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NIDA IRP

National Institute on Drug Abuse - Intramural Research Program

  National Institute on Drug Abuse | NIH IRP | Treatment Information
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    • Featured Paper of the Month
    • Reviews to Read
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    • About NIDA IRP
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    • Directions and Map
    • Careers at NIDA IRP
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    • Office of the Scientific Director
    • Office of the Clinical Director
    • Office of Education and Career Development
    • Administrative Management Branch
    • Molecular Targets and Medications Discovery Branch
    • Cellular and Neurocomputational Systems Branch
    • Molecular Neuropsychiatry Research Branch
    • Neuroimaging Research Branch
    • Behavioral Neuroscience Research Branch
    • Integrative Neuroscience Research Branch
    • Translational Addiction Medicine Branch
    • Core Facilities
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  • Study Volunteers

David H. Epstein, Ph.D.

David H. Epstein, Ph.D.

Position

Chief, Real-world Assessment, Prediction, and Treatment Unit

Contact

Biomedical Research Center
251 Bayview Blvd.
Suite 200
Room 01B606
Baltimore, MD 21224

Phone: 443-740-2328

Email: depstein@intra.nida.nih.gov

Research Interests

The RAPT Unit was established by Dr. Epstein in 2017 to bring the IRP’s treatment research into the age of predictive analytics and personalized medicine.  Implicit in the name—“Real-world Assessment, Prediction, and Treatment”—is our intent to show that when addiction research moves forward, so do prevention and treatment.

So our watchword, even if it sounds like a buzzword, is actionable:

  • We derive actionable information from our use of smartphones, GPS, and biosensors in everyday assessment of people’s moods, exposure to built and social environments, and drug use. That information can help us deliver mobile treatments, electronically, when and where they’re needed.
  • We formulate actionable ideas from neuroscience and laboratory-based behavioral sciences, collaborating closely with colleagues at the IRP and worldwide to translate their discoveries into treatments.

Our aim is to maintain a portfolio of studies that, taken together, address the whole continuum of causes of addiction, from the psychosocial to the neurobiological, and to use our wide in-house expertise to match the tool to the task for different kinds of patients.

Publications


PubMed | Google Scholar

Selected Publications

2018

Preston, Kenzie L; Kowalczyk, William J; Phillips, Karran A; Jobes, Michelle L; Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H

Exacerbated Craving in the Presence of Stress and Drug Cues in Drug-Dependent Patients. Journal Article

In: Neuropsychopharmacology, vol. 43, no. 4, pp. 859–867, 2018, ISSN: 1740-634X (Electronic); 0893-133X (Linking).

Abstract | Links

@article{Preston:2018aa,
title = {Exacerbated Craving in the Presence of Stress and Drug Cues in Drug-Dependent Patients.},
author = {Kenzie L Preston and William J Kowalczyk and Karran A Phillips and Michelle L Jobes and Massoud Vahabzadeh and Jia-Ling Lin and Mustapha Mezghanni and David H Epstein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29105663},
doi = {10.1038/npp.2017.275},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2018},
date = {2018-03-01},
journal = {Neuropsychopharmacology},
volume = {43},
number = {4},
pages = {859--867},
address = {Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.},
abstract = {In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress x Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress x Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress x Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress x Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/29105663
  • doi:10.1038/npp.2017.275

Close

2017

Kowalczyk, William J; Bertz, Jeremiah W; Moran, Landhing M; Phillips, Karran A; Ghitza, Udi E; Epstein, David H; Preston, Kenzie L

Clonidine Increases the Likelihood That Abstinence Can Withstand Unstructured Time in Buprenorphine-maintained Outpatients. Journal Article

In: J Addict Med, vol. 11, no. 6, pp. 454–460, 2017, ISSN: 1935-3227 (Electronic); 1932-0620 (Linking).

Abstract | Links

@article{Kowalczyk:2017ab,
title = {Clonidine Increases the Likelihood That Abstinence Can Withstand Unstructured Time in Buprenorphine-maintained Outpatients.},
author = {William J Kowalczyk and Jeremiah W Bertz and Landhing M Moran and Karran A Phillips and Udi E Ghitza and David H Epstein and Kenzie L Preston},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28759482},
doi = {10.1097/ADM.0000000000000345},
issn = {1935-3227 (Electronic); 1932-0620 (Linking)},
year = {2017},
date = {2017-11-01},
journal = {J Addict Med},
volume = {11},
number = {6},
pages = {454--460},
address = {National Institute on Drug Abuse, Intramural Research Center, Clinical Pharmacology and Therapeutics Research Branch, Baltimore, MD (WJK, JWB, LMM, KAP, DHE, KLP); National Institute on Drug Abuse, Center for Clinical Trials Network, Bethesda, MD (UEG).},
abstract = {OBJECTIVE: In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. METHODS: Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. RESULTS: Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. CONCLUSIONS: The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

OBJECTIVE: In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. METHODS: Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. RESULTS: Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. CONCLUSIONS: The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/28759482
  • doi:10.1097/ADM.0000000000000345

Close

Preston, Kenzie L; Kowalczyk, William J; Phillips, Karran A; Jobes, Michelle L; Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H

Context and craving during stressful events in the daily lives of drug-dependent patients. Journal Article

In: Psychopharmacology (Berl), vol. 234, no. 17, pp. 2631–2642, 2017, ISSN: 1432-2072 (Electronic); 0033-3158 (Linking).

