Deficits in Dopamine D2 Receptors and Presynaptic Dopamine in Heroin Dependence: Commonalities and Differences with Other Types of Addiction A genetic determinant of the striatal dopamine response to alcohol in men Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain Dopamine transporter and D2-receptor density in late-onset alcoholism Characteristics of subgroups of individuals with psychotic illness and a comorbid substance use disorder. Dopamine transporter availability in heroin-dependent subjects and controls: longitudinal changes during abstinence and the effects of Jitai tablets treatment Sex Differences in Striatal Dopamine Release in Healthy Adults Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele Cannabis Abstinence During Treatment and One-Year Follow-Up: Relationship to Neural Activity in Men Opiate-Induced Dopamine Release Is Modulated by Severity of Alcohol Dependence: An [18F]Fallypride Positron Emission Tomography Study Changes in Specific Substance Involvement Scores among SBIRT recipients in an HIV primary care setting Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease. 5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride Characteristics and problems of 600 adolescent cannabis abusers in outpatient treatment. Addictive behaviors related to opioid use for chronic pain: A population-based study Striatal dopamine release during performance of executive functions: A [11C] raclopride PET study Switching outpatients with bipolar or schizoaffective disorders and substance abuse from their current antipsychotic to aripiprazole. Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium [Association between drug, alcohol and tobacco use in adolescents and socio-familiar factors]. Transitions from first substance use to substance use disorders in adolescence: is early onset associated with a rapid escalation?
BACKGROUND Positron emission tomography ( PET ) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3 ) receptor binding and decreased presynaptic dopamine release in the striatum . Some studies have also shown that these reductions are associated with the severity of addiction . For example , in cocaine dependence , low dopamine release is associated with the choice to self-administer cocaine . The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior . METHODS Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration ( methylpheni date ) to measure striatal D(2/3 ) receptor binding and presynaptic dopamine release . After the PET scans , the heroin-dependent subjects performed heroin self-administration sessions . RESULTS Both striatal D(2/3 ) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects . However , neither PET measure of dopamine transmission predicted the choice to self-administer heroin . CONCLUSIONS These findings show that heroin addiction , like addiction to other drugs of abuse , is associated with low D(2/3 ) receptor binding and low presynaptic dopamine . However , neither of these outcome measures was associated with the choice to self-administer heroin Excessive alcohol use , a major cause of morbidity and mortality , is less well understood than other addictive disorders . Dopamine release in ventral striatum is a common element of drug reward , but alcohol has an unusually complex pharmacology , and humans vary greatly in their alcohol responses . This variation is related to genetic susceptibility for alcoholism , which contributes more than half of alcoholism risk . Here , we report that a functional OPRM1 A118 G polymorphism is a major determinant of striatal dopamine responses to alcohol . Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions , and examined for striatal dopamine release using positron emission tomography and [11C]-raclopride displacement . A striatal dopamine response to alcohol was restricted to carriers of the minor 118 G allele . To directly establish the causal role of OPRM1 A118 G variation , we generated two humanized mouse lines , carrying the respective human sequence variant . Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1 - 118GG than in h/mOPRM1 - 118AA mice . OPRM1 A118 G variation is a genetic determinant of dopamine responses to alcohol , a mechanism by which it likely modulates alcohol reward Cannabis is the most frequently used illicit drug worldwide , but little is known about the mechanisms underlying continued cannabis use . Cue-reactivity ( the physical , psychological , behavioural and neural reaction to substance-related cues ) might be related to continued cannabis use . In this 3-year prospect i ve neuroimaging study we investigated whether cannabis cue-induced brain activity predicted continued cannabis use and associated problem severity 3 years later . In addition , baseline brain activations were compared between dependent and non-dependent cannabis users at follow-up . Analyses were focussed on brain areas known to be important in cannabis cue-reactivity : anterior cingulate cortex , orbitofrontal cortex , ventral tegmental area , amygdala and striatum . At baseline , 31 treatment-naive frequent cannabis users performed a  cue-reactivity functional magnetic resonance imaging task . Of these participants , 23 completed the 3-year follow-up . None of the cue-induced