The Neurobiology of Opioid Addiction:
Opioid-Related Learning & Memory
Opioid class drugs underlie the most dangerous and intractable forms of addiction. Globally, the opioid addiction crisis continues unabated and there is a desperate need for pre-clinical research to unravel the neuronal, behavioural and molecular substrates underlying the addictive properties of opioids. Our research program focuses on identifying the neurobiological mechanisms underlying the power of opioids to produce powerful associative memories linked to the drug-taking experience. With a special focus on the amygdala-prefrontal cortical circuitry, we are characterizing how chronic exposure to opioids induces 'molecular switching mechanisms' within these brain circuits, leading to compulsive opioid seeking, withdrawal memory formation and relapse. Our research suggests that rather than representing a permanent brain adaptation, the process of opioid addiction involves discrete, plastic processes within memory-related brain circuits that can be prevented or reversed with targeting of these molecular adaptations.
Neurodevelopmental Effects of Cannabinoids: Implications for Mental Health
Marijuana is the most widely consumed drug on the planet and a high percentage of adolescents are regular users of cannabis. In addition, increasing numbers of pregnant women are turning to cannabis for the alleviation of morning sickness and pregnancy-related anxiety. Given the extreme vulnerability of the adolescent and pre-natal brains to drug exposure, there is an urgent need to identify and characterize the effects of neurodevelopmental cannabis exposure on the development of brain circuitry associated with mental health. We are currently exploring these phenomena using pre-clincal, translational rodent models of THC exposure, to determine how exposure to THC, the primary psychoactive compound in cannabis, may alter neuronal, behavioural and molecular pathways linked to increased vulnerability to disorders like schizophrenia, anxiety, depression and addiction. These studies use a combination of in vivo exposure, as well as cerebral brain organoids in order to model prenatal brain development during the earliest phases of brain development.
UCLA Broad Stem Cell Research Center/Cell Reports
Development and Characterization of Phytocannabinoids as Treatments for Neuropsychiatric Disorders
Cannabis contains over 100 distinct phytochemicals. While the primary psychoactive component in cannabis, THC, has been associated with psychiatric symptoms in some individuals, the largest non-psychoactive compound in cannabis, cannabidiol (CBD), has been demonstrated in both clinical and pre-clinical studies to possess significant clinical potential in the treatment of various mental health disorders, including schizophrenia, anxiety, depression and PTSD. Research in our laboratory has identified the specific neuronal and molecular mechanisms by which CBD produces anti-psychotic effects in translational models of schizophrenia and PTSD. In addition, we are currently examining the mechanisms by which CBD may alleviate symptoms of anxiety, PTSD and depression, using a combination of pre-clinical modelling, molecular and neuronal assays. In addition, we are currently exploring the potential therapeutic potential of several lesser known phytocannabinoids, including cannabichromene and cannabigerol, as well as several monoterpene compounds.
Characterizing the Addictive and Neurodevelopmental Effects of Nicotine