The Discriminative Effects of Tramadol in Humans

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eric Strain, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00499746
First received: July 9, 2007
Last updated: April 21, 2012
Last verified: April 2012
  Purpose

This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. It has effects similar to morphine, and it may also have effects similar to other drugs like stimulants. The doses of tramadol used in this study are higher than those generally used for the treatment of pain. To be in this study a participant must be a user of opioids (drugs like heroin) and stimulants (drugs like cocaine), but cannot be addicted to either. The person must be between 21-55 years old, and generally healthy. Up to 12 people will take part in this study.


Condition Intervention Phase
Opioid Abuse
Opioid Addiction
Stimulant Abuse
Stimulant Addiction
Drug: tramadol
Drug: hydromorphone
Drug: methylphenidate
Drug: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Medications Development for Drug Abuse Disorders

Resource links provided by NLM:


Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Accuracy of testing of acquisition [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Generalization results for experimental conditions [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Proportions of identifications as training conditions [ Time Frame: 1day ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Psychomotor/cognitive performance measures [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Physiologic measures [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Self-reported opioid agonist effects [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Self-reported stimulant effects [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Observer ratings of opioid and stimulant effects [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: November 2007
Study Completion Date: August 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: tramadol
    oral dose, once per day
    Other Name: Ultram
    Drug: hydromorphone
    oral dose, once per day
    Other Name: Dilaudid
    Drug: methylphenidate
    oral dose, once per day
    Other Name: stimulant
    Drug: placebo
    oral dose, once per day
    Other Name: sugar pill
Detailed Description:

This is a human laboratory study that tests the effects of tramadol as a step in the possible development of this medication as a new treatment for opioid dependence. Tramadol is a mild/moderate mu agonist opioid currently marketed as an analgesic that has a unique profile of effects. One of the primary metabolites of tramadol, mono-O-demethyltramadol (referred to as M1) exerts opioid agonist effects at the mu receptor. In addition, tramadol and M1 produce reuptake blockade of monoamines, and this latter effect may positively influence its analgesic efficacy, in addition to influencing the subjective effects produced by tramadol. Preclinical evidence suggests that tramadol's effects on monoamine reuptake may have antidepressant qualities as well. Given tramadol's diverse pharmacodynamic profile, a systematic characterization of its subjective effects in opioid-experienced subjects would provide valuable information regarding its abuse liability, and its potential utility as a treatment for opioid dependence.

The characterization of an opioid medication's profile can be accomplished through a variety of experimental procedures. One useful procedure for assessing the profile of an opioid is a drug discrimination procedure. In this methodology, subjects are first trained to discriminate reference drugs such as placebo and an opioid agonist, and then administered doses of a novel compound to determine how like (or unlike) it is to the reference training conditions. Our laboratory has a long history of using this drug discrimination methodology to study and to characterize opioids with varying opioid receptor activity profiles. Studies have generally included either two or three training conditions in humans. Using this technique in volunteers, studies have characterized the profile of a number of opioids including (for example) butorphanol, nalbuphine, pentazocine, and buprenorphine.

While most of these studies testing the effects of mixed agonist-antagonist opioids have used an opioid agonist and placebo as the training conditions, tramadol's profile of effects suggests that there may be a non-opioid component of action at serotonin and norepinephrine sites that will be useful to distinguish. In particular, it is of interest to determine the extent to which tramadol is identified as being like a prototypic mu agonist opioid, whether it is substantially identified as being like a non-opioid compound, and if this non-opioid component is related to enhancement of monoamine effects. In order to provide a meaningful non-opioid contrast training condition, this study will compare different doses of tramadol to training conditions of placebo, a mu agonist opioid, and a prototypic stimulant.

Overall, this evaluation will provide a greater understanding of the subjective effect profile of tramadol in comparison to a prototypic mu opioid and a prototypic stimulant. If tramadol is to be useful in the treatment of opioid dependence, a thorough assessment of its subjective effects in experienced opioid and stimulant abusers is warranted.

  Eligibility

Ages Eligible for Study:   21 Months to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Study subjects are male and female non-dependent opioid users with active stimulant use.
  • Between the ages of 21-55
  • In good physical health
  • Without significant psychiatric illness besides their drug use.
  • Females are required to provide a negative pregnancy test prior to study participation.

Exclusion Criteria:

  • Subjects are excluded if they have evidence of significant medical (e.g., insulin dependent diabetes mellitus) or psychiatric (e.g., schizophrenia) illness.
  • Subjects with a history of seizures will be excluded.
  • Persons with current history of significant alcohol or sedative/hypnotic drug use will be excluded from study participation.
  • Applicants seeking treatment for their substance abuse will not be admitted to the study, and will be provided information about treatment services available.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00499746

Locations
United States, Maryland
Behavioral Pharmacology Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Investigators
Principal Investigator: Eric C Strain, M.D. Johns Hopkins University
  More Information

Publications:
Responsible Party: Eric Strain, MD, Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00499746     History of Changes
Other Study ID Numbers: NIDA-18125-3, R01DA018125, DPMCDA
Study First Received: July 9, 2007
Last Updated: April 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute on Drug Abuse (NIDA):
drug discrimination
opioid pharmacology
behavioral pharmacology
human research

Additional relevant MeSH terms:
Behavior, Addictive
Compulsive Behavior
Impulsive Behavior
Hydromorphone
Tramadol
Methylphenidate
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotics
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Central Nervous System Stimulants

ClinicalTrials.gov processed this record on April 23, 2014