Faculty Bibliography

BACKGROUND: Attrition in studies of substance use disorder treatment is problematic, potentially introducing bias into data analysis. OBJECTIVES: This study aimed to determine the effect of participant compensation amounts on rates of missing data and observed rates of drug use. METHODS: We performed a secondary analysis of a clinical trial of buprenorphine/naloxone among 152 treatment-seeking opioid-dependent subjects aged 15-21 during participation in a randomized trial. Subjects were randomized to a 2-week detoxification with buprenorphine/naloxone (DETOX; N = 78) or 12 weeks buprenorphine/naloxone (BUP; N = 74). Participants were compensated $5 for weekly urine drug screens and self-reported drug use information and $75 for more extensive assessments at weeks 4, 8, and 12. RESULTS: Though BUP assignment decreased the likelihood of missing data, there were significantly less missing data at 4, 8, and 12 weeks than other weeks, and the effect of compensation on the probability of urine screens being positive was more pronounced in DETOX subjects. CONCLUSION: These findings suggest that variations in the amount of compensation for completing assessments can differentially affect outcome measurements, depending on treatment group assignment. SCIENTIFIC SIGNIFICANCE: Adequate financial compensation may minimize bias when treatment condition is associated with differential dropout and may be a cost-effective way to reduce attrition. Moreover, active users may be more likely than non-active users to drop out if compensation is inadequate, especially in control groups or in groups who are not receiving active treatment.

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors

ABSTRACT Primary care is understudied as a reentry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid-dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail versus community referrals. Postrelease patients were either (a) induced to buprenorphine in-jail as part of a clinical trial, or (b) seeking buprenorphine induction post release. From 2007 to 2008, N = 142 patients were new to primary care buprenorphine: n = 32 postrelease; n = 110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for postrelease (37%) versus community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Postrelease patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence versus community-referred patients

Reports an error in "Obituary: Malcolm S. Reid (1962-2010)" by Edward Nunes and John Rotrosen (The American Journal of Drug and Alcohol Abuse, 2011[Sep], Vol 37[5], 273-274). In the obituary of Dr. Malcolm S. Reid, his death date was published as 20 April 2010, but should read 23 April 2010. (The following abstract of the original article appeared in record 2011-19594-002). Presents an obituary for Malcolm S. Reid, (1962-2010). He passed away after a year-long struggle with leukemia. Malcolm completed his undergraduate work at Brown University in 1984. He began his graduate work in pharmacology at the Karolinska Institute in Stockholm, leading to a PhD in 1990. Malcolm went on to a post-doctoral fellowship at the Sleep Disorders Research Center at Stanford from 1990 to 1993, and a second fellowship in the NIDA-funded Substance Abuse Treatment Research Program at the University of California at San Francisco (UCSF). Malcolm was a dedicated father, who, despite the demands of a research career, always made time for his wife, children, and extended family. Malcolm was also a dedicated teacher and mentor helping shape the careers of members of his research team, many of whom have gone on to get advanced degrees, and undergraduate and medical students. Through to the end, Malcolm remained an indomitable, fun-loving spirit with an infectious exuberance for life. His love of family was matched only by his dogged commitment to his lifelong goal of improving the treatment and care of substance-dependent patients.

Food restriction (FR) decreases brain-derived neurotrophic factor (BDNF) expression in hypothalamic and hindbrain regions that regulate feeding and metabolic efficiency, while increasing expression in hippocampal and neocortical regions. Drugs of abuse alter BDNF expression within the mesocorticolimbic dopamine (DA) pathway, and modifications of BDNF expression within this pathway alter drug-directed behavior. Although FR produces a variety of striatal neuroadaptations and potentiates the rewarding effects of abused drugs, the effects of FR on BDNF expression and function within the DA pathway are unknown. The primary purpose of the present study was to examine the effect of FR on protein levels of BDNF and its tropomyosin receptor kinase B (TrkB) receptor in component structures of the mesocorticolimbic pathway. Three to four weeks of FR, with stabilization of rats at 80% of initial body weight, did not alter BDNF or TrkB levels in nucleus accumbens, caudate-putamen, or medial prefrontal cortex. However, FR decreased TrkB levels in the ventral tegmental area (VTA), without change in levels of BDNF protein or mRNA. The finding that FR also decreased TrkB levels in substantia nigra, with elevation of BDNF protein, suggests that decreased TrkB in VTA could be a residual effect of increased BDNF during an earlier phase of FR. Voltage-clamp recordings in VTA DA neurons indicated decreased glutamate receptor transmission. These data might predict lower average firing rates in FR relative to ad libitum fed subjects, which would be consistent with previous evidence of decreased striatal DA transmission and upregulation of postsynaptic DA receptor signaling. However, FR subjects also displayed elevated VTA levels of phospho-ERK1/2, which is an established mediator of synaptic plasticity. Because VTA neurons are heterogeneous with regard to neurochemistry, function, and target projections, the relationship(s) between the three changes observed in VTA, and their involvement in the augmented striatal and behavioral responsiveness of FR subjects to drugs of abuse, remains speculative

