Dr. Isabelle Boileau

An Interview with Dr. Isabelle Boileau on Imaging an Addicted Brain

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Dr. Isabelle Boileau
Head of the Addiction Imaging Research Group, CAMH
Associate Professor, Department of Psychiatry, UofT
Associated Professor, Institute of Medical Science, UofT

By: Göcke Özdemir
Photo courtesy of CAMH

Have you ever felt like you just can’t get enough of something? Think of a chocolate bar that you opened for just one piece but ended consuming the entire thing, or being next to someone you love and are inseparable from because of how happy they make you. It’s a funny thing the brain. It has a constant hunger for whatever it wants, and it is not easy to say no to.

But what brain characteristics determine whether an individual will become addicted to a certain substance? How do addictions to drugs of abuse develop, and importantly, what factors contribute to relapse? Dr. Isabelle Boileau, Head of the Addiction Imaging Research Group at the Centre for Addiction and Mental Health (CAMH), is using neuroimaging to investigate how drugs of abuse affect the brain.

Currently an Associate Professor of Psychiatry and an Associate Member of the Institute of Medical Science at the University of Toronto, Dr. Boileau began her training studying the neural mechanisms behind addiction at McGill University. Here, she completed a PhD studying the increase in levels of dopamine that occur upon acute drug administration (alcohol and amphetamines in particular) using positron emission tomography (PET). PET is an imaging technique that uses radioactive tracers to measure metabolic activity, levels of receptors and enzyme in the body, including in the brain. She then went on to New York City to complete her post-doctoral fellowship at Columbia University and then returned to continue her science career in Toronto.

Dr. Boileau’s research investigates the neural pathways involved in pathological gambling, as well as compares the dopamine systems of patients with Parkinson’s disease (caused by lack of dopamine producing cells) to people with amphetamine addiction. Dr. Boileau is currently looking at factors that may contribute to the chronic nature of addiction in the dopamine and endocannabinoid systems, as well as investigating glial cell markers as indications of whether chronic drug use causes brain damage.

Regarding the dopamine system, a recent study from Dr. Boileau’s laboratory used a radiotracer ([11C]-(+)-PHNO) that is specific to dopamine D3 receptors to show that these receptors are expressed at higher levels in the brain of people who chronically use drugs than in healthy controls, and are related to “wanting” more drugs. Conversely, D2 receptor density and dopamine levels are down regulated in drug users. Low D2 receptor expression and low synaptic dopamine have been suggested as factors that make an individual more vulnerable to addiction, whereas other studies suggest that high D2 receptor density protects against addiction 1. The finding of higher D3 receptor density in addicted individuals suggests that any therapeutic effort to increase “deficient” activity at the D2 receptor may increase an individual’s motivation to use drugs –clinical trials targeting the dopamine system need to consider the contradictory effects of stimulating D2 versus D3 receptors.

Although no research has been able to prove whether different levels of D2 or D3 receptors are causes of addiction or consequences of drug use, Dr. Boileau believes that it’s likely both. For example, a recent study suggests that individuals with high familial risk for addiction have differences in the dopamine system which predate drug use, suggesting an inherent vulnerability 2. However, studies (including the work of Dr Boileau) have linked drug use severity with the magnitude of the D2 receptor deficit, and longitudinal studies also exist where people detoxifying from drugs show a normalization of dopamine neurons and transporters. This indicates that abnormal dopamine receptor density represents both a “state” associated with chronic drug use and a predisposing “trait”. More research is needed to understand how genetics and natural brain chemistry might predispose (or protect) us from developing addictions.

Another project that Dr. Boileau’s team is working on is related to fatty acid amide hydrolase (FAAH), an enzyme that metabolizes endocannabinoids. Using a probe that attaches itself to FAAH, they have discovered that in response to early withdrawal from cannabis or alcohol, FAAH is downregulated. “Our gut interpretation is that this might be a compensatory response to acute exposure: FAAH downregulates in an effort to increase anandamide (an endocannabinoid neurotransmitter, the body’s own version of cannabis) in the brain, and this might be a reason why the withdrawal signs are not present early on in cannabis use disorder”, says Dr. Boileau. Despite the relatively low risk of addiction and less intense withdrawal symptoms with cannabis, she highlighted that exposure to cannabis during development may change one’s ability to learn, and warns younger users to be responsible and avoid using cannabis in school.

When asked what the most rewarding part of her job is, Dr. Boileau said: “This is. I think sharing knowledge is very fun, especially with students, because working with motivated and curious students brings me back to science and to the questions, and away from the paperwork!”

As to where the future of addiction research is headed, because PET scans can confirm where in the brain medications are acting and rate at which they are metabolized, Dr. Boileau hopes that PET findings will contribute to the development of evidence-based therapeutics: “Often we go in blind; we try medications in different populations and hope for the best. With more resources invested in PET, we can know better whether there are valid reasons to use a certain medication or not, and it’ll help us approach the right target.”

She also added some advice for graduate students: “Zoom out from time to time from your work to understand the relevance of it all, and where you want to go with it. It’s a very fun career but one in which you have to keep reinventing yourself. It’s relentless, and you always have to keep going, so it’s important to think about every new step you’re taking and why you’re doing it rather than just following the path blindly.”

While there are still many unanswered questions about how a “high” brain is different or how addiction can be alleviated, Dr. Boileau is optimistic about the potential role PET imaging can play in developing better medications and better outcomes for those dealing with addiction.

References

  1. Thanos PK, Volkiw ND, Freimuth P, et al. Overexpression of dopamine D2 receptors reduces alcohol self-administration. J Neurochem. 2001 Sep;78(5):1094-103.
  2. Casey KF, Benkelfat C, Cherkasova M, et al. Reduced dopamine response to amphetamine in subjects at ultra-high risk for addiction. Biol Psychiatry. 2014 Jul;76(1):23-30.