Lisa K. Brents, Ph.D.

Lisa K. Brents, Ph.D.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

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

View Dr. Brents’s Publication List