The Discriminative Effects of Tramadol in Humans
Condition: Opioid Abuse; Opioid Addiction; Stimulant Abuse; Stimulant Addiction
MeSH terms: Opioid-Related Disorders; Behavior, Addictive
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): tramadol; placebo; Hydromorphone; Methylphenidate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): oral dose, once per day; oral dose, once per day; oral dose, once per day; oral dose, once per day
Other intervention name(s): Ultram; sugar pill; Dilaudid; stimulant
Intervention MeSH terms: Tramadol; Hydromorphone; Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: drug discrimination; opioid pharmacology; behavioral pharmacology; human research