Such studies have revealed that substance use disorders are accompanied by either low or unaltered dopamine synthesis capacity , possibly reflecting variability in presynaptic dopamine cell injury due to varying amounts of excessive drug use or differences in drug induced neuroplasticity . We argue that this difference between pathological gambling and substance use disorders might reflect the absence of substance-specific confounds, including toxicity of drugs on the dopamine system, in the case of pathological gambling. This highlights the potential of studying pathological gambling, which does not involve the administration of exogenous substances, for investigating the role of dopamine in addiction. An alternative possibility is that pathological gambling might not be as good a model of addiction as hitherto thought or at least might not be as similar to stimulant addiction as previously hypothesized . Importantly, research has shown that various substance use disorders are associated with varying degrees of dopamine abnormality, suggesting that addiction is likely a multi-pleneuro transmitter disorder . Previous work has shown increased gambling-induced dopamine release in the ventral striatum as a function of gambling severity/excitement level as well as reduced ventral striatal dopamine D2/D3 receptor availability as a function of sensation seeking/impulsivity . In light of the positive relationship between dopamine synthesis capacity and dopamine release , on the one hand, and the negative relationship between dopamine synthesis capacity and D2/D3 receptor availability observed in HCs ,cannabis grow equipment on the other [but see ], the current results raise the hypothesis that increased striatal dopamine release and reduced D2/D3 receptor availability in pathological gambling may reflect increased dopamine synthesis capacity.

However, it is noteworthy that another recent [18F]DOPA PET study did not find evidence of dopamine synthesis abnormality in PGs compared with HCs . The basis of this discrepancy is unclear, but we speculate that differences in drug dependence history might play a role, although this information was not provided in the article by Majuri et al. . The incidence of smoking was higher in their study compared with the current study . Given that nicotine/ drugs of abuse can affect dopamine synthesis capacity , it is possible that differences in nicotine/drug dependence history between the populations of the two studies contributed to the observed differences in dopamine synthesis levels. Another factor that has been suggested to contribute to mixed results in gambling research is the heterogeneity among PGs . In particular, it has been proposed that different subtypes of PGs, who gamble for different motives, might be characterized by different underlying brain mechanisms. For example, PGs who gamble to cope with negative affect might be primarily characterized by abnormal functioning of the amygdala circuit, whereas PGs who gamble to enhance positive affect might be primarily characterized by a hyperactive orbitofron to-striatal circuitry . More research is needed to elucidate the various endophenotypes underlying pathological gambling sub-types and to assess their validity in research and clinical treatment. Future studies will be needed to replicate the current findings and better understand the interplay among dopamine synthesis capacity, dopamine release, and D2/D3 receptor availability. The observation that higher dopamine synthesis capacity in PGs was most consistently found in the dorsal parts of the striatum is striking and overlaps with the location of increased striatal dopamine release previously reported as a result of amphetamine administration in the anterior caudate and putamen . The dorsal striatum is thought to play a crucial role in habitual control of behavior, as evidenced by dorsolateral striatal lesions disrupting habit formation in animals , for instance. Increased dopamine synthesis capacity in the dorsal putamen in PGs also fits with incentive sensitization studies in humans, showing that after repeated exposure to amphetamine the dorsal putamen becomes progressively involved .

Note that such increased dopamine response to rewarding stimuli could also reflect a vulnerability to develop addictive behaviors . Indeed, animals with increased addiction vulnerability show increased dopamine release in the nucleus accumbens and dorsomedial striatum following psychostimulant administration, as assessed using voltammetry . Thus, increased dopamine synthesis capacity, especially in the dorsal putamen, could be a vulnerability and/or consequence of addictive behavior driving excessive reward-seeking behavior. However, our study was not designed to dissect whether alterations in dopamine synthesis capacity are a direct cause or consequence of pathological gambling, and the origin of this alteration is still speculative. One possibility is that genetic factors affecting components of the dopamine synthesis pathway, such as variants in the dopa decarboxylase gene found to be associated with gambling disorder , might play a role there. Our results should be interpreted with the following limitations in mind. First, the study included a small sample of only male subjects. This strategy led to a homogeneous population without psychiatric comorbidities—in particular, without drug dependence—which enabled us to measure dopamine synthesis capacity in pathological gambling without confounding factors. However, one should note that, with the exception of current and past-year drug dependence history, all other clinical assessments were performed away from the PET study on the occasion of a preceding pharmaco-fMRI study. In addition, 5 HCs and 5 PGs scored $8 on the Alcohol UseDisorders Identification Test questionnaire, indicating possible alcohol problems. However, because groups did not differ on Alcohol Use Disorders Identification Test scores, it is unlikely that this would have influenced our main finding of enhanced dopamine synthesis capacity in PGs relative to HCs. Interestingly, at the time of the PET scan, only 4 of the 13 gamblers were experiencing acute problems with gambling . It is unclear how this might have affected our results, but because dopamine synthesis capacity is thought to be a stable measure over long periods of time , the increased dopamine synthesis capacity found in our PGs might reflect a vulnerability in the dopamine system rather than a consequence of current gambling problems.

