Clinical Neuroscience
Head: Dr. Usoa Busto
The Clinical Neuroscience Section studies the behavioural and pharmacological
effects of psychotropic drugs in humans. For the past few years, we have
been working on many studies to expand our understanding of the different
factors that contribute to the development and maintenance of substance
use disorders in humans.
Many factors operate simultaneously to influence compulsive drug-taking
behaviours. These can be factors that depend on the drug, the host and
the environment.
Abuse Liability of Drugs
The intrinsic pharmacological characteristics of drugs of abuse (such
as potency, the ability to produce reinforcing effects and drug kinetics)
are essential to drug-taking behaviour. Thus, an important line of research
is the determination of the comparative abuse liability of currently available
drugs as well as new compounds. Current studies in our section explore
the comparative pharmacology, behavioural effects and abuse potential
of heroin and hydromorphone in human subjects (with Drs. Brands and Marsh).
Host Factors Contributing
to Substance Use Disorders
Another line of research relates to host factors contributing to substance
use disorders, including multiple drug use, psychiatric comorbidity and
genetics. Current studies in this area examine the role of the brain reward
system in major depressive disorder (with Drs. Naranjo, Mayberg and Graham)
and the role of nicotine in modulating symptoms of depression in smokers
and non-smokers who have depression (with Drs. Cardenas, Zack, Houle,
Kapur and Mayberg).
Also in this line, the group studies genetic factors influencing drug
use problems and dependence. Studies underway are examining the role of
the enzyme P 450 2C19 in the abuse liability of flunitrazepam in Caucasian
and Asian populations (with Drs. Sellers and Tyndale).
The section also studies the role of environmental factors influencing
drug use problems, including drug availability, cost and utilization.
Recently, we have begun examining age as a factor, and we are studying
the effects of hypnotic medications in older adults (with Drs. Sproule
and Herrmann).
Biobehavioural Moderators
of Addiction
Processes regulating addictive behaviour are the overarching focus of
three additional lines of research: activation of brain systems involved
in compulsive drug-seeking and gambling; inhibition/disinhibition of brain
systems involved in compulsive drug-seeking and gambling; and pre-clinical
assessment of potential medications for the treatment of these syndromes.
Drs. Zack and Poulos, along with collaborators Corrigall, Fletcher, Kish,
and MacLeod, are investigating these questions in addicted populations
as well as in non-addicted or prodromal populations (e.g., university
students, adolescent smokers), using pharmacological and environmental
stimuli as probes to assess physiological, cognitive (e.g., reaction time)
and subjective responses.
Recently, our research has begun to identify common cognitive-behavioural
deficits that appear to characterize the increasing severity of addiction.
Thus, from a clinical standpoint, our research investigates processes
that may be involved in the transition to dependence on alcohol, drugs
and addictive behaviours such as problem gambling.
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