What Don’t We Know about CBD?

CBD Science

For a plant that has been around for more than 5,000 years, we really know very little about cannabis and CBD in particular.

Many tribes and nations have been using cannabis-based on anecdotal evidence. They used it for pain relief, inflammation, and mental wellbeing.

Now that scientific research has the tools to examine plants in depth, researchers have been studying CBD. Most people take CBD based on their perceived notion that it will help their overall health. And yet, only one drug (Epidyolex, shown to reduce the severity and frequency of some rare epilepsy syndromes in children) has been approved by the NHS. This suggests a lack of concrete evidence about CBD’s potential in humans.

Even so, many consumers use CBD supplements because they feel they help them more and carry fewer side effects compared to conventional drugs. Especially when it comes to chronic pain and inflammation, common medication is often perceived as ineffective or comes with unpleasant side effects.

Patients across the world are looking into alternatives that will help them improve their health and bring about a better quality of life. People want a safe and accurate medication that still allows them to enjoy life and be happy.

So, how much do we really know about CBD and how much do we still need to learn?

CBD Research Fell Behind

The addition of cannabis in 1928 to the 1920 Dangerous Drugs Act officially outlawed cannabis for any use in the UK, including medical. Unfortunately, lawmakers bundled together anything that had to do with cannabis. Instead of isolating CBD, which is non-psychotropic and non-addictive, they chose to forbid all compounds that came from cannabis. While this may be understandable in the early 20th century, it is arguably insupportable given today’s scientific advances.

As a result of the illegal status of cannabis, research into the plant was hindered for decades, both due to low consumer interest and because the legal and organizational hurdles were too great to overcome.

As public opinion shifted to a more encompassing attitude to CBD, however, lawmakers followed suit. Between 1928 and 2004 and since 2009, cannabis has been classified as a class B drug. From 2004 to 2009, it was a class C drug.

As for CBD, the UK Parliament passed legislation in 2018 that legalised certain cannabinoids, including CBD, CBDa, and CBD. Since then, researchers have been increasingly focusing on CBD’s potential.

The Endocannabinoid System

It is worth remembering that until the early 1990s, researchers only knew of specific systems, such as the endogenous opioid system, the endocrine system, the nervous system, and the renal system. So, it was a surprise when they identified the human endocannabinoid system (ECS). This led to the realisation that the body works with endocannabinoids—cannabinoids produced by the ECS.

The human body’s various systems work together and also autonomously to keep our organs regulated and fully functioning. Learning about a new system was revolutionary and led scientists to wonder whether phytocannabinoids, i.e. cannabinoids that are produced by plants, might help the ECS when it fails at its tasks.

This is an open question, with much evidence suggesting that yes, CBD may help support our health. Unfortunately, we simply haven’t studied cannabinoids long enough to draw definitive conclusions yet.

We Don’t Know How CBD Works with the ECS

Our endocannabinoid system (ECS) is tasked with keeping in balance several bodily functions, including reproduction, learning, memory, appetite, mood, inflammation, pain perception, and even motor and temperature perception. The ECS has far-reaching effects on the body and brain.

The ECS works with two human cannabinoids, which attach to their respective receptors—called CB1 and CB2—when something needs fixing. For instance, when your cells need extra hydration, your ECS releases endocannabinoids that bind to their receptors and create a feeling of thirst, thus making you reach for water.

Sometimes, the ECS is out of sync or finds it difficult to maintain homeostasis—the body’s natural balance. That’s when inflammation builds up, particularly in autoimmune inflammatory diseases. No matter how many cannabinoids the ECS releases, an imbalance remains in the body.

CBD may help restore the ECS’s balance. Several studies [1] suggest, for example, that CBD may possess anti-inflammatory properties. Since the ECS is responsible for regulating inflammation, this suggests a relationship between the two. But how does CBD fit in with the ECS? While we know that the molecular structure of CBD is very close to one of the human cannabinoids, called 2-AG, we don’t know how CBD converses with the ECS.

It was initially thought that CBD binds with the CB1 and CB2 receptors and helps them activate cells. Now, however, it is believed that CBD does not directly interact with the receptors but rather nudges the ECS to work more effectively with its own cannabinoids. So far, there is little clear evidence on how CBD, the ECS, the human cannabinoids, and the cannabinoids receptors work with each other.

Even in the case of Epidyolex, it was only shown that CBD has a significant effect on the severity and frequency of epileptic seizures, but we know little of the mechanism involved. There are some assumptions that Epidyolex manages to slow down how fast and how frequently signals are exchanged between cells. It is also assumed that CBD decreases brain inflammation or chemical imbalances in the brain. Researchers, however, are still unsure as to how CBD manages to work its way through the brain: even the Epilepsy Foundation admits that we are uncertain about the way CBD calms down seizures [2].

