Assistant Professor
Phone: 501-526-5657
Fax: 501-686-8970
LBRENTS@uams.edu
Education
Ph.D. – University of Arkansas for Medical Sciences, 2013
Research Interests
The objective of my laboratory is to develop treatment strategies for opioid use disorder that can be administered to pregnant women without negatively affecting fetuses. Current pharmacological treatments for opioid use disorder during pregnancy include the opioids methadone and buprenorphine, to which the fetus can become physically dependent. This physical dependence leads to neonatal abstinence syndrome (NAS) during the first days and weeks of life. NAS is a potentially life-threatening withdrawal syndrome that is characterized by inconsolable high-pitched crying, tremor, vomiting, diarrhea, sleep disturbances, and hypersensitivity to stimuli that are normally well tolerated by newborns. Additionally, the life-long effects of in utero opioid exposure or experiencing NAS are poorly understood. Although methadone and buprenorphine often cause NAS, maternal and neonatal outcomes following treatment with the medications are substantially improved relative to no treatment; thus methadone and buprenorphine represent the current best treatments for opioid use disorder during pregnancy.
Buprenorphine treatment is associated with less severe NAS than methadone; therefore, my laboratory is focused on understanding the factors that drive buprenorphine-associated NAS so that we can develop strategies to combat it. Our active projects are examining the contributions of an active metabolite of buprenorphine, called norbuprenorphine, to NAS. Evidence suggests that this metabolite is not important for maternal treatment but is associated with NAS. We envision that reducing fetal exposure to norbuprenorphine during maternal buprenorphine treatment will improve neonatal and life-long outcomes for the offspring. Potential methods to accomplish this goal that we are investigating include shunting buprenorphine metabolism from norbuprenorphine to minor, inactive metabolites, and increasing placental transport of norbuprenorphine from fetal to maternal circulation by p-glycoprotein.
Meet Dr. Brents’ Research Team
Recent Research Support
Current Research
- UAMS Fellow-to-Faculty Award (07/01/16 – 06/30/19)
“Maternofetal Buprenorphine Pharmacokinetics in the Development of Neonatal Abstinence Syndrome (NAS)” - AWD00052185 RPGACH UAMS College of Medicine (06/26/17 – 06/25/19)
“The Role of Norbuprenorphine in the Development of Neonatal Abstinence Syndrome” - AWD00052450 KL2 2017-01 UAMS/CTSA (10/01/17 – 09/30/19)
“The Metabolic and Pharmacodynamic Profile of Deuterated Buprenorphine”
Completed Research
T32 DA022981 NIH/NIDA (01/13/13 – 01/13/16)
“Translational Training in Addiction”
Publications
- Tobacyk J, Brents LK. Response to article – alternative interpretation of “there is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome”. J Matern Fetal Neonatal Med. 2023 Dec;36(1):2183469. doi: 10.1080/14767058.2023.2183469. PMID: 36863717; PMCID: PMC10246566.
- Tobacyk J, Parks BJ, Salazar P, Coward LU, Berquist MD, Gorman GS, Brents LK. Interaction between buprenorphine and norbuprenorphine in neonatal opioid withdrawal syndrome. Drug Alcohol Depend. 2023 Aug 1;249:110832. doi: 10.1016/j.drugalcdep.2023.110832. Epub 2023 Jun 21. PMID: 37385117; PMCID: PMC10573081.
- Janganati V, Salazar P, Parks BJ, Gorman GS, Prather PL, Peterson EC, Alund AW, Moran JH, Crooks PA, Brents LK. Deuterated buprenorphine retains pharmacodynamic properties of buprenorphine and resists metabolism to the active metabolite norbuprenorphine in rats. Front Pharmacol. 2023 May 9;14:1123261. doi: 10.3389/fphar.2023.1123261. PMID: 37229250; PMCID: PMC10204800.
- Tobacyk J, Parks BJ, Lovelady N, Brents LK. Qualitative content analysis of public responses to an FDA inquiry on the impact of scheduling changes to kratom. Int J Drug Policy. 2022 Oct;108:103817. doi: 10.1016/j.drugpo.2022.103817. Epub 2022 Aug 8. PMID: 35952436; PMCID: PMC10243221.
