Table 2.

The summary of currently available data about the impact of G protein biased μ-opioid receptor agonists on physiological and subjective aspects of addictive behavior

Agonist	Physiological aspects of addiction	Subjective aspects of addiction
TRV130 (oliceridine)	Increased resistance to antinociceptive tolerance [55–57] Physical dependence resulting in withdrawal symptoms [56]	Lack of rewarding effects at low dose, reward-associated behavior at high dose measured in conditioned place preference test [56, 58] Moderate abuse-related effects in drug discrimination test [53] Abuse-related effects in intracranial self-stimulation after repeated administration, a weak effect following acute treatment [55] Reinforcing effects in self-administration procedure [54] Morphine-like “high” feelings (in humans) [59]
Kratom alkaloids
Mitragynine pseudoindoxyl	Slower development of antinociceptive tolerance [66] Limited physical dependence measured by abolished withdrawal symptoms [66, 69]	Lack of rewarding properties in conditioned place preference test [66]
7-Hydroxymitragynine	Development of antinociceptive tolerance [72] Physical dependence measured by withdrawal symptoms [72]	Rewarding properties in conditioned place preference test [73] Reinforcing effects in self-administration paradigm [74]
Mitragynine	Diminished physical dependence measured by withdrawal symptoms [69]	Limited reinforcing effects in self-administration paradigm [74, 75] Discriminative stimulus properties in drug discrimination test [76]
MGM-9	Development of tolerance to antinociception [67]	Reduced hyperlocomotion [67] Abolished rewarding effects in conditioned place preference test [67]
Kurkinorin	Reduced development of tolerance to antinociception [78]	Diminished rewarding effects in conditioned place preference test [78]
Carfentanil-amide opioids	Possibly abolished physical dependence and withdrawal symptoms [80]
KGFF09	Increased resistance to antinociceptive tolerance [81] Reduced physical dependence measured by withdrawal symptoms [81]
PZM21	Development of antinociceptive tolerance [82, 83] Physical dependence resulting in withdrawal symptoms, but only at high dose [83]	Lack of rewarding effects in conditioned place preference test [58, 83] No enhancement of locomotor activity and no locomotor sensitization [58, 83] No reinforcing effects in self-administration study in rodents and no drug-seeking behaviors [83] Reinforcing effects in self-administration paradigm in primates [84]
Piperidine benzimidazoles (SR-compounds)
SR-14968		Attenuated discriminative stimulus properties in drug discrimination test [53]
SR-17018	Increased resistance to antinociceptive tolerance in hot plate test [85], development of tolerance in tail immersion test but no tolerance after repeated treatment in mice with inflammatory and neuropathic pain [86] Abstinence-induced withdrawal symptoms [85]

Data are derived from rodent studies unless otherwise noted