CBD is Certainly a Big Deal!

At at time when over 60% of Americans favor legalizing marijuana, this has been an interesting few weeks for marijuana policy wonks. Several important initiatives have advanced bringing marijuana back into the spotlight. First, the US Food and Drug Administration approved the use of a CBD-based drugto treat certain rare forms of epilepsy. This happened at about the same time that Senate Minority Leader Chuck Schumer introduced a billin the US senate to federally decriminalize marijuana and remove it from the Controlled Substances Act. The timing of both of these events is intriguing because in October 2018, Canada will become the second country in the world to legalize and regulate recreational use of marijuana. We want to highlight the work of Dr. Barbara Kaplan, whose research investigates the effects of marijuana on the immune system. –JMO

At the end of last month, the US Food and Drug Administration (FDA) approved Epidiolex® (GW Pharmaceuticals), an oral cannabidiol (CBD) medication, to treat two rare forms of epilepsy: Lennox-Gastaut syndrome (LGS) and Dravet syndrome. It is the fourth cannabis-based medicine to get FDA approval. The other FDA-approved cannabis-based medicines are Marinol® (Abbvie) and Cesamet® (Mylan Specialty LP), two synthetic forms of tetrahydrocannabinol (THC) available in pill form, and Syndros®,  a liquid form of synthetic THC (INSYS Therapeutics). The latter three approved cannabis-based medicines differ from Epidiolex® in that they are prescribed for nausea associated with chemotherapy and appetite stimulation for those with severe weight loss due to AIDS or cancer; Epidiolex® is only approved to treat the indicated forms of epilepsy.

What is CBD and how does it differ from marijuana, medical marijuana, and THC? With new cannabis-based medicine available on the US market, it seems like a good time to review some of what we know about THC and CBD, two of the chemicals found in marijuana. Let’s start with marijuana, which usually refers the the plant itself. A common species of the marijuana plant is Cannabis sativa, a plant that contains over 600 natural chemicals, of which CBD and THC are two. Because of their chemical structure and how they interact with your body, CBD and THC fall into a group of chemicals from the plant referred to as cannabinoids. “Medical marijuana” is a loose category that typically refers to physician-approved or -prescribed smoking of the marijuana plant or ingesting marijuana in cookies, brownies or teas (or other edibles) for a variety of ailments as determined by the user. Many states allow for the medical use of cannabis through state-regulated medical marijuana dispensaries, however some states are more stringent than others with regard to which ailments can be treated with medical marijuana. Cannabis-based FDA-approved medicines are also referred to as medical marijuana but there are at least two important distinctions: 1) Marinol®, Cesamet® and Syndros® are FDA-approved drugs available by prescription while medical marijuana is still illegal federally; and 2) Marinol®, Cesamet® and Syndros® are purified, synthetic THC while medical marijuana contains over 600 chemicals.

Now let’s consider the differences between THC and CBD. Both chemicals come from the plant, but THC is the main chemical that makes you feel high after smoking or ingesting marijuana. CBD does not make you feel high because it does not have the “rewarding properties of THC.” The rewarding properties of THC are due to the fact that THC interacts with proteins in the brain called cannabinoid receptors. CBD does not interact with cannabinoid receptors very well so it does not produce the reward, or high. This does not mean that CBD is not active in the brain; on the contrary, we know it must be active in the brain as it is effective in treating some forms of epilepsy. In fact, for many years CBD was referred to as “non-psychoactive” because it did not contribute to the high, but since we know it is active in the brain, CBD should not be referred to as non-psychoactive and I have stopped referring to it as such in my own work.

My work is focused on understanding the degree to which CBD is active in the immune system, which is responsible for protecting you from disease. We and others have shown that cannabinoids, including CBD, do affect the immune system. For instance, we conducted a broad range of studies using mouse and human cells and showed that CBD decreases their immune function. Specifically, CBD prevents the cells from producing proteins that are released that allow them to communicate with other cells. Cell-cell communication is critical for an effective immune response; your immune system can use more than 10 different cells to fight disease so these cells need to be able to signal to each other. CBD also prevents the cells from proliferating, or expanding. Again, for an effective immune response, some of your immune cells need to expand so they can enhance their fighting power against the infectious agent. Together our data and others suggest that CBD could be effective for some people to treat immune-mediated diseases, such as autoimmune diseases or allergies. CBD, as Epidiolex®, underwent several studies in order to get it to the point where it’s known to be a promising treatment for some forms of epilepsy, so we should keep studying CBD to see whether it would be effective for other diseases as well.

Edited by Jason Organ, PhD, Indiana University School of Medicine.

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