BACKGROUND: Prior research suggests that both social networks and parent drug use influence individual drug use among adolescents and that peers continue to influence drug use among adults. This analysis aims to determine whether parent drug use during childhood is associated with having drug-using networks in adulthood after adjusting for individual adult drug use. METHODS: 650 young adult drug users were recruited through targeted street outreach and respondent-driven sampling in New York City (2006-2009). Baseline surveys ascertained demographics, network characteristics, drug use behaviors, and parental drug use during childhood. Negative binomial regression was used to evaluate this association. RESULTS: The median age was 33 years, 22% injected, 49% were Black, and during childhood 26% of mothers, 32% of fathers, and 13% of primary caregivers used drugs. After adjustment, having >1 parent who used drugs was associated with having a greater proportion of drug using (Adjusted Prevalence Ratio [APR]=1.18; 95%CI: 1.01-1.38) and specifically crack-smoking networks (APR=1.71; 95%CI: 1.21-2.43) in adulthood. Females' networks consisted of more drug users (APR=1.18; 95%CI: 1.01-1.38), injectors (APR=1.44; 95%CI: 1.09-1.90), crack smokers (APR=1.48; 95%CI: 1.18-1.87) and heroin users (APR=1.43; 95%CI: 1.13-1.81); blacks had a greater proportion of crack smoking (APR=1.41; 95%CI: 1.09-1.82), but a smaller proportion of injecting (APR=0.64; 95%CI: 0.43-0.94) and heroin smoking (APR=0.60; 95%CI: 0.47-0.77) networks as adults. CONCLUSIONS: These data suggest that parental drug use is independently associated with having drug-using networks in adulthood. Interventions that target parents and caregivers and that promote drug cessation could impede risky network formation in both adolescents and adults.

To investigate the extent of methamphetamine and other drug use among American Indians (AIs) in the Four Corners region, we developed collaborations with Southwestern tribal entities and treatment programs in and around New Mexico. We held nine focus groups, mostly with Southwestern AI participants (N = 81) from three diverse New Mexico communities to understand community members, treatment providers, and clients/relatives views on methamphetamine. We conducted a telephone survey of staff (N = 100) from agencies across New Mexico to assess perceptions of methamphetamine use among people working with AI populations. We collected and analyzed self-reported drug use data from 300 AI clients/relatives who completed the Addiction Severity Index (ASI) in the context of treatment at three diverse addiction treatment programs. Each focus group offered a unique perspective about the effect of drugs and alcohol on each respective community. Though data from the phone surveys and ASIs suggested concerning rates of methamphetamine use, with women more adversely affected by substance use in general, alcohol was identified as the biggest substance use problem for AI populations in the Southwest. There appears to be agreement that methamphetamine use is a significant problem in these communities, but that alcohol is much more prevalent and problematic. There was less agreement about what should be done to prevent and treat methamphetamine use. Future research should attend to regional and tribal differences due to variability in drug use patterns, and should focus on identifying and improving dissemination of effective substance use interventions.

Recruiting a representative sample using respondent driven sampling (RDS) relies on successful peer recruitment. While prior studies have identified individual-level characteristics associated with peer recruitment, study- and neighborhood-level factors may also influence peer recruitment. This analysis aimed to identify individual-, study-, and neighborhood-level factors associated with RDS peer recruitment. 390 young adult (18-40 years) heroin, crack and/or cocaine users in New York City (NYC) were recruited via RDS into a cohort study aiming to identify social risk factors for transitioning from non-injection to injection drug use (2006-2009). Individual-level baseline characteristics (demographics, drug use, and network characteristics) and study factors (number of recruitment coupons received and participant attendance at RDS training sessions (RDST) on peer recruitment) were ascertained. Aggregate measures of neighborhood attitudes about drug use, drug users, and HIV were obtained from a separate anonymous NYC resident random-digit-dialing survey (2002) and linked with baseline data by zip code. Descriptive statistics and multilevel modeling were used to identify factors associated with peer recruitment. After adjustment, recruiting each additional eligible peer recruit was associated with receiving additional recruitment coupons, RDST attendance, and a greater proportion of community residents in one's recruitment neighborhood believing that clean needles should be made available to IDUs; heroin use was negatively associated with recruiting additional eligible peers. After adjustment, recruiting each additional peer (regardless of eligibility) was associated with receiving additional recruitment coupons and RDST attendance. Our data highlight the importance of neighborhood factors and suggest that RDS may not be as effective in areas characterized by negative attitudes about drug use. Group-facilitated recruitment training sessions may help counter negative social norms when implementing RDS in drug user studies.

Insertion and removal of AMPA receptors from the synaptic membrane underlie dynamic tuning of synaptic transmission and enduring changes in synaptic strength. Preclinical addiction research suggests that AMPA receptor trafficking plays an important role in nucleus accumbens (NAc) neuroplasticity underlying the compulsive and persistent quality of drug-seeking. Considering the parallels between drug addiction and compulsive eating, plus the supranormal reward properties of sucrose, and the role of dieting as a risk factor in development of binge pathology, the present study used a biochemical subcellular fractionation approach to determine whether brief intake of a 10% sucrose solution increases synaptic delivery of AMPA receptors in NAc of chronically food-restricted (FR) relative to ad libitum fed (AL) rats. FR, alone, produced a small but significant increase in synaptic expression of AMPA receptors. This may contribute to NAc integrative mechanisms that mediate the enhanced behavioral responsiveness of FR subjects to phasic reward stimuli, including food and drugs. Brief intake of sucrose increased GluR1 in the PSD, regardless of dietary condition, though the net effect was greater in FR than AL subjects. A marked increase in GluR2 was also observed, but only in FR rats. This set of results suggests that in FR subjects, sucrose may have primarily increased delivery of GluR1/GluR2 heteromers to the PSD, while in AL subjects sucrose increased delivery of GluR2-lacking channels. The functional consequences of these possible differences in subunit composition of trafficked AMPA receptors between diet groups remain to be determined. Nevertheless, the present set of results suggest a promising new avenue to pursue in the effort to understand synaptic plasticity involved in adaptive and pathological food-directed behavior and the mechanistic basis of severe dieting as a risk factor for the latter. Synapse, 2011. (c) 2011 Wiley-Liss, Inc