Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment
•Illicit fentanyl is sold as an adulterant to heroin and other drugs. The extent to which fentanyl alone is sold or sought out by drug users is unclear.•Fentanyl is a potent mu opioid agonist with high efficacy. Compared to morphine, it may produce greater activation of beta-arrestin complexes.•Nalo...
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| Published in | Neuroscience and biobehavioral reviews Vol. 106; pp. 49 - 57 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Ltd
01.11.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0149-7634 1873-7528 1873-7528 |
| DOI | 10.1016/j.neubiorev.2018.12.005 |
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| Abstract | •Illicit fentanyl is sold as an adulterant to heroin and other drugs. The extent to which fentanyl alone is sold or sought out by drug users is unclear.•Fentanyl is a potent mu opioid agonist with high efficacy. Compared to morphine, it may produce greater activation of beta-arrestin complexes.•Naloxone and naltrexone antagonize the effects of most commonly abused opioids, including fentanyl, through a competitive interaction.•Opioid cross-tolerance is smaller to opioids with high compared to low efficacy.•Research on the optimal doses and regimens of naltrexone, methadone, and buprenorphine for treating illicit fentanyl use is urgently needed.
Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use. |
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| AbstractList | Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use. •Illicit fentanyl is sold as an adulterant to heroin and other drugs. The extent to which fentanyl alone is sold or sought out by drug users is unclear.•Fentanyl is a potent mu opioid agonist with high efficacy. Compared to morphine, it may produce greater activation of beta-arrestin complexes.•Naloxone and naltrexone antagonize the effects of most commonly abused opioids, including fentanyl, through a competitive interaction.•Opioid cross-tolerance is smaller to opioids with high compared to low efficacy.•Research on the optimal doses and regimens of naltrexone, methadone, and buprenorphine for treating illicit fentanyl use is urgently needed. Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use. Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use.Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use. |
| Author | Comer, Sandra D. Cahill, Catherine M. |
| AuthorAffiliation | b Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, 90095, United States a New York State Psychiatric Institute and Columbia University, New York, NY, 10027, United States |
| AuthorAffiliation_xml | – name: b Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, 90095, United States – name: a New York State Psychiatric Institute and Columbia University, New York, NY, 10027, United States |
| Author_xml | – sequence: 1 givenname: Sandra D. surname: Comer fullname: Comer, Sandra D. email: sdc10@cumc.columbia.edu organization: New York State Psychiatric Institute and Columbia University, New York, NY, 10027, United States – sequence: 2 givenname: Catherine M. surname: Cahill fullname: Cahill, Catherine M. organization: Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, 90095, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30528374$$D View this record in MEDLINE/PubMed |
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| Keywords | Self-administration Abuse Subjective effects Beta-arrestin Fentanyl Efficacy Pharmacology Methadone Naltrexone Pain Treatment Buprenorphine Illicit Heroin |
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| Snippet | •Illicit fentanyl is sold as an adulterant to heroin and other drugs. The extent to which fentanyl alone is sold or sought out by drug users is... Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has... |
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| SubjectTerms | Abuse Beta-arrestin Buprenorphine Efficacy Fentanyl Heroin Illicit Methadone Naltrexone Pain Pharmacology Self-administration Subjective effects Treatment |
| Title | Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment |
| URI | https://dx.doi.org/10.1016/j.neubiorev.2018.12.005 https://www.ncbi.nlm.nih.gov/pubmed/30528374 https://www.proquest.com/docview/2155151068 https://pubmed.ncbi.nlm.nih.gov/PMC7233332 |
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