The science behind cannabis and its medicinal benefits is still fresh and unbeknownst to many users and enthusiasts. Boulder is a hotspot for the scientific community as an established aerospace engineering locale and host of a bourgeoning Nobel Prize-winning physics community at the University of Colorado. Thus, Green Dream Health Services is privileged to serve patients who employ these high-education skills in their daily lives. If there ever was such a group that breaks the “stoner” stereotype, it is the active academic clientele at Green Dream.
One such patient is Nick Varra. He is a research assistant in a molecular neuroendocrinology lab at the University of Colorado-Boulder and is a pioneering team member researching the effects of stress, among other conditions, on human health. I sat down with him to discuss his work and how his research is important to the cannabis community.
Richard Klassen: Why is studying stress important in your opinion?
Nick Varra: Stress is so pervasive in our everyday lives. Every organism from single-celled bacteria to humans encounter some form of stress. And we don’t yet really know the implications of chronic stress. Stress can be a major contributor to heart disease and diabetes as well as cognitive and neurological malfunctions so it’s important to uncover the role that stress plays in these diseases and also how to buffer the stress response.
RK: What health complications can be experienced with somebody that has too much stress?
MV: A wide range of illnesses; from cancer and diabetes to major depressive disorder and Post Traumatic Stress Disorder (PTSD). We don’t yet have an exact link between the two, but more and more we are finding individuals afflicted with these diseases that have clock gene malformations. One of the theories is that clock genes control the cell cycle and tell the cell when to divide and when not to. When these genes are disrupted the cell may start dividing uncontrollably and lead to a tumor. A little bit of stress is an evolutionary benefit but chronic stress may have a serious detrimental effect.
RK: What is your specific area of work?
NV: My lab studies how stress impacts circadian cycling.
RK: And what is the circadian cycle, exactly?
NV: The circadian cycle has evolved to help us anticipate day/night changes. We are diurnal animals which means we are awake during the day and all of our systems are synchronized to a robust 24 hour cycle. We study the genes that are involved in carrying out the cycle. We have discovered many genes that act as time-keepers that are expressed in a rhythmic manner, and indeed, they are called “clock genes”. There are several clock genes that interact with each other to form positive and negative self-regulatory feedback loops that govern an approximate 24-hour cycle. There is an area in the hypothalamus called the Suprachiasmatic Nucleus (SCN for short) that has been shown to be the “master clock” that governs the synchronization of the circadian cycle. There needs to be clock gene oscillations in the SCN for there to be any circadian rhythms to be expressed.
RK: What methods do you use in the lab to study the circadian cycle?
NV: One of our first jobs is to try to see if specific brain areas have these clock genes. We make a complementary strand of RNA and bind a radioactive tag to it. If the clock genes are present the complementary strand will be expressed on an x-ray and we can calculate the response. Once we have determined that clock genes are present in a certain area, say, the amygdala for example, which is responsible for emotional regulation, we run a behavioral stress paradigm analysis on the animal to see the effect it has on the gene.
RK: What areas of our daily lives do the clock genes play a part?
NV: I don’t need to tell you that when you are stressed out you have a hard time sleeping, concentrating, and eating. Those could be physiologic aspects controlled by clock genes. Many things fall under a circadian cycle: Sleep/wake, digestion, blood pressure, kidney and liver function. Optimal cognition, memory, and important to our conversation, even endocannabinoid expression could be under the control of these genes.
RK: Shifting toward cannabis and the effect on the brain, what is the endocannabinoid system?
NV: Endocannabinoids are lipid molecules that can easily cross the outer membrane of other neurons. They stop the overexcitement of neurons so I like to think of the endocannabinoid system as the brake pads of the brain. The two main endocannabinoids – Anadamide and 2-AG – have an inhibitory effect on neurons and when CB1 or CB2 receptors are activated the cell is less likely to fire an action potential.
RK: What is the difference between the two known cannabinoid receptors in our body, CB1 and CB2?
NV: We’ve found that CB1 receptors are one of the most ubiquitous receptors in the brain and are highly dense in areas specifically associated with stress, emotional regulation, and pain responses. CB2 receptors are mostly found on immune cells.
RK: So how does our brain respond to cannabis in terms of inflammation that might stem from a physical stress or injury?
NV: One of the main therapeutic effects of cannabis is its role in bringing down inflammation. A lab in our department does a lot of work on neuro-inflammation that just wreaks havoc on the whole body. When CB2 receptors are activated they inhibit neurons in the immune system from sending out those inflammatory signals.
RK: What makes cannabinoids distinct in the health of our bodies?
NV: Endocannabinoids are different from the more traditionally-understood messenger molecules like serotonin, dopamine, and acetylcholine in that instead of moving in the direction of neuron A to neuron B in the brain they actually move in a retrograde manner. What this means is that when neuron A is sending too many signals neuron B will synthesize endocannabinoid molecules and they will act on neuron A to “quiet the signals.” It’s really crazy how they evolved specifically to keep cell signaling in balance and not let it get too out of hand. That’s why CBD could be so helpful in treating epilepsy because it slows down overactive neurons. Cannabinoids also probably also interact with the molecular clock somehow to keep the cell cycle in balance. And something that I just learned is that THC is actually a modulator of the opioid system. The body becomes more sensitive to the natural presence of endorphins when THC is present and that helps explain its role in reducing pain and as a method for opiate addicts to wean themselves without experiencing terrible withdrawal symptoms.
RK: Finally, what research is on the forefront of cannabis science?
MV: Despite a lot of promising research being stymied because many cannabinoids are schedule I- illegal compounds, we have found several non-psychoactive properties of the plant that contribute to significant therapeutic benefits. One of these is the terpene Beta-Caryophyllene, a spicy-smelling terpene and cannabinoid that is also prevalent in black pepper, cloves, and basil.
Check out Highlighted Flowers, Ed. 8: Girl Scout Cookies for a further examination of Beta-Caryophyllene. Mr. Varra is diligent in his approach to cannabis and the associated science with stress in the human body. He is able to hypothesize experimentation on a level of expertise and curiosity foreign to many in his field by combining his passion for cannabis with his career. The staff at Green Dream Health Services is proud to serve him and countless other Boulder intellectuals that inspire to incorporate cannabis and holistic medicine into their future careers. You can find out more about the endocannabinoid system and its associated relation with cannabis by asking your budtender on your next visit to Green Dream.