Our lab focuses on studying neuroinflammation and understanding the mechanisms involved in inflammatory responses within the brain. We study the role of neuroinflammation in the context of different disease states, insults, and stressors. Understanding the context, course and duration of the neuroinflammatory response is vital to understanding the corresponding behavioral and biochemical consequences. Additionally, neuroinflammation plays a central role in the underlying pathophysiology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease as well as various substance use disorders such as alcohol use disorder and stimulant use disorder. Thus, the aim of our laboratory is to understand the role of neuroinflammation in the pathophysiology of several classes of disorders listed below and study the role of novel, anti-inflammatory compounds as potential therapeutic interventions for these conditions. 

The image on the left depicts  Glial fibrillary acidic protein (GFAP) staining for astrocytes as a marker of astrogliosis in the rat hippocampus.

Approximately 20 million adults in the United States suffer from alcohol use disorder (AUD)
Current treatments for AUD include naltrexone, disulfuram, and acomprosate. However, a high percentage of AUD patients remain refractory to such therapy. Thus, we are studying neuropharmacological and neurobiological systems that mediate alcohol abuse and dependence, with an emphasis on brain serotonin systems and neuroinflammation to potentially develop new therapeutics for AUD.  We specifically use techniques and measures such as the two bottle-choice ethanol drinking paradigm, ethanol-induced conditioned place preference (CPP) and ethanol-induced loss of righting reflex (LORR) assay.  We use these assays to evaluate the potency and efficacy of several anti-inflammatory compounds such as the phytochemical beta-caryophyllene (BCP), its derivative  oxide (BCPO) and the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI)  for AUD. 

The graph on the left depicts data from mice drinking either  ethanol or water using the two bottle-choice ethanol drinking paradigm

Our lab is involved in assessing the persistent behavioral and neurochemical effects of exposure to various classes of stimulants such as methamphetamine, MDMA and synthetic cathinones such α-pyrrolidinopropiophenone (α-PPP). Additionally, we also aim to identify novel drug targets to prevent the devastating adverse events associated with stimulant overdose.  Thus, current research in our laboratory involves characterizing the neurotoxic effects of stimulant overdose such as stimulant-induced lethality, hyperthermia, convulsions, seizures and monoamine neurochemistry depletion. Additionally, we also study various agents like HT2A receptor antagonist M100907 ,the sigma 1 (σ1) receptor antagonist BD 1047 and other anti-inflammatory compounds and peptides to attenuate adverse effects of stimulant overdose using techniques such as behavioral pharmacology,surgical telemetric probe implantation, electroencephalography and neurochemistry analysis by High Performance Liquid Chromatography (HPLC). 

TThe image on the left depicts representative electroencephalography waveforms over a period of 60 s following administration of 78 mg/kg of methamphetamine (or baseline). Data showing the effects of pretreatment with vehicle, M100907 (1 mg/kg), BD 1047 (10 mg/kg), and the combination of M100907/BD 1047 (1/10 mg/kg) on seizures are shown.

Alzheimer's disease (AD) is responsible for major financial and health-care burdens to society. It is estimated that the costs are likely to grow as our population ages further. Current therapeutics for AD only provide transient symptom management and do not alter the course of the disease. Interestingly, AD affects a greater proportion of females as compared to males. A leading hypothesis for the pathology of AD involves the production of toxic forms of Amyloid-beta plaques and neurofibrillary tangles in the brain which trigger inflammation-mediated neurotoxicity. The cholinergic system is most widely studied for AD related pathophysiology. However, more recent studies also implicate other neurotransmitter systems such as serotonin and norepinephrine which play vital roles in modulating behaviors such as fear and anxiety.  Thus, our research focuses on studying different neurotransmitter systems implicated in AD and characterizing sex differences and epigenetic alterations in AD. Additionally we are also investigating the  role of novel anti-inflammatory agents as potential therapeutics for AD using techniques such as behavioral pharmacology, autoradiography, proteomics, immunohistochemistry and neurochemical analysis. 

The image on the left shows App knock-in mice from our breeding colony that were specifically engineered by researchers at the Riken Brain Science Institute in Japan to display AD-like pathology.

The blood-brain barrier (BBB) limits the therapeutic use of large molecules and peptides as it prevents them from passively entering the brain following administration by conventional routes. We use nanotechnology drug delivery systems for encapsulating peptides such as Oxytocin and Neuropeptide Y to increase their brain bioavailability through active transport and increase their duration of action through encapsulation and sustained release. Preclinical and clinical studies suggest pro-social behavioral effects of these peptides and therapeutic promise. Thus, we specifically evaluate the therapeutic effects and increased bioavailability of these formulations for conditions such as alcohol use disorder (AUD) , Substance use disorder and opioid use disorder using in vitro  techniques such as cell-culture model of the BBB, and in vivo techniques such as bioimaging, cerebrospinal fluid analysis, behavioral testing and EEG (electroencephalography).

