2020 Project Narratives and Anticipated Impacts
Hemp derived extracellular vesicles (EVs) for the treatment of glioblastoma
Hassan Azari, PhD
Research Assistant Professor
College of Medicine
University of Florida
Project Narrative
Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis despite surgery and chemoradiotherapy. We have isolated and characterized extracellular vesicles (EVs) like nanoparticles (NPs) with strong anti-glioma effects from the hemp plant. These NPs contain cannabinoids in their acidic form and can be delivered into the brain via a non-invasive intranasal route. This project will examine anti-glioma therapeutic efficacy of the hemp EVs on mouse models of glioma and also their impact on standard of care temozolomide chemotherapy.
Anticipated Impact
Hemp EVs with their natural payload of non-psychoactive acidic cannabinoids represent a novel natural nanodrug source for brain tumor therapy. While we are initially testing this therapy in a model of primary brain cancer it could be applied to a broad range of other cancers metastasizing to the brain, and inflammatory neurodegenerative diseases. Given the scalability of hemp EVs and the simplicity of its application, positive results from this study would provide a strong rationale to test the approach clinically in a wide range of neurological disorders.
Cannabinoid medication for treatment of a preclinical model of anorexia nervosa
Lisa Eckel, PhD
Professor
College of Arts and Sciences
Florida State University
Project Narrative
Anorexia nervosa (AN) is a serious psychiatric illness with poor treatment outcome. Our work examines the endocannabinoid system (ECS) as a novel therapeutic target for AN, based on the critical role it plays in regulating food intake, energy expenditure, and reward processing, all of which are dysregulated in AN. The goal of this study is to investigate whether treatment with THC and/or CBD attenuates weight loss and normalizes ECS function in a pre-clinical animal model of AN.
Anticipated Impact
This pre-clinical study investigating the therapeutic potential of THC and CBD in alleviating AN symptoms in rodents, offers a translational model for the development of new cannabinoid-based pharmacotherapies, including the use of MMJ, that would help to ease the high personal and societal costs of AN.
Mechanisms of Action for Cannabidiol (CBD) in a Mouse Model of Anxiety
Debra Fadool, PhD
Professor
College of Arts and Sciences
Florida State University
Project Narrative
CBD is a nonpsychoactive ingredient of cannabis that has demonstrated changes in anxiety, chronic pain, sleep, and prevention of substance abuse in mouse and human subjects. We are using a newly found mouse model that exhibits anxiety and attention deficit to examine behavioral intervention of chronic CBD therapy across three stages of development (fetal, young adult, aged). We are also pairing our behavior studies with energy expenditure and eating behavior.
Anticipated Impact
Investigators can either induce anxiety by adding a stressor (“state” anxiety), or use a mouse model whereby the “trait” anxiety does not vary over time. Because CBD is not addictive, it has high therapeutic potential for chronic treatments and the use of the latter model affords an advantageous tool to explore reduction or elimination of anxiety- or ADHD-associated behaviors. This study will develop a preclinical tool for probing the molecular and electrical changes that mitigate anxiety and attention deficit behaviors.
Patterns, Motives, and Risks Associated with Marijuana Use: A Comparison of Medical Marijuana Patients and Non-Patient Marijuana Users in Florida
Jason Ford, PhD
Associate Professor
College of Sciences
University of Central Florida
Project Narrative
Little is known about medical cannabis among young adults, even though they are the age group with the highest prevalence of substance use. The main goal is to compare medical cannabis patients to non-patient cannabis users with regard to patterns and motives of use, psychosocial correlates of use, associations with substance use and other risky behaviors, and the effects of the COVID-19 pandemic on cannabis use. Regarding medical cannabis patients, we can assess the various health-related conditions they use cannabis to treat, their experiences at medical cannabis dispensaries, any side effects experienced due to cannabis use, and how patterns of cannabis use change after becoming a patient.
Anticipated Impact
The current research will help us understand patterns and characteristics associated with cannabis use among young adults in the state of Florida, particularly how use is associated with physical and mental health. An important outcome is identifying how medical cannabis users are different from non-patient users. We will be able to determine how the COVID-19 pandemic impacted patterns of cannabis use and learn about medical cannabis patients’ experiences with licensed dispensaries.
