Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

Han, Ying; Cao, Lu; Yuan, Kai; Shi, Jie; Yan, Wei; Lü, Lin

doi:10.1007/s12264-022-00872-3

Cited by 18 publications

(12 citation statements)

References 149 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Much of our understanding of chronic fentanyl use has been well documented in behavioral studies of animal models ( Han et al, 2022 ). However, how chronic fentanyl exposure regulates brain activity that leads to changes in behavior remains poorly understood, particularly in in vitro and in vivo models.…”

Section: Discussionmentioning

confidence: 99%

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

et al. 2022

View full text Add to dashboard Cite

Fentanyl is one of the most common opioid analgesics administered to patients undergoing surgery or for chronic pain management. While the side effects of chronic fentanyl abuse are recognized (e.g., addiction, tolerance, impairment of cognitive functions, and inhibit nociception, arousal, and respiration), it remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. Here, we examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 μM) and high (10 μM) dose. Primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte precursor cells, were seeded in wells on either a 6-well multi-electrode array (MEA, for electrophysiology) or a 96-well tissue culture plate (for serial endpoint bulk RNA sequencing analysis). Once networks matured (at 28 days in vitro), co-cultures were treated with 0.01 or 10 μM of fentanyl for 4 days and monitored daily. Only high dose exposure to fentanyl resulted in a decline in features of spiking and bursting activity as early as 30 min post-exposure and sustained for 4 days in cultures. Transcriptomic analysis of the complex cultures after 4 days of fentanyl exposure revealed that both the low and high dose induced gene expression changes involved in synaptic transmission, inflammation, and organization of the extracellular matrix. Collectively, the findings of this in vitro study suggest that while neuroadaptive changes to neural network activity at a systems level was detected only at the high dose of fentanyl, transcriptomic changes were also detected at the low dose conditions, suggesting that fentanyl rapidly elicits changes in plasticity.

show abstract

Section: Discussionmentioning

confidence: 99%

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Several fentanyl and heroin vaccines have been studied in rodents and nonhuman primates, but they are still in preclinical phases and need to be implemented to clinical use of fentanyl overdose. 180…”

Section: Treatment/management Naloxonementioning

confidence: 99%

Abuse potential of fentanyl and fentanyl analogues

Thumma,

Mfoafo,

Babanejad

et al. 2024

Bioimpacts

View full text Add to dashboard Cite

Introduction: In this perspective review, we evaluated the clinical management of fatal fentanyl overdose in several routes of administration, concentrating on both legally prescribed and illegally produced formulations. Methods: A literature search was conducted on Web of Science, PubMed, and Google Scholar databases, using the following keywords: fentanyl, illicit fentanyl, deaths, misuse, abuse, and naloxone. We included only articles whose abstracts were available in English. All articles were screened using their abstracts to determine their relevance to the current review. Results: The gold standard for treating both acute and chronic pain is fentanyl, but abuse of the drug has exploded globally since the late 2000s. Fentanyl abuse has been shown to frequently result in serious harm and even death. Conclusions: By educating patients and physicians, making rescue kits easily accessible, developing vaccines to prevent opioid addiction, and perhaps even creating new tamper-resistant fentanyl formulations, it may be possible to prevent fentanyl misuse, therapeutic errors, and the repercussions that follow.

show abstract

“…The rise in availability of fentanyl and fentanyl analogues has been implicated in the rapid increase in overdose fatalities over the past decade. 1 , 2 , 3 , 4 , 5 , 6 , 7 Because of its potency (30-50 times more potent than heroin), 7 , 8 , 9 , 10 rapid distribution, lipophilicity, and propensity to induce muscle rigidity, fentanyl is more likely to cause an overdose than other opioids, including heroin. 3 , 11 People who use illicit drugs often lack awareness that fentanyl is present in the drugs they buy, which further increases overdose risk.…”

Section: Introductionmentioning

confidence: 99%

Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use

Nunes,

Comer,

Lofwall

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceFentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.ObjectiveTo assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.Design, Setting, and ParticipantsPost hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.InterventionWeekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.Main Outcomes and MeasuresRetention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.ResultsOf 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, −3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, −1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.Conclusions and RelevanceIn this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.Trial RegistrationClinicalTrials.gov Identifier: NCT02651584

show abstract

Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

Cited by 18 publications

References 149 publications

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

Abuse potential of fentanyl and fentanyl analogues

Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use

Contact Info

Product

Resources

About