The image on the left shows brain uptake in mice at 30 minutes (above) or 4 hours (below) of an encapsulated large-molecule dye in a nanoformulation (left and middle). The red uptake in the Tf-NP nanoparticles shows that our technology has actively transported this dye into the brain successfully.

Parkinson’s Disease (PD) is amongst the most common neurodegenerative diseases. It is clinically manifested by motor symptoms including resting tremors, postural instability, rigidity, and bradykinesia. The neuropathogenesis of PD symptomology is directly linked to the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SN), where cell death leads to subsequent depletion of the key neurotransmitter dopamine (DA). Polyunsaturated fatty acids (PUFA), including the family of omega-3 fatty acids (w3FA) that contains a-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have a long record of linkage to brain function. Thus, our research focuses on studying the neuroprotective and dopamine synthesizing effects of omega-3 fatty acids for PD and investigating the potential mechanisms through which they act using behavioral, molecular and neurochemical techniques.   

 

The image above shows a UHPLC coupled to electrochemical detectors (ECD) used to quantify tissue levels of neurotansmitters such as Dopamine and its primary metabolite DOPAC. 

Additional research focus areas of the laboratory include:

• Studying the effects of a high fat diet on monoamine neurochemistry
• Comparing the psychoactive effects of various psychedelics such as 2,5-Dimethoxy-4-iodoamphetamine (DOI) and other tryptamines
• Investigating the anxiolytic and sedative properties of various naturally occurring sesquiterpenes
• Using optogenetics as a tool to investigate into mechanisms associated with anxiety with the ultimate aim to develop therapeutic interventions for anxiety related disorders

