Previous TRICE Award Recipients
Rama Maganti, M.D.
University of Wisconsin-Madison, Madison, WI
Cannabidiol, mTOR and the excitation/inhibition balance in epilepsy
Cannabidiol (CBD) is a major component in marijuana believed to offer anticonvulsant effects in certain patient groups with epilepsy. CBD is believed to have neuroprotective effects, and limited experimental studies suggest that it may work by reducing over-excitation cause by glutamate or by improving sleep. Nonetheless, the mechanism linking CBD to these measures or other mechanisms remains non-compelling and/or insufficient. The neurological mechanism is likely complex, yet mechanistic understanding would inform CBD dosing and patient population selection. To unveil the mechanism behind CBD’s potential as an anti-epileptic, we propose to investigate major metabolic signaling pathways critical to neuronal health and survival and we will undertake a thorough investigation of CBD action on the excitatory/inhibitory balance in the brain. To do so we will employ various mouse models of epilepsy to assess electrophysiological changes and sleep outcomes linked to CBD use. Understanding the mechanism behind CBD’s anticonvulsant potential will inform neurologists as to the appropriate patient groups and epilepsy syndromes which would potentially be alleviated by CBD.
Angela Birnbaum, Ph.D.
University of Minnesota, Minneapolis, MN
Pharmacokinetic and Cognitive Side Effects of Cannabidiol in Adult Patients
Listen to the Research Updates webinar on Cannabinoids in Epilepsy
Extensive media coverage of dramatic control of intractable seizures, especially in children with Dravet’s syndrome, has led to state laws allowing various preparations derived from marijuana to be used in patients. These laws have been adopted with little being known about how the various substances are handled by the body (pharmacokinetics), how safe they are, if they interact with other medications, and how much is needed to control seizures. A high grade product is available in Minnesota making it possible for a detailed study to evaluate how cannabidiol (CBD) is handled in the body and what effect it has on thinking and mood. The proposed study will give adult patients with intractable epilepsy a pure form of CBD to evaluate its pharmacokinetics and side effects during three scenarios: with food, fasting, and during chronic therapy providing data needed to create dosing and treatment guidelines. The long-term goal of this study is to provide information about CBD that will help design larger, longer term studies. This study will also inform later studies that may use different formulations of cannabinoids (varying amounts of THC and CBD).
Misty Smith, Ph.D.
University of Utah, Salt Lake City, UT
Analysis of Cannabidiol Interactions with Antiseizure Drugs
Misty Smith presented a poster on her project at the 2015 American Epilepsy Society Annual Meeting.
Little is known concerning the interactions of cannabidiol (CBD) with other anti seizure (ASDs) and how these interactions will impact the efficacy and safety of CBD when given concomitantly with other ASDs to patients with epilepsy. The optimal CBD/ASD drug combinations identified in this proposal will also be evaluated in assays that reflect the comorbidities of epilepsy, including anxiety and depression, and potential adverse motor effects of the drugs and their combinations. In that way, potential therapeutic benefits or liabilities of combined ASD treatment with cannabidiol will be rapidly identified. This proposal directly addresses the Request For Proposals (RFP) from the Epilepsy Foundation of America (EFA) seeking a better understanding of the potential synergistic, additive, or antagonist interactions of CBD with concomitant ASDs in order to find more efficacious and/or safer therapeutic options.