Supplement Spotlight – Cannabidiol (CBD)

If you haven’t tried “CBD” by now, you might be the only person on the planet. Sold in oils, tablets, capsules, gummies, creams, and even bath bombs, there are numerous ways to get it into your system. But the big question is – why would you want to? Or perhaps we should start with – what is it?

CBD is an abbreviation for cannabidiol. It is an oil extracted from the plant Cannabis sativa, otherwise known as marijuana. More precisely, it is extracted from hemp, which is what is left over after the psychoactive component tetrahydrocannabinol (THC) is removed. And over the last few years it has become an insanely popular supplement. There are a whole host of reported benefits, but most people do not really understand what it is they are taking, and why it might theoretically help them. In this article, we will explore the basics of CBD and the relationship between it and its cousin THC. We will review a bit of the science behind its effects, why people try it, and importantly who should avoid it.

Some Words on “Weed”

Let’s start with the basics. There are 3 main species of marijuana – Cannabis sativa, indica, and ruderalis. Incidentally, it has high nutritional content. It is truly an ancient plant species and began its spread around the world sometime around 2200 BC as it left Asia for Europe.

Within the plant, there are hundreds of active chemicals, known collectively as “cannabinoids”. The two known to be the most active are THC and CBD, and they act on the human body through what is called the “Endocannabinoid system” (discovered in the 1990s). In fact, as you might expect, our bodies make messengers that interact with these receptors as well. But plants do it with much greater potency, and a given plant can have many different substances that might interact with these receptors. For the sake of simplicity, we have 2 main receptors in our bodies: CB1 and CB2. CB1 receptors are most prominent in the brain, and these are most affected by THC. CB2 receptors are more concentrated in the immune system and other organs, and these are more affected by CB2. These receptors have been shown to be involved in pathways that relate to many uncomfortable feelings such as pain, anxiety, nausea, and inflammation to name a few.

THC? CBD? Hemp? Cannabinoids? What is the difference????

Now let’s turn specifically to CBD. As mentioned, the marijuana plant contains all the cannabinoids; at least 480 of them according to recent reports. If you then cultivate a variant that strips out all the THC, or at least gets it down to less than less than 0.3%, you are now below the requirement by the FDA to keep it off the Schedule I narcotics list, and you have hemp. This theoretically contains all the cannabinoids but THC. Finally, you purify it to take out the most active remaining compound, cannabidiol – here is your CBD.

As we noted, THC has a higher affinity for the CB receptors in the brain (CB1), therefore it is easier to see why these lead to the euphoric and psychoactive effects. And for that reason, it was categorized as a schedule I narcotic and its use has been restricted, at least by the FDA. There are synthetic forms of THC which have been used for some time as a pharmaceutical. Dronabinol, which is synthetic delta-9-THC, was approved by the FDA in 1985 as a medication used to treat nausea, particularly in the setting of chemotherapy. It has also been used as an appetite stimulant. This is different from “medical marijuana,” which is simply the legal use of the marijuana plant under the direction of a licensed and certified clinician.

On the contrary, CBD (at least in its pure form), should not have similar, potent psychoactive properties. Make no mistake, CBD does have effects on the brain. It has been shown to have neuroprotective effects in several types of brain related conditions and has a pharmaceutical application (a purified medication called Epidiolex) for certain types of childhood seizure disorders.

CBD can be taken into the body in many forms, such as oil, cream, lotion, tea, edibles, or it can even be smoked. If ingested, it is metabolized quickly by the liver to its active metabolite and tends to collect in lipid-rich tissues like the brain and fat cells.

CBD has been used in various forms for all sorts of ailments over time, and there are many claims about what it can do. Unfortunately, these are not always backed up by science. But it has been shown in various studies to have biologic effects, whether that be in the research lab, animals, and humans.

