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Marijuana: More Than Just The High

Marijuana is a controversial subject–it is illegal according to federal law, even while 29 states (and Washington, DC) have legalized medical use in some form or another. Furthermore, the science behind marijuana use is ongoing, especially in the context of medicine. Today, we feature a piece by Dr. Barbara Kaplan, who studies the effects of marijuana on the immune system, and is working hard to educate the public about her science. We are thrilled to publish this work and hope you will find it enlightening. To keep up to date with SciCommPLOS, please follow us on Twitter. More information on medical marijuana published in PLOS journals and blogs can be found here. –Jason Organ

I have been experimenting with marijuana for over 15 years—but not in the way you think. I am a basic research scientist, and my job is to study the immune system—the body system that wards off infection and disease. I used to avoid telling people what I do for a living because I assumed that they weren’t interested, they might not understand, and that I’m not the right person to teach them about science. Several years ago, a colleague set me straight: people are interested, they understand more than scientists give them credit for, and that I absolutely should be the one to be talking about science because I AM A SCIENTIST.

My scientific area of expertise is called immunotoxicology. What that means is that I study how chemicals affect the immune system. We live in a world full of chemicals. Drugs, like antibiotics used to treat bacterial infections, are chemicals, as are things like pesticides, paints, solvents, and even plants and foods. One of my areas of research involves studying how the natural chemicals in marijuana plants interact with the immune system.

Marijuana is a controversial subject with wide interest and appeal. In the United States, marijuana use has increased over the last several years as many states have voted to legalize it for medical use and/or decriminalize (or outright legalize) it for recreational use.  At the federal level, marijuana is still illegal regardless of use—it is classified as a Schedule I drug (i.e., chemicals with no known medical use) by the US Drug Enforcement Agency, placing it in the same category as heroin and LSD, among others. There is, however, a synthetic form of the psychoactive chemical, THC (tetrahydrocannabinol), marketed as Marinol®, which is used to help reduce nausea following chemotherapy, and as an appetite stimulant for those experiencing severe weight loss, such as AIDS and cancer patients. Currently, THC and other marijuana-derived chemicals are being studied in clinical trials to assess their potential for medical use, such as treatment for neuropathic pain, or to combat autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and Crohn’s disease. One such chemical receiving a considerable amount of attention is CBD (cannabidiol), because many have reported it to also be very effective in treating seizures (1).

Whereas both CBD and THC are natural marijuana-derived chemicals, CBD does not produce the high associated with THC. Despite this difference, work in my laboratory and others demonstrates that THC and CBD both affect the immune system.  For example, some cells of the immune system (white blood cells such as macrophages and T cells) detect foreign invaders of your body (e.g., viruses) and try to destroy them by producing defensive proteins.  THC and CBD suppress the abilities of macrophages and T cells to make those proteins (2, 3). In other words, THC and CBD suppress the immune system’s ability to work properly, so the foreign invader has an advantage.

With a disease like influenza, suppression of the immune system by THC or CBD may result in more severe symptoms or a longer duration until recovery. This is clear from studies performed with animals, although similar studies in human cells suggest this could also happen in people. In mice, infection with influenza leads to lethargy, anti-social behavior, and weight loss, but recovery usually happens within a week or two because high numbers of macrophages and T cells are able to fight off the virus in the lungs. When mice are treated with THC while infected with influenza, the number of macrophages and T cells traveling to the lungs to fight off the virus is reduced, and recovery takes longer (4).

In the context of autoimmune diseases, suppression of the immune system by THC and CBD would be a welcome outcome, and indeed is the current target of therapy. Autoimmune diseases like multiple sclerosis, rheumatoid arthritis, and Crohn’s disease occur because the immune system is overactive and responds by attacking normal cells and organs instead of (or in addition to) foreign invaders. So in this case, use of THC or CBD to suppress the immune system might be beneficial. Like with influenza, the use of THC and CBD to suppress the immune system in the context of autoimmune disease is currently under investigation in humans (5), based on strong evidence in favor of this approach using mice (6).

In thinking about just these two examples, it is clear that THC and CBD have important roles in suppressing immune function, and that in some cases this suppression is not good (i.e., if you are fighting off influenza) and in others it may be beneficial (i.e., if you have autoimmune disease). And, this suppressive action of THC and CBD on the immune system is not unique to these chemicals. In fact, many important and widely-used drugs to treat autoimmune diseases suppress immune function, so are a benefit to those with disease, but potentially detrimental if taken by those without disease. So where does this leave me and my research now? My path forward is to continue to determine how these natural chemicals from marijuana act in the immune system. The studies in my lab and others will provide strong data for those who make decisions about which chemicals to formulate into drugs, and perhaps this will lead to development of another marijuana-based medicine in the coming years. But perhaps just as important, I hope my message will resonate with marijuana users who need to understand how this drug affects their body, for better or for worse.

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

References:

  1. A. Leo, E. Russo, M. Elia, Cannabidiol and epilepsy: Rationale and therapeutic potential. Pharmacol Res 107, 85-92 (2016).
  2. T. K. Eisenstein, J. J. Meissler, Effects of Cannabinoids on T-cell Function and Resistance to Infection. J Neuroimmune Pharmacol 10, 204-216 (2015).
  3. K. L. McCoy, Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation. Mediators Inflamm 2016, 5831315 (2016).
  4. J. P. Buchweitz, P. W. Karmaus, J. R. Harkema, K. J. Williams, N. E. Kaminski, Modulation of airway responses to influenza A/PR/8/34 by Delta9-tetrahydrocannabinol in C57BL/6 mice. J Pharmacol Exp Ther 323, 675-683 (2007).
  5. D. Katz, I. Katz, B. S. Porat-Katz, Y. Shoenfeld, Medical cannabis: Another piece in the mosaic of autoimmunity? Clin Pharmacol Ther 101, 230-238 (2017).
  6. E. Kozela, N. Lev, N. Kaushansky, R. Eilam, N. Rimmerman, R. Levy, A. Ben-Nun, A. Juknat, Z. Vogel, Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol 163, 1507-1519 (2011).

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About the Author
  • Barbara LF Kaplan

    Barbara Kaplan is an Assistant Professor in the Center for Environmental Health Sciences, Department of Basic Sciences in the College of Veterinary Medicine at Mississippi State University. She has a BS in Environmental Toxicology from UC Davis and a PhD in Pharmacology and Toxicology from Michigan State University.

Discussion
  1. I wonder about the relevance of these findings to the common belief that cannabinoids can help fight cancer. This would seem to contradict that possibility, at least inasmuch as tumors often succeed by flying under the immunological radar.

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