Projects and Grants
We have a number of ongoing projects in which we investigate the neurobiology underlying addiction disorders and related psychiatric illnesses.
Some of the NIDA-funded research projects in our lab include:
The opioid mesolimbic systems in heroin abuse [R01DA015446]
Heroin is a highly addictive drug and its abuse continues to be a major public health problem. Extensive research efforts have been dedicated to understanding the regulation of mu-opioid receptor (MOR), molecular target of heroin, but limited studies have been conducted directly in the human brain regarding MOR and its intracellular signaling in relation to heroin abuse. The goal of this project is to investigate more thoroughly the regulation of MOR; the intracellular G-protein signaling cascades that mediates the physiological actions of this receptor in heroin abusers and in relation to the polymorphism of the mu opioid receptor gene. Factors that modulate MOR function such as receptor density, phoshorylation state and coupling to 2-arrestin will be studied. Cluster and network analysis will be conducted on RNA data already collected from microarray analysis and customized real-time PCR datasets to identify the intracellular regulatory pathways linked to opioid receptor G-protein signaling. Key proteins within these networks will also be studied to validate the functional disturbances in relation to heroin use and the OPMR1 mutation. Expanding knowledge regarding MOR and its intracellular signaling machinery directly in the human brain will provide a major insight as to the neurobiological correlates linked with heroin abuse vulnerability and targets for medication development.
The neuronal basis of cannabis-induced developmental deficits in the CNS [R01DA023214]
While marijuana smoking during pregnancy causes life-long motor and cognitive deficits in the offspring, the cellular and molecular mechanisms through which marijuana impairs neuronal development and synaptogenesis, and causes permanent deficits in neuronal microcircuits in the brain are unknown. In this project we will: (1) define the cellular consequences of THC exposure during critical periods of neuronal precursor migration and neuronal synaptogenesis with particular emphasis on their association with GABAergic and dopaminergic neurons in the mesocorticolimbic system and (2) identify cellular regulatory mechanisms on the transcriptome level that are relevant to THC-induced developmental changes. An integrative, multidiscplinary series of studies will be performed in green fluorescent protein-expressing reporter mice that allow selective visualization of genetically-tagged target neurons. Subsequently, transcriptome analysis from animal model studies of prenatal delta 9-tetrahydrocannabinol (THC) administration will be combined with identifying developmentally-regulated gene sets in mesocorticolimbic neurons whose expression is differentially regulated by prenatal THC in a unique material of cannabis-exposed human fetal brain specimens. The results of this project will expand our current understanding of the functional significance of the endogenous cannabinoid signaling system during brain development and the pathological mechanisms associated with prenatal cannabis exposure. Such insights are of significant importance considering that marijuana is the most commonly used illicit drug by pregnant women and young women of childbearing age.
Cannabidol as treatment intervention for opiate relapse [R21DA027781]
Opioid abuse is a significant global public health problem. Of the over million opiate-dependent subjects today, only less than a quarter of such individuals receive treatment. Using a strategy of indirectly regulating neural systems to modulate opioid-related behavior, our preclinical rodent studies demonstrated that cannabidiol (CBD), a nonpsychoactive component of cannabis, specifically inhibits cue-induced heroin-seeking behavior. The fact that drug craving is generally triggered by exposure to conditioned cues suggests that CBD might be an effective treatment for heroin craving, specially given its protracted impact on behavior. It is the goal of this project to (1) determine the safety and basic pharmacokinetic characteristics of cannabidol when administered concomitantly with opiate in humans and (2) characterize the acute and short-term effects of cannabidol administration on cue-induced craving in drug-abstinent heroin-dependent subjects using a random double blind design.
Yasmin Hurd, PhD
Hess Center for Science and Medicine
10th Floor Room 105
1470 Madison Avenue
New York, NY 10029