The rise of CBD

I manage a cannabinoid-centric clinical practice in San Diego, California. I have been providing this type of specialty care for over three years now. About two years ago my clinical practice changed. My patient population shifted from a majority of very sick people using THC-dominant products to a majority of mild to moderately sick people using CBD-dominant products.

A few different phenomena led to this shift. Foremost among them was the emergence of CBD, which has taken the world by storm. It is the new miracle molecule. I credit Sanjay Gupta’s CNN Special Report entitled "Weed" for launching the CBD craze.

The first episode told the story of Charlotte Figgi, a child with a severe seizure disorder who benefitted greatly by using CBD products to control her seizures. Her story went viral and CBD flashed on the radar of many families in similar circumstances. Within the year, nine states with no medical marijuana program enacted limited laws that allowed the use of CBD products for treating seizure disorders.

Perhaps an unintended consequence of "Weed", at least in my opinion, was a dichotomization of medical Cannabis. Within a short period of time, CBD was being declared the “medical” phytocannabinoid and THC was a pariah due to its intoxicating potential. This thinking is scientifically and clinically flawed.

Nonetheless, patients started to schedule appointments with me specifically to use CBD. These patients were/are very clear: They don’t want to get high and they don’t want to inhale. By this logic, according to them, they need CBD.

Marijuana-derived CBD products were only available in states with regulated medical marijuana programs. Hemp-derived CBD products, however, began appearing online and at certain health stores. These products are now ubiquitous, despite the fact that FDA has made it explicitly clear that CBD is an approved drug and not a dietary ingredient. According to FDA, all the available hemp-derived CBD products on the market are in violation of FDA regulation. The vast majority of consumers are unaware of this irony. These products are everywhere, yet they are illegal. I’m not sure most healthcare professionals understand this either. "Integrative medicine" clinics all over the country are currently selling CBD products as they would fish oil, vitamin D or probiotic products.

Using CBD in clinical practice is challenging for a few different reasons. The first is all the hype. I’d like to illustrate this point with an anecdote. I once had a patient who came to me with severe anxiety. She wanted to use CBD for its anxiolytic effects. She was aware of some clinical trials that had been conducted at the University of Sao Paolo in Brazil. We tried two different hemp-derived products at various dosages. There was no change in her anxiety. We tried a purified CBD product at the effective dosage used in a clinical trial. No change. She was incredulous. She literally could not understand why it wasn’t helping her. This was the first indication to me that CBD could become a victim to its own hype.

The second reason why CBD is challenging to use in clinical practice is the confusion around dosing. There is a relative scarcity of randomized controlled clinical trials (RCTs) demonstrating effective dosages of CBD for various medical conditions. In the US, those RCTs have been impeded by the federal classification of marijuana and hemp as Controlled Substances. It wasn’t until December of 2018 that the Farm Bill made it explicitly clear that hemp, and its derivatives, including CBD, are not controlled substances.

There are some RCTs, mostly conducted in other countries, but they have used purified CBD products, almost exclusively. On one hand, this makes sense because we want to be able to draw cause-and-effect relationships between a single substance – the active ingredient – and a given set of outcomes. Also, a drug with a single active ingredient is easier to develop, produce, prescribe and regulate.

On the other hand, consumers are not using CBD as a single ingredient. The vast majority of the products that consumers are using are not purified CBD products. They are non-purified Cannabis extracts rich in CBD, along with a multitude of other biologically active compounds, including other cannabinoids, like THC.

Can we apply the findings from studies using purified CBD products to non-purified CBD products?

Are the safety, tolerability and efficacy profiles the same?

Are we comparing apples to apples or are we comparing apples to oranges?

We need more research to answer these questions.

Ideally, we as healthcare professionals would use clinical guidelines based on RCTs to inform our dosing and administration. We don’t have those for non-purified CBD products. We are making this up as we go along.

There is a widespread belief among consumers, patients and many healthcare professionals that there is an Entourage Effect, a synergy created amongst the various constituents in a non-purified Cannabis extract. As the story goes, this synergy allows one to use a lower dose of CBD in a non-purified product to achieve the same therapeutic outcome as a higher dose in a purified product, with fewer adverse effects.

In reality, there is little robust evidence to support this contention (There is some, but not a lot, and not of high quality). In fact, I am not aware of a single RCT that has compared these two types of CBD products in humans. Further, I am only aware of one RCT that used a hemp-derived CBD product as an investigational agent (Funded by CV Sciences. Soon to be published).

The 2018 Farm Bill should change that, but the FDA needs to promulgate regulations before industry is going to invest heavily in research. Clinical research is expensive.

It is important to acknowledge that there is a pervasive mythology surrounding Cannabis. There are advocates without sufficient scientific and medical training who are proselytizing the therapeutic potential of this plant. I don't fault these people. They are mostly well-intentioned, but they don't know what they don't know (Do any of us?). There is a huge gap between science and culture. It is my hope that manufacturers of non-purified hemp-derived CBD products will invest in research and close that gap.

Nonetheless, healthcare professionals, and their patients, often report positive outcomes using doses of CBD in non-purified hemp-derived products that researchers would scoff at. What’s going on here? Is this a placebo effect or an Entourage Effect? We need to find out.

One other point here. Medical marijuana advocates will often say that CBD from marijuana is clinically superior to CBD from hemp. They will say it just like that. Obviously, that’s not true. The molecule itself is the same, regardless of its source. Chemically speaking, there is no difference. What may be different however, is the members of the entourage. The members of the entourage in a marijuana-derived product are probably different than the members of the entourage in a hemp-derived product, especially in terms of the concentration of THC. There are no members in a purified CBD product.

My co-investigators and I conducted a cross-sectional study that should be published in the next couple of months. It is a complex survey of healthcare providers who recommend the medical use of Cannabis to their patients. Sixty-five percent of the healthcare providers surveyed reported that they believed marijuana-derived CBD products were superior to hemp-derived CBD products. I'm not sure how they could conclude that without an RCT. Clinical observation is highly susceptible to bias. Nonetheless, it’s important to understand that in the minds of many advocates (Healthcare providers are not exempt from being advocates), the term “industrial hemp” is a dirty word. They envision tall, thin Cannabis plants grown for industrial purposes. As a result, they deem them to be deficient in secondary cannabinoids, terpenes and terpenoids, etc.

Anyone who has seen modern-day cultivated hemp, or manufactured products derived from it, understands that this notion is no longer accurate, if it ever was. You can walk thru fields of hemp plants in Colorado, or Oregon, that look identical to marijuana plants. You wouldn’t know which type of Cannabis plant they were without testing the plant material in a lab.

On average, marijuana-derived products probably ARE chemically different from hemp-derived products, but that doesn’t mean they are more therapeutic. And if they are, my bet is that it’s probably due to the amount of THC, not the other cannabinoids, terpenes and terpenoids. And to be clear, hemp-derived products are different from ONE ANOTHER, let alone different from marijuana products. And these differences need to be measured and reported in scientific publications. Again, are we talking about apples and oranges? We don't know yet.

This is an exciting time for this much maligned plant, and even more so for those who may benefit from its therapeutic constituents. The gap between our cultural beliefs and our scientific understanding is narrowing, but we have a long way to go. We need more research that investigates the products that people are using, not the ones that researchers are administering to research participants.