A Facility-Wide Plan to Increase Access to Medication for Opioid Use Disorder in Primary Care and General Mental Health Settings.

BACKGROUND: The opioid epidemic in the United States has generated a pressing need to enhance access to medications for opioid use disorder (MOUD). This program description illustrates a quality-improvement effort to extend MOUD to primary care and general mental health clinics within the US Department of Veterans Affairs (VA) Connecticut Healthcare system (VACHS), and to examine barriers and facilitators to implementation of MOUD in target clinics. OBSERVATIONS: As part of the national VA Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative to improve MOUD access, a VACHS team identified and resolved barriers to MOUD in target clinics. Key interventions were to obtain leadership support, increase waivered prescribers, and develop processes and tools to enhance prescribing. New initiatives included quarterly educational sessions, templated progress notes, and instant messaging for addiction specialist electronic consultations. MOUD receipt and prescriber characteristics were evaluated before and 1 year after implementation. There was a 4% increase in eligible patients receiving MOUD, from 552 (44%) to 582 (48%) (P = .04). The number of waivered prescribers increased from 67 to 131, and the number of buprenorphine prescribers increased from 35 to 52 over a 6-month span, and the percentage of health care practitioners capable of prescribing within the electronic health record increased from 75% to 89% (P = .01). CONCLUSIONS: An interdisciplinary team approach to identifying and overcoming barriers to MOUD target clinics expands access. Key interventions include interdisciplinary leadership engagement, proactive education and incentivization of target prescribers, removal of procedural barriers, and development of tools to facilitate and support prescribing. These concrete interventions can help inform other institutions interested in expanding MOUD access.

Integrating ecological momentary assessment and functional brain imaging methods: new avenues for studying and treating tobacco dependence.

INTRODUCTION: Ecological momentary assessment (EMA) and related methods typically entail repeatedly and intensively sampling behavior as it occurs over time and under naturalistic conditions. Although the methodological features of EMA make it a highly valuable research technique in its own right, EMA can also be a potent counterpart to other approaches. One methodological partnership with substantial yet largely untapped potential for the study of tobacco dependence is the pairing of EMA with functional brain imaging. METHODS: The goal of this review is to outline the promise of this approach, with a focus on the combined use of EMA and functional magnetic resonance imaging (fMRI). Due to the unique and complementary strengths of each method, the merger of EMA and fMRI methods has the potential to advance the understanding of tobacco dependence in ways difficult or impossible to achieve through the use of either method in isolation. RESULTS: In addition to describing a conceptual basis for combining EMA with fMRI, we provide a preliminary empirical illustration of this integrative approach using data from an ongoing study. CONCLUSIONS: EMA and fMRI have independently yielded important findings regarding the nature and treatment of tobacco dependence. The integration of these powerful research methods, however, holds even greater potential for the field of tobacco research. Additionally, recent advances are paving the way for the synergistic use of fMRI and EMA-based methods to develop innovative approaches to tobacco cessation.

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm.

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or "resting state networks" (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien). Zolpidem is a positive modulator of γ-aminobutyric acid(A) (GABA(A)) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n=12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABA(A) receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects.

Nicotine content and abstinence state have different effects on subjective ratings of positive versus negative reinforcement from smoking.

Despite the well-known adverse health consequences of smoking, approximately 20% of US adults smoke tobacco cigarettes. Much of the research on smoking reinforcement and the maintenance of tobacco smoking behavior has focused on nicotine; however, a number of other non-nicotine factors are likely to influence the reinforcing effects of smoked tobacco. A growing number of studies suggest that non-nicotine factors, through many pairings with nicotine, are partially responsible for the reinforcing effect of smoking. Additionally, both clinical studies and preclinical advances in our understanding of nicotinic receptor regulation suggest that abstinence from smoking may influence smoking reinforcement. These experiments were conducted for 2 reasons: to validate a MRI-compatible cigarette smoking device; and to simultaneously investigate the impact of nicotine, smoking-associated conditioned reinforcers, and smoking abstinence state on subjective ratings of smoking reinforcement. Participants smoked nicotine and placebo cigarettes through an fMRI compatible device in an overnight-abstinent state or in a nonabstinent state, after having smoked a cigarette 25minutes prior. Outcome measures were within-subject changes in physiology and subjective ratings of craving and drug effect during the smoking of nicotine or placebo cigarettes on different days in both abstinence states. Cigarette type (nicotine vs. placebo) had a significant effect on positive subjective ratings of smoking reinforcement ("High", "Like Drug", "Feel Drug"; nicotine>placebo). In contrast, abstinence state was found to have significant effects on both positive and negative ratings of smoking reinforcement ("Crave", "Anxiety", "Irritability"; abstinence>nonabstinence). Interaction effects between abstinence and nicotine provide clues about the importance of neuroadaptive mechanisms operating in dependence, as well as the impact of conditioned reinforcement on subjective ratings of smoking-induced high.

