Drug liking and abuse liability are useful concepts, but we do not fully understand the strength of correlation to drug using. Even if drug liking is the correct target, we do not know, for example, how it correlates to use. For example, it would be useful to know that if we could decrease drug liking by 20%, we could reduce abuse of that drug by a given percentage.
Behavioral targets for drug development seem practical, but further study is needed, in particular of opioid abusers who are rarely included in current studies (those with a major psychiatric comorbidity, chronic pain patients, and those with another substance abuse problem) and populations of sporadic users who may go unrecognized (the chemical copper, the rave abuser). What is known about opioid abuser behavior should be correlated against actual use patterns when possible.
At the core of this problem is the nature of addiction itself, which has both neurobiological and psychological components and remains to be more clearly elucidated. Biological targets for the development of new abuse-deterrent opioids are beyond the scope of this paper but remain an important goal for future research. Our current approach to opioid pharmacodynamics requires some retooling to address opioid abuse. For example, a better understanding of maximum effect and time to maximum effect rather than Cmax and Tmax values may be helpful in this context.
Four main models for abuse-deterrent opioids exist currently; those with a physical barrier (which do not prevent the drug from being abused by those who take it intact, but do make it difficult to snort, smoke, or inject the drug); those with an opioid agonist or antagonist that is released when the drug is misused; those with an aversive agent (niacin); and prodrug, a compound that must undergo a chemical change within the body before becoming active. The list of products in is complete to the extent of our knowledge. As these products come into more widespread use, actual experience with the drugs will help shape the next generation of products.
Of course, the authors do not believe that abuse-deterrent opioids will end opioid abuse. The goals of abuse-deterrent opioid formulations are limited and specific to the agents studied. It may be that abuse-deterrent formulations will simply lead to new drug choices by abusers. Surprisingly, there appears to be some degree of “brand loyalty” among recreational abusers in that some products are so well liked that online forums (Opiophile.com, Topix.com opioid forum, Prescriptiondrug-info.com, etc.) discuss how to circumvent tamper-proof mechanisms. That actual real-world effect of these drugs remains to be seen.