2021 Project Narratives and Anticipated Impacts
Acceptance of and access to medical marijuana and CBD as a palliative care and hospice treatments for nursing home patients
Jennifer Attonito, PhD
Instructor
College of Business
Florida Atlantic University
Project Narrative
Cannabis products, including Medical Marijuana (MMJ) have been found effective to improve multiple symptoms that are commonly observed among nursing home patients. This study will examine Florida nursing home clinicians’ knowledge of MMJ effects, contraindications, dosing, and prescribing/procuring processes; attitudes, and beliefs surrounding use of MMJ for their patients; barriers to accessing MMJ as a treatment; and regional, institutional, and economic factors that may be linked to variations in MMJ access in this setting. In addition, structured interviews of patients/caregivers will be conducted to explore their understanding of the process for accessing and perceived outcomes of utilizing MMJ for their conditions and symptoms.
Anticipated Impact
MMJ is rarely utilized as a therapy in long-term care settings where patients might find symptom relief from these products. This study creates a base of knowledge around MMJ knowledge, utilization, access, and acceptance around MMJ among nursing home clinicians and patients. Outcomes will provide a foundation for larger scale research that will further elucidate barriers to access to MMJ and test interventions for improving knowledge and access for patients, clinicians, and caregivers. The long-term objective is to translate research findings to clinical guidelines, standardized treatment protocols, and policies related to the use of MMJ in nursing homes.
Characterizing adverse drug events reports involving cannabis and cannabinoid
Joshua Brown, PharmD, PhD, MS
Assistant Professor
College of Pharmacy
University of Florida
Project Narrative
This project aims to understand the impact cannabis and cannabinoids have on adverse drug events and the contribution of drug interactions to this risk. We will identify common serious adverse events associated with cannabis use and conduct reviews of case reports to understand the causes and contributions to these events.
Anticipated Impact
This study aims to bring more attention to adverse effects of cannabis and to identify contributing factors, such as drug interactions or underlying health conditions. Output from this project will help set priorities for future research in adverse drug events and drug interactions with cannabis and will provide novel evidence to patients and physicians to make better decisions when using medical cannabis.
Investigating cannabidiol anti-headache actions through PPAR signaling
Andrea Cippitelli, PhD
Research Assistant Professor
College of Medicine
Florida Atlantic University
Project Narrative
This project aims at identifying a specific mechanism that mediates the observed anti-headache properties of cannabidiol (CBD) and evaluating the effects of a new class of compounds that promote peroxisome proliferating-activated receptors (PPAR) activity, or concurrently affect PPAR and cannabinoid-like activity, in the complex migraine symptomatology.
Anticipated Impact
Migraine is a debilitating disease lacking successful treatment options. Cannabidiol (CBD) appears to play a role in reducing head pain but the mechanism through which this effect occurs is unknown. This research will tell us whether activation of a group of receptor proteins called PPARs by CBD is responsible for relieving the pain associated with migraine and whether a new class of compounds with CBD-like activities can serve as a novel and effective treatment for migraines.
Cannabinoid modulation of neuroinflammation in a pre-clinical animal 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 outcomes. 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. Our study uses a pre-clinical animal model of AN to (i) investigate whether progressive weight loss promotes inflammation in brain areas that regulate food intake and (ii) test the therapeutic potential of cannabinoid-based medications in restoring normal immune function, improving appetite, and attenuating weight loss.
Anticipated Impact
This pre-clinical study investigating the therapeutic potential of cannabinoid drugs in alleviating AN symptoms in rodents offers a translational model for the development of new cannabinoid-based pharmacotherapies, including the use of medical marijuana, that would help to ease the high personal and societal costs of AN.
The role of endocannabinoids and cannabinoids in the clearance of bacterial infections and macrophage polarization
Mariola Edelmann, PhD
Assistant Professor
College of Agricultural and Life Sciences
College of Liberal Arts and Sciences
University of Florida
Project Narrative
In this proposal, we will uncover the function of immunometabolism in infectious disease and design new therapeutic approaches using cannabinoids by creating the framework supporting novel antimicrobial compound discovery. We will test cannabinoids in the preclinical study as candidates for host-directed therapies controlling bacterial clearance that stimulate the host defense mechanism and limit gastrointestinal inflammation.
Anticipated Impact
At the completion of the proposed research, we will determine the mechanisms by which endocannabinoids regulate innate immune response in infections with Gram-negative Salmonella and identify novel cannabinoids priming the host survival during this infection. The mechanism-based understanding of the lipid homeostasis in infection with Salmonella will provide a framework for the future development of specific cannabinoid-based therapeutic applications in the treatment of Gram-negative infections and inflammatory conditions caused by these infections.
Early Developmental 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 during gestation and perinatal life (two weeks prior to pregnancy, during fetal development, and during lactation). We want to understand if CBD fetal exposure affects brain development and may persist to reflect changes in anxiety as an adult.
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 gestational and perinatal study will develop a preclinical tool for probing the neuronal excitability, brain development (neural imaging), and anxiety and attention deficit behaviors that may accompany CBD, fetal-exposed mice that are then raised to early adults.
