Opioid dependence is a significant public health problem and the most widespread single intervention is pharmacological treatment (e.g., methadone maintenance). An important benefit of pharmacotherapy is that it can provide the stability necessary to initiate lifestyle changes, obtain steady employment and function in society. Thus, a critical question is the extent to which pharmacotherapy is associated with impairment in psychomotor and cognitive performance that might affect functioning. Yet, few well-controlled studies using sophisticated assessment techniques have addressed this question. In this research application with translational implications, four experiments are proposed to evaluate the effects of pharmacotherapy for opioid dependence on a wide range of functions relevant to performance of daily activities and to participating in and benefiting from cognitive/psychosocial aspects of substance abuse treatment, including oculomotor function, sensory perception, psychomotor coordination, reaction time, visual tracking, attention (focused, selective, and divided), conceptual flexibility, working memory, episodic memory, and metamemory/metacognition, using state-of-the-art assessment techniques and sophisticated pharmacological manipulations.
Specific Aim 1 is to compare the chronic effects on performance of methadone and the newly-approved buprenorphine/naloxone combination product, and will be tested in Experiment 1 using an experimental dosing design in dependent opioid abusers.
Specific Aim 2 is to evaluate the chronic effects of high-dose methadone on performance, and will be tested in Experiment 1 using an experimental dosing design and in Experiment 2 using a patient group comparison design to compare the performance of three pre-existing groups of methadone maintenance patients in local clinics, including a group maintained on higher doses than those previously evaluated in controlled studies.
Specific Aims 3 -4 are to evaluate the acute effects of methadone on performance and the effects on performance of methadone in combination with alcohol (a drug commonly abused by opioid abusers), and will be tested in an acute dosing design in Experiments 3-4 in dependent and non-dependent opioid abusers.
Specific Aim 5 is to evaluate the magnitude of methadone-induced performance impairment relative to that induced by a drug with well-documented effects on functioning, and will be tested in Experiment 4 using alcohol as a reference. Information obtained from this project can be used by clinicians to guide important decisions such as medication selection and dosing schedules, to educate patients about expected effects and interactions, as well as potential activity restrictions, and to tailor non-pharmacological treatment interventions to the specific cognitive capabilities of opioid abusers being treated with pharmacotherapy. Data from this project may also enhance the scientific understanding of pharmacological and cognitive mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA017688-03
Application #
7242538
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Oversby, Steven
Project Start
2005-09-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$452,171
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kleykamp, Bethea A; Vandrey, Ryan G; Bigelow, George E et al. (2015) Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers. Am J Drug Alcohol Abuse 41:251-6
Rass, Olga; Kleykamp, Bethea A; Vandrey, Ryan G et al. (2014) Cognitive performance in methadone maintenance patients: effects of time relative to dosing and maintenance dose level. Exp Clin Psychopharmacol 22:248-256
Henry, Porche K; Umbricht, Annie; Kleykamp, Bethea A et al. (2012) Comparison of cognitive performance in methadone maintenance patients with and without current cocaine dependence. Drug Alcohol Depend 124:167-71
Mintzer, Miriam Z; Lanier, Ryan K; Lofwall, Michelle R et al. (2010) Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers. Drug Alcohol Depend 111:265-8
Carter, Lawrence P; Griffiths, Roland R; Mintzer, Miriam Z (2009) Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers. Psychopharmacology (Berl) 206:141-54