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.
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
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 .