Heads Above the Rest

Dr. Christine A. Rabinak has always been passionate about psychology, especially learning and memory. But in her early training as a basic scientist, she was used to conducting research on animals in a lab, studying how their brains encode different types of associative learning. Think Pavlov’s dogs, but instead of associating a bell with food, rodents were linking fear to a benign environmental cue that happened to be present during a traumatic event.

Rabinak’s research was producing outcomes that had the potential to significantly impact treatment for patients suffering from traumas, particularly posttraumatic stress disorder, but one key component was missing from her lab work: humans.

“I felt so far removed from what an actual clinical application might be,” she said. “I kept thinking, ‘Is this what someone with PTSD is experiencing?’”

To answer that question, and more like it, she knew the next step in her career should be to expand her research toolbox, learn new skills, and translate the data she was seeing in animals into future patient treatments.

Making the Leap From Rodents to Humans

The opportunity to work in clinical research came during a three-year postdoc, which began at the Mental Health Service in the VA Ann Arbor Healthcare System under the mentorship of Dr. K. Luan Phan. There she assisted with a research study of Veterans returning from Iraq and Afghanistan who were exposed to combat-related trauma and had developed PTSD.

The research team examined images of Veterans’ brains prior to and upon completion of a 12-week SSRI treatment to understand how their brain and symptoms changed as a result of treatment. Rabinak and her colleagues were looking at two things: First, for those who respond to treatment, what are the changes in the brain after treatment compared to before treatment that might be linked to relief of symptoms? Second, is there a particular pattern of brain activation before treatment that could predict who might not respond to treatment?

“This was my first experience with human research and it was definitely eye-opening,” she said. Approximately a year later, she was accepted as a Postdoctoral Translational Scholar in the Michigan Institute for Clinical & Health Research (MICHR), an NIH-supported institutional postdoctoral fellowship program which provided her with even more clinical immersion. “I did everything I could—participated in clinic team meetings, watched clinical assessments and exposure-based therapies, spoke to patients suffering from anxiety and mood disorders. It gave me an appreciation for the condition and the way we approach treatment for those suffering from this condition. I knew I wanted to keep working with patients and come up with new ways to think about some of these problems.”

Pharmacy Was the Right Fit

Rabinak knew she wanted to continue working with patients in a collaborative environment but also in one that would allow her to flourish as an independent investigator. A search for positions in neuroscience at Wayne State led her to a posting for a faculty position with a research focus in neuroscience within the Department of Pharmacy Practice. The fit seemed perfect: She was bringing a neuroscience perspective to the pharmacy curriculum while expanding the department’s research portfolio and filling a need for trauma-related research in the Detroit area.

“Because neuroscience is such a broad area, it cuts across many different disciplines,” she noted. “We’re getting to a point where we need to show that what we’re doing in animal models is applicable to human trials. But before drugs are marketed for treatment, we must understand what a drug is doing at the basic level before we assume it will work for some people and without caring about the long-term effect. We [researchers] have a duty to the general public to bridge that gap. Moving forward from basic science research is key.”

A Look Inside the Lab

Now the director of the Translational Neuropsychopharmacology Lab (TNP2 Lab; www.tnp2lab.org), Rabinak has merged her training in basic and translational research to lead efforts aimed at understanding and treating a number of anxiety disorders. In one such project, the TNP2 lab is currently looking at the role of the cannabinoid system in the brain in the treatment for PTSD. Cannabinoid receptors are one of the most numerous receptors in the brain and play a significant role in the control of other neurotransmitter systems. Studies indicate that the cannabinoid system is disrupted in mood-related disorders and knowing that people will self-medicate with cannabis to alleviate anxiety and elevate mood, Rabinak is exploring the role a cannabis-like substance can play in the treatment of these disorders.

Using exposure-based therapy, researchers repeatedly expose subjects to the reminders of the traumatic event, like sounds, smells, remembering the event, that make them anxious or fearful in order to help them try to suppress or control those feelings. The cannabinoid system in the brain is critical for this type of learning, Rabinak said. Blocking this system from functioning properly in animal models showed that there was an initial suppression of fear but when tested later, they presented a recovery of fear responses. When doing the reverse—activating that system by administering THC—the animals showed an extinction of fear and a maintenance of that extinction over time.

“It seems counterintuitive but this is the first evidence suggesting that if you activate the cannabinoid system prior to extinction of fear, you can actually facilitate the long-term retention of the good memory,” Rabinak explained. “What’s key is that when people with PTSD undergo exposure therapy, they’ll be able to suppress fear during the session, but their maintenance to the next session is not sustained, and so they retain those anxious or fearful feelings. We need to maintain the therapeutic gains over time.”

Using a low dose of synthetic THC that doesn’t produce any psychoactive impairments, Rabinak began testing her theory in healthy people and those with PTSD. The healthy controls who received THC prior to extinction therapy showed lower fear responses than the people who had a placebo. When she conducted the same trial in those with PTSD, who struggle to maintain the extinction of fear over time, those who received THC showed a suppression of fear compared to those who received a placebo and exhibited a recovery of fear.

“People mistake what I’m doing as advocating for medical marijuana as a treatment for PTSD, but it’s not about treating symptoms, it’s about targeting the system in a different way,” she said. “Because current prescription drugs just treat symptoms, they serve as a band aid. The same can be said for medical marijuana—it’s just a band aid unless you use it to get at the root of the problem. Here we are using cannabis-like drugs as an adjunct to therapy to boost learning. The idea is that we’re trying to give people their lives back.”

Research Meets the Real World

Rabinak welcomes opportunities to share outcomes from her work with external groups, whether it’s within the research community or to local audiences. It’s these experiences that remind her who she’s ultimately trying to help: patients.

At a poster session hosted by a Department of Defense PTSD working group, a wounded veteran approached her on crutches. He was intrigued by her findings, curious to learn more about the THC treatment, and thankful for the work she’s doing in her lab.

“He said he’d like to have something that he wouldn’t have to rely on for the rest of his life to feel OK,” she said. “Those moments remind you why you’re doing what you’re doing.”

Maureen Thielemans is Associate
Director of Communications at AACP.