Preclinical and longitudinal studies are needed to address whether heightened dopamine synthesis capacity in pathological gambling existed before the onset of problematic gambling or developed as a consequence of the disorder. Another caveat is that although we observed a clearly enhanced dopamine synthesis capacity in PGs compared with HCs in the non PVC ROIs—specifically in the dorsal putamen, caudate body, and ventral striatum—this group difference was less striking in the PVC ROIs and significant only in the dorsal putamen ROI . These differences between non-PVC and PVC results are explained by the incorporation of the size and shape of the ROIs, as well as their proximity to white matter and cerebral spinal fluid, in the latter method. Using PVC ROIs is not always the most sensitive method because PVC methods can amplify the existing noise such as increasing the variance in the time–activity curves . Given the scarcity of reports examining [18F]DOPA differences in pathological gambling, we included different analysis methods to comprehensively test the reproducibility of the results. We believe that our analyses reveal robust findings of higher dopamine synthesis capacity in the dorsal putamen in PGs. At the clinical level, our results suggest that it could be beneficial to reduce dopamine levels in pathological gambling. However, two double-blind, placebo-controlled trials of the atypical antipsychotic olanzapine,mobile grow system a dopamine and serotonin antagonist, have shown no benefit over placebo , similar to what was found with bupropion, a dopamine and norepinephrine transporter inhibitor . Multiple psychopharmacological studies using the dopamine D2/D3 receptor antagonists sulpiride and haloperidol have also yielded inconclusive results regarding the ability of these drugs to normalize reward processing in pathological gambling . However, a small single-blind study using the D1 receptor antagonist ecopipam in PGs did lead to significant reductions in gambling severity measures . Clearly, more research is needed to assess whether and how striatal dopamine receptor blockade would be effective in treating pathological gambling. Finally, addiction is a complex mixture of behaviors and cognitions that is reflected in the heterogeneity of the patients and also varies from drug to drug, game to game, and drug to game. As emphasized by Nutt et al. , “it is unlikely that a single neurotransmitter could explain every aspect of addiction.”Disparate rates of felony drug arrests and convictions across race and geography have implications for inequalities in health and social outcomes linked to criminal justice exposure. California Proposition 47 , passed in 2014, reduced drug possession offenses classified as felonies or wobblers unintended consequences with regards to drug-related hospital visits. For objective 1: using data on all drug arrests made in California from 2011-2016, we compared the immediate and one year post-policy changes in racial disparities in drug arrests between Whites, Blacks, and Latinos, controlling for secular and seasonal trends. For objective 2: after propensity score matching arrests made in the year after the implementation of Prop 47 to similar arrests in the year prior to Prop 47, we used mixed models to estimate the change in county variance in the probability of felony conviction. For objective 3: Incorporating data on all drug-related hospital visits in California from 2011-2015 with drug arrests data, we use county fixed effects models to estimate expected rates in the 10- months post-policy, and calculate the difference compared to observed rates.

We use linear regression to test whether county-level changes in drug arrest rates were associated with changes in drug-related hospital visit rates. In the month following passage, absolute Black-White disparities in monthly felony drug arrests decreased from 81 to 44 per 100,000 and continued to decrease over time. The probability of a felony conviction among those arrested for Prop 47 drug offenses declined by 14 percentage points , from 0.21 to 0.07 . Counties with higher felony conviction probabilities pre-Prop 47 declined most, reducing cross-county variance, with no evidence of increases in felony convictions for concurrent offenses. Declines in arrests were not associated with increases in drug-related hospital visits.Over seven million Americans had an illicit substance use disorder in 2014 , and substance-related disorders excluding alcohol were the primary diagnosis in over 700,000 emergency department visits that year . The U.S. has taken an increasingly punitive approach to substance use in recent decades, which has disproportionately affected people of color. Twenty years after the war on drugs was launched in 1986, arrests for drug possession had grown by 150%, and Black-White disparities widened from 3:1 to 5:1 . The collateral consequences of felony drug convictions are severe. Impacts on parental custody rights, immigration status, and access to professional licensing, employment, health and social benefits, housing, and financial support for higher education may exacerbate racial/ethnic disparities in health and social outcomes . Felony convictions also increase the likelihood and length of incarceration for future convictions, exposure to which has negative health effects. Of the 1.5 million jail and prison inmates with substance use disorders, just 11% have received any type of treatment since admission , and few jails and prisons offer evidence-based strategies like medication-assisted treatment . Ultimately, incarceration may increase injecting, infectious diseases, and mortality post-release, while disrupting access to health services . The mental and physical health of partners and children is also affected – incarceration can lead to family break-up and economic strain – with family income declining by 22% during a father’s incarceration and 15% following release . Taken together, criminal justice involvement has been identified as a significant social determinant of health for an already vulnerable population . Exposure to felony convictions is both profoundly unequal across race/ethnicity, and strikingly prevalent for some: an estimated 8% of all adults and 33% of Black men have a felony conviction . Rates of felony disenfranchisement are three to four times higher in predominantly Black communities than predominantly White communities, disadvantaging low-income communities of color and obstructing their impact on public policies that could reduce inequalities.Research conducted in 2010 in California found the proportion of arrests for possession of a controlled substance that were charged as felonies varied across California counties from 25 to 100 percent . Even after controlling for case characteristics and criminal history, county of residence was a strong predictor of felony filings following arrest . Many states are beginning to reduce criminal penalties for drug possession. While many drug law reforms have focused on marijuana, California passed Proposition 47: The Safe Neighborhoods and Schools Act in 2014, which made more expansive changes by reducing possession of narcotics , possession of a controlled substance and possession of concentrated cannabis (H&S 11357 to misdemeanors, as well as several property offenses.