CRx MAGAZINE

Summer 2020

Research: The Role of Cannabis in Brain Health

Research reveals cannabis has promise in the treatment of brain illnesses, including brain tumor.

The brain is the most complex organ in the human body. And it’s arguably also the most important. Thus, the scientific community continually studies the effects various chemicals have on brain functioning, and medical cannabis is no exception.

Bill Code, MD, is an anesthesiologist, integrative medicine specialist, and international speaker and author. A medical practitioner for 40 years, he’s studied integrative medicine under Andrew Weil, MD, at the University of Arizona, and is a leading expert in pain management. Code says medical cannabis can help considerably in health by supporting the endocannabinoid system (ECS) within the body. “THC acts primarily on the type 1 receptors. CBD reduces the ‘trippiness’ of the THC and has other benefits such as reducing anxiety [and] seizures, and increasing brain-derived neurotropic factor,” Code says. “This helps create new neutrons and increase connections between existing neutrons. Both of these can therefore enhance brain function.”

Anxiety, Stress, and Trauma
According to Junella Chin, DO, chief medical advisor at CannabisMD.com, the ECS is critical to human survival. At the most basic level, it controls how we eat, sleep, relax, forget, and protect ourselves. “One of our own internal cannabis molecules, anandamide, helps us temper stress and balances our nervous system, so we are not spiraling out of control on a high sympathetic nervous system overdrive,” she says.

As mentioned previously, the ECS controls forgetting, which is a crucial aspect of treating anxiety, stress, and PTSD. As Chin explains, trauma survivors have been found to have problems with neurotransmitter signaling of serotonin and glutamate. These neurotransmitters correlate with the fight-or-flight response. “Excessive glutamate signaling will lock in fear-related memories that are most painful for survivors. Cannabinoids can help release these painful memories by facilitating memory extinction and help survivors extinguish those traumatic memories,” she says.

Cannabis reduces anxiety by mediating the neurotransmitter gamma-aminobutyric acid (GABA), which directs the body to power down, to tell our body that we are safe, Chin explains. It helps reduce anxiety, calms the nervous system, fosters sleep, and relaxes the muscles.

“Cannabinoids are GABA uptake inhibitors. Cannabis creates a surplus of GABA in the brain, which creates the quieting and calming effect,” Chin says. “Patients report medical cannabis working to ‘take the edge off’ and ‘turn the volume down’ on anxiety. Once their racing thoughts and the fight-or-flight response are lessened, patients report feeling ‘more comfortable in their own skin.’”

With cannabis supplementation, patients can often quell racing thoughts that paralyze them at work or cause them to lie awake in bed at night. According to Chin, cannabis can help trauma survivors change their responses to stimuli that previously would have triggered symptoms such as anxiety, panic, and flashbacks.

According to Eloise Theisen, RN, MSN, AGPCNP-BC, a full-time medical cannabis program faculty member at the Pacific College of Health and Science and current president of the American Cannabis Nurses Association, studies have looked at the role cannabinoids play in protecting brain cells and slowing the progression of certain neurodegenerative diseases such as Parkinson’s, Alzheimer’s, multiple sclerosis, and amyotrophic lateral sclerosis. “More clinical research is needed in these areas to better understand how cannabinoids can be used to treat or prevent such diseases,” she says.

It’s important to note that there are more than 100 cannabinoids found in the cannabis plant. Because THC is the most abundant and most commonly consumed cannabinoid, research has not focused as much on other cannabinoids. Over the last 10 years, researchers have put a spotlight on CBD, the second most abundant cannabinoid identified in Cannabis sativa. As the focus on CBD has increased, so too has the amount of research on its effect on the brain. A 2018 study suggested that CBD has anti-inflammatory, neuroprotective, and immuno-modulating effects.1

Theisen also points to a study by Staci Gruber, PhD, and her team, in which cognitive performance in medical cannabis users was examined at baseline and after months of use.2 “Their findings demonstrated that medical cannabis users had improvements on tasks of executive functioning without any reductions in performance,” Theisen says. “The authors hypothesized that the improvements may have been linked to a decrease in other pharmaceuticals as well as a reduction in clinical symptoms. Also of note was the different cannabinoid profile typically used by medical users vs recreational/adult users. Most medical cannabis users had higher levels of CBD in their products.”

More recent research has focused on the role that the ECS plays in brain health. “The ECS has been shown to play a large role in regulating mood,” Theisen says. “A 2018 study found that a dysfunctional ECS may contribute to depression.3 The stimulation of our endocannabinoid receptors has been shown to increase serotonin levels, thereby increasing mood and memory and decreasing hypervigilance, hyperarousal, and intrusive memories. And additional studies have evaluated how CBD interacts with our 5HT1A and TRPV1 receptors known to regulate our fear and anxiety-related behaviors.”

Seizure Disorders
CBD, according to Chin, is being investigated as a treatment for a multitude of disorders due to its anticonvulsant, anxiolytic, and antipsychotic properties. Importantly, CBD has been demonstrated to have a low risk profile. “The far-reaching clinical benefits of CBD and other phytocannabinoids are mediated through changes in the endocannabinoid system,” Chin says. “The anticonvulsant properties of phytocannabinoids like CBD indicate that the brain’s endocannabinoid system helps to provide protection against convulsive activity, presumably by promoting neuronal balance and seizure control.”