region of interest activations predicted the amount of cannabis use at follow-up . However , cue-induced activation in the left striatum ( putamen ) significantly and independently predicted problem severity at follow-up ( p < 0.001 ) as assessed with the Cannabis Use Disorder Identification Test . Also , clinical ly dependent cannabis users at follow-up showed higher baseline activation at trend level in the left striatum compared with non-dependent users . This indicates that neural cue-reactivity in the dorsal striatum is an independent predictor of cannabis use-related problems . Given the relatively small sample size , these results are preliminary and should be replicated in larger sample s of cannabis users Striatal D2 dopamine receptor characteristics of nine male patients with alcohol dependence abstinent for 1–68 weeks and eight healthy male volunteers were studied in vivo with positron emission tomography . The selective D2 receptor lig and [11C]raclopride and equilibrium model was used for D2 receptor density ( Bmax ) and affinity ( Kd ) measurements . A trend for a decreased striatal D2 receptor density and for reduced D2 receptor affinity was observed in patients with alcohol dependence . These parameters were not statistically significantly different between alcoholics and controls , but the ratio between D2 receptor density and affinity ( Bmax/Kd or the striatum/cerebellum ratio from the high specific activity scan ) was highly significantly lower in alcoholics than that of controls . In conclusion , the low D2 dopamine receptor Bmax/Kd ratio ( striatum/cerebellum ratio ) indicates that specific aspects of striatal [11C]raclopride binding in vivo are deviant in alcoholics compared to controls . The result is compatible with a reduced avidity of striatal dopamine D2 receptors in alcoholics , which is in line with the idea that D2 dopaminergic mechanisms are involved in the biology of alcohol dependence in man ABSTRACT Background : Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades , possibly accounting for the current opioid addiction epidemic . Co-morbid drug use in those prescribed opioid analgesics is common , but there are few data on polysubstance use patterns . Objective : We explored patterns of use of cigarette , alcohol , and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics .  Methods : We conducted a secondary data analysis of screening interviews conducted as part of a parent r and omized trial of financial incentives to improve HIV outcomes among drug users . In a convenience sample of people with HIV and chronic pain , we collected self-report data on demographic characteristics ; pain ; patterns of opioid analgesic use  ( both prescribed and illicit ) ; cigarette , alcohol , and illicit drug use ( including cannabis , heroin , and cocaine ) within the past 30 days ; and current treatment for drug use and HIV . Results : Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use ( N = 372 , 47.1 % ) . Illicit drug use was common ( N = 505 , 63.9 % ) , and cannabis was the most commonly used illicit substance ( N = 311 , 39.4 % ) . In multivariate analyses , only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use ( adjusted odds ratio = 0.57 ; 95 % confidence interval : 0.38–0.87 ) . Conclusions / Importance : Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management , which could help to address adverse events associated with opioid analgesic use Abstract Rationale : Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect . Therefore , it is relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter ( DAT ) densities among alcoholics . Objective : We investigated DAT densities , along with striatal and extrastriatal dopamine D2-receptor densities , in nine non-violent late-onset male alcoholics , who had no major mental disorder nor antisocial personality disorder ( ASPD ) , and nine healthy controls . Methods : [123I]PE2I and [123I]epidepride were used in SPECT imaging . Results : DAT occupancy ratios ( striatum/cerebellum ) were significantly lower among alcoholics than in controls . Extrastriatal D2-receptor occupancy ratios ( temporal pole/cerebellum ) were not significantly different between the groups . Conclusions : Striatal presynaptic DAT densities are decreased among type 1 alcoholics , and this finding is not associated with recent alcohol abuse OBJECTIVES The co-occurrence of severe mental illness and substance use disorder , or dual diagnosis , is prevalent and is associated with significant clinical and social problems . Most studies have treated persons with a dual diagnosis as a homogeneous population , grouping together different substances of misuse . This study investigated whether subgroups defined by their main substances of misuse were heterogeneous . The primary hypothesis was that users of stimulants , such as cocaine or amphetamines  , would be characterized by especially high rates of inpatient admission , violence , and self-harm . METHODS Case managers ' ratings were used to identify individuals with serious mental illness and comorbid substance abuse or dependence who were being treated by 13 community mental health teams in South London . St and ardized instruments were used to elicit sociodemographic , clinical , social , and service use data . RESULTS A total of 233 cases of comorbid substance use disorder and psychotic illness were identified . On the basis of best available information , 78 ( 34 percent ) patients were classified as alcohol misusers only , 52 ( 22 percent ) as alcohol and cannabis users , 29 ( 12 percent ) as users of cannabis only , and 55 ( 24 percent ) as stimulant users ; 19 patients ( 8 percent ) were excluded from the analysis . No significant differences were found between subgroups in the use of inpatient services and lifetime history of self-harm , but there was a significant difference in lifetime history of violence , which was more frequent among stimulant users . The alcohol users were older and more likely to be white , but otherwise few differences between subgroups were suggested by exploratory analyses . CONCLUSIONS Apart from differences in history of violence , little heterogeneity was found among subgroups of patients with different types of substance misuse Rationale Previous imaging studies have indicated that the levels of the dopamine transporter ( DAT ) are reduced in the brains of heroin users . However , whether these changes can be reversed by abstinence and /or treatment remains unclear . Objectives This study aims to investigate DAT availability in heroin users and changes in DAT availability after abstinence and treatment with the Jitai tablets , a traditional Chinese medicinal product that is approved for the treatment of opioid addiction . Methods Single-photon emission computed tomography ( SPECT ) with [ 99mTc ] TRODAT-1 was performed on heroin-dependent patients ( n = 64 ) and healthy controls ( n = 15 ) . The patients were r and omly assigned to treatment with either placebo or the Jitai . All patients underwent SPECT imaging both at baseline and after 6 months of treatment . DAT availability was assessed in the cau date and putamen . Depression and anxiety were evaluated at baseline . Results DAT availability remained at low levels during a 6-month period in the placebo-treated group but was increased ( 14–17 % ) in the Jitai-treated group . The ratio of DAT availability at month 6 to that at baseline in the Jitai-treated group was significantly higher than that in the placebo-treated group in both the bilateral cau date and putamen . DAT uptake in the striatum was significantly correlated with daily heroin dose , years of heroin use , and depression . Conclusions These findings suggest that chronic heroin use induces long-lasting striatal DAT reductions . DAT availability remained unchanged during a 6-month period of abstinence . Treatment with Jitai appears to be effective at increasing striatal DAT availability BACKGROUND Sex differences in addictive disorders have been described . Pre clinical studies have implicated the striatal dopamine system in these differences , but human studies have yet to substantiate these findings . METHODS Using positron emission tomography ( PET ) scans with high-specific-activity [ 11C ] raclopride and a reference tissue approach , we compared baseline striatal dopamine binding potential ( BP ) and dopamine release in men and women following amphetamine and placebo challenges .  Subjective drug effects and plasma cortisol and growth hormone responses were also examined . RESULTS Although there was no sex difference in baseline BP , men had markedly greater dopamine release than women in the ventral striatum . Secondary analyses indicated that men also had greater dopamine release in three of four additional striatal regions . Paralleling the PET findings , men 's ratings of the positive effects of amphetamine were greater than women 's . We found no sex difference in neuroendocrine hormone responses . CONCLUSIONS We report for the first time a sex difference in dopamine release in humans . The robust dopamine release in men could account for increased vulnerability to stimulant use disorders and methamphetamine toxicity . Our findings indicate that future studies should control for sex and may have implication s for the interpretation of sex differences in other illnesses involving the striatum The dorsal striatum plays a role in consummatory food reward , and striatal dopamine receptors are reduced in obese individuals , relative to lean individuals , which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity . Thus , we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism , which is associated with dopamine D2 receptor ( DRD2 ) gene binding in the striatum and compromised striatal dopamine signaling . Cross-sectional and prospect i ve data from two functional magnetic resonance imaging studies support these hypotheses , which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum , particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region Cannabis is among the most frequently abused substances in the United States . Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response . Therefore , we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up . Cannabis-dependent males ( N=20 ) completed a functional magnetic resonance imaging ( fMRI ) cognitive-control ( Stroop ) task before a 12-week r and omized controlled trial of cognitive – behavioral therapy and /or contingency management .  