702 North Walnut Grove Ave.
Bloomington, IN 47405-2204
My research goal is to identify novel therapeutic interventions for treating pain that lack abuse liability and adverse side effects. The discovery of cannabinoid receptors and identification of brain constituents that act at these receptors established the existence of an endogenous cannabis-like (endocannabinoid) transmitter system. My lab has focused on harnessing the therapeutic potential of the endocannabinoid signaling system to suppress neuropathic pain while minimizing unwanted side effects (i.e., psychoactivity and addiction). The endocannabinoid system consists of cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes catalyzing endocannabinoid synthesis and degradation. My lab has identified functional roles of the endocannabinoid system in the nervous system and mapped its distribution in sensory pathways. My research has identified enzymes implicated in endocannabinoid deactivation as novel therapeutic targets for pain and stress-related disorders. My laboratory strives to maximize the therapeutic potential of endocannabinoid signaling systems while minimizing unwanted central nervous system side effects (e.g., psychoactivity and addiction). My lab has also disrupted protein-protein interactions downstream of NMDA receptors to suppress pronociceptive signaling cascades without the adverse effects of NMDAR antagonists (i.e., by targeting interactions between neuronal nitric oxide synthase and its upstream [PSD95] or downstream [NOS1AP] protein partners). My laboratory combines approaches from behavioral pharmacology, neurophysiology, neuroanatomy, biochemistry, and molecular biology.
Written by: Elisabeth Andrews
Andrea Hohmann learned early in her career to set aside any squeamishness. As a graduate student at Brown University, she would regularly visit slaughterhouses to obtain tissue samples, undaunted by the task of sawing into cows' brains to extract their brains and pituitary glands.
"The part that made me most worried was driving home," she remembers. "I was careful not to speed because if a cop pulled me over they would find a cooler full of brains packed in ice and bloodied saws and chisels."
The gore was a small price to pay for the chance to study neurotransmitter receptors in the lab of her mentor, Michael Walker (who later became the Gill Center’s first director). It was there that Hohmann became interested in the endocannabinoid system, the body's own cannabis-like signaling system. Very little was known about the functions of this system when she first encountered it in the early '90s.
"It was an incredible opportunity to ask some basic questions that had not yet been asked," she says. At the time, Hohmann explains, there was a great deal of skepticism in the scientific community about whether cannabinoid compounds produced any true analgesic effects.
"Although there were animal behavioral studies showing a reduced pain response, the conventional wisdom in the pain field was that cannabis made the animals high so they didn’t care about the pain, or it produced motor impairment and because of that they were not able to behaviorally withdraw from stimuli," she says.
Hohmann's persistence in the face of this skepticism was fueled by a determination to uncover processes that could point toward better pain treatments with fewer unwanted side effects.
Having seen both her parents suffer through cancer and chemotherapy and having worked as research assistant in alcohol and addiction studies prior to graduate school, she recognized the devastating shortcomings of opioid therapies that lead to tolerance, addiction, and withdrawal.
In order to bypass the criticisms of behavioral cannabinoid studies, Hohmann zeroed in on neurons, asking whether cannabinoids suppress activity in the neurons that code information about pain and examining the impact of cannabinoids on neurochemical markers associated with pain signaling. This work, which she completed in Walker’s lab, was the first to show that cannabinoids suppress the processing of pain information.
Her trailblazing investigations continued as a postdoctoral fellow under Miles Herkenham at the National Institute of Mental Health. Hohmann focused on mapping cannabinoid receptors within pain pathways and identifying the types of cells that contained them. She was part of the team that characterized the impact of genetic deletion of CB1 receptors, verifying that one type of receptor, CB1, is located primarily in the brain, while another type, CB2, is found mainly in the immune system.
At her subsequent post as an assistant professor at the University of Georgia, Hohmann turned her attention to the body's production of endocannabinoid compounds. She began by investigating stress-induced analgesia, the suppression of pain associated with exposure to physical or mental trauma.
"The phenomenon had been known since the 1980s, but it was classified into two types, opioid and non-opioid stress-induced analgesia, and no one had previously identified the transmitter system responsible for the non-opioid type," she says.
Hohmann's lab demonstrated that non-opioid stress-induced analgesia was mediated by the release of endocannabinoids. Building on this work with her collaborator Daniele Piomelli at University of California at Irvine, she was able to uncover some of the processes by which endocannabinoids are produced and mobilized on demand in the body, as well as the processes involved in their breakdown. These studies established an enzyme involved in the breakdown of the endocannabinoid 2-AG as a previously unrecognized therapeutic target for treating pain- and stress-related disorders.
Upon joining the Gill Center in 2010, Hohmann further expanded her repertoire of approaches, borrowing from the fields of drug abuse and pharmacology. This research has been critical in suggesting that cannabinoids may provide a valuable alternative to opioid pain medications without the risk of addiction. Additionally, Hohmann has also researched the potential benefits of administering cannabinoids and opioids in combination. In recent research, she has demonstrated that use of a compound targeting the CB2 receptor can prevent opioid tolerance, meaning that in the presence of the cannabinoid, the opioid will continue to block pain at the initial dose rather than requiring increasing dosage to remain effective. The same treatment also reduced symptoms of opioid withdrawal.
Presently, Hohmann is engaged in a new approach to pain alleviation that shifts the focus from neurotransmitters to proteins that interact within the neuronal cell during pain signaling.
"What's exciting about this approach is that it is so specific," she explains. "It targets interactions between proteins that are only associated during a pain state, so it's far less likely to cause unwanted side effects."
As Hohmann's work continues to evolve toward new techniques and directions, she emphasizes that, while she's glad to be done sawing through cattle brains, she'll always be open to any scientific approach that will help her find answers to important scientific questions.