• Daphney CM, Canal CE, Milfort M, Kelley K, Samedy L, Momary KM, Saido TC, and Murnane KS (In Preparation) Differences in serotonin 2A receptor expression and function across age, sex, and genotype. Behavioral Brain Research
• Polaka S, Sharma P, Patisaul PE, Kolluru G, Daphney CM, Benveniste M, Owens B, Chitre NM, and Murnane KS (In Preparation) Sex-specific behavioral and cognitive dysfunction in APPNL-G-F knock-in mice: Therapeutic potential of β-caryophyllene through CB2 receptor signaling and modulation of neuroinflammation. Neurobiology of Aging (Impact Factor 5.1
• Gannon BM and Murnane KS (In Preparation) The CB2 receptor agonist beta-caryophyllene attenuates methamphetamine and oxycodone self-administration while increasing anti-nociception. Journal of Pharmacology and Experimental Therapeutics
• Ray A and Murnane KS (In Preparation) Neurotoxic effects of ring substituted derivatives of the second generation “bath salt” cathinone alpha-pyrrolidinopropiophenone (α-PPP). Psychopharmacology
• Dumitrescu AM, Vest MF, and Murnane KS (In Preparation) Intrinsic whole-brain brain functional connectivity patterns in individuals recently abstinent from methamphetamine. Neuropsychopharmacology (Impact Factor 8.3)
• Chitre NM, Gannon BM and Murnane KS (In Preparation) Assessing the physiological and pharmacological mechanisms by which synthetic cathinones ("Bath salts") induce drug-induced parkinsonism (DIP) using prototypical methcathinones and pyrrolidines. European Journal of Pharmacology
• Patisaul PE, Polaka S, Sharma P, and Murnane KS (In Preparation) Microfluidics nanoparticle-encapsulated oxytocin attenuates hyperactivity in a genetic mouse model of Dravet Syndrome. European Journal of Neuroscience
• Vest MF, Dumitrescu AM, Patterson JC, and Murnane KS (In Preparation) Multimodal characterization of striatal neurochemical and functional connectivity alterations associated with cognitive flexibility deficits in methamphetamine use disorder Drug and Alcohol Dependence
• Polaka S, Patisaul PE, Sharma P, Bhumireddy A, Kolluru G, Kevil CG, Benveniste M, D’Souza M, Escayg A, Wong JC, and Murnane KS (In Preparation) Intranasal oxytocin ameliorates social deficits and hippocampal oxidative stress in Scn1a+/− mice. Redox Biology (Impact Factor 16.2
• Wood BJ, Patisaul PE, Barnes M, Cannon CE, Rice KC, Blough BE, Nye JA, Lotkiz S, and Murnane KS (In Preparation) Effects of the 5-HT2A agonist (-)-2,5,-dimethoxy-4-iodoamphetamine R(–)DOI on methamphetamine self-administration and PET-based brain measures in rats. Drug and Alcohol Dependence
• Wood BJ, Vest MF, Carfagno C, Lutz J, Blough BE, Kooti F, Bicher J, Sitte HH, McCorvy J, and Murnane KS (In Preparation) Psychoactive and anxiolytic characterization of novel psilocybin analogues. Psychedelic Medicine (Impact Factor 5.0)
• D’Aoust PM, Graber TE, Wong CH, Nguyen TB, Plaza-Diaz J, Wan S, Renouf EM, Gonzalez R, Karaolia P, Yang MI, Kocamemi BA, Hokajärvi A, Mansfeldt C, Fatta-Kassinos D, Frigon D, Celikkol S, Murnane KS, Pang X, Reynolds LJ, Bivins A, Naughton CC, Kitajima M, Székely AJ, Towhid ST, Ahmed W, Wyler E, Edwards E, Ziels R, McKay RM, and Delatoll R (In Preparation) A novel, globally validated PMMoV PCR assay for wastewater & environmental surveillance data normalization. Environmental Research (Impact Factor 7.7
• Sharma P, Scheinost A, Hall NM, Lamon K, Kolluru GK, Polaka S, Dayton R, Kumar D, Pandit R, Yurdagul A, and Murnane KS (Submitted) Comparison of the anti-inflammatory effects of cannabinoids and terpenes commonly present in cannabis-derived products. Journal of Cannabis Research
• Dayton RD, Baldwin WM, Goeders NE, Patterson JC, Nam HW, Latimer B, Bivins A, Subedi B, Peach JT, Bhuiyan MAN, Owens H, Vanchiere JA, Queen K, Keil DE, Jones JO, Snead B, Daniel W, and Murnane KS (Submitted) Wastewater analysis in north Louisiana validates conventional local and statewide health metrics of the methamphetamine epidemic Science of the Total Environment (Impact Factor 8.2
• Sawaya MF, Lifshitz DJ, Ayers S, Fontenot C, Nordberg ME, Dumitrescu AM, Vest MF, and Murnane KS (Submitted) Polysubstance use disorder burden predicts depression and anxiety severity among substance use treatment-seeking individuals Drug and Alcohol Dependence
• Wood BJ*, McComb NJE*, Jadwin GT, Patisaul PE, Blough BE, Toms J, Murnane KS, and Kumbhare D (Submitted) Modulation of default mode network by the psychedelic 2,5-dimethoxy-4-iodoamphetamine in freely moving Sprague-Dawley rats. Psychopharmacology (Asterisks denote equal first author contributions)
• Xing D, Smith D, Murnane KS, Bhuiyan MS, Goeders NE, Patterson JC, Vanchiere JA, Kevil CG, and Bhuiyan MAN (Submitted) Recent trends in stimulant use associated with emergency visits, hospitalizations, and deaths in Louisiana. Drug and Alcohol Dependence
• Chitre NM, Gannon BM, Blough BE, and Murnane KS (Submitted) Direct comparison of the effects of functionally equivalent dosing regimens of methamphetamine, methcathinone, and α-pyrrolidinopropiophenone on behavioral and neurochemical markers of neurotoxicity. Psychopharmacology
• Dumitrescu AM*, Vest MF*, Fleckenstein AE, Patterson JC 2nd, Ledbetter C, Goeders NE, Loftis JM, Thompson E, Lofton K, and Murnane KS (In Press) Trail making test performance in early abstinence from methamphetamine: human evidence for a drug-associated Parkinsonian-like phenotype. Frontiers in Psychiatry (Impact Factor 5.4) PMID: 41947808 (Asterisks denote equal first author contributions)
• Dumitrescu AM, Vest MF, and Murnane KS (In Press) Fronto-striatal neurometabolite signatures of impulsivity in early abstinence from methamphetamine. NeuroImage: Clinical PMID: 42235208
• Charoenpong P, Hall NM, Keller CM, Kumar A, Chen L, Gatuz J, Siddiqui N, Yazdi FST, Fels Elliott DR, Dhillon NK, Murnane KS, Goeders NE, and Walter RE. (In Press) Pulmonary vascular remodeling in rats following methamphetamine self-administration: toward a model of methamphetamine-associated pulmonary arterial hypertension. Toxicological Sciences (Impact Factor 5.2) PMID: 42271610
• Wood BJ, Vest MF, Carfagno C, Bartley K, Sharma P, Halberstadt AL, Blough BE, and Murnane KS (2026) Differential effects of acute and chronic fluoxetine on psychedelic-induced behavior in mice: Implications for clinical trials. ACS Pharmacology & Translational Science Mar 3;9(3):585-595 PMID: 41852641
• Tynes BE, Murnane KS, Vest MF, Gelir F, Sawaya MF, Bhuiyan MAN, and Murnane SE (In Press) Development and administration of a skin survey questionnaire for methamphetamine users. Dermatology Online PMID: 41426886
• Wood BJ, Hall NM, Vest MF, Sharma P, and Murnane KS (In Press) Swiss-Webster and C57BL/6 mice are differentially sensitive to the stimulant effects of methamphetamine. Pharmacology, Biochemistry, and Behavior PMID: 40914335
• Moghaddam F, Binwal M, Green AJ, Rambacher KM, Murnane KS, and Moniri NH (In Press) Agonism of FFA4/GPR120 activates tyrosine hydroxylase and confers neuroprotection in cellular and in 6-OHDA models of Parkinson’s disease. Biochemical Pharmacology (Impact Factor 5.6) PMID: 41506541
• Reeda SL, Aiania LM, Benveniste M, D’Souza M, Murnane KS, Escayg A, and Wong JC (2026) Nanoparticle encapsulated neuropeptide Y provides robust seizure protection in Scn1a-derived epilepsy. Epilepsia (Impact Factor 5.6) Jan;67(1):424-436 PMID: 4107460
• Wood BJ, Brackett ED, Hall NM, Cannon CE, Dayton RD, Keller CM, Goeders NE, and Murnane KS (2026) 96-h methamphetamine self-administration elicits striatal dopamine depletion in male and female rats: a model of binge-like use. Psychopharmacology 243(1):177-187 PMID: 40914335