A healthy-comparison group ( N=20 ) also completed the fMRI task . Cannabis use was assessed by urine toxicology and self-report during treatment , and by self-report across a 1-year follow-up period ( N=18 ) . The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions , including those strongly implicated in cognitive-control and addiction-related processes ( eg , dorsolateral prefrontal cortex and ventral striatum ) . The groups did not differ significantly in response times ( cannabis-dependent , N=12 ; healthy-comparison , N=14 ) . Within the cannabis-dependent group , greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment . Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up . These data suggest that lower cognitive-control-related neural activity in classic ‘ control ’ regions ( eg , dorsolateral prefrontal cortex and dorsal anterior cingulate ) and classic ‘ salience/reward/learning ’ regions ( eg , ventral striatum ) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up . Clinical ly , results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence BACKGROUND Pre clinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain . Specifically , alcohol-induced release of β-endorphins stimulates μ-opioid receptors ( MORs ) , which is believed to cause dopamine release in the brain reward system . Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol . In the present study , a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system . METHODS Availability of D(2/3 ) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride . Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding ( Δ%BP(ND ) ) . RESULTS The [(18)F]fallypride binding potentials ( BP(ND)s ) were significantly reduced in the ventral striatum , dorsal putamen , and amygdala after remifentanil application in both patients and control subjects . In the patient group , ventral striatum Δ%BP(ND ) was correlated with the Alcohol Use Disorders Identification Test score . CONCLUSIONS The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system , supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway . No difference in dopamine release was found between patients and control subjects , but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found Abstract Background Substance use is common among people living with HIV ( PLHIV ) and is associated with worse outcomes along the HIV care continuum . One potentially effective clinic-based approach to addressing unhealthy substance use is screening , brief intervention , and referral to treatment ( SBIRT ) . Methods We conducted a two-arm r and omized trial to examine the effects of a self-administered , computerized SBIRT intervention compared to a clinician-administered SBIRT intervention in an HIV primary clinic . Patients were surveyed before receiving the intervention and again at 1 , 3 , and 6 months . We administered the WHO Alcohol , Smoking and Substance Involvement Screening Test to determine Specific Substance Involvement Scores ( SSIS ) and to assign participants to categories of lower , moderate , or high risk to health and other problems for each substance . We collapsed moderate or severe risk responses into a single moderate – high risk category . Based on low rates of participation in the computerized arm , we conducted an “ as treated ” analysis to examine 6-month changes in mean SSIS among SBIRT intervention participants . Results For the overall sample ( n = 208 ) , baseline mean SSIS were in the moderate risk category for alcohol , tobacco , cannabis , cocaine , amphetamine , sedatives and opioids . Of those enrolled , 134 ( 64.4 % ) received the intervention , and 109 ( 52.4 % ) completed the 6-month follow up . There was a statistically significant decline in mean SSIS for all substances except tobacco and cannabis among participants who were at moderate – high risk at baseline . We also observed a statistically significant increase in mean SSIS for all substances except amphetamines and sedatives among participants who were at lower risk at baseline . Conclusions Substance use among patients in this urban , safety-net , HIV primary care clinic was near universal , and moderate risk substance use was common . Among participants who received the SBIRT intervention  , mean SSISs decreased among those at moderate – high risk at baseline , but increased among those at lower risk at baseline over the 6-month study period . Additional research should examine the clinical significance of SSIS changes for PLHIV , which SBIRT components drive changes in substance use scores , and what other interventions might support those patients at lower risk to maintain health and engagement along the HIV care continuum . Trial registration Clinical Trials.gov study AIMS Cocaine use by patients on methadone maintenance treatment is a widespread problem and is associated with a poorer prognosis . Recent studies have evaluated disulfiram as a treatment for individuals with comorbid alcohol and cocaine abuse . We evaluated the efficacy of disulfiram for cocaine dependence , both with and without co-morbid alcohol abuse , in a group of methadone-maintained opioid addicts . DESIGN R and omized double-blind , placebo-controlled trial . SETTING Urban methadone maintenance clinic . PARTICIPANTS Sixty-seven cocaine-dependent , methadone-maintained , opioid-dependent subjects ( 52 % female ; 51 % Caucasian ) . INTERVENTION Study medication , either disulfiram or placebo , was placed directly in the methadone to ensure compliance for 12 weeks . MEASUREMENTS Primary outcome measures included weekly assessment s of the frequency and quantity of drug and alcohol use , weekly urine toxicology screens and breathalyzer readings . FINDINGS Disulfiram treated subjects decreased the quantity and frequency of cocaine use significantly more than those treated with placebo .  