This grant has funded human laboratory studies examining the pharmacological characteristics of tramadol, an atypical opioid analgesic. Results show tramadol exerts psychoactive effects, these effects differ from both placebo and a prototypic mu agonist opioid, but under chronic dosing conditions tramadol can produce opioid physical dependence. This provides an evidence base supporting the idea that tramadol may have therapeutic efficacy beyond its use as a non-controlled opioid analgesic. Specifically, these studies provide a foundation supporting the potential utility of this medication for the treatment of opioid withdrawal. It is important to acknowledge that the use of medically supervised withdrawal from opioids (aka detoxification) has limited effectiveness for many patients with opioid dependence. Especially for patients with longer histories of opioid addiction and those with higher levels of physical dependence, detoxification is often a short-term intervention that simply leads to subsequent relapse to drug use. However, there are populations for which detoxification may be preferred or indicated (e.g., persons with relatively short histories of opioid addiction, patients with a lower level of physical dependence, younger patients, and those with early physical dependence on opioids). The Drug Addiction Treatment Act of 2000, which is currently limited in its application to the use of buprenorphine, does not specifically mention buprenorphine - thus allowing other medications to be developed for office based opioid dependence treatment. This is a proposal to study tramadol as an agent for short-term opioid withdrawal treatment. A randomized, double blind clinical trial comparing the efficacy and safety of the extended release form of tramadol to clonidine and buprenorphine in the short-term treatment of opioid withdrawal will be conducted. Opioid dependent participants will be treated on a residential unit. There are three primary phases to the project: an initial stabilization on morphine (to establish a common level of physical dependence, with a naloxone challenge during this phase with results from that challenge used as one stratification variable);a withdrawal period with one of the three medications;and, a transition to double-blind oral naltrexone at the end of the residential stay. The use of tramadol in this way is novel and innovative. In addition, the study includes CYP2D6 genotyping of participants, which will be used as a stratification variable given tramadol's metabolism by 2D6. The primary outcome measure is opioid withdrawal symptoms during the second phase of the study.

Public Health Relevance

Opioid dependence is a significant problem in the United States, especially misuse and dependence upon prescription opioids. This is a residential controlled clinical trial that will test the efficacy and safety of tramadol compared to clonidine and buprenorphine in the treatment of opioid withdrawal.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DA018125-10
Application #
8675813
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Biswas, Jamie
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Duke, Angela N; Bigelow, George E; Lanier, Ryan K et al. (2011) Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther 338:255-62
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
Lanier, Ryan K; Lofwall, Michelle R; Mintzer, Miriam Z et al. (2010) Physical dependence potential of daily tramadol dosing in humans. Psychopharmacology (Berl) 211:457-66
Lofwall, Michelle R; Walsh, Sharon L; Bigelow, George E et al. (2007) Experimentally-induced spontaneous opiate withdrawal: relationship to cigarette craving and expired air carbon monoxide. Am J Addict 16:310-5
Lofwall, Michelle R; Walsh, Sharon L; Bigelow, George E et al. (2007) Modest opioid withdrawal suppression efficacy of oral tramadol in humans. Psychopharmacology (Berl) 194:381-93
Carroll, C Patrick; Walsh, Sharon L; Bigelow, George E et al. (2006) Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans. Exp Clin Psychopharmacol 14:109-20