• Dumitrescu, A. M., Vest, M. F., Fleckenstein, A. E., Patterson, J. C., Ledbetter, C., Goeders, N. E., ... & Murnane, K. S. (2026). Trail Making Test performance in early abstinence from methamphetamine: human evidence for a drug-associated Parkinsonian-like phenotype. Frontiers in Psychiatry, 17, 1773668.
• Dumitrescu, A. M., Vest, M. F., Loftis, J. M., & Murnane, K. S. (2026). Fronto-striatal neurometabolite signatures of impulsivity in early abstinence from methamphetamine. NeuroImage: Clinical, 50, 104015.

• Company MC, Lifshitz DJ, Sawaya MF, Murnane KS. Psychedelics and Reward Processing: Before and After the 1970 Controlled Substances Act. Psychedelic Medicine. 2026 Jul 24. 
• Anwar AI, Hegazi AA, Sawaya MF, Nelson JR, Lashley AE, Gatti JM, Pham KM, Hachem IA, McNulty ME, Murnane KS, Kaye AD. Ibogaine for Substance Use Disorders. [Submitted to Advances in Therapy - Acceptance Pending]
• Sawaya MF, McNulty ME, St. Germain CJ, Hachem IA, Calix MS, Lormand RM, McComb NJE, Abu Shehab AA, Wrightson J, Anwar AI, Kaye AD, Murnane KS. Brixadi for Stimulant Use Disorder: Evolving Pharmacologic Considerations and Clinical Implications. [Submitted to Advances in Therapy - Acceptance Pending]
• Anwar AI, Hegazi AA, Bhuchakra HP, Nelson JR, Birdsong TL, Fontenot CJ, Zeibo M, Fazal-ur-Rehman MM, Bieber HP, Spring CJ, Smith JL, Hachem IA, Singh T, Sawaya MF, Murnane KS, Kaye AD. Pridopidine-Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases. [Submitted to Neurology International - Acceptance Pending]
• Sharma P, Sawaya MF, Dumitrescu AM, Kolluru GK, Schmoutz CD, Salinas A, Cannon CE, Kumbhare D, Korneeva N, Vest MF, Wood BJ, Bracey P, McNeill S, Kaye AD, Murnane S, Jordan J, Keys K, Brackett E, Avadhanula K, Murnane KS. Novel Neurotherapeutic Targets for Substance Use Disorders: Neuroplasticity, Neuroinflammation, Gasotransmitters and Non-Canonical Organ Systems. Neurotherapeutics. 2025;22(6):e00770.
• Tynes BE, Murnane KS, Vest MF, Gelir F, Sawaya MF, Bhuiyan MAN, Murnane S. Development and Administration of a Skin Survey Questionnaire for Methamphetamine Users. Cureus. 2025 Nov 19. doi:10.7759/cureus.97266.
• Anwar AI, Hegazi AA, Bhuchakra HP, Nelson JR, Birdsong TL, Fontenot CJ, Zeibo M, Fazal-ur-Rehman MM, Bieber HP, Spring CJ, Smith JL, Hachem IA, Singh T, Sawaya MF, Murnane KS, Kaye AD. Pridopidine-Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.[Submitted to Neurology International - Acceptance Pending]