Dr. French Explains CBD
BY DR. BAYNE FRENCH
I’m not ashamed to disclose that cannabis has always confused me. I don’t mean that I use it and then get confused. The terminology is just so puzzling. What is cannabis, anyway? Is it a plant, really, or just a colloquially used garbage can word? And hemp? Come on. Through my day I would go, purposely oblivious, nodding at patients’ anecdotes of use like I knew what they were talking about. Who has time to learn about plants, anyway? I have kids that need to be herded, ducks to butcher, endless government medical regulation to navigate.
Unfortunately, I am both incapable and unable to advise you. However, there is no question in my mind that something very powerful is going on here biologically. There are common reported effects from CBD use that I feel are very plausible, including alleviated mood swings, maintained immune function, and reduced stress and tension. Joint health and improved flexibility are also reported. The anecdotes have reached a crescendo. And I recently heard something about a Farm Bill that did something legally, with some stuff, for a thing, with a deal. When not herding my children, I read everything about these topics my wife printed off for me. Then when Brian Frank thrust CBD (Cannabidiol): A Clinical Review by Mark W. DelBello, M.D., into my hands and said, “Learn it, quack,” suddenly I found the time to begin my study. I am not an expert. How about we learn together? I am going to distill a massively complicated cellular signaling system into basic constructs (more for me than you) and try to figure out what CBD and related compounds are good for, all the while not riling any government agency. Set, hut, hut!
I sat in classrooms for so long rigor mortis set in, and never did I learn about our endocannabinoid system (ECS). As Dr. DelBello explains, the ECS is a cellular communication system that is not unique to Homo sapiens. It resides in virtually every cell type we possess, prominently in nerve tissue where it regulates appetite, mood, and pain. In peripheral tissues, the ECS acts on our immune system, purportedly to prevent dysfunctional and dysregulated immune responses. To simplify the ECS, it consists of two endocannabinoids (AEA and 2-AG, which are produced in our bodies), two receptors on cells (CB-1 and CB-2, which AEA and 2-AG interact with), and the protein enzymes that produce and degrade AEA and 2-AG. It’s interesting to consider how and why we have developed this system. We as Homo sapiens likely interacted with the cannabis plant for over two million years and adapted alongside it. Much of what the ECS is capable of has not yet been elucidated. What we do know is that it interacts with our endocannabinoids (cannabinoids produced within the body) as well as phytocannabinoids (from plants) and exocannabinoids (any cannabinoid produced outside the body, including synthetic ones). Let’s turn to the plant itself. Cannabis is Latin for hemp. It appears that it is a general term for a plant of three different “species”: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. This, however, is a business designation, which is why “species” is in quotes. The scientific opinion is that Cannabis exhibits monotypia, meaning it consists of a single species named Cannabis sativa L. and the different “species” are merely subtypes (the “L” stands for Linnaeus. Carolus Linnaeus is the father of taxonomy and most likely was an endurance athlete but records are sparse). Maybe the division of the plant is a bit semantical.
What does matter are the chemical differences between the plants, namely drug-type (marijuana) plants and fiber-type (hemp) plants. Just as how apple trees and wheat are bred to produce a certain yield, so too is Cannabis selectively bred to produce a desired profile, and there are more than 700 different cultivars, or plant varieties, of Cannabis. All subtypes of Cannabis possess a wide array of compounds, including both cannabinoids and hydrocarbon terpenes. Of the over 100 different cannabinoids, the two of largest concentration in Cannabis and the most widely studied are delta 9-tetrahydrocannabinol (THC for short) and cannabidiol (CBD). Fiber-type hemp plants possess high ratios of CBD to THC (with ratios as high as 30:1) and, by legal definition, contain less than 0.3% THC. Drug-type plants obviously contain more THC, on average an amount that is about 5% of their makeup, and sometimes as high as 20%. CBD and other cannabinoids are oils. They are lipids, and thus not soluble in water. As mentioned, there are very many different cannabinoids.
There is also a completely different class of compounds known as terpenes, which are hydrocarbons. The individual constituents and their relative concentrations are accurately quantifiable using gas chromatography. What is not known is what the heck they are all doing in our bodies!
A quick read-up on hemp informs us of its myriad textile uses and potentially medicinal uses as well. So why has it been lumped in with drug-type Cannabis? Because banning is the easiest method of control: convenient, however not the most effective, as shown with Prohibition. But no sociological or philosophical digression.
We have to outline hemp’s outlaw status, its recent extrication from that status, and more. So what, exactly, is legal? I’m not sure I know, but hopefully we will both learn over the next few paragraphs. The Brookings Institution and the National Law Review recently had excellent reviews of the Farm Bill which explained hemp’s legal status. All Cannabis plant types were effectively made illegal in 1937 and made formally illegal under the Controlled Substances Act in 1970. But change has been recently afoot; the 2014 Farm Bill extended protection to hemp research. For the 2018 Farm Bill, Senate Majority Leader Mitch McConnell, hailing from the fertile, hemp-happy soil of Kentucky, championed further reform legislation and President Trump signed it on December 20, 2018. This latest bill defines hemp as any part of the Cannabis sativa L. plant that contains less than 0.3% THC by weight, and offers the states regulatory authority over its production within their borders. Hemp is now like any other agricultural commodity—heck, now it’s a mainstream crop. This is great news for hemp farmers who may now have protection against evil forces like climate and pestilence. CBD, however, is far from legally unfettered. It’s exempted from being a Schedule I drug if and only if its production follows numerous regulations.
