Cannabis: A Medical Perspective

This special issue on medical cannabis did not seem complete without putting the analysis of cannabis into the context of how it is used in medical practice. To get this perspective, we spoke to a medical doctor, Uma Dhanabalan. Dhanabalan, known as Dr. Uma, practices medicine at Uplifting Health and Wellness in Natick, Massachusetts, and is certified by the American Academy of Cannabinoid Medicine and practices as a Cannabis Therapeutics Specialist. She is an educator, activist, and advocate for the medical benefits of cannabis.

What do we know currently about what compounds drive the reported therapeutic effects of marijuana? Is the mechanism of action of these compounds well understood?

What we know now is that cannabis contains over 400 different compounds, including over 80 different cannabinoids and terpenes. Are they well understood? Absolutely not.

We do know the spectrum of psychoactivity: Tetrahydrocannabinol (THC) is the most psychoactive component, cannabidiol (CBD) is the nonpsychoactive component, and cannabinol (CBN) has about one-tenth of the psychoactive properties of THC.

But as far as the mechanism, much more remains to be understood.

What is the endocannabinoid system and how does it work?

I learned nothing about the endocannabinoid system during medical school, my residencies, or my fellowships. I started learning about it approximately six years ago. It’s one of my favorite systems now. I describe the endocannabinoid system as a system of homeostasis, balance, life.

When we speak about cannabinoids, we speak about endocannabinoids, which are produced within the human body, phytocannabinoids, which come from plants, and synthetic cannabinoids, which are produced in the laboratory.

We know that all three of these work with receptors in our body. CB1 (cannabinoid receptor 1) was the first cannabinoid receptor identified, in 1988, and was found primarily in the brain. A few years later, CB2 (cannabinoid receptor 2) was found, primarily in the immune system. But both of these receptors are found throughout the body. The endocannabinoid system is involved in many parts of the body and many biological activities, which is why cannabis works so beautifully for so many different ailments.

How does the mechanism of action of the compounds in marijuana compare to that of the innate endocannabinoid system?

What we have found is that THC in cannabis mimics the body’s natural endocannabinoid, anandamide, and binds with the receptors in our body.

We’re also finding out that endocannabinoids have a very short life span; they are degraded very rapidly. We also have learned that they are produced from the postsynaptic portion of the neuron, unlike most neurotransmitters, such as serotonin, which are produced in the presynaptic portion of the neuron. Endocannabinoids are produced from the postsynaptic portion of the neuron and bind to the receptors that are located on the presynaptic portion of the neuron.

Therefore, cannabinoids constantly balance our system. In the words of Dr. Vincenzo Di Marzo, of the Institute of Biomolecular Chemistry of the National Research Council in Pozzuoli, in Naples, Italy, the endocannabinoid system is meant for us to “relax, eat, forget, and protect.”

In the current absence of a federal legal system for medical marijuana, is there a good way to gather clinical data from its current use?

Absolutely. Even though some consider it to all be anecdotal, research is being conducted and data are being collected. Now, getting that research published is another matter. For example, I may have data from two years of practice, but if I want to get it published I first have to get an IRB (Investigational Review Board) approval since we are talking about human subjects, and we need to protect patient information. That makes it difficult. But there are plenty of data and studies done. If you go to PubMed and enter the word cannabis, you will find over 10,000 articles published throughout the world.

Now, one of the concerns that we have right now is that cannabis is in [the Drug Enforcement Administration’s] Schedule I, meaning that it has no medical use and has potential for abuse. Due to its Schedule I status, there is not enough medical research on cannabis in the United States.

You have objected to proposed laws that would require clinical studies before marijuana can be approved for medical use. Why?

We don’t need additional research to prove that the medicine is safe. There have been zero deaths from cannabis in the world, and nobody-I repeat nobody-has ever overdosed from this plant medicine. So, when we’ve got over 47,000 deaths from opioids per year and rising, why can’t marijuana be used for harm reduction? That is my question.

Are clinical trials still needed to better understand how the drug works and what the proper doses are?

Absolutely. More trials are needed.

You bring up another word, dosing. The concept of dosing is part of a Western medicine mentality. We are taught, as clinicians, to make a diagnosis and prescribe a medication as part of a standard treatment plan: a specific dose, taken say once or twice a day. With cannabis, we struggle with this concept of dosing. I talk about titrating rather than dosing. And I tell my patients to start out low and slow, or very low and slow.

We do need more research to understand this plant better. We need to have ISO-certified laboratories and better laboratory testing and standards so that we know that the numbers-for example, the percent THC of the strain of cannabis that a patient is taking-are accurate and reproducible. Right now, with cannabis, we’re not getting that consistency. We are not able to clearly say exactly what the patient is consuming. One of the most fundamental concerns of a doctor is to do no harm. We need consistency so that we know exactly what the patient is receiving.

But I still want to stress that we know this medicine is safe. We know that there are zero overdoses from this medicine.

So what is the best way to ensure that dosages of medical marijuana are controlled and suitable for the patient, whether that be an adult, a child, or an infant?

I’d like to see a product label, in the form of a pie chart or dial, that would indicate the cannabinoid profile and list the percentages of THC, CBD, CBN, cannabigerol (CBG), and so on. That would help us to guide the patient’s treatment of care. It would enable accurate and consistent dosing, whether the patient be an adult, child, or infant.