Effects of transcutaneous electric acupoint stimulation on drug use and responses to cue-induced craving: a pilot study.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) avoids the use of needles, and instead delivers a mild electric current at traditional acupoints. This technique has been used for treating heroin addiction, but has not been systematically tested for other drugs of abuse. This study aims to investigate the effects of TEAS on drug addiction. METHODS: Volunteers who were either cocaine-dependent (n = 9) or cannabis-dependent (n = 11) but were not seeking treatment for their dependence participated in a within-subject, single-blind study. Treatment consisted of twice daily 30-minute sessions of TEAS or sham stimulation for 3.5 days. The active TEAS levels were individually adjusted to produce a distinct twitching response in the fingers, while the sham stimulation involved 2 minutes of stimulation at threshold levels followed by 28 minutes of stimulation below the detection levels. The participants recorded their drug use and drug cravings daily. At 1 hour after the last morning session of TEAS or sham stimulation, a cue-induced craving EEG evaluation was conducted. Event-related P300 potentials (ERPs) were recorded, sorted, and analyzed for specific image types (neutral objects, non-drug-related arousing images, or drug-related images). RESULTS: TEAS treatment did not significantly reduce the drug use or drug cravings, or significantly alter the ERP peak voltage or latency to peak response. However, the TEAS treatment did significantly modulate several self-reported measures of mood and anxiety. CONCLUSION: The results of this pilot study with a limited sample size suggest that the acupoint stimulation techniques and protocol used in this trial alone do not significantly reduce cravings for or use of cocaine or cannabis. The findings that TEAS modulates mood and anxiety suggest that TEAS could be used as an adjunct in a multimodal therapy program to treat cocaine and cannabis dependence if confirmed in a full randomized controlled clinical trial.

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation.

fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence.

Cocaine use is associated with poorer HIV clinical outcomes and may contribute to neurobiological impairments associated with impulsive decision making. This study examined the effect of cocaine dependence on brain activation during a delay discounting task involving choices between smaller immediate rewards and larger delayed ones. Participants were 39 HIV-positive adults on antiretroviral therapy who had current cocaine dependence ("active," n=15), past cocaine dependence ("recovered," n=13), or no lifetime substance dependence ("naïve," n=11). Based on responses on a traditional delay discounting task, three types of choices were individualized for presentation during functional magnetic resonance imaging: hard (similarly valued), easy (disparately valued), and no (single option). Active participants had significantly smaller increases in activation than naïve participants during hard versus easy choices bilaterally in the precentral gyrus and anterior cingulate cortex and in the right frontal pole (including dorsolateral, ventrolateral, and orbitofrontal cortex). During hard and easy choices relative to no choices, active participants had smaller increases in activation compared to naïve participants in frontoparietal cortical regions. These deficits in the executive network during delay discounting choices may contribute to impulsive decision making among HIV-positive cocaine users, with implications for risk behaviors associated with disease transmission and progression.

Modest abuse-related subjective effects of zolpidem in drug-naive volunteers.

Recent case reports suggest that the short-acting benzodiazepine-like hypnotic, zolpidem, may have abuse potential among individuals who have no personal history of abusing drugs or alcohol, particularly at doses higher than those recommended for treating insomnia. This study recruited drug-naive volunteers to assess the subjective effects of multiple doses of zolpidem (0, 5, 10, or 20 mg) administered in a within-subject double-blind design. Participants (n=11) answered computerized questionnaires (Addiction Research Center Inventory, visual analog scales, and a hypothetical Drug versus Money Choice) to address the hypothesis that a supratherapeutic dose (20 mg) would increase ratings of abuse-related subjective effects, while lower therapeutic doses (5 and 10 mg) would not. Although participants rated some effects as negative at 10 and 20 mg, the highest dose engendered predominantly positive abuse-like effects such as 'High', 'Like', and 'Good Effects'. However, no dose of zolpidem was chosen over money ($0.35-$10) when participants made hypothetical choices between them. Results suggest that although individuals without a drug abuse history are not inclined to choose zolpidem when presented with an alternative reinforcer such as money, it may possess moderate abuse potential that limits its clinical utility.

Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers.

BACKGROUND: Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol's effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. METHODS: Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double-blinded, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. RESULTS: Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants' subjective responses to the alcohol challenge or to alcohol's effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. CONCLUSIONS: These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences, and furthermore the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol's subjective or psychomotor effects.