Sera Sermet’s paper seeks to understand how cannabinoids alleviate inflammation

Most people who use medical marijuana turn to it as a means of alleviating chronic pain. But the effects of marijuana on chronic conditions reach beyond simple pain relief. Pain and inflammation are intrinsically linked in that pain is one of the cardinal signs of inflammation.

For Doctoral candidate Sera Sermet, understanding the interactions between cannabinoids and inflammation has become the subject of her overarching research as well as a recently published paper on the topic.

“We want to understand how we might be able to use cannabinoids (compounds found in the cannabis plant) to help alleviate neuroinflammation experienced by HIV patients and, really, for inflammation throughout the body,” she said.

The key is the two main ingredients in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), which have long been known to interact with the immune system and serve as powerful anti-inflammatory agents. The difference between the two is that THC acts as an anti-inflammatory but also causes the well-known psychotropic effects often referred to as being “high”, while CBD battles inflammation without causing the same psychotropic effects.

In the lab of Dr. Norb Kaminski, a world leader in the field of immunotoxicology, Sermet is conducting research to elucidate how cannabinoids exert their anti-inflammatory properties. And while she has made some inroads, the answers are steeped in the complex biology of the immune system.

“The issue is we don’t fully understand all of the molecular targets with which these cannabinoids interact with in the human immune system,” she said. “A significant amount of research has been conducted over decades using animal models; however, the more we learn about the human immune system we discover some similarities to other animal species and also marked differences. In our lab, the unique part is studying the effect on human cells.”

A large portion of Sermet’s work revolves around the study of an immune cell type called the monocyte. An important function of these cells is to patrol the body for invading pathogens, through activation of toll-like-receptors (TLRs) found on the surface and within monocytes. TLR activation can result in inflammation, which the Kaminski laboratory is looking to alleviate with cannabinoid treatments.

“A long-term goal of my laboratory has been to capitalize on the immunomodulatory and anti-inflammatory properties of this class of cannabinoids while finding molecules like CBD that do not possess the psychotropic properties that THC possesses,” she said.

In a recent paper published with the assistance of Dr. Kaminski, doctoral candidate Brianna Finn, and lab manager Robert Crawford, Sermet found that THC, more than CBD, can suppress the inflammatory response of those activated human monocytes.

“Because we have previously observed that monocyte-derived IL-1ß (an inflammatory factor mainly produced by activated monocytes) can be suppressed by cannabinoids, we wanted to see if cannabinoids do this by inhibiting the machinery that processes IL-1ß into its mature active form,” Sermet said.

The paper found that THC and CBD reduced the amount of an inflammatory cytokine (a protein important for cell communication and triggering inflammation). They also found that THC and CBD both suppressed IL-1ß, which is produced by activated human monocytes, by blocking intracellular mechanisms necessary for processing and maturing IL-1ß (caspase-1 activity and inflammasome formation).

Sermet’s suggestion was that both CBD and THC could be useful for treating diseases linked to chronic inflammation. But she said there are still questions to answer.

Her remaining goal is to understand how these cannabinoids might help mitigate neuroinflammation associated with HIV infection. While about 40-50 percent of people living with HIV are diagnosed with neurocognitive disorder, medical marijuana has improved their prognosis by reducing systemic inflammation and likely also decreases neuroinflammation as cannabinoids readily cross the blood brain barrier.

“The big takeaway from the paper is that we found that THC and CBD reduce a key inflammatory molecule in human immune cells by blocking the process that readies it for release,” she said.