Brain Tumors and Medical Cannabis
What’s the impact of medical cannabis on brain tumors? In 2016, Claudia Dumitru, Dr. rer. nat., of the department of neurosurgery at Nordstadt Hospital Hannover in Hannover, Germany, conducted research showing that cannabinoids, which target programmed cell death, show promise in the treatment of glioblastoma multiforme (GBM), a malignant, deadly, extremely aggressive form of brain cancer. And despite the use of various therapeutic approaches including surgery and radio-chemotherapy, more than 95% of glioblastoma patients die within five years after diagnosis. In her research, Dumitru has shown the therapeutic effect of cannabinoids is based on the reduction of brain tumor growth by inhibiting tumor proliferation. In addition, cannabinoids have been shown to inhibit the stem cell–like properties of GBM tumors and the overall invasiveness of the tumor. Dumitru’s research notes that phase II clinical trials have had positive results regarding the survival of GBM patients receiving cannabinoid treatment.4

Theisen says that preclinical data have indicated that cannabinoids can be potent antitumor agents that target the cancerous cells and not the healthy cells. A study by Torres and colleagues in Molecular Cancer Therapeutics indicated that, for GBM, cannabinoids were shown to enhance the standard therapy when used concurrently. Specifically, the researchers were interested in seeing whether CBD can reduce the growth of glioma xenografts. They investigated whether the “combined utilization of THC and CBD could be effective in reducing the viability of glioma cells.” They found that the “treatment with submaximal doses of THC and CBD greatly reduced the viability of several human glioma cell lines as well as primary cultures of human glioma cells.” The research also showed that the combined submaximal doses of THC and CBD “reduced the growth of U87MG cell–derived subcutaneous xenografts at a higher extent than the treatment with the individual agents and at the same extent than an effective dose of THC, supporting that the combined use of submaximal doses of THC and CBD could be equally effective compared with THC in reducing the growth of glioma xenografts.”5

“More clinical studies are needed to better understand the role different combinations of CBD and THC as well as other cannabinoids may play in the treatment of brain tumors,” Theisen says.

Without large clinical studies to demonstrate the effectiveness of cannabinoids on brain cancer, Theisen says, it’s difficult to determine risks associated with the treatment. “For decades, cannabis users have been self-exploring and self-navigating treatments for various conditions. In more recent years, many people have turned to cannabis as a potential treatment for their cancer. Because there is a lack of clinical trials to establish protocols for cancer and cannabis, many people will be self-treating based on anecdotal reports. Risks associated with this could be inappropriate doses and adverse effects that are not properly monitored,” Theisen says.

The Future
“As we understand medical marijuana better and physicians learn more of optimal use, then many more will receive and benefit from medical marijuana,” Code says. “I have followed over 2,000 patients for up to 10 years with tremendous benefit overall. Many of these were neuropathic pain, usually of brain origin.”

Theisen believes cannabis holds a lot of promise in regulating brain health. However, she says, “it is imperative that research restrictions change and that cannabis is removed from the Schedule I status. Having the ability to study larger populations will lead to a better understanding of the ECS in maintaining health and wellness as well as treating disease.”

James Giordano, PhD, a professor of neurology and biochemistry at Georgetown University Medical Center, says that as we learn more about the cannabinoid system of the brain—and about the pharmacology of THC, CBD, and cannabis strains, and hybrid preparations—we will gain further insights to the potential benefits of its use to treat certain medical conditions and will also acquire a more complete understanding of side effects, burdensome effects, and their mechanisms.

“Further research is both necessary and important,” Giordano says. “Research will more fully define those ways in which marijuana—and its constituent substances—may prove to be viable and valuable in clinical care.”

— Maura Keller is a Minneapolis-based writer and editor who focuses on health care, business, technology, law, and other topics for regional and national publications.

References

1. Maroon J, Bost J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int. 2018;9:91.

2. Gruber SA, Sagar KA, Dahlgren MK, Racine MT, Smith RT, Lukas SE. Splendor in the grass? A pilot study assessing the impact of medical marijuana on executive function. Front Pharmacol. 2016;7:355.

3. Ibarra-Lecue I, Pilar-Cuéllar F, Muguruza C, et al. The endocannabinoid system in mental disorders: evidence from human brain studies. Biochem Pharmacol. 2018;157:97-107.

4. Dumitru CA, Sandalcioglu IE, Karsak M. Cannabinoids in glioblastoma therapy: new applications for old drugs. Front Mol Neurosci. 2018;11:159.

5. Torres S,, Lorente M, Rodríguez-Fornés F, et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther. 2011;10(1):90-10

RELATED CONTENT

How the Coronavirus Pandemic Will Affect the Cannabis Industry

FORBES.COM

By Kris Krane


Cannabis Use for Treating Disease

TODAY'S DIETITIAN

By Janice Newell Bissex, MS, RDN


Medical and Recreational Marijuana Use

TODAY'S DIETITIAN

By Liz Marr, MS, RDN, FAND


Medical Cannabis — Continuing Controversy

TODAY'S GERIATRIC MEDICINE

By Mark D. Coggins, PharmD, BCGP, FASCP