Alcohol use was minimal for all subjects regardless of the medication . CONCLUSIONS Disulfiram may be an effective pharmacotherapy for cocaine abuse among methadone-maintained opioid addicts , even in those individuals without co-morbid alcohol abuse . Disulfiram inhibits dopamine beta-hydroxylase result ing in an excess of dopamine and decreased synthesis of norepinephrine . Since cocaine is a potent catecholamine re-uptake inhibitor , disulfiram may blunt cocaine craving or alter the " high " , result ing in a decreased desire to use cocaine The basal ganglia play a role in controlling movement during gait . The aim of the present study was to investigate changes in dopamine transporter ( DAT ) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson 's disease . This was done by comparing DAT radiolig and uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe , 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl ) tropane ( [11C]CFT ) and PET .  Physiological parameters were stable during and after gait in both groups . The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping ( SPM96 ) showed that [11C]CFT uptake in the striatum ( specifically the putamen ) was decreased by gait to a greater extent in normal subjects , whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the cau date and orbitofrontal cortex in Parkinson 's disease patients . These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour , i.e. gait . Alterations in this availability in Parkinson 's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait The modulating effects of serotonin on dopamine neurotransmission are not well understood , particularly in acute psychotic states .  Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo  and a  psychotomimetic dose of psilocybin ( n = 7 ) .  Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist . Psilocybin administration ( 0.25 mg/kg p.o . ) produced changes in mood , disturbances in thinking , illusions , elementary and complex visual hallucinations and impaired ego-functioning .  Psilocybin significantly decreased [11C]raclopride receptor binding potential ( BP ) bilaterally in the cau date nucleus ( 19 % ) and putamen ( 20 % ) consistent with an increase in endogenous dopamine . Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria . Together with previous reports of 5-HT receptor involvement in striatal dopamine release , it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses . The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states AIMS Risk factors among adolescent substance abusers have been shown to correlate with substance use severity . Characteristics related to severity , such as demographic and family factors , peer influences , psychiatric co-morbidity and HIV risk behaviors , are examined for a sample of adolescent cannabis users entering treatment . DESIGN These data are from a clinical trial study utilizing blocked r and om assignment of clients to one of five treatment conditions . The study targeted adolescents entering outpatient treatment for primarily cannabis abuse or dependence . SETTING Treatment and research facilities in four metropolitan areas of the US were used to recruit study participants . Treatment was delivered in outpatient drug-free setting s. PARTICIPANTS Participants were 600 clients , ages 12 - 18 , admitted to outpatient substance abuse treatment programs for cannabis problems , 96 % with DSM-IV diagnoses of substance abuse or dependence , with the remaining 4 % having at least one symptom of dependence plus significant problems indicating need for treatment . MEASUREMENTS The Global Appraisal of Individual Needs ( GAIN ) was used to collect the information presented in this paper . The GAIN incorporates DSM-IV criteria for substance use disorders , conduct disorder and attention deficit hyperactivity disorder , as well as dimensional ( scale ) measures for physical and mental health . FINDINGS All participants reported at least one symptom of substance use disorders , and 46 % met the DSM-IV criteria for substance dependence , while 50 % met criteria for a diagnosis of abuse . Only 20 % of the participants perceived any need for help with problems associated with their drug or alcohol use . Clients participating in the study typically presented multiple problems at treatment entry , most often including conduct disorder , attention deficit hyperactivity disorder ( ADHD ) , internal ( mental ) distress , and physical health distress . The co-occurrence of conduct disorder and ADHD was found in 30 % of the sample . Clients meeting criteria for substance dependence tended to have more