorphism appears play an important role in CUD patients' response to doxazosin treatment, supporting a pharmacogenetic association and potential application for personalized medicine.
journal_name
Addict Bioljournal_title
Addiction biologyauthors
Zhang X,Nielsen DA,Domingo CB,Shorter DI,Nielsen EM,Kosten TRdoi
10.1111/adb.12611subject
Has Abstractpub_date
2019-05-01 00:00:00pages
531-538issue
3eissn
1355-6215issn
1369-1600journal_volume
24pub_type
杂志文章,随机对照试验abstract：:The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administra...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/j.1369-1600.2011.00314.x
更新日期：2012-01-01 00:00:00
abstract：:The striatum, a major central nervous system structure modulating movement, is enriched with glutamatergic and dopaminergic innervation. By altering activities of both glutamatergic and dopaminergic transmissions the psychostimulants, amphetamine and cocaine, induce behavioral changes in experimental animals. Activati...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1080/13556219971641
更新日期：1999-04-01 00:00:00
abstract：:Associations between nicotine in cigarettes and food consumption may alter the incentive value of food such that food cue-reactivity is exaggerated during abstinence from smoking. This effect may contribute to the weight gain associated with cessation of smoking. We examined the effects of nicotine (0.4 mg/kg base sub...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/j.1369-1600.2012.00436.x
更新日期：2012-05-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) regulates a variety of physiological processes, and several studies have explored the role of BDNF in addiction-related brain regions like the nucleus accumbens core (NAcore). We sought to understand the rapid effects of endogenous BDNF on cocaine seeking. Rats were trained to ...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12638
更新日期：2019-09-01 00:00:00
abstract：:Exposure to smoking-associated environmental cues during smoke cessation elicits self-reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue-induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue-...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12480
更新日期：2018-01-01 00:00:00
abstract：:This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice par...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12495
更新日期：2018-01-01 00:00:00
abstract：:We measured hippocampal volumes and cognitive functioning in crack-cocaine and crack-cocaine/alcoholdependent subjects (abstinent approximately 10-12 weeks) compared to age-matched controls. Cognitive function was evaluated using the computerized MicroCog Assessment of Cognitive Functioning (which includes tests of ex...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1080/13556219872074
更新日期：1998-07-01 00:00:00
abstract：:The posterior hippocampus (pHp) plays a major role in the processing and storage of drug-related cues and is linked to striatal-limbic brain circuits involved with craving and drug salience. We have recently reported that increased basal regional cerebral blood flow (rCBF) in a pHp loci, as measured by pseudo-continuo...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12361
更新日期：2017-05-01 00:00:00
abstract：:Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health risks within a harm reduction approach. In fact, the reviewed 63 studies indicate that ...
journal_title：Addiction biology
pub_type： 杂志文章,评审
doi：10.1111/adb.12414
更新日期：2017-09-01 00:00:00
abstract：:Obesity represents an important risk factor contributing to the global burden of disease. The current obesogenic environment with easy access to calorie-dense foods is fueling this obesity epidemic. However, how these foods contribute to the progression of feeding behavior changes that lead to overeating is not well u...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12595
更新日期：2018-03-01 00:00:00
abstract：:Poor working memory is linked to future risk-taking behaviors. Lifelong risk of habitual drug use is highest in individuals who initiate use in early adolescence. We sought to determine in rats whether juvenile traits, specifically poor working memory and low salivary brain-derived neurotrophic factor (BDNF), are rela...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12535
更新日期：2018-05-01 00:00:00
abstract：:Long-term alcohol use affects cognitive and neurophysiological functioning as well as structural brain development. Combining simultaneous electroencephalogram (EEG) recording with transcranial magnetic stimulation (TMS) enables direct, in vivo exploration of cortical excitability and assessment of effective and funct...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12486
更新日期：2018-01-01 00:00:00
abstract：:Numerous studies have explored the morphological differences of the brain between subjects with alcohol use disorder (AUD) and control subjects, but very few have investigated the impact of the duration of alcohol use disorder (DAD) and current level of alcohol consumption (CAC) within AUD subjects using magnetic reso...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12751
更新日期：2020-03-01 00:00:00
