BDNF Val 66 Met genotype is associated with drug‐seeking phenotypes in heroin‐dependent individuals: a pilot study

Brain‐derived neurotrophic factor (BDNF) Val 66 Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug‐seeking behavior. Heroin‐dependent volunteers ( n  = 128) completed an interview that assessed past‐month naturalistic drug‐seeking/use behaviors. In African Americans ( n  = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans ( n  = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers ( n  = 20) reported more time‐ and cost‐intensive heroin‐seeking and more cigarette use than Val homozygotes ( n  = 34). BDNF Val 66 Met genotype predicted 18.4% of variance in ‘weekly heroin investment’ (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a ‘preferred drug‐invested’ phenotype, resistant to moderating effects of higher drug prices and non‐drug reinforcement. These preliminary hypothesis‐generating findings require replication, but are consistent with pre‐clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99593/1/adb431.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99593/2/adb431_sm_fig_s1.pd

Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder

BACKGROUND: Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. METHODS: This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant\u27s preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. RESULTS: Lifetime BZD misuse is significantly (p \u3c 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. CONCLUSION: Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes

Childhood-Onset Attention-Deficit/Hyperactivity Disorder Exacerbates Opioid Use Disorder Consequences: Mediation by Impulsive Phenotypes

Background: Attention deficit hyperactivity disorder (ADHD) is highly prevalent and associated with opioid use disorder (OUD). Yet, little is known about the mechanisms by which ADHD (which is a heterogeneous construct/diagnosis) might alter the trajectory of OUD outcomes. Aim: This cross-sectional study examines relationships between childhood ADHD (inferred as predating substance use) and the extent to which the effects of ADHD on lifetime heroin-use consequences are mediated by foreshortened time perspective and drug-use impulsivity. Methods: Individuals who report heroin use (N=214) were screened using the Assessment of Hyperactivity and Attention (AHA), Impulsive Relapse Questionnaire (IRQ), Stanford Time Perception Inventory (STPI), and a comprehensive assessment of lifetime and current substance use and substance-related consequences. Results: Relative to participants whose AHA scores did not meet criteria for lifetime ADHD diagnosis (n=88), those with persistent ADHD (childhood and adult, n=62) endorsed significantly more total lifetime heroin-use consequences despite comparable heroin-use severity. Likewise, there was a significant indirect effect of the combined ADHD subtype in childhood on lifetime heroin-use consequences. This effect was mediated by STPI scores indicating less future (and more hedonism in the present) temporal perspective and by IRQ scores indicating less capacity for delaying drug use. Conclusion: The combined ADHD subtype in childhood is significantly associated with lifetime heroin-use consequences, and this effect is mediated through higher drug-use impulsivity (less capacity for delay) and lower future temporal perspective. Keywords: ADHD; heroin; opioid use disorder; impulsivity; time perspectiv

Effects of Cocaine and/or Heroin Use on Resting Cardiovascular Function

Background: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease (CVD), but confounded by other factors. Objectives: We examined effects of chronic (years of regular use) and recent (past-month) use of cocaine and heroin, controlling for other factors, on resting cardiovascular function. Methods: In a sample of cocaine and/or heroin users (N=292), we obtained data on demographics, body mass index (BMI), history of substance use, and electrocardiogram, heart rate (HR) and blood pressure (BP). Following bivariate correlations, three-block (1: demographics, BMI; 2: tobacco, alcohol, marijuana; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures. Results: Higher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Recent substance use had more reliable effects than chronic use on cardiovascular measures. Past-month marijuana-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation, whereas average daily marijuana use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HRbpm). Past-month tobacco-use days predicted shorter QTc interval and increased likelihood of profound bradycardia (HRbpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval. Conclusions: Cocaine and heroin incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and marijuana before assuming cocaine and heroin affect these measures

Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers

Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46373/1/213_2006_Article_330.pd

Negative Cocaine Effect Expectancies are Associated with Subjective Response to Cocaine Challenge in Recreational Cocaine Users

Although many studies have shown that cognitive effect expectancies are associated with drug use and drug treatment outcomes, few studies have compared effect expectancies with drug response following drug challenge. Healthy male and female volunteers (n = 19, ages 21-35) who reported using cocaine 1-4 times per month completed the Cocaine Effect Expectancy Questionnaire (CEEQ: [Schafer, J. and Brown, S.A. (199 1). Marijuana and cocaine effect expectancies and drug use patterns. Journal of Consulting and Clinical Psychology, 59, 558-565.]), were challenged with cocaine (0.9 mg/kg, i.n.), then completed a series of visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI) at 15 min intervals for 3 h following cocaine administration. Significant positive correlations were found between global negative expectancies and peak responses on the VAS measures "Good," "Happy," "High," "Stimulated," and "Desire to Use Cocaine," and on the LSD subscale of the ARCI post-cocaine administration, and between global positive expectancies and the MBG subscale of the ARCI, and on VAS items "Anxious" and "Good" post-cocaine administration. Global positive expectancies also were positively correlated with peak systolic blood pressure, and global negative expectancies with peak heart rate after cocaine administration. These results suggest that negative and positive effect expectancies both play a complex role in the subjective experience of cocaine effects, and thus likely in the progression of non-use to recreational use, in the transition to abuse, and in individualized treatment strategies.Psycholog

Functional mu opioid receptor polymorphism (OPRM1 A118G) associated with heroin use outcomes in Caucasian males: A pilot study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111777/1/ajad12187.pd