Differential response to IV carfentanil in chronic cocaine users and healthy controls
Open accessAbstract
Chronic cocaine exposure in both rodents and humans increases regional brain mu‐opioid receptor (mOR) binding potential, suggesting that cocaine users might have an altered response to mOR agonists. We evaluated the response to IV carfentanil (a selective mOR agonist) in 23 cocaine users [mean (standard deviation) age 33.8 (4.0) years, 83% men] who underwent positron emission tomography (PET) scanning with [C‐11]‐carfentanil [44.7 (19.5) ng/kg] while housed on a closed research ward and 15 healthy non‐drug‐using controls [43.9 (14.2) years, 80% men] scanned [49.5 (12.6) ng/kg] as outpatients. Cocaine users had used for 8.7 (4.3) years and on 73 (22)% of days in the two weeks prior to PET scanning. Common adverse effects associated with mOR agonists (nausea, dizziness, headache, vomiting, itchiness) were assessed by self‐report (five‐point Likert scales) during and for 90 minutes after the scans. Cocaine users were significantly less likely than controls to report any symptom (30.4% versus 60%) and had fewer total symptoms [0.43 (0.73) versus 1.1 (1.0)] during scans, even after statistically controlling for age and carfentanil dose. These differences were also present after the scans and at repeat scans performed after about one week or 12 weeks of monitored cocaine abstinence. In a larger group of cocaine users and separate controls, there was no significant group difference in carfentanil half‐life, suggesting that the observed difference was pharmacodynamically, rather than pharmacokinetically, based. These findings suggest that cocaine users are less responsive than healthy controls to mOR agonist adverse effects despite having increased regional brain mOR binding potential.
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Other withdrawal changes include increased μ opioid receptor responsivity during opioid withdrawal and decreased GABAergic and increased NMDA glutamatergic transmission in the nucleus accumbens.
“Other observed changes include increases in μ opioid receptor responsivity during opioid withdrawal,71,72 and decreases in GABAergic and increases in NMDA glutamatergic transmission in the nucleus accumbens.”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [72]
The citation is attached to the claim of increased μ-opioid receptor responsivity during opioid withdrawal, not the later GABAergic/NMDA clause. The Discussion (page unavailable) examines cocaine abstinence instead and reports fewer adverse effects from a μ-opioid receptor agonist in cocaine users than in controls. A search for opioid withdrawal and receptor responsivity found no passage addressing the cited claim. (LLM, conf=0.76)
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Neurobiology of addiction: a neurocircuitry analysis
Koob, G. F., & Volkow, N. D. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)00104-8 · Cited by 3,698 · see citing works
- Authors
- Minkowski, C. P., Epstein, D., Frost, J. J., & Gorelick, D. A.
- Affiliations
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Corresponding author
- Gorelick, David A.
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2010-11-04
- Volume
- 17
- Issue
- 1
- Pages
- 149-155
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC3117107
- OpenAlex
- W1867524622
- Cited by
- 33
- References
- 31
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 1 · 2013: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01da009479-03, 5r01da011774-02)
- National Institute on Drug Abuse (DA-11774, DA-09479, ZIADA000241, R01DA012274, DA-12274)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- carfentanil, cocaine users, mu-opioid receptor agonists, opioid side effects, cocaine abstinence, pharmacodynamics
- MeSH terms
- Adult, Analgesics, Opioid, Brain, Dizziness, Female, Fentanyl, Half-Life, Headache, Humans, Injections, Intravenous, Male, Nausea, Pruritus, Time Factors, Vomiting, Cocaine-Related Disorders, Positron-Emission Tomography
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