ICR State Fiscal Year 2023

Kent Hutchison, PhD

Institute of Cognitive Science Affiliated Faculty & Professor, University of Colorado Boulder

Cannabinoids and Traumatic Brain Injury: A Randomized, Placebo Controlled Trial

Traumatic brain injury (TBI) represents a major public health burden due to chronic neuropsychiatric sequelae (emotional, physical and cognitive) that negatively affect vocational activities, interpersonal relationships and independent living. Responses of these chronic symptoms to any particular treatment are both variable and, too often, suboptimal. As a result, persons with TBI are frequently prescribed numerous therapies which may or may not be efficacious. Cannabinoids (both CBD and THC) have gained significant public attention as a potential alternative treatment for TBI sequelae. However, the growing perception of the efficacy of cannabinoids for TBI and related pain, mood, and anxiety disorders can be directly contrasted with the limited scientific evidence. Moreover, due to complex regulatory requirements, many individuals use medical cannabis on an “off-label” basis without the appropriate scientific controls to establish efficacy. This project will identify the potential therapeutic effects associated with widely available cannabinoid formulations on TBI-related deficits in cognitive function and self-reported anxiety, depression, sleep, and pain. The proposed study relies on a gold standard methodology and maximizes generalizability of findings, despite the current regulatory environment for cannabis research.

Christopher Lowry, PhD

Associate Professor, Integrative Physiology, University of Colorado Boulder

Preventative and treatment effects of broad-spectrum cannabidiol (CBD) in a rat model of comorbid autism and epilepsy: A mechanistic study

Over 50% of children with autism spectrum disorder (ASD) show sub-clinical epileptic spikes by adolescence and 5-40% develop chronic epilepsy. Similarly, approximately 30% of children with epilepsy are also diagnosed with ASD. As a likely etiology, the role of inflammation in epilepsy is under intense investigation and there is increasing evidence for inflammation in the comorbidity of autism and epilepsy. Broad-spectrum cannabidiol (CBD) is a major bioactive component of marijuana that lacks the euphoria/intoxication associated with delta-9-tetrahydrocannabinol (THC)-related cannabinoids yet has been shown to have powerful anti-inflammatory effects in the brain. These anti-inflammatory effects introduce the possibility of its use in preventing and/or treating certain neurological disorders associated with inflammation, specifically ASD and epilepsy to be studied in this project. We hypothesize that the marked comorbidity between autistic behavior and epilepsy reflects limbic hyperexcitability produced by neuroinflammation. Yet, until now, there has been no preclinical animal model of comorbid autism and epilepsy, requisite to study mechanisms (e.g., neuroinflammation) and possible interventions. The primary aim of this project is to determine if administration of CBD during maternal or postnatal periods can prevent development of a comorbid ASD/epilepsy phenotype. In this project we will answer three questions: 1) Does maternal administration of CBD reduce comorbid ASD/epilepsy in rat pups? 2) Does postnatal (PN10–PN30; before epileptic spikes appear; administration of CBD reduce comorbid ASD/epilepsy in rat pups? 3) Does combined maternal and postnatal administration of CBD reduce comorbid ASD/epilepsy in rat pups? Successful outcomes may lead to novel approaches for prevention of comorbid ASD/epilepsy in children of high-risk mothers.

Duncan Mackie, PhD, Director of Pharmacology & Experimental Therapeutics, MedPharm Holdings

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Cinnamon Bidwell, PhD, Institute of Cognitive Science Faculty, Assistant Professor, University of Colorado Boulder

Isolation and Pharmacological Evaluation of Phytocannabinoids for Alzheimer’s Disease

 Our research group has a longstanding interest in the activity of cannabinoids for the treatment of inflammatory neurological diseases such as Alzheimer’s disease. The purpose of this proposal is to further develop methods of isolation to purify unique cannabinoids and characterize the effects of cannabinoids and cannabinoid mixtures on immune function via microglia activation states. Microglia are macrophages located in the central nervous system (CNS) and are the main immune defense in the CNS. During neurodegenerative disorders, microglia actively secrete inflammatory factors. This abundance of inflammatory signaling contributes to the neuronal damage observed in Alzheimer’s disease. To resolve the pro-inflammatory condition, microglia switch activation states and are able to inhibit the inflammatory response. Our hypothesis is that purified cannabinoids will attenuate the activation of microglia by shifting the microglia into the inhibitory state and thus reducing microglial inflammatory signaling. Ultimately, this work will provide the mechanistic basis for the development of cannabis-derived therapeutics for the treatment of neurological diseases with an inflammatory component.

Punya Nachappa, PhD

Associate Professor, Entomology, Department of Agricultural Biology, Colorado State University

Examining the adaptive roles of plant defensive chemistry on pest resistance in Cannabis sativa

Understanding how plants respond to insect herbivores can provide new insights into plant-insect chemical communication and coevolution and facilitate new approaches to crop protection. Cannabis is known for the presence of cannabinoids, which include Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and more than 100 related secondary metabolites. In addition to cannabinoids, C. sativa also possesses a range of defense mechanisms (namely terpenes and phenolic compounds) that are conserved across dicots and well described in other model plant species. To date, no study has analyzed the degree to which cannabinoids confer pest resistance relative to other defensive traits in C. sativa. Hence, the goal of our project is to understand how variation in secondary metabolites in C. sativa affects key hemp pests by using and developing novel genetic tools and technology. Outcomes of this research will not only advance basic research in the field of plant-insect coevolution but also has practical applications for breeding for pest resistance in hemp.

Mike Van Dyke, PhD

Associate Professor, Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado Anschutz Medical Campus

Potential Health Effects of Heavy Metals in Cannabis Flower, Concentrates, Vape Devices, and Vape Emissions

Inhalation exposure to heavy metals such as lead, cadmium, arsenic, nickel, mercury, and manganese can increase the risk for cancer as well as neurological, renal, cardiovascular, and hepatic outcomes. Smoking or vaping cannabis products can result in inhalation exposure to many different heavy metals due to plant absorption of these metals from soil, irrigation water, or fertilizers and leaching of these metals from vape hardware. Currently, cannabis is regulated for only four heavy metals (lead, cadmium, arsenic, and mercury) despite known health effects from other co-occurring heavy metals. Pharmaceutical products are regulated for 24 heavy metal or “elemental” impurities. Metal exposure from cannabis vaping represents a problem with significant public health urgency, given that cannabis vaping as the primary method of use has increased 50% between 2017 and 2019 in the U.S., and that past research has identified chromium, lead, tin, and nickel as detectable in cannabis vapors at higher concentrations than in tobacco smoke. This project brings together an innovative partnership between academic researchers and Kaycha Laboratories, a national cannabis testing laboratory, to answer important public health questions including the levels of 21 heavy metals in commercially grown cannabis, vape device construction and use conditions important in leaching of these heavy metals into cannabis oils, and most importantly, the potential health risks from exposure to these heavy metals through smoking or vaping cannabis.