The (very) early evidence of oxycodone addiction liability

Between 2000 and 2022, annual opioid overdose fatalities in the United States rose from 10 000 per year to over 80 000 per year. It is generally agreed that a major contributing factor to the US opioid crisis was the increased and widespread availability of the prescription opioid oxycodone during the 1990s and early 2000s. While the opioid crisis and oxycodone's contribution to it have been well documented, it remains underappreciated just how early after its introduction this drug's tendency towards diversion, misuse, dependence and addiction became apparent. This paper reviews the scientific and public health literature that accumulated during the 20th century indicating oxycodone's addiction liability to be of equivalent concern to that of morphine.

A narrative review drawing from original scientific, clinical and public health literature obtained from digital archives relevant to the period of interest.

Attention was first drawn to oxycodone's addiction liability by concerned clinicians as early as two years after the drug became commercially available in Germany in 1917, with additional evidence accumulating both in that country and abroad over the subsequent decades. This, combined with research conducted under the supervision of the Committee on Drug Addiction and Narcotics (CDAN) within the Medical Sciences Division of the US National Research Council, led to global recognition of the fact that oxycodone should not be considered any less an addiction liability than morphine. Concerns raised by clinicians about oxycodone throughout that period, and speculation on the causal factors underlying the rapid increase in oxycodone's misuse frequency, are reminiscent of those accepted as contributory to the current global opioid crisis, including lax prescription practices, misleading marketing strategies and inconsistent government oversight. Attempts to draw on this early body of evidence to influence drug policy regarding oxycodone were undermined by a tendency to assess the addiction potential of drug formulations independently of their active ingredients.