Cue-induced craving to paraphernalia and drug images in opioid dependence

McHugh, R. Kathryn; Fulciniti, Francesca; Mashhoon, Yasmin; Weiss, Roger D.

doi:10.1111/ajad.12344

Cited by 30 publications

(24 citation statements)

References 21 publications

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“…We found that oral drug cues reliably reinstated extinguished drug-seeking behavior in both male and female mice. These data support the observation that both oral and intravenous-associated drug cues are capable of causing cravings in human users (McHugh, Fulciniti, Mashhoon et al, 2016). In addition, these data indicate that drugs associated with oral ingestion, despite having less immediate effects than intravenous use (Gasior, Bond & Malamut, 2016;Kirsh, Peppin & Coleman, 2012;Leow, Smith, Watt et al, 1992), are nonetheless capable of invigorating drug-seeking behavior.…”

Section: Discussionsupporting

confidence: 82%

“…Environmental stimuli such as drug-associated cues influence relapse in opioid addicted individuals (Hyman, Fox, Hong et al, 2007;O'Brien, Childress, McLellan et al, 1990). In the clinic, intravenous users selfreport significantly higher ratings of craving than oral users in response to drug-associated cues (McHugh, Fulciniti, Mashhoon et al, 2016;McHugh, Park & Weiss, 2014). These data predict that oral prescription opioid users are less susceptible to relapse triggered by drug-associated cues than intravenous users.…”

Section: Introductionmentioning

confidence: 93%

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Oral prescription opioid-seeking behavior in male and female mice

Phillips¹,

McGovern²,

Lee³

et al. 2019

Preprint

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A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally selfadministered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 93%

Oral prescription opioid-seeking behavior in male and female mice

Phillips¹,

McGovern²,

Lee³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…These data support the observation that both oral and intravenous-associated drug cues are capable of causing cravings in human users. 20 In addition, these data indicate that drugs associated with oral ingestion, despite having less immediate effects than intravenous use, 6,7,10 are nonetheless capable of invigorating drug-seeking. Further research will be necessary to evaluate the roles of other reinstating stimuli (stress, drug-prime), extinction (punished, non-drug choice), and potential for incubation effects in the oral route.…”

Section: Resultsmentioning

confidence: 99%

Oral prescription opioid‐seeking behavior in male and female mice

et al. 2019

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A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug seeking. However, intravenous models may not characterize oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated cue-induced reinstatement following abstinence. In separate mice, we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior following abstinence without prior postprandial or water self-administration training. During self-administration, we incidentally found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal studies were performed in which we found divergent responses where ovariectomy-enhanced and orchiectomy-suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that (a) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, (b) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and (c) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.

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“…Even among heroin users who have been abstinent for greater than a year, drug-related cues still have the potential to elicit craving responses (47, 48), highlighting the enduring nature of craving among patients with a history of drug dependence. The influence of different cues on craving may also be dependent on the type of opioid dependence: in heroin dependence, cue-related craving was stimulated more intensely by paraphernalia images (e.g., needles), whereas patients with analgesic dependence were more stimulated by pills and pill bottles (46). The relationship between life stressors, craving, and relapse is complex and likely to be subject to significant inter-individual differences.…”

Section: Craving In Clinical Practicementioning

confidence: 99%

Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice

et al. 2019

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Opioid use disorder (OUD) is a major public health issue that has reached epidemic levels in some parts of the world. It is a chronic and complex neurobiological disease associated with frequent relapse to drug taking. Craving, defined as an overwhelmingly strong desire or need to use a drug, is a central component of OUD and other substance use disorders. In this review, we describe the neurobiological and neuroendocrine pathways that underpin craving in OUD and also focus on the importance of assessing and treating craving in clinical practice. Craving is strongly associated with patients returning to opioid misuse and is therefore an important treatment target to reduce the risk of relapse and improve patients’ quality of life. Opioid agonist therapies (OAT), such as buprenorphine and methadone, can significantly reduce craving and relapse risk, and it is essential that patients are treated optimally with these therapies. There is also evidence to support the benefits of non-pharmacological approaches, such as cognitive behavioral therapy and mindfulness-based interventions, as supplementary treatments to opioid agonist therapies. However, despite the positive impact of these treatments on craving, many OUD patients continue to suffer with negative affect and dysphoria. There is a clear need for further studies to progress our understanding of the neurobiological basis of craving and addiction and to identify novel therapeutic strategies as well as to optimize the use of existing treatments to improve outcomes for the growing numbers of patients affected by OUD.

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Cue-induced craving to paraphernalia and drug images in opioid dependence

Cited by 30 publications

References 21 publications

Oral prescription opioid-seeking behavior in male and female mice

Oral prescription opioid-seeking behavior in male and female mice

Oral prescription opioid‐seeking behavior in male and female mice

Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice

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