Abstract | Links

@article{Preston:2017aa,
title = {Context and craving during stressful events in the daily lives of drug-dependent patients.},
author = {Kenzie L Preston and William J Kowalczyk and Karran A Phillips and Michelle L Jobes and Massoud Vahabzadeh and Jia-Ling Lin and Mustapha Mezghanni and David H Epstein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28593441},
doi = {10.1007/s00213-017-4663-0},
issn = {1432-2072 (Electronic); 0033-3158 (Linking)},
year = {2017},
date = {2017-09-23},
journal = {Psychopharmacology (Berl)},
volume = {234},
number = {17},
pages = {2631--2642},
address = {Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA. kpreston@intra.nida.nih.gov.},
abstract = {RATIONALE: Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile "just in time" treatment. OBJECTIVES: The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. METHODS: For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. RESULTS: Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, -0.14; child, -0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (-0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. CONCLUSIONS: The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

RATIONALE: Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile "just in time" treatment. OBJECTIVES: The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. METHODS: For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. RESULTS: Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, -0.14; child, -0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (-0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. CONCLUSIONS: The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/28593441
  • doi:10.1007/s00213-017-4663-0

Close

2016

Epstein, David H; Kennedy, Ashley P; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A; Preston, Kenzie L

Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving. Journal Article

In: Psychopharmacology (Berl), vol. 233, no. 23-24, pp. 3921–3932, 2016, ISSN: 1432-2072 (Electronic); 0033-3158 (Linking).

Abstract | Links

@article{Epstein:2016aa,
title = {Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.},
author = {David H Epstein and Ashley P Kennedy and Melody Furnari and Markus Heilig and Yavin Shaham and Karran A Phillips and Kenzie L Preston},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27595147},
doi = {10.1007/s00213-016-4424-5},
issn = {1432-2072 (Electronic); 0033-3158 (Linking)},
year = {2016},
date = {2016-12-23},
journal = {Psychopharmacology (Berl)},
volume = {233},
number = {23-24},
pages = {3921--3932},
address = {National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA. depstein@intra.nida.nih.gov.},
abstract = {RATIONALE: In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. OBJECTIVE: To test anticraving properties of the CRF1 antagonist pexacerfont in humans. METHODS: We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). RESULTS: The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. CONCLUSIONS: The findings may support further investigation of the anticraving properties of CRF1 antagonists, especially for food.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

RATIONALE: In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. OBJECTIVE: To test anticraving properties of the CRF1 antagonist pexacerfont in humans. METHODS: We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). RESULTS: The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. CONCLUSIONS: The findings may support further investigation of the anticraving properties of CRF1 antagonists, especially for food.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/27595147
  • doi:10.1007/s00213-016-4424-5

Close

Heilig, Markus; Epstein, David H; Nader, Michael A; Shaham, Yavin

Time to connect: bringing social context into addiction neuroscience. Journal Article

In: Nat Rev Neurosci, vol. 17, no. 9, pp. 592–599, 2016, ISSN: 1471-0048 (Electronic); 1471-003X (Linking).

Abstract | Links

@article{Heilig:2016aa,
title = {Time to connect: bringing social context into addiction neuroscience.},
author = {Markus Heilig and David H Epstein and Michael A Nader and Yavin Shaham},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27277868},
doi = {10.1038/nrn.2016.67},
issn = {1471-0048 (Electronic); 1471-003X (Linking)},
year = {2016},
date = {2016-09-17},
journal = {Nat Rev Neurosci},
volume = {17},
number = {9},
pages = {592--599},
address = {Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine (IKE), Linkoping University, SE-581 83 Linkoping, Sweden.},
abstract = {Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/27277868
  • doi:10.1038/nrn.2016.67

Close

2015

Kowalczyk, William J; Phillips, Karran A; Jobes, Michelle L; Kennedy, Ashley P; Ghitza, Udi E; Agage, Daniel A; Schmittner, John P; Epstein, David H; Preston, Kenzie L

Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. Journal Article

In: Am J Psychiatry, vol. 172, no. 8, pp. 760–767, 2015.