A glance at some applications, and the evidence behind them:

•  Anxiety: The support for the use of CBD for anxiety comes from the evidence that, in situational anxiety disorders, particularly social anxiety disorder, there have been small but positive studies showing an effect in reducing symptoms. This often requires high doses, such as 400 – 600 mg, and was limited to a short lived of relief. One notable study suggested an improvement in anxiety related to public speaking. There is less evidence in the role of generalized anxiety, however preclinical and imaging trials suggest a benefit. More studies are needed.  
• Depression: CBD appears to have an effect on several different neural signaling pathways that are related to depression. There is promising evidence in animal models of an antidepressant effect. However, no convincing data on this one yet.  
• Pain: The good news is that, in both laboratory and animal models of pain, CBD has demonstrated the possibility of having a positive effect. The bad news is that there are no clear studies suggesting this effect is present in humans. Part of this may stem from the fact that the chemical properties are CBD are still very much unknown as it has been studied far less than THC. When pooling the results of several studies, there is some degree of evidence that it might be helpful in select patients with chronic pain, particularly those with neuropathic pain such as in the case of long-term diabetes. 
• Sleep: This is another area in which CBD shows promise. A review article of several trials studying the effects of both THC and CBD showed modest evidence that cannabidiol did lead to some improvements in sleep as a side benefit in its use for various clinical conditions.  
• Post-traumatic stress disorder (PTSD): A small study of 11 patients showed that CBD reduced the severity of symptoms in people with documented PTSD. The average dose was approximately 48 mg per day, taken as a capsule or spray, and there were no severe side effects reported.  
• Oxidative stress: This may be the most exciting area of future research for CBD, although the toughest to relate to downstream clinical effects. Oxidative stress is a general term that refers to the damage our bodies sustain at a cellular level on a day-to-day basis from by-products of cellular metabolism. In response to injury, or exposure to toxins, our enzymes systems generate “reactive oxygen species”, molecules that can cause further tissue injury. When these build up, we have oxidative stress. It’s the job of the immune system to regulate this, and ideally repair it, but over time negative effects can accumulate. Oxidative stress can alter the lipids and proteins within our bodies, which can affect many aspects of our cells such as cell wall structure and cell metabolism, respectively. Many believe these have long term negative effects which directly impact aging, tissue dysfunction, and possibly cancer development. CBD has been shown to have a wide range of antioxidant properties. In research models, it has been shown to prevent oxidation reactions from occurring and prevent or modulate tissue damage can occur from oxidative stress.  

CBD can cause a dangerous increase in the levels of some medications

There is certainly one group that should avoid the use of CBD, or at least only use it in close associating with monitoring by a clinician. This would include people on certain medications that are processed by the liver through what is known as the “Cytochrome p450 system”. Some medications affect enzymes in this system, which can lead to higher levels CBD in the bloodstream.  Certain enzymes in the system can be slowed by CBD, which could lead to toxic levels of medications that go through this system. In fact, up to 60% of medications are metabolized by one of these enzymes, so it would critical that anyone on prescription medications made sure the use of CBD was safe, especially if they used it regularly.  

Metabolic drug–drug interactions between cannabidiol and enzyme substrates, inhibitors, or inducers. 

Adapted from Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989. PMID: 31288397; PMCID: PMC6678684.

Summary

The primary concern with any medication or supplement should always be safety, and it would seem clear that CBD, taken at a reasonable dosage, appears to be safe in adults, at least in short term use. The one exception would be those taking medication processed through the p450 enzyme system as noted above. CBD does appear to have a range of biological activity throughout the body, and more information abouts it effects will most certainly be coming soon. The evidence for effectiveness in any particular condition is limited at the moment. There are no definitive studies showing that CBD is consistently helpful, but some small studies are encouraging. The benefit seems to be concentrated mostly in short term anxiety relief and perhaps improving sleep, although this is variable.

This article is not meant to be construed as medical advice, rather printed for informational purposes only. Everyone’s health situation is different. As always, it is critical to discuss the use of any supplements with a licensed health care provider to ensure that any use is safe and potential effective in your medical status and condition.

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