An Assessment of the Drug Interaction Potential Between Oral Cannabidiol (Epidiolex®) and the CES1 Substrate Methylphenidate in Healthy Volunteers
John Markowitz, PharmD, BCPP
Professor
College of Pharmacy
University of Florida
Project Narrative
Drug-drug interactions (DDIs) are a significant cause of emergency department visits, hospital admissions and increased morbidity and mortality, yet most are preventable. The DDI potential of conventional prescription medications is evaluated as part of the FDA approval process, a process not applied to medical cannabis which is frequently used in combination with prescription medications. The present DDI assessment is a rigorous clinical study in healthy subjects (n=12) which will determine if the major medical cannabis constituent, cannabidiol (CBD) can inhibit a major drug metabolizing enzyme (CES1) in a clinically significant manner.
Anticipated Impact
The results of the project will be impactful in several ways. First, it will inform the scientific and medical community as to whether in vitro DDI study methodology (more rapid and relatively inexpensive) can accurately predict clinical DDIs in healthy volunteers. Secondly, as numerous therapeutics agents are CES1 substrates and reliant on the enzyme for both detoxification and clearance as well as activation of certain prodrugs, the study results will have implications for co-prescribing of prescription medications with medical cannabis. Numerous drugs are potentially affected including many ACE Inhibitors, several antivirals, immunosuppressive drugs, some antiplatelet drugs and others. Project results can be rapidly disseminated to the scientific and clinical community.
Assessing and Supporting Effective and Safe Use of Medical Marijuana for Older Adults with Chronic Pain
David Newman, PhD, MA, MS
Associate Professor and Statistician
Christine E. Lynn College of Nursing
Florida Atlantic University
Project Narrative
The proportion of Florida’s older population is growing rapidly. Among this older group musculoskeletal disorders with associated chronic pain are common, but symptom management including chronic pain management can be challenging. Medications to relieve these symptoms, especially opioids, can increase the risk of confusion, constipation, falls and injury. This purpose of this mixed methods study is to identify what older adults need, to effectively and safely use MMJ, and to identify what age appropriate, evidence-based education is required.
Anticipated Impact
Develop evidence-based education for the safe and effective use of MMJ for older adults as well as provide guidance for policy for clinical practice.
Preclinical evaluation of exosomal cannabinoid formulations in chemotherapy induced peripheral Neuropathy
Mandip Singh Sachdeva, PhD
Professor
College of Pharmacy
Florida A&M University
Project Narrative
Docetaxel (DTX) is widely used for Triple negative breast cancer (TNBC), but DTXinduced peripheral neuropathy (DIPN) is a major clinical concern. Cannabidiol (CBD) alleviates mechanical allodynia and anxiety in peripheral neuropathy models by acting on (TRPV1)/CB2/5-HT1A/α3-Glycine receptors. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have potential clinical applications especially in peripheral nerve injury induced neuropathy. Hence a synergistic effect can be expected if we constitute an exosomal CBD formulation. We hypothesize that oral administration of Enteric Coated Mini Capsules encapsulating CBD exosomes will serve as an ideal delivery platform for significant alleviation of DIPN in non-tumor and MDA-MB-231 tumor bearing mice.
Anticipated Impact
This project will allow us to evaluate the role of CBD exosomes formulation to treat peripheral neuropathy induced by chemotherapy, which impacts majority of the breast cancer patients. Further this approach can also be extended for other ailments like Diabetes induced neuropathy.
The influence of cannabinoid receptors on olfactory function
Douglas Storace, PhD
Assistant Professor
College of Arts and Sciences
Florida State University
Project Narrative
Cannabinoids play an important therapeutic role in the stimulation of appetite and promotion of food seeking behavior. One potential underlying mechanism is the modulation of the olfactory system by cannabinoids. The current study uses a combination of functional imaging and behavior assays to determine how cannabinoid receptor modulation alters olfactory sensory processing and perception.
Anticipated Impact
Although our hunger level is determined by physiological signals that reflect our nutritional status, external sensory cues such as olfactory stimuli can enhance our appetite. Changes in the perception of a food-related odor could impact appetite and food-seeking behavior. The goal of these studies is to define how cannabinoids alter the representation of olfactory stimuli in the brain, and to link these changes to perception.
Endocannabinoid mechanism in the neural processing of food-predicting sensory cues
Roberto Vincis, PhD
Assistant Professor
College of Arts and Sciences
Florida State University
Project Narrative
In this proposal we aim to investigate the role of cannabinoid modulation of the mouse insular cortex (IC), a cortical area known to process motivationally salient stimuli associated with food reward cues and drive food-oriented behaviors.
Anticipated Impact
Investigating the neuromodulatory effects of endocannabinoids on neural processing of food-predicting cues within the IC will increase our understanding of the neurobiological mechanisms of cannabinoid actions and provide crucial information for the development of cannabinoid-based pharmacotherapies.