co-occurring problems and significantly less denial at admission . CONCLUSIONS The characteristics of this sample exemplify the complex nature of adolescent substance use and abuse among adolescents entering outpatient treatment programs . Patterns of co-occurring problems are at rates comparable to those found in other clinical studies . Those with more severe substance use disorders tend to manifest more problems of social functioning , more mental health problems , and physical health problems . Implication s of these findings are discussed in terms of treatment needs , challenges , and prognostic implication Summary An intricate relationship between chronic pain , opioid use and addictive behaviors was demonstrated , and certain addictive behaviors seem to predict or be associated with opioid use in chronic non‐cancer pain . Abstract The growing body of research showing increased opioid use in patients with chronic pain coupled with concerns regarding addiction encouraged the development of this population ‐based study . The goal of the study was to investigate the co‐occurrence of indicators of addictive behaviors in patients with chronic non‐cancer pain in long‐term opioid treatment . The study combined data from the  individual‐based Danish Health Survey in 2010 and the official Danish health and socio‐economic , individual‐based registers . From a simple r and om sample of 25,000 adults ( 16 years or older ) living in Denmark , 13,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain ( lasting ≥6 months ) , opioid use , health behavior , and body mass index . Six potential addictive behaviors were identified : daily smoking ; high alcohol intake ; illicit drug use in the past year ; obesity ; long‐term use of benzodiazepines ; and long‐term use of benzodiazepine‐related drugs . At least 2 of the 6 addictive behaviors were observed in 22.6 % of the long‐term opioid users with chronic pain compared with 11.5 % of the non‐opioid users with chronic pain and 8.9 % of the individuals without chronic pain . Thus , a strong association was demonstrated between long‐term opioid use and the clustering of addictive behaviors . An intricate relationship between chronic pain , opioid use , and addictive behaviors was observed in this study , which deserves both clinical attention and further research To date , while the contribution of the striatum in executive processes is well documented , the role played by striatal dopamine during tasks requiring executive functions is still unknown . We used D2-dopamine receptor lig and [ (11)C ] raclopride PET in healthy subjects while performing the Montreal Card Sorting Task ( MCST ) .  We observed a striatal reduction in [ (11)C ] raclopride binding potential during planning of a set-shift when compared with matching according to an ongoing rule . These findings suggest that striatal dopamine neurotransmission increases significantly during the performance of specific executive processes confirming previous evidence of striatal activation during fMRI studies . The present observation may provide some insights on the origin of cognitive deficits underlying certain neurological disorders associated with dopamine dysfunction , such as Parkinson 's disease OBJECTIVE Substance abuse is extremely common in patients with bipolar disorders , although minimal data are available on the treatment of this important clinical population . Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action , acting as a dopamine-2 receptor partial agonist , thereby increasing dopamine release in some parts of the brain and decreasing dopa-mine release in other brain regions . Dopamine release is implicated in substance use , and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse . To our knowledge , dopa-mine receptor partial agonists have not been investigated for treatment of substance abuse in humans . METHOD Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripipra-zole using an overlap and taper method . At baseline , diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria . Psychiatric symptoms , side effects , and substance use and craving were assessed over 12 weeks . Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Young Mania Rating Scale ( YMRS ) , and Brief Psychiatric Rating Scale ( BPRS ) . Substance craving was assessed with visual analogue scales , and side effects were monitored using the Abnormal Involuntary Movement Scale , Simpson-Angus Scale , Barnes Akathisia Scale , and patient report .  Study enrollment was from April 2003 to February 2004 . RESULTS Significant baseline-to-exit improvement in HAM-D ( p = .002 ) , YMRS ( p = .021 ) , and BPRS ( p = .000 ) scores were observed without a significant change in antipsychotic-induced side effect scales . In 17 participants with current alcohol dependence , significant reductions in dollars spent on alcohol ( p = .042 ) and alcohol craving ( p = .003 ) were found . In 9 participants with cocaine-related disorders , significant reductions in cocaine craving ( p = .014 ) , but not use , were found . CONCLUSION A change to aripiprazole was associated with symptomatic improvement . Limitations of the study include a small sample size , high attrition , and an open-label design . Controlled trials in dual-diagnosis patients are needed to confirm these findings Hereditary factors confer susceptibility to alcohol dependence . Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system . The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene ( DAT1 ) might contribute to individual differences in vulnerability to addictive behavior . Our population -based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinical ly more homogeneous subgroups formed by : positive family history , early age-at-onset , delirium , withdrawal seizures , antisocial tendencies , type 1 and 2 alcoholics . Analyzing a VNTR polymorphism in the 3 ' untranslated region of DAT1 , we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium  , compared with 93 ethnically matched nonalcoholic controls ( p = 0.003 ; OR = 2.44 ; 95 % confidence interval : 1.35 - 4.43 ) . Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms Substance abuse is the result of interaction between constitutional , environmental and socio-demographic factors . Several studies have been demonstrated that the adolescent substance abuse is a serious and growing problem . The aim of our study is to investigate the association between substance , alcohol and tobacco abuse and socio-familiar factors , to evaluate a substance abuse prevention program which decreases substance use in adolescents . A cross-sectional survey was developed and carried out by involving a group of adolescents , r and omly selected from the secondary school of Teramo province . Data were collected by a self-administered question naire . The associations between substance use and the determinants taken into account was evaluated by the chi-square test of Fisher exact test or trend test when appropriated . Our data show that the alcohol abuse is more frequent in males ( 41.1 % , p = 0.000 ) , while the nicotine abuse is more frequent in females ( 46.1 % , p = 0.005 ) . However , our results show that the abuse of alcohol , nicotine , heroine , cocaine and ecstasy is associated to lack of stability in the family , respectively : 61.5 % ( p = 0.001 ) ; 61.5 % ( p = 0.022 ) ; 7.7 % ( p = 0.018 ) ; 7.7 % ( p = 0.010 ) : 7.7 % ( p = 0.004 ) . The nicotine abuse is higher in adolescents living with a smoker : 50.3 % ( p = 0.000 ) . Finally , the substance abuse is higher in adolescents having friends that are drug-addicts , in particular : alcohol 49.6 % ( p = 0.000 ) , nicotine 43.0 % ( p = 0.000 ) , cannabis 27.9 % ( p = 0.000 ) . This survey suggests that the knowledge of factors influencing the initiation , combination and cessation of the use of substance is crucial for the prevention of drug use among adolescents BACKGROUND Early substance use ( SU ) in adolescence is known to be associated with an elevated risk of developing substance use disorders ( SUD ) ; it remains unclear though whether early SU is associated with more rapid transitions to SUD . OBJECTIVE To examine the risk and speed of transition from first SU ( alcohol , nicotine , cannabis ) to SUD as a function of age of first use . METHODS N=3021 community subjects aged 14 - 24 years at baseline were followed-up prospect ively over 10-years . SU and SUD were assessed using the DSM-IV/M-CIDI . RESULTS ( 1 ) The conditional probability of substance-specific SU-SUD transition was the greatest for nicotine ( 36.0 % ) and the least for cannabis ( 18.3 % for abuse , 6.2 % for dependence ) with alcohol in between ( 25.3 % for abuse ; 11.2 % for dependence ) . ( 2 ) In addition to confirming early SU as a risk factor for SUD we find : ( 3 ) higher age of onset of any SU to be associated with faster transitions to SUD , except for cannabis dependence . ( 4 ) Transitions from first cannabis use ( CU ) to cannabis use disorders ( CUD ) occurred faster than for alcohol and nicotine . ( 5 ) Use of other substances co-occurred with risk and speed of transitions to specific SUDs . CONCLUSION Type of substance and concurrent use of other drugs are of importance for the association between age of first use and the speed of transitions to substance use disorders . Given that further research will identify moderators and mediators affecting these differential associations , these findings may have important implication s for design ing early and targeted interventions to prevent disorder progression
Our analysis indicated that changes of dopamine receptors and transporters are moderated by the duration of abstinence .
Our analysis provides strong evidence for a central role of the striatal dopamine system in use of alcohol or opioids .
Use of alcohol , cannabis and opioids is highly prevalent and is associated with global disease burden and high economic costs .
The exact pathophysiology of abuse or addiction associated with these sedative substances is not completely understood , but previous research implicates the important role of the striatal dopamine system in the addiction process .
Multiple studies investigated changes in the striatal dopamine systems of users of sedative substances , but currently these results are very heterogeneous .
Therefore , we conducted a meta- analysis of in vivo neuroimaging studies investigating dopaminergic alterations in the striatum of users of alcohol , opioids or cannabis .