The Discriminative Effects of Tramadol in Humans
Information source: National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Opioid Abuse; Opioid Addiction; Stimulant Abuse; Stimulant Addiction
Intervention: tramadol (Drug); hydromorphone (Drug); methylphenidate (Drug); placebo (Drug)
Phase: Phase 1/Phase 2
Sponsored by: National Institute on Drug Abuse (NIDA)
Official(s) and/or principal investigator(s):
Eric C Strain, M.D., Principal Investigator, Affiliation: Johns Hopkins University
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.
Official title: Medications Development for Drug Abuse Disorders
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
Accuracy of testing of acquisition
Generalization results for experimental conditions
Proportions of identifications as training conditions
Psychomotor/cognitive performance measures
Self-reported opioid agonist effects
Self-reported stimulant effects
Observer ratings of opioid and stimulant effects
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.
Minimum age: 21 Months.
Maximum age: 55 Years.
- Study subjects are male and female non-dependent opioid users with active stimulant
- 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
- 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.
Locations and Contacts
Behavioral Pharmacology Research Unit, Baltimore, Maryland 21224, United States
Starting date: November 2007
Last updated: April 21, 2012