Opiate-Induced Dopamine Release Is Modulated by Severity of Alcohol Dependence: An [18F]Fallypride Positron Emission Tomography Study PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users. A genetic determinant of the striatal dopamine response to alcohol in men Cannabis Abstinence During Treatment and One-Year Follow-Up: Relationship to Neural Activity in Men Cocaine-specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse. Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Dissociable Deficits in the Decision-Making Cognition of Chronic Amphetamine Abusers, Opiate Abusers, Patients with Focal Damage to Prefrontal Cortex, and Tryptophan-Depleted Normal Volunteers: Evidence for Monoaminergic Mechanisms 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 Abnormal brain activity in prefrontal brain regions in abstinent marijuana users Deficits in Dopamine D2 Receptors and Presynaptic Dopamine in Heroin Dependence: Commonalities and Differences with Other Types of Addiction Substance abuse and trauma in Cape Town. Psychopathological correlates of reduced dopamine receptor sensitivity in depression, schizophrenia, and opiate and alcohol dependence. Occurrence of comorbid substance use disorders among acute psychiatric inpatients at Stikland Hospital in the Western Cape, South Africa. Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Switching outpatients with bipolar or schizoaffective disorders and substance abuse from their current antipsychotic to aripiprazole. Characteristics of subgroups of individuals with psychotic illness and a comorbid substance use disorder.
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 It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users . However , it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum . To establish whether chronic opiate use might impair brain dopamine neurons in humans , we assessed dopamine transporter ( DAT ) uptake function in the striatum ( cau date and putamen ) , and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment .  Binding of [(11)C]-2beta-carbomethoxy-3beta-aryltropane ( [ (11)C ] CFT ) as a brain dopamine transporter lig and was measured with positron emission tomography ( PET ) in eleven former heroin users with prolonged abstinence , ten patients receiving methadone maintenance treatment and ten healthy control subjects .  Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined . In comparison with healthy control subjects , methadone maintenance treatment subjects had lower DAT uptake function in the bilateral cau date and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral cau date . Moreover , in comparison to the prolonged abstinence subjects , the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen . DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects ; however , DAT uptake function in the bilateral cau date was significantly correlated with subjective anxiety in methadone maintenance treatment subjects . Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment , and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain 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 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 AIMS To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling , via a resting-state functional connectivity approach ; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity , compulsivity and drug relapse . DESIGN Cross-sectional study of 20 individuals with cocaine dependence ( CD ) , 19 individuals with pathological gambling ( PG ) and 21 healthy controls ( HC ) , and a prospect i ve cohort study of 20 CD followed-up for 12 weeks to measure drug relapse . SETTING AND PARTICIPANTS CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment ( Centro Provincial de Drogodependencias ) and a public clinic specialized in gambling treatment ( AGRAJER ) , respectively ; HC were recruited through community advertisement in the same area in Granada ( Spain ) . MEASUREMENTS Seed-based functional connectivity in the ventral striatum ( ventral cau date and ventral putamen ) and dorsal striatum ( dorsal cau date and dorsal putamen ) , the Kirby delay-discounting question naire , the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests . FINDINGS CD relative to PG exhibit enhanced connectivity between the ventral cau date seed and subgenual anterior cingulate cortex , the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula ( P≤0.001 , kE=108 ) . Connectivity between the ventral cau date seed and subgenual anterior cingulate cortex is associated with steeper delay discounting ( P≤0.001 , kE=108 ) and cocaine relapse ( P≤0.005 , kE=34 ) . CONCLUSIONS Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse Neuropsychological investigations of substance abusers have reported impairments on tasks mediated by the frontal executive system , including functions associated with behavioral inhibition and decision making . The higher order or executive components which are involved in decision making include selective attention and short term storage of information , inhibition of response to irrelevant information , initiation of response to relevant information , self-monitoring of performance , and changing internal and external contingencies in order to " stay the course " towards the ultimate goal . Given the hypothesized role of frontal systems in decision making and the previous evidence that executive dysfunctions and structural brain changes exist in subjects who use illicit drugs , we applied fMRI and diffusion tensor imaging ( DTI ) techniques in a pilot investigation of heavy cannabis smokers and matched control subjects while performing a modification of the classic Stroop task .  