Faculty Bibliography

Energy homeostasis is achieved, in part, by metabolic signals that regulate the incentive motivating effects of food and its cues, thereby driving or curtailing procurement and consumption. The neural underpinnings of these regulated incentive effects have been identified as elements within the mesolimbic dopamine pathway. A separate line of research has shown that most drugs with abuse liability increase dopamine transmission in this same pathway and thereby reinforce self-administration. Consequently, one might expect shifts in energy balance and metabolic signaling to impact drug abuse risk. Basic science studies have yielded numerous examples of drug responses altered by diet manipulation. Considering the prevalence of weight loss dieting in Western societies, and the anorexigenic effects of many abused drugs themselves, we have focused on CNS and behavioral effects of food restriction in rats. Food restriction has been shown to increase the reward magnitude of diverse drugs of abuse, and these effects have been attributed to neuroadaptations in the dopamine-innervated nucleus accumbens. The changes induced by food restriction include synaptic incorporation of calcium-permeable AMPA receptors and increased signaling downstream of D1 dopamine receptor stimulation. Recent studies suggest a mechanistic model in which concurrent stimulation of D1 and GluA2-lacking AMPA receptors enables increased stimulus-induced trafficking of GluA1/GluA2 AMPARs into the postsynaptic density, thereby increasing the incentive effects of food, drugs, and associated cues. In addition, the established role of AMPA receptor trafficking in enduring synaptic plasticity prompts speculation that drug use during food restriction may more strongly ingrain behavior relative to similar use under free-feeding conditions.

This chapter describes recent clinical trials for opioid use disorder (OUD), an area that has rapidly accelerated in response to the opioid overdose crisis in the USA and newly appropriated funding. Trials involve a wide range of compounds including cannabinoids and psychedelics, new and existing compounds targeting domains emerging from addiction neuroscience, agents repurposed from other indications, and novel strategies including vaccines, enzymes, and other biologicals. In parallel, new formulations of existing compounds offer immediate promise, as do a variety of web-based interventions and smartphone-delivered apps. Trials focused on implementing existing effective interventions in mainstream healthcare settings, and others focused on special populations, e.g., adolescents, criminal justice, pregnant women, native Americans, etc., have the potential to vastly expand treatment in the near term. Given the range of ongoing and recent trials, this chapter is not intended to be an exhaustive review but rather to present an overview of approaches within the framework of the opioid treatment cascade and the context of current OUD pharmacotherapies.

OBJECTIVES/OBJECTIVE:To investigate the psychometric properties of the frequently used Alcohol Dependence Scale (ADS) in older adults and the associations between ADS scores and alcohol use and DSM-5 AUD symptom counts. METHODS:Using baseline data from an international multicenter RCT on outpatient AUD treatment for adults aged 60+ with DSM-5 alcohol use disorder (AUD; n = 529), we computed Cronbach's alpha (α) and applied confirmatory (CFA) and exploratory factor analysis (EFA) to determine the underlying factor structure. A structural equation model (SEM) explored the interrelationship of latent ADS factors with alcohol use and number of DSM-5 criteria endorsed. RESULTS:Internal consistency of the ADS (α = 0.81) was good. EFA revealed a three-factor structure. Factor 1 ("Severe withdrawal symptoms") consisted of severe psychoperceptual and psychophysical consequences of excessive drinking, Factor 2 ("Loss of control") consisted of acute physical reactions of intoxication, and Factor 3 ("Obsessive-compulsive drinking") described habitual drinking. The SEM suggested that only Factor 3 had large effects on DSM-5 symptom score and drinking behavior. CONCLUSION/CONCLUSIONS:Lowering the ADS threshold or focusing on ADS items from Factor 3 may be more suitable measures of severity of alcohol dependence in treatment-seeking older adults as ADS scores are low and not closely related to DSM-5 AUD.

BACKGROUND:Substance use frequently goes undetected in primary care. Though barriers to implementing systematic screening for alcohol and drug use have been examined in urban settings, less is known about screening in rural primary care. OBJECTIVE:To identify current screening practices, barriers, facilitators, and recommendations for the implementation of substance use screening in rural federally qualified health centers (FQHCs). DESIGN/METHODS:As part of a multi-phase study implementing electronic health record-integrated screening, focus groups (n = 60: all stakeholder groups) and individual interviews (n = 10 primary care providers (PCPs)) were conducted. PARTICIPANTS/METHODS:Three stakeholder groups (PCPs, medical assistants (MAs), and patients) at three rural FQHCs in Maine. APPROACH/METHODS:Focus groups and interviews were recorded, transcribed, and content analyzed. Themes surrounding current substance use screening practices, barriers to screening, and recommendations for implementation were identified and organized by the Knowledge to Action (KTA) Framework. KEY RESULTS/RESULTS:Identifying the problem: Stakeholders unanimously agreed that screening is important, and that universal screening is preferred to targeted approaches. Adapting to the local context: PCPs and MAs agreed that screening should be done annually. Views were mixed regarding the delivery of screening; patients preferred self-administered, tablet-based screening, while MAs and PCPs were divided between self-administered and face-to-face approaches. Assessing barriers: For patients, barriers to screening centered around a perceived lack of rapport with providers, which contributed to concerns about trust, judgment, and privacy. For PCPs and MAs, barriers included lack of comfort, training, and preparedness to address screening results and offer treatment. CONCLUSIONS:Though stakeholders agree on the importance of implementing universal screening, concerns about the patient-provider relationship, the consequences of disclosure, and privacy appear heightened by the rural context. Findings highlight that strong relationships with providers are critical for patients, while in-clinic resources and training are needed to increase provider comfort and preparedness to address substance use.

Objectives: In a US randomized clinical trial testing the effectiveness of preventing opioid relapse among individuals initiating extended-release naltrexone (XR-NTX) compared to buprenorphine-naloxone (BUP-NX) in an inpatient detoxification setting, the additional time required to detoxify from opioids prior to initiating XR-NTX resulted in fewer persons initiating XR-NTX, leading to a higher opioid relapse rate, and higher detoxification costs compared to BUP-NX. The objective of this study was to use trial data to estimate whether an efficient model of inpatient opioid detoxification would improve the economic value of XR-NTX compared to BUP-NX.
Method(s): We identified efficient models of inpatient detoxification for trial participants assigned to XR-NTX using 1) latent class analysis to identify detoxification pharmacotherapy use patterns, 2) a multivariable generalized structural equation model to explore determinants of XR-NTX initiation and detoxification duration, while controlling for endogeneity, and 3) data from the trial on detoxification daily cost by site. We then estimated trial cost-effectiveness outcomes from the healthcare sector perspective assuming alternative detoxification models for trial participants.
Result(s): Five latent pharmacotherapy classes were identified and included in the multivariable model. Site effects were the largest determinants of both XRT-NTX initiation and detoxification duration. The predicted probabilities of successful initiation per detoxification-day ranged from 0.13-0.15 at the four sites with significant effects, and the predicted durations ranged from 5.5 to 6.9 days. The predicted cost/detoxification-day varied from $115-$348, largely due to different staffing models. We estimated that the most efficient site model would result in non-significant cost and effectiveness differences between initiating XR-NTX or BUP-NX.
Conclusion(s): Adopting an efficient model of XR-NTX initiation could result in XR-NTX and BUP-NX having similar economic value from the healthcare sector perspective for the average patient requiring residential detoxification before initiating XR-NTX. The feasibility of implementing more efficient detoxification models needs to be explored.
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