Characterizing the subjective, observer-rated, and physiological effects of hydromorphone relative to heroin in a human laboratory study

• Published in: Psychopharmacology 2018-04, Vol.235 (4), p.971-981
• Main Authors: Dunn, Kelly E., Brands, Bruna, Marsh, David C., Bigelow, George E.
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Analgesics, Opioid - administration & dosage; Analysis; Behavior Observation Techniques - methods; Biomedical and Life Sciences; Biomedicine; Blindness; Blood Gas Analysis - methods; Clinical trials; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug abuse; Drug dependence; Electrocardiography - drug effects; Electrocardiography - methods; Emotions - drug effects; Emotions - physiology; Health aspects; Heroin; Heroin - administration & dosage; Humans; Hydromorphone; Hydromorphone - administration & dosage; Injections, Subcutaneous; Intravenous administration; Laboratories; Male; Narcotics; Neurosciences; Opioids; Original Investigation; Oxygen content; Pharmacology/Toxicology; Physiological aspects; Physiological effects; Physiology; Psychiatry; Pupil - drug effects; Pupil - physiology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-017-4814-3

Background This study compared the effects of the several doses of the opioid agonists heroin and hydromorphone across two routes of administration in humans. The goal was to guide development of human laboratory studies of opioid effects and inform subsequent injection pharmacotherapy trials of hydromorphone-assisted treatment. Methods A within-subject ( N  = 16), double-blind, double-dummy, placebo-controlled, evaluation of acute doses of heroin and hydromorphone was completed at four dose levels (placebo, low, medium, high) across two routes of administration (intravenous, subcutaneous) in non-physically dependent, opioid-experienced individuals. Subject and observer ratings, as well as physiological outcomes, were assessed. Results Within each route of administration, heroin and hydromorphone produced effects that were qualitatively similar on most variables across the doses examined. All effects were dose-dependent. The drugs produced different effects on VAS ratings of “Feels Like Heroin,” a Heroin Identification Test, observer agonist ratings, and oxygen saturation levels. Drug-dependent differences emerged at the highest doses in all cases. Few significant main effects of Route were identified and their pattern was not uniform. Relative potency calculations across all subject, observer, and physiological outcomes that met analysis criteria revealed similar profiles and resulted in mean heroin:hydromorphone potencies of 3.35:1 and 2.88:1 for the intravenous and subcutaneous routes, respectively, and intravenous:subcutaneous potencies of 0.47:1 and 0.49:1 for heroin and hydromorphone, respectively. Conclusions Hydromorphone produced similar subjective and physiological effects as heroin, but was more potent than heroin. The current findings support the use of hydromorphone as a model for heroin in human laboratory and clinical treatment studies, and help identify appropriate hydromorphone dose conversion ratios to produce effects qualitatively similar to heroin.