abstract：:Neuroimaging of opiate-dependent individuals indicates both altered brain structure and function. Magnetic resonance-based arterial spin labeling has been used to measure noninvasively cerebral blood flow (i.e. perfusion) in alcohol, tobacco and stimulant dependence; only one arterial spin labeling paper in opiate-dep...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12523
更新日期：2018-03-01 00:00:00
abstract：:The aim of this study was to observe the effect of electroacupuncture (EA) on chronic morphine-induced neuronal morphological changes in the ventral tegmental area (VTA) in rats at electron-microscopic level. Fourteen days of administering escalating doses of morphine induced pathological morphological changes of neur...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/j.1369-1600.2007.00092.x
更新日期：2008-03-01 00:00:00
abstract：:Converging epidemiological studies show that a life-threatening event increases the incidence of posttraumatic stress disorder (PTSD), which carries 30% to 50% comorbidity with substance use disorders (SUDs). Such comorbidity results in greater drug use and poorer treatment outcomes. There is overlap between the endur...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12798
更新日期：2020-09-01 00:00:00
abstract：:Major advances have been made in understanding nicotine addiction and smoking behaviour in recent years. In particular, evidence for the relative importance of genetic and environmental effects on smoking initiation and persistence has emerged from behaviour genetic studies. These data have supported evidence from mol...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1080/13556210020040181
更新日期：2001-04-01 00:00:00
abstract：:Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 ...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12677
更新日期：2019-09-01 00:00:00
abstract：:The multifaceted gut-brain peptide ghrelin and its receptor (GHSR-1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre-clinical models, we have shown that ghrelin increases whereas GHSR-1a antagonists decrease alcohol consumption and the motivation to consum...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12277
更新日期：2016-03-01 00:00:00
abstract：:The co-occurrence of chronic pain and alcohol use disorders (AUDs) involves complex interactions between genetic and neurophysiological aspects, and the research has reported mixed findings when they both co-occur. There is also an indication of a gender-dependent effect; males are more likely to use alcohol to cope w...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12784
更新日期：2019-09-01 00:00:00
abstract：:In light of the upcoming eleventh edition of the International Classification of Diseases (ICD-11), the question arises as to the most appropriate classification of 'Pathological Gambling' ('PG'). Some academic opinion favors leaving PG in the 'Impulse Control Disorder' ('ICD') category, as in ICD-10, whereas others a...
journal_title：Addiction biology
pub_type： 杂志文章,评审
doi：10.1111/adb.12378
更新日期：2017-07-01 00:00:00
abstract：:One aspect of the addictive process that has not been thoroughly investigated is the consequence of the frustrated state occurring when the drug is not available. The present study aimed to validate a novel operant model of frustrated expected reward in mice. C57BL/6J mice were trained in operant conditioning maintain...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/j.1369-1600.2011.00423.x
更新日期：2012-07-01 00:00:00
abstract：:Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CU...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12762
更新日期：2020-05-01 00:00:00
abstract：:Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they ...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12802
更新日期：2020-07-01 00:00:00
abstract：:Several studies have emphasized the role of learning in the development of rapid and chronic tolerances. Recently, it was shown that the NMDA antagonists MK-801(dizocilpine) and ketamine block the development of tolerance to ethanol in rats submitted to tilt-plane apparatus. The present study examines the generality o...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1080/13556219872344
更新日期：1998-01-01 00:00:00
abstract：:In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), ...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12183
更新日期：2016-01-01 00:00:00
abstract：:Recreational use of the drug 4-methylmethcathinone (mephedrone; 4-MMC) became increasingly popular in the United Kingdom in recent years, spurred in part by the fact that it was not criminalized until April 2010. Although several fatalities have been associated with consumption of 4-MMC and cautions for recreational u...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12038
更新日期：2013-09-01 00:00:00
abstract：:Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12223
更新日期：2015-09-01 00:00:00
abstract：:Activation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)-seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high-dose MA, but microglial status in human MA users is unc...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12876
更新日期：2021-01-01 00:00:00
abstract：:This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain react...
journal_title：Addiction biology
pub_type： 杂志文章
doi：10.1111/adb.12184
更新日期：2016-01-01 00:00:00