Abstract | Links

@article{Kowalczyk2015b,
title = {Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. },
author = {Kowalczyk, William J and Phillips, Karran A and Jobes, Michelle L and Kennedy, Ashley P and Ghitza, Udi E and Agage, Daniel A and Schmittner, John P and Epstein, David H and Preston, Kenzie L},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25783757},
doi = {10.1176/appi.ajp.2014.14081014},
year = {2015},
date = {2015-08-01},
journal = {Am J Psychiatry},
volume = {172},
number = {8},
pages = {760--767},
abstract = {OBJECTIVE: The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. METHOD: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. RESULTS: In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. CONCLUSIONS: Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

OBJECTIVE: The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. METHOD: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. RESULTS: In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. CONCLUSIONS: Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/25783757
  • doi:10.1176/appi.ajp.2014.14081014

Close

2013

Epstein, David H; Tyburski, Matthew; Craig, Ian M; Phillips, Karran A; Jobes, Michelle L; Vahabzadeh, Massoud; Mezghanni, Mustapha; Lin, Jia-Ling; Furr-Holden, Debra C M; Preston, Kenzie L

Real-time tracking of neighborhood surroundings and mood in urban drug misusers: application of a new method to study behavior in its geographical context. Journal Article

In: Drug Alcohol Depend, vol. 134, pp. 22–29, 2013, ISSN: 1879-0046 (Electronic); 0376-8716 (Linking).

Abstract | Links

@article{Epstein2013,
title = {Real-time tracking of neighborhood surroundings and mood in urban drug misusers: application of a new method to study behavior in its geographical context.},
author = {David H Epstein and Matthew Tyburski and Ian M Craig and Karran A Phillips and Michelle L Jobes and Massoud Vahabzadeh and Mustapha Mezghanni and Jia-Ling Lin and Debra C M Furr-Holden and Kenzie L Preston},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24332365},
doi = {10.1016/j.drugalcdep.2013.09.007},
issn = {1879-0046 (Electronic); 0376-8716 (Linking)},
year = {2013},
date = {2013-09-14},
journal = {Drug Alcohol Depend},
volume = {134},
pages = {22--29},
address = {Treatment Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, 251 Bayview Blvd., Suite 200, National Institute on Drug Abuse, Baltimore, MD 21224, United States.},
abstract = {BACKGROUND: Maladaptive behaviors may be more fully understood and efficiently prevented by ambulatory tools that assess people's ongoing experience in the context of their environment. METHODS: To demonstrate new field-deployable methods for assessing mood and behavior as a function of neighborhood surroundings (geographical momentary assessment; GMA), we collected time-stamped GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and drug craving over 16 weeks at randomly prompted times during the waking hours of opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA entries and participants' travel tracks calculated for the 12 before each EMA entry were mapped. Associations between subjective ratings and objective environmental ratings were evaluated at the whole neighborhood and 12-h track levels. RESULTS: Participants (N=27) were compliant with GMA data collection; 3711 randomly prompted EMA entries were matched to specific locations. At the neighborhood level, physical disorder was negatively correlated with negative mood, stress, and heroin and cocaine craving (ps<.0001-.0335); drug activity was negatively correlated with stress, heroin and cocaine craving (ps .0009-.0134). Similar relationships were found for the environments around respondents' tracks in the 12h preceding EMA entries. CONCLUSIONS: The results support the feasibility of GMA. The relationships between neighborhood characteristics and participants' reports were counterintuitive and counter-hypothesized, and challenge some assumptions about how ostensibly stressful environments are associated with lived experience and how such environments ultimately impair health. GMA methodology may have applications for development of individual- or neighborhood-level interventions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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BACKGROUND: Maladaptive behaviors may be more fully understood and efficiently prevented by ambulatory tools that assess people's ongoing experience in the context of their environment. METHODS: To demonstrate new field-deployable methods for assessing mood and behavior as a function of neighborhood surroundings (geographical momentary assessment; GMA), we collected time-stamped GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and drug craving over 16 weeks at randomly prompted times during the waking hours of opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA entries and participants' travel tracks calculated for the 12 before each EMA entry were mapped. Associations between subjective ratings and objective environmental ratings were evaluated at the whole neighborhood and 12-h track levels. RESULTS: Participants (N=27) were compliant with GMA data collection; 3711 randomly prompted EMA entries were matched to specific locations. At the neighborhood level, physical disorder was negatively correlated with negative mood, stress, and heroin and cocaine craving (ps<.0001-.0335); drug activity was negatively correlated with stress, heroin and cocaine craving (ps .0009-.0134). Similar relationships were found for the environments around respondents' tracks in the 12h preceding EMA entries. CONCLUSIONS: The results support the feasibility of GMA. The relationships between neighborhood characteristics and participants' reports were counterintuitive and counter-hypothesized, and challenge some assumptions about how ostensibly stressful environments are associated with lived experience and how such environments ultimately impair health. GMA methodology may have applications for development of individual- or neighborhood-level interventions.

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  • https://www.ncbi.nlm.nih.gov/pubmed/24332365
  • doi:10.1016/j.drugalcdep.2013.09.007

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