Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

BACKGROUND: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. CONCLUSION: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Mindfulness and clinical correlates in methamphetamine use disorder.

BACKGROUND: Mindfulness-based interventions are increasingly used for the treatment of substance use disorders, including methamphetamine use disorder (MUD). Literature indicates that trait mindfulness may play a key role in the effectiveness of these treatments on therapeutic outcome, yet no prior studies have tested for differences in trait mindfulness between individuals with MUD and healthy control participants. Such differences are important for treatment implementation. OBJECTIVES: The goals of this study were to evaluate trait mindfulness and to determine its clinical correlates in individuals with MUD. METHODS: A group of participants with MUD at varying lengths of abstinence from methamphetamine (< 1h to 90 days; mean 5.4 ± 12.5 days; N=95, 53 female, 42 male) and a healthy control group (N=65, 30 female, 35 male) completed the Mindfulness Attention Awareness Scale (MAAS). Group differences and relationships between trait mindfulness and several measures of drug use and psychiatric symptoms were evaluated. RESULTS: In participants with MUD, trait mindfulness was 10% lower than in healthy controls (p < 0.001), but it was not significantly correlated with measures of drug use or craving. Across both groups, trait mindfulness was negatively correlated with state anxiety, depression, emotional dysregulation, impulsivity, and a history of childhood trauma, while it was positively correlated with self-compassion (ps < 0.001). CONCLUSION: The deficit in trait mindfulness in MUD presents a capacity that can be targeted for improved treatment outcome with mindfulness-based therapies. Trait mindfulness is inversely related to mood dysregulation.

No significant elevation of translocator protein binding in the brains of recently abstinent methamphetamine users.

BACKGROUND: Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence. METHODS: We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). RESULTS: Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. CONCLUSIONS: The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.