I tell my patients three things. First, always hydrate before you medicate because we know the side effects of dry mouth, dry throat, and dry eyes. Second, start out with a low or very low amount and slowly titrate up. Third, journal how and what you use. These are the three things that I instruct all my patients to do, because at the present time I am unable to tell my patients the equivalent of “Go to the store and get an 81-mg aspirin, and get one that’s coated.” We’re not there yet.

What are the primary medical conditions that are currently being treated with medical marijuana? And what data exist about the effectiveness of medical marijuana for those conditions?

Again, this might sound anecdotal but there’s lots of research out there. NORML, the National Organization for the Reform of Marijuana Laws, put out a very nice booklet (1) that lists the research related to conditions like chronic pain, Alzheimer’s, tumors, multiple sclerosis (MS), methicillin-resistant Staphylococcus aureus (MRSA), glaucoma, fibromyalgia, and the list goes on.

I am fortunate to practice medicine in Massachusetts, where it is left to the doctor’s discretion what debilitating conditions meet the criteria for recommending medical marijuana. In my practice, I use cannabis for an array of conditions, from chronic pain to multiple sclerosis to post-traumatic stress to glaucoma to different types of cancers, anxiety, depression, irritable bowel syndrome, Crohn’s disease, lupus, Lyme disease, multiple neuropathies, and neuralgias. I have also recommended it for people who have had different types of surgeries, such as back surgery and neck surgery, and phantom pain from limb amputations. I can go on and on; it’s a whole array of symptoms and illnesses.

What I have been able to do in my practice is actually have patients decrease and even eliminate many of their medications for a variety of ailments, such as diabetes, high blood pressure, acid reflux, insomnia, anxiety, PTS D and pain. I have patients that only use cannabis for their symptoms. Cannabis is not for everyone, yet it should be a first-line option, not the last resort.

I don’t have a prescription pad in my office. I’m proud to say that Dr. Uma Dhanabalan does not contribute to the opioid epidemic. I have not written a prescription for an opioid in over eight years. In my practice, I have been recommending cannabis instead for the past 4 years. And I have stated very clearly that cannabis is not an entrance drug; it is an exit drug from pharmaceuticals and narcotics.

What do you think about efforts being made by some pharmaceutical companies to isolate individual compounds from cannabis and make prescription drugs from them?

I have a lot of concerns. Synthetic drugs, which are made in a laboratory, can kill you, because there is a potential for overdose with these medications.

The pharmaceutical companies would have 80 different pills for the 80 different cannabinoids. That’s also a concern. We need the whole plant. That’s how the plant is meant to be consumed-as a whole plant.

When pharmaceutical companies start developing synthetic molecules, we have overdoses and other safety concerns. For example, one company created a drug, rimonabant (Acomplia), that selectively blocked CB1 receptors. They said, “Everybody gets the munchies from using cannabis so let’s just block the receptors and use it for appetite suppression and weight loss.” Well, guess what? That medicine never made it to the United States because people taking it committed suicide. And this is the kind of concern that I have when pharmaceutical companies get involved in creating synthetic products.

What do you feel should be the top priorities for the near and long term regarding medical cannabis?

First of all, education. Every health care provider needs to learn about the endocannabinoid system. We also need to have a specialty of cannabinoid medicine. There are very few of us that are actually certified in this, and I am one of them; I am certified through the American Academy of Cannabinoid Medicine.

Number two, there are three facts that everyone should know: One, nobody has ever overdosed or died from cannabis, worldwide. Two, the US government has had a patent for cannabinoids as an antioxidant and neuroprotectant since October 2003 (2). Three, doctors were able to write a prescription for cannabis; it was in the US Pharmacopeia from 1850 to 1942.

Cannabis was placed in the DEA’s Schedule I in 1970 not because of evidence-based medicine, but due to politics.

What else do you want people to understand about medical cannabis?

I want people to understand that I was among the doctors that did not know about this plant medicine. I did not know about the endocannabinoid system. I do want people to understand that much more needs to be learned, but that there is so much information out there already. And the truth has to be shared by everybody. We need health care providers to get their heads out of the sand and understand that this is an option and to please not alienate our patients. The stigma has to change.

We say “do no harm.” This plant has done no harm. There have been no overdoses in the history of mankind due to this plant.

Uma V.A. Dhanabalan, MD, received her medical degree from the University of Medicine and Dentistry of Newark, New Jersey, and completed her residency in Family Medicine at the Medical University of South Carolina in Charleston, South Carolina. She also has a master’s degree in Public Health from the Harvard School of Public Health in Boston, Massachusetts, and completed an Occupational and Environmental Medicine Residency and Fellowship at Harvard School of Public Health. Dhanabalan is the founder and CEO of Global Health & Hygiene Solutions, LLC, in Cambridge, Massachusetts, whose mission is to promote wellness and prevent illness. She is certified in Cannabis Medicine by the American Academy of Cannabinoid Medicine. Her passion is to educate, embrace, and empower the world.

Disclosures:

This article was originally published in "Advancing The Science of Medical Cannabis," e-book for LCGC in September 2016. The full e-book is available for download here: www.chromatographyonline.com/lcgc-ebooks-09-01-2016

References:

1. P. Armentano, Emerging Clinical Applications for Cannabis and Cannabinoids. A Review of the Recent Scientific Literature (The National Organization for the Reform of Marijuana Laws, Washington, D.C., 2015). Available at: http://norml.org/pdf_files/NORML_Clinical_Applications_for_Cannabis_and_Cannabinoids.pdf
2. The United States of America as represented by the Department of Health and Human Services, Cannabinoids as Antioxidants and Neuroprotectants, Patent Number 6,630,507, October 7, 2003).