Throughout my time in academia, I have done research and coordinated studies among animals and humans with addictions. My research has spanned many different types of addiction, including cocaine, cannabis, opioids, alcohol, and internet addiction. My journey through addiction research began when I witnessed many of my peers attending rave parties and using stimulants and psychedelics in the late 1990s. I began to independently research the drugs that my friends were using and took classes such as Human Brain and Behavior, Clinical Neuropsychology, and Drugs and the Brain at the Department of Psychology of the University of Toronto, which helped me better understand the mechanisms of psychoactive substances. My interest culminated in a Thesis in Neuroscience where I showed that cerebral injections of a stress-associated neuropeptide produced reinstatement of cocaine self-administration behavior (unpublished data). Subsequently, I did a Master of Science at the Department of Psychiatry of the Université de Montreal. I showed that chronic amphetamine administration produces deficits in reward upon withdrawal, as measured by electrical self-stimulation of dopamine rich brain regions.1 For my doctoral dissertation, I showed that alcohol and cocaine were associated with increased parkinsonism among schizophrenia patients with substance use disorders (SUDs), whereas alcohol and cannabis were associated with akathisia (an inner sense of restlessness) among individuals with SUD without a diagnosis of schizophrenia.2 I continued my research in addiction at the Department of Psychiatry of the Yale University School of Medicine. I coordinated several large trials using functional magnetic resonance in conjunction with cognition and physiological measures among individuals with cocaine and alcohol use disorders. In one study, I showed that cocaine dependent subjects had hypoactive skin conductive response to negative emotional stimuli and less diminution of skin conductance response was associated with higher cocaine craving and lower activation in the midcingulate cortex to negative emotional images. This suggested that a hub of the limbic motor circuit, the midcingulate cortex may translate chronic cocaine craving into physiological responses that precipitate cocaine seeking.3 In another study, I used the cue-elicited alcohol craving paradigm to show that thalamic responses to alcohol cues contribute to at-risk drinking and positive alcohol expectancy among non-dependent drinkers, which is a cognitive model that predicts how people will drink and behave based on their beliefs about the positive effects of alcohol.4 To date, my research has culminated in over thirty peer-reviewed publications and one book chapter directly related to the field of addiction.
Addiction is an important topic given the changing landscape surrounding legalization of previously illegal narcotics as well as the rapid emergence of novel addictive substances that may lead to unforeseen issues among users. With the widespread legalization of cannabis in the U.S., Canada, and abroad, there has been an explosion of novel products such as Δ9-tetrahydrocannabinol (THC) based vaporized concentrates, oral formulations as well as synthetic analogues and semi-synthetic derivatives. Emerging cannabinoid products are typically many times more potent than smoked cannabis flower, which has been the focus of research to date. This is because they either: 1) activate cannabinoid receptors to a greater degree than naturally occurring compounds, 2) contain much greater concentrations of cannabinoids (e.g., many concentrates have levels of THC >90% and lower levels of cannabidiol, which counteracts THC effects), or 3) possess pharmacokinetic properties that leave much greater concentrations of these compounds in the body for longer periods of time (e.g. edibles). However, there is currently little research on the cognitive effects of novel cannabinoid products. Alarmingly, there has been an explosion of unlicensed dispensaries in the United States, so much so that unlicensed dispensaries outnumber legal ones around New York City and some of the product is 10 times as potent as what can be legally sold in New York.5 Increased use of high strength cannabinoid agonists is problematic since cannabis may accelerate brain aging. Indeed, in a meta-analysis, I showed that synthetic and natural cannabinoid agonists produce deficits in several cognitive domains, including verbal learning/memory, working memory, attention, and cognitive control.6
In my lab, I plan to develop a research program that examines the gap in research surrounding the potentially harmful cognitive effects of these ultra-potent cannabinoid compounds wherein users are left with reduced cognitive control and short-term memory deficits as well as side-effects such as akathisia and insomnia, which perpetuate the cycle of addiction.2 In addition, I plan to investigate perceptions of novel cannabinoids in the community as well as how enticing packaging and advertising can stimulate craving and further loss of self-regulation of cannabinoid use. The other side of the coin is that there are certain phytocannabinoids that block the cannabinoid receptor, which counteract some of the negative effects of cannabinoid agonists. In my review of cannabidiol, I found that this agent can improve cognitive deficits associated with cannabinoid agonists and can treat insomnia.7 Newer cannabinoid antagonists such as cannabigerol, cannabinol, and cannabichromene may also do the same thing, but research is scant. Cannabinoid antagonists are frequently combined with cannabinoid agonists in product formulations or sold by themselves to promote sleep and reduce pain. I plan to investigate what effect these agents have on cue-elicited craving, cognition, and side-effects associated with novel cannabinoid agonists currently on the market, and whether they are effective for the indications that they are being marketed for.
1 Zhornitsky S, Potvin S, Stip E, Rompré PP (2010). Acute quetiapine dose-dependently exacerbates anhedonia induced by withdrawal from escalating doses of d-amphetamine. European Neuropsychopharmacology. 20:695-703.
2 Zhornitsky S, Stip E, Pampoulova T, Rizkallah E, Lipp O, Bentaleb LA, Chiasson JP, Potvin S (2010). Extrapyramidal symptoms in substance abusers with and without schizophrenia and in nonabusing patients with schizophrenia. Movement Disorders. 25:2188-94.
3 Zhornitsky S, Le TM, Wang W, Dhingra I, Chen Y, Li CR, Zhang S (2021). Midcingulate Cortical Activations Interrelate Chronic Craving and Physiological Responses to Negative Emotions in Cocaine Addiction. Biological Psychiatry Global Open Science. 1:37-47.
4 Zhornitsky S, Zhang S, Ide JS, Chao HH, Wang W, Le TM, Leeman RF, Bi J, Krystal JH, Li CR (2019). Alcohol Expectancy and Cerebral Responses to Cue-Elicited Craving in Adult Nondependent Drinkers. Biological Psychiatry Cognitive Neuroscience Neuroimaging. 4:493-504.
5 CBSNews (July 2024). NYC illegal marijuana shops facing surprise raids, big fines. Here's what we saw on a ride-along. https://www.cbsnews.com/newyork/news/new-york-city-illegal-marijuana-shops-anthony-miranda-eric-adams/.
6 Zhornitsky S, Pelletier J, Assaf R, Giroux S, Li CR, Potvin S (2021). Acute effects of partial CB1 receptor agonists on cognition – A meta-analysis of human studies. Progress in Neuropsychopharmacology and Biological Psychiatry. 104:110063.
7 Zhornitsky S, Potvin S (2012). Cannabidiol in humans – the quest for therapeutic targets. Pharmaceuticals. 5:529-552.
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