- Kulbeth HJ, Fukuda S, Brents LK. Automated quantification of opioid withdrawal in neonatal rat pups using Ethovision® XT software. Neurotoxicol Teratol. 2021 Mar-Apr;84:106959. doi: 10.1016/j.ntt.2021.106959. Epub 2021 Jan 30. PMID: 33529734; PMCID: PMC7965335.
- Griffin BA, Caperton CO, Russell LN, Cabanlong CV, Wilson CD, Urquhart KR, Martins BS, Zita MD, Patton AL, Alund AW, Owens SM, Fantegrossi WE, Moran JH, Brents LK. In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome. J Pharmacol Exp Ther. 2019 Jul;370(1):9-17. doi: 10.1124/jpet.118.254219. Epub 2019 Apr 26. PMID: 31028107; PMCID: PMC6538887.
- Brents LK, James GA, Cisler JM, Kilts CD. Personality variables modify the relationship between childhood maltreatment history and poor functional outcomes. Psychiatry Res. 2018 Oct;268:229-237. doi: 10.1016/j.psychres.2018.07.010. Epub 2018 Jul 6. PubMed PMID: 30064070. Handbook of Cannabis and Related Pathologies
- Brents LK. 1st ed. Preedy VR, editor. London, UK: Academic Press; 2017. Chapter 17, Correlates and Consequences of Prenatal Cannabis Exposure (PCE): Identifying and Characterizing Vulnerable Maternal Populations and Determining Outcomes for Exposed Offspring; p.160-170. 1170p.
- Brents LK. Marijuana, the Endocannabinoid System and the Female Reproductive System. The Yale journal of biology and medicine. 89(2):175-91, 2016. PMID: 27354844
- Tai S, Hyatt WS, Gu C, Franks LN, Vasiljevik T, Brents LK, Prather PL, Fantegrossi WE. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. Pharmacological research. 102:22-32, 2015. PMID: 26361728
- Brents LK, Tripathi SP, Young J, James GA, Kilts CD. The role of childhood maltreatment in the altered trait and global expression of personality in cocaine addiction. Journal of psychiatric research. 64:23-31, 2015. PMID: 25805246
- Marshell R, Kearney-Ramos T, Brents LK, Hyatt WS, Tai S, Prather PL, Fantegrossi In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection. Pharmacology, biochemistry, and behavior. 124:40-7, 2014. PMID: 24857780
- Brents LK, Prather PL. The K2/Spice phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products. Drug metabolism reviews. 46(1):72-85, 2014. PMID: 24063277
- Brents LK, Zimmerman SM, Saffell AR, Fantegrossi WE, Prather PL, Differential Drug-Drug Interactions of the Synthetic Cannabinoids JWH-018 and JWH-073: Implications for Drug Abuse Liability and Pain Therapy. Journal of Pharmacology and Experimental Therapeutics. 346(3): 350-61, 2013. PMID: 23801678
- Rajasekaran M, Brents LK, Franks LN, Moran JH, Prather PL, Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 in K2/Spice Retain CB2 affinity and exhibit properties predicted to enhance receptor signaling. Toxicology and Applied Pharmacology. 269(2): 100-8, 2013. PMID: 23537664
- Chimalakonda KC, Seely KA, Bratton SM, Brents LK, Moran CL, Endres GW, James LP, Hollenberg PF, Prather PL, Radominska-Pandya A, Moran JH, Cytochrome P450-mediated oxidative metabolism of abused synthetic cannabinoids found in “K2/Spice”: Identification of novel cannabinoid receptor ligands. Drug Metabolism and Disposition. 40(11):2174-84, 2012. PMID: 22904561
- Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL, AM-251 Exhibits Direct Antagonist/Inverse Agonist Activity at Mu-Opioid Receptors: Implications for Opioid/Cannabinoid Interaction Studies. Neuropharmacology. 63(5): 905-15, 2012. PMID: 22771770
- Seely KA, Brents LK, Radominska-Pandya A, Endres GW, Keyes GS, Moran JH, Prather PL. A Major Glucuronidated Metabolite of JWH-018 Is a Neutral Antagonist at CB1 Receptors. Chemical Research in Toxicology. 25(4): 825-7, 2012. PMID: 22404317
- Brents LK, Gallus-Zawada A, Radominska-Pandya A, Vasiljevik T, Prisinzano TE, Fantegrossi WE, Moran JH, Prather PL. Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity. Biochemical Pharmacology. 83(7):952-61, 2012. PMID: 22266354
- Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL, Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS One. 6(7): e21917, 2011. PMID: 21755008