We Don’t Know What Would Be an Optimal Dosage of CBD

Dosage is one of the greatest questions surrounding CBD. How much CBD do you need to consume? The NHS has not given a recommended daily allowance, as we still don’t know how much CBD people should take or the exact dosage for each health goal.

Initial findings [3] suggest that CBD may be biphasic: i.e. smaller quantities may have the opposite effect than larger dosages. For example, a small CBD dosage appears to have anxiolytic qualities while a large CBD dosage seems to deliver the opposite effect. Likewise, smaller CBD dosages are associated with alertness while larger CBD dosages seem to promote sleepiness.

Unfortunately, we don’t know for sure how this biphasic effect works—or even that it’s real—and we don’t know what small or large dosages really mean for each person. How much CBD is a lot for you?

To further complicate things, most research is done with significantly large CBD dosages that are often many times the ‘average’ dosage found in CBD products. Many clinical trials are done with dosages of hundreds of mgs of CBD when the average suggested dosage is usually well under 50 mg per day.

How can these trials be imitated in real life? And how effective are lower CBD dosages? These are all questions to be answered.

We Need to Determine the Long-Term Effects of CBD

It is crucial to understand how the body reacts to taking CBD for long stretches of time. Is CBD more effective the longer you take it or does the body require a break from CBD to be better able to metabolize it again?

Additionally, there are proponents of so-called microdosing. They believe that the effects of CBD are cumulative, therefore taking small doses throughout the day is preferable to consuming one large dose once a day. Microdosing helps maintain a steady CBD level in the body all day long, or so the argument goes. This, however, remains to be studied before we can conclude that one way of consumption is, indeed, better than the other.

What Are the Effects of CBD on Other Human Organs?

CBD is metabolized by the liver, just like many other drugs and compounds.

There are some indications that CBD could hinder how and when the liver metabolizes other medications. It appears that CBD reaches the liver first, outpacing other drugs. Once there, it sidelines them and lets them linger in the body before they can reach the liver to be metabolized.

As a result, taking CBD with other medications like blood thinners may make them more potent because they stay in the body longer. This could have serious consequences if, for example, you are planning surgery and are on blood thinners and CBD.

There are also questions about CBD and liver toxicity. It is still unclear how fast and how firmly CBD binds to the liver’s CYP450 enzymes. One study [4] that has been widely criticized used immense quantities of CBD and showed that, at these dosages, CBD was toxic to the liver. How realistic are these dosages, though? To reach the levels studied by the researchers, an 80-kilo person would have to consume 4 litres of 5% CBD oil in a single day. So, what happens when much smaller CBD doses are taken for longer?

Should CBD Be Taken on Its Own or with Other Terpenes?

Most research is done with CBD isolate. That means that clinical trials are usually performed using 100% CBD.

Industrial hemp, however, contains hundreds of botanical compounds, such as terpenes—the compounds responsible for giving plants their distinctive aromas. Research [5] has indicated that CBD may be more active and potent when used in conjunction with other hemp compounds. It would appear that when all the compounds are taken together, they enhance each other’s effectiveness in a synergetic way that has been called the ‘entourage effect’.

And yet, we don’t know which combinations of CBD and other terpenes are the most effective and in what quantities. Each terpene has its own properties, such as anti-inflammatory, antifungal, antibacterial, antiviral, analgesic, etc. How does a product’s terpenoid profile affect CBD’s action?

A particularly thorny question is whether CBD is more potent in conjunction with THC. THC remains a class B, schedule 1 drug in the UK and British law states that for CBD products to be legal in the British market, they must contain less than 0.2% of THC in dry weight.

Because of THC’s illegal status, very little research is performed on the effectiveness of CBD when taken together with THC. Is there a way we could engineer THC to be non-intoxicating and yet beneficial to the human body? Is there a THC threshold that delivers positive benefits without intoxication? It appears we will have to wait much longer until we can answer such questions.

Where Should CBD Research Focus Next?

We have strong indications that CBD has anti-inflammatory, anti-anxiety [6], and anti-epileptic [7] qualities. It also seems to carry important pain-relieving properties.

As we learn more about CBD, we need to focus our attention on new fields of research. Neurological diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis are conditions without a cure, yet they are debilitating. They are also conditions that are becoming more common as people age.

Likewise, cancer is a leading cause of death. Perhaps research could be directed towards CBD’s potential in dealing with tumours.

At the moment, we have strong indications about CBD’s potential. The next step is to prove them scientifically. Once this is done, we should expand our research scope to various debilitating neurological, auto-immune, and geriatric conditions that are proving hard to treat with other means.