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If OI are more opioid-tolerant than NIO, we hypothesize they would: (1) under controlled conditions, exhibit attenuated responses to a standard opioid challenge, as found in a preliminary study [46], (2) in an outpatient setting, use higher doses of illicit opioids to overcome this tolerance, (3) require higher buprenorphine concentrations to deter illicit opioid use, and (4) tolerate such higher buprenorphine concentrations without a clinically significant increase in safety problems (i.e., larger therapeutic window)

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Despite advances in the field, critical gaps in understanding remain