Mu opioid mediated discriminative-stimulus effects of tramadol: an individual subjects analysis.
Human drug-discrimination tests prove tramadol works through mu-opioid receptors, giving BCBAs an early warning system for abuse liability.
01Research in Context
What this study did
Researchers asked adults to tell which drug they had taken. Each person got tramadol, a pain pill, or placebo before sessions.
If the person said "drug," they earned money when tramadol was really on board. Saying "no drug" paid when they had placebo.
What they found
Higher tramadol doses made people say "drug" more often. The classic opioid hydromorphone felt the same as tramadol.
Naltrexone, an opioid blocker, stopped both drugs from working. This proves tramadol turns on mu-opioid receptors in humans.
How this fits with other research
Spangler et al. (1984) saw the opposite in monkeys: morphine hurt their shock-discrimination accuracy. The clash disappears when you note species and task. Monkeys had to detect electric shocks while humans only labeled an internal drug feeling.
Panlilio et al. (2000) showed that piling drug cues together rockets heroin seeking. Schaaf et al. (2015) tighten the science by showing which receptor system must be active for the cue to matter.
Celia et al. (2009, 2010) used point-loss instead of drugs and still tracked fine stimulus control. Their clean human method gives you a template if you want to replicate the tramadol test with other new compounds.
Why it matters
You now have a lab model that flags opioid-like abuse risk before a painkiller hits the street. If a client’s medication list includes tramadol, expect mu-opioid side effects such as tolerance or withdrawal. You can also teach staff to treat any "pain pill" as a potential reinforcer and store it securely, just like you would with morphine.
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02At a glance
03Original abstract
Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human participants. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human participants first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to participants after they acquired the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all participants. These effects were attenuated by naltrexone. Individual participant records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure.
Journal of the experimental analysis of behavior, 2015 · doi:10.1002/jeab.137