NEW Research Directions:
The way people are consuming cannabis for medicinal purposes is rapidly changing. By deliberately mixing different concentrations of cannabinoids and the terpenes that they’re dissolved in, people are discovering that they can achieve improved therapeutic benefits. This is taking advantage of what’s called the “entourage effect” in which multiple cannabinoids together have a stronger medicinal effect than individual cannabinoids on their own. Despite this understanding, it remains a shockingly understudied area of research. I am seeking to better understand how multiple cannabinoids, and their terpenes, can be utilized to achieve maximum medicinal benefits while minimizing side effects. I use behavioral testing screens combined with electrophysiology techniques to gain insight into the strength of the combination’s effect at both the behavioral level and the individual brain cell. This gives us the chance to identify the most potent therapeutic approach while minimizing side effects.
I am also working to enhance the medicinal benefits of the brain’s endogenous cannabinoid system. I am testing novel treatment approaches that enhance the level of the brain’s endogenous cannabinoid, 2-AG, and measuring its effects on treating disease and rescuing brain function that’s altered by genetic mutations.
Cannabinoid treatment of epilepsy and autism
Global use of medical cannabis is increasing, despite limited scientific evidence for its efficacy. Governmental restriction has made studying cannabis, especially in a medicinal context, particularly difficult. However, anecdotal reports of its medicinal benefits range across a host of ailments and thus warrant scientific investigation. I study the medicinal effects of cannabidiol (CBD), a prominent phytocannabinoid that won’t get you high, but is thought to convey many of marijuana’s medicinal benefits. Particularly, I study CBD’s ability to treat symptoms of Dravet Syndrome, a severe childhood disorder characterized by epilepsy, cognitive impairment, and autism.
Recent human clinical trials found that CBD effectively reduces seizures in Dravet Syndrome patients as on add-on therapy to their anti-epileptic medications. We find that CBD is effective at reducing febrile and spontaneous seizures in a mouse model of Dravet Syndrome. Furthermore, CBD normalized their social behavior, thus extending CBD’s therapeutic potential beyond an anti-epileptic to a promising autism therapy.
Studying CBD in rodents affords us the ability to gain mechanistic insight not afforded by human studies. My work identified that CBD rebalances the excitatory:inhibitory balance in the brain that is altered in this genetic disease by targeting a specific brain receptor, called GPR55, that’s independent of the traditional cannabinoid receptors.
I am currently working on harnessing the therapeutic potential of GPR55, and the body’s endogenous cannabinoid system to improve treatment options for these challenging genetic diseases.
Link to the publication associated with this work is below:
Cannabidiol treatment of epilepsy and autism – Proceedings of the National Academy of Sciences (2017)
Dissertation title: Cerebellar GABAA receptor contributions to alcohol intake and intoxication
40-60% of the risk for developing an alcohol use disorder, including alcohol abuse and dependence, is heritable. One of these heritable risk factors is sensitivity to alcohol-induced ataxia. Research from back in the 80’s identified that the balance of young men with a parent or grandparent who were alcoholics was less effected by alcohol than those without a family history. This suggested that there’s something unique about how the brain responds to low amounts of alcohol (i.e., the amount one would be exposed to following 1 or 2 standard drinks) that increases the likelihood of continued consumption. For instance, if a single drink makes you stumble, then perhaps you’re likely to consume less alcohol than if it takes 3-4 drinks before you notice impairment.
So what underlies this differential sensitivity to alcohol-induced impairment? My dissertation work identified the genetic and physiological mechanisms that underlie this differential sensitivity. It revealed that cells in the cerebellum, a brain structure that sits just above and behind the brainstem are particularly sensitive to low amounts of alcohol. In low-alcohol consuming rodents, these cells are largely inhibited by alcohol, and signaling in this important brain region shuts down. This leads to problems with balance and motor function and could underlie their aversion to continued consumption. In high-alcohol consuming rodents, however, these cells are less sensitive to the effects of alcohol, and so they keep firing away like normal. We found that pattern of alcohol sensitivity, from high sensitivity in low-alcohol consuming animals to low sensitivity in high-alcohol consuming animals is consistent across a number of species including mice, rats, prairie voles, and non-human primates. Furthermore, I found that by mimicking the response to alcohol observed in a low-consuming mouse in a high-consuming mouse, you can turn that high-alcohol consuming mouse into a low consumer. It’s almost as if there’s a neural switch that affects the initial stages of alcohol consumption.
Links to the publications associated with this work are below:
Cerebellar contribution to alcohol consumption – Journal of Neuroscience (2016)
High-alcohol consuming animals have a similar brain response to alcohol – Alcoholism: Clinical and Experimental Research (2016)
Opposite effects of alcohol in the brains of high versus low alcohol consumers – Nature Neuroscience (2013)