CBD-induced biomarkers of inflammation reduction in people living with HIV at the single cell level
Simone Marini, PhD
Research Assistant Professor
College of Public Health and Health Professions
College of Medicine
University of Florida
Project Narrative
People living with HIV (PLWH) are affected by comorbidities, including myocardial infarction and cancer, typically occurring earlier than in healthy individuals. These comorbidities appear to be strongly related to chronic inflammation, a condition characterizing PLWH. Cannabidiol (CBD) is known for its anti-inflammatory properties, however, the molecular mechanisms used to alter inflammation poorly understood. We propose to study the effects of CBD on inflammation in PLWH to understand the molecular role of different cells involved in the inflammation process.
Anticipated Impact
Showing the mechanisms of CBD in curbing chronic inflammation in PLWH could help reducing or resolving inflammation-related comorbidities that currently affect PLWH.
Evaluation of Minor Cannabinoids loaded Exosomes in Chronic Diabetic Neuropathy
Mandip Singh Sachdeva, PhD
Professor
College of Pharmacy
Florida A&M University
Project Narrative
Diabetic Peripheral Neuropathy (DPN) is the major clinical manifestations of diabetes and affects 50-70% of the diabetic population despite with the limited treatment options. Recently, we have optimized loading cannabinoids in extracellular vesicles derived from human umbilical cord derived stem cells/stromal cells (hUCMSCs-EVs) grown in PBS-vertical wheel (PBS-VW) bioreactors and our formulations have shown excellent role in offering neuroprotection against chemotherapy induced neuropathy. Based on these results, we will now be studying the effects of CBD/CBG/THCV loaded EVs either alone or in combination against diabetic pain.
Anticipated Impact
This study will provide insights about the therapeutic potential of minor cannabinoids (CBD, CBG & THCV) loaded exosomes in alleviating experimental DPN. This study would also suggest the beneficial effects of using exosomes derived from neural stem cells/hUCMSCs as novel drug carriers for therapy of painful DPN.
Alleviation of phantom limb pain in a rat model by treatment with components of Cannabis
Jacqueline Sagen, PhD, MBA
Professor
Miller College of Medicine
University of Miami
Project Narrative
Phantom limb pain is a frequent and debilitating consequence of medically-required amputation and is poorly managed by currently available therapies. The most frequently reported use of medical marijuana is for pain relief, and may be particularly indicated for treatment of complex chronic pain syndromes like phantom limb pain due to the wealth of cannabinoid compounds and terpenes acting via distinct complementary mechanisms. The goal of the study is to evaluate the potential beneficial effects of major Cannabis components and their combination in preventing and reducing phantom limb pain using a preclinical rodent model. Analgesic dose-ranging, side effects, and effects on reducing opioid use will be tested to provide the foundation for further development of medical marijuana in the treatment of this debilitating chronic neuropathic pain syndrome.
Anticipated Impact
There is a compelling need for improved treatment options for chronic pain patients through the identification of new and potent therapeutics. Solid preclinical evidence supporting the use of Cannabis-derived compounds for management of challenging neuropathic pain syndromes such as phantom limb pain is lacking. The study will address this knowledge gap to provide needed preclinical evidence in guiding policy decision-making on the medical use of marijuana for the clinical management of complex neuropathic pain syndromes.
Translational examination of the pharmacological interactions of medical marijuana with neuropathic pain analgesics in both young and older adults
Jenny L. Wilkerson, PhD
Research Assistant Professor
College of Pharmacy
University of Florida
Project Narrative
This work will directly address the Consortium’s charge to investigate drug-drug interactions with medical marijuana. Specifically, we will conduct a multi-disciplinary study moving from bedside to bench and back to bedside to understand what happens in the real-world, fill gaps in knowledge using animal models, and conclude with recommendations for best practices.
Anticipated Impact
Output from this study aims to inform combination therapy for a debilitating pain condition and to make recommendations to physicians regarding appropriate therapy. Our stratification by young and older adults will be further informative to reducing potentially high-risk prescribing among vulnerable populations.
The Effect of Delta-9-tetrahydrocannabinol (THC) on Intestinal Inflammation and Fibrosis in Experimental Crohn’s disease
Ellen Zimmermann, MD
Associate Dean & Professor
College of Medicine
University of Florida
Project Narrative
Crohn’s disease (CD) causes intestinal inflammation that leads to fibrotic strictures that often require surgical resection. Cannabinoids improve symptoms of CD and have become a popular adjunct to traditional immunosuppressive therapy. Surprisingly little is known about how cannabinoids work in CD and whether they effect intestinal inflammation or fibrosis. If cannabinoids improve fibrosis in our CD patients it would be a great benefit. However, a major adverse effect could result if patients using cannabinoids to calm their GI symptoms increased the fibrosis in their gut leading to surgery.
Our aim is to study the most abundant psychoactive substance in cannabis, delta-9-tetrahydrocannabinol (THC), in an animal model of CD and in cultured human tissue to lend insight into their mechanism of action and safety. Our outcome measures are standard histologic and molecular measures of inflammation and fibrosis that are used in therapeutic trials in CD.
Anticipated Impact
The impact of our studies is to better understand how cannabinoids work for Crohn’s disease and to have more confidence in their safety. A better understanding of the mechanism of action could lead to the development of more effective therapies for these difficult diseases.