The take-home is that under the 2018 Farm Bill, CBD will be much more available and legal. But knowing the legitimacy of your source or the brand you buy from is critical. The CBD industry is burgeoning. According to the research firm Brightfield Group, legalization of hemp could result in a CBD market of $22 billion by 2022, and this group considers themselves “highly conservative analysts.” Brightfield states, “CBD is the next healthcare phenomenon.” They recognize that, in the current environment, CBD’s impressive growth has been primarily word-of-mouth given heavy FDA regulation. The United States Food and Drug Administration (FDA) has issued statements clarifying its role as a result of the Farm Bill changes. ANY cannabis product whose marketing makes medical claims must be approved by the FDA before it can be sold.
If you know anything about the medicine approval process you’ll know that it’s daunting. “Expensive” and “time-consuming” are understatements, so many products now exist with no associated explicit claims of their medicinal value. And in an appeal to lots of folks with lots of problems, numerous formulations and delivery mechanisms for CBD exist. Transdermal, transmucosal, inhaled, and oral methods, nasal routes via oral disintegrating tabs (known as ODT), lollipops, sprays, gel caps, and lozenges exist. Self-emulsifying drug delivery systems (SEDDS) are researched and water- soluble versions and nanoscale-range powders have enhanced bioavailability. The bioavailability of CBD has been a problem. Only 6% of orally ingested CBD actually reaches the blood stream and sublingual (under the tongue) and transmucosal methods from lozenges and sprays also offer relatively poor absorption. One of the few reliable intake methods for CBD appears to be taking it with a high-fat meal (we’re going to nail this one in future articles), which results in much-enhanced bioavailability, especially when the dose is divided twice daily, as pharmacokinetic studies cited in Del- Bello’s text would suggest. Not unlike readily accepted indications for use, solid dosing guidelines for CBD products are also lacking and usually just empirical. Many patients galvanize this sentiment, reporting a dizzying array of maladies helped by their CBD du jour. Dr. DelBello, thankfully, is a voice of reason. In his excellent Clinical Review he outlines the evidence behind these anecdotes and objectifies what is known, what we think is occurring, what isn’t known, and the research involving dozens of health conditions. Dr. DelBello outlines a study that I have obtained and read comparing purified CBD vs. Cannabis extracts (mixture of compounds). There was a considerably higher number of patients reporting improvement using the extracts. Furthermore, the average dose of the extracts was more than four times lower than the purified CBD dose and had fewer adverse effects. These findings certainly raise questions about potential synergy between components. Synergy is a well-known phenomenon describing the enhanced effect of combining more than one agent when compared to the effect seen from the agents individually. In relation to Cannabis, synergy was termed the “entourage effect” in a 1998 study. The internet is filthy with references to the entourage effect, but that study showed only an association of enhanced effect from one chemical with another. In no way has extensive scientific investigation been done or true causality established for the effect. “Full spectrum CBD” is a common term of trade, signifying the product has undergone less processing, and that a mixture of compounds exist in it. Some insight into the potential and physiological potency of CBD may be had by looking at two of the three FDA-approved Cannabis medications. Epidiolex, approved just last year, is a purified form of CBD oil and treats two rare and severe seizure disorders. Dronabinol (Marinol), with its two indications approved in 1985 and 1992, is a synthetic cannabinoid with THC qualities. It is approved to treat nausea and vomiting that occurs due to chemotherapy and, more recently, for weight loss associated with AIDS. Nabiximols (Sativex) is not approved in the US but is used in numerous other countries as an anti-inflammatory treatment against muscle spasms that come with multiple sclerosis. Nabiximols is a 1:1 ratio of CBD and THC. To quote Dr. DelBello, “Because CBD and cannabinoids are a new field of therapeutics, even physicians feel uncomfortable and not knowledgeable about advising patients.” I’m not that guy. With all the medications we don’t bat an eye at prescribing every day, sometimes in combination, I have no personal reservations about the safety of a broad spectrum CBD compound. The risk/ benefit ratio I view as being very favorable. So, as we conclude, what have we learned? Please don’t say, “To never read another Dr. French article.” We all possess a well-developed internal system of cellular communication and signaling that utilizes synthesized cannabinoids and we have definitive evidence of their numerous favorable effects on health.
It seems to me that encountering similar compounds in nature or our food supply is not at all an unnatural occurrence. Many within my profession feel that supplementation is unnecessary, and warn patients that it only results in expensive urine. Well, my urine represents such a goodly sum that I almost hate to part with it. Given our brief insertion at this time in history, into the glorious theatre of humanity, I find it highly probable that many important nutrients are deficient and improbable that they may be adequately replaced via food. Although “as-needed” CBD appears to help a wide array of ailments, I feel its regular supplementation is akin to that of omega-3, trace minerals, vitamin D, etc.
In addition to an outstanding diet of “human animal food,” the uniqueness of this compound may offer another advantage in our quest for well-being and disease avoidance. There is much that is still unknown. What seems clear is that a reputable source of CBD is critical. It is safe and legally available. Twice daily dosing with a meal containing fat seems to offer the best absorption and bioavailability. Beyond that, fellow sapiens, as with all things involving your health, it’s up to you.