Marijuana smokers demonstrated significantly lower anterior cingulate activity in focal areas of the anterior cingulate cortex and higher midcingulate activity relative to controls , although both groups were able to perform the task within normal limits . Normal controls also demonstrated increased activity within the right dorsolateral prefrontal cortex ( DLPFC ) during the interference condition , while marijuana smokers demonstrated a more diffuse , bilateral pattern of DLPFC activation . Similarly , although both groups performed the task well , marijuana smokers made more errors of commission than controls during the interference condition , which were associated with different brain regions than control subjects . These findings suggest that marijuana smokers exhibit different patterns of BOLD response and error response during the Stroop interference condition compared to normal controls despite similar task performance . Furthermore , DTI measures in frontal regions , which include the genu and splenium of the corpus callosum and bilateral anterior cingulate white matter regions , showed no between group differences in fractional anisotropy ( FA ) , a measure of directional coherence within white matter fiber tracts , but a notable increase in trace , a measure of overall isotropic diffusivity in marijuana smokers compared to controls . Overall , results from the present study indicate significant differences in the magnitude and pattern of signal intensity change within the anterior cingulate and the DLPFC during the Stroop interference subtest in chronic marijuana smokers compared to normal controls . Furthermore , although chronic marijuana smokers were able to perform the task reasonably well , the functional activation findings suggest they utilize different cortical processes from the control subjects in order to do so . Findings from this study are consistent with the notion that substance abusers demonstrate evidence of altered frontal neural function during the performance of tasks that involve inhibition and performance monitoring , which may affect the ability to make decisions We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers , chronic opiate abusers , and patients with focal lesions of orbital prefrontal cortex ( PFC ) or dorsolateral/medial PFC . We also assessed the effects of reducing central 5-hydroxytryptamine ( 5-HT ) activity using a tryptophan-depleting amino acid drink in normal volunteers . Chronic amphetamine abusers showed sub-optimal decisions ( correlated with years of abuse ) , and deliberated for significantly longer before making their choices . The opiate abusers exhibited only the second of these behavioral changes . Importantly , both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC . Qualitatively , the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse , consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers . Overall , these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC . These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine ( DA ) projections 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 We used PET (15)O and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana ( MJ ) users have persistent deficits in executive cognitive functioning ( ECF ) and brain activity . Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent , heavy marijuana users ( n = 11 ) , and a matched comparison group ( n = 11 ) . The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group . Despite the lack of performance differences , the marijuana users showed hypoactivity in the left perigenual anterior cingulate cortex ( ACC ) and the left lateral prefrontal cortex ( LPFC ) and hyperactivity in the hippocampus bilaterally , when compared to the comparison group . These results suggest that marijuana users display persistent metabolic alterations in brain regions responsible for ECF . It may be that marijuana users recruit an alternative neural network as a compensatory mechanism during performance on a modified version of the Stroop task . These differences in brain activity may be a common denominator in the evolution of maladaptive behaviors such as substance abuse and other neuropsychiatric disorders 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 OBJECTIVE To obtain baseline data on the incidence of acute alcohol intoxication , chronic alcoholism and illicit drug usage among a cohort of injured patients . DESIGN A prospect i ve , descriptive study of 254 injured patients presenting at the trauma unit of Groote Schuur Hospital over an idealized week in 1997 .  Alcohol consumption  was assessed by means of the Lion SD2 alcolmeter . Chronic alcoholism was assessed using the CAGE question naire . Each patient 's urine was analysed for four drugs ( cannabis , morphine , opiates and methaqualone ) using conventional ' wet ' analysis . Sweat  was tested for cannabis using a Drugwipe . MAIN OUTCOME MEASURES Socio-demographics , cause of injury , injury severity , acute alcohol intoxication , chronic alcohol usage and illicit drug involvement . RESULTS Patients were predominantly male , coloured and an average of 31.3 years old . The majority had been injured as a result of interpersonal violence . Self-reported alcohol consumption was reliable but this was not so for self-reported drug usage . Sixty per cent of patients had positive alcohol levels on breath analysis . More than one-quarter of all the patients could be classified as chronic alcoholics on the CAGE question naire . On urine analysis , 40 % of patients were found to have used at least one illicit drug in the recent past . The most commonly abused drugs were cannabis or a combination of cannabis and M and rax , locally called a ' white pipe ' . Use of the white pipe was confined almost exclusively to patients injured as a result of interpersonal violence . CONCLUSIONS Alcohol remains the most commonly abused substance among trauma patients , but there are growing numbers of patients who simultaneously abuse illicit drugs . This study will be conducted annually to detect trends and identify emerging problems A dysfunction of central dopaminergic neurotransmission has been found in various neuropsychiatric diseases , and may be associated with a common psychopathological correlate . One hypothesis suggests that dopaminergic stimulation of the brain reward system reinforces behavior because it is experienced as pleasurable , and that dopaminergic dysfunction leads to anhedonia , the inability to experience pleasure . An alternative hypothesis assumes that dopaminergic stimulation does not promote pleasure or " liking " of a reward but rather mediates " wanting " of a reward , and suggests that dopaminergic dysfunction is associated with a failure to be motivated by stimuli that indicate reward . We measured negative symptoms , psychomotor slowing and dopamine receptor sensitivity in twelve drug-free patients with major depression , seventeen alcohol-dependent and sixteen opiate-dependent patients , ten schizophrenics with neuroleptic medication , and ten healthy controls . The sensitivity of central dopamine receptors was assessed with the growth hormone response to apomorphine application . Psychomotor slowing was measured in a reaction-time test and anhedonia and other negative symptoms were assessed with self-rating scales and the Scale for the Assessment of Negative Symptoms . Patients with major depression , alcohol dependence and neuroleptic medication displayed a reduced sensitivity of central dopamine receptors compared to control subjects . Anhedonia was not a common correlate of dopamine receptor dysfunction . Instead , affective flattening was associated with both dopamine receptor sensitivity and psychomotor slowing . Our findings thus do not support the anhedonia hypothesis of central dopaminergic dysfunction . Rather , affective flattening may result from the lack of an emotional response towards reward-indicating stimuli . These findings indicate that patients with dopaminergic dysfunction are not unable to experience pleasure , but may fail to be motivated by environmental stimuli to seek reward OBJECTIVE Little is known about the epidemiology of substance use disorders ( SUD ) among psychiatric in patients in the Western Cape , South Africa . Therefore , this study was conducted to examine the prevalence of SUD among acute adult psychiatric in patients at Stikl and Hospital , one of three state acute psychiatric hospitals in the Western Cape . METHOD A prospect i ve descriptive prevalence survey was undertaken over a three-month period . During this period , data was collected on psychiatric patients ( N=298 ) who were hospitalized in the acute psychiatric wards at Stikl and . This included patient demography , psychiatric and substance use history . Urine was also collected and analyzed for substances commonly abused in the Western Cape . RESULTS A co-morbid SUD ( abuse or dependence ) was diagnosed in 51 % of patients . In addition , a diagnosis of a substance-induced psychiatric disorder was made in 8 % of these patients , 1 % of who was diagnosed with a substance-induced mood disorder , while 7 % was diagnosed with a substance induced psychotic disorder . Patients diagnosed with a co-morbid SUD were younger than those without a SUD and more likely to have been involuntary admissions . These patients also displayed more violence prior to admission that contributed to their admission and were more likely to have used cannabis or methamphetamine as their preferred drug of abuse . Only a small group of patients had documented evidence of any prior interventions for their SUD . CONCLUSION SUD are prevalent among psychiatric in patients and contribute to their morbidity . This has implication s for staff training and service development Cognitive deficits that are reported in heavy marijuana users  ( attention , memory , affect perception , decision-making ) appear to be completely reversible after a prolonged abstinence period of about 28 days . However , it remains unclear whether the reversibility of these cognitive deficits indicates that ( 1 ) chronic marijuana use is not associated with long-lasting changes in cortical networks or ( 2 ) that such changes occur but the brain adapts to and compensates for the drug-induced changes . Therefore , we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm ( Risk Task ) while undergoing sham or active transcranial direct current stimulation ( tDCS ) of the dorsolateral prefrontal cortex ( DLPFC ) . Twenty-five chronic marijuana users who were abstinent for at least 24h were r and omly assigned to receive left anodal/right cathodal tDCS of DLPFC ( n=8 ) , right anodal/left cathodal tDCS of DLPFC ( n=9 ) , or sham stimulation ( n=8 ) ; results on  Risk Task  during sham/active tDCS were compared to healthy volunteers from a previously published data set . Chronic marijuana users demonstrated more conservative ( i.e. less risky ) decision-making during sham stimulation . While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers , both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users . These findings reveal alterations in the decision-making neural networks among chronic marijuana users . Finally , we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana 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 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
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 .