By now we’ve all heard the classic clichés surrounding cannabidiol, or CBD. That it’s the “medicinal” cannabinoid. That it’s non-psychoactive. Basically, it’s less fun, and less rewarding than THC (Δ9-tetrahydrocannabinol). Oh yeah, and it’s mostly for older people that don’t want to get high. But is that really the whole story on this compound coming from our beloved cannabis plant?
Is it even true to say that CBD is non psychoactive? How can it be hailed as a therapy for anxiety and depression but not be psychoactive? In truth CBD is psychoactive. CBD does have important interactions at the cannabinoid receptors including CB1, and CBD has important entourage effects that assist THC in maintaining a steady mellow high, without the anxiety and paranoia associated with over-consumption.
Non-Psychoactive Vs. Non-Intoxicating
One key area of confusion surrounding CBD is the common misconception that CBD is not psychoactive. This statement is simply not true. A psychoactive compound is anything that has a mechanism of action that affects the mind. CBD has a number of cellular targets that are located in the central and peripheral nervous system, which will all create an effect on the mind. The most common targets associated with cannabinoids including CBD are the cannabinoid receptors, however, there is significant overlap between the endocannabinoid system and other neurotransmitter systems.
This overlap includes serotonin receptors, dopamine receptors, opioid receptors, adenosine receptors and more. The large number of cellular targets that affect the control of neurotransmitters in the brain, means that CBD is in fact very psychoactive! However, CBD is not intoxicating. This is where the confusion lies. Unlike THC, CBD will not cause the intoxicating effects associated with getting high.
The Pharmacodynamics of CBD
Much of the confusion surrounding CBD comes from the difficult to understand pharmacodynamics of CBD. Pharmacodynamics simply means what the drug does to the body. This includes the various targets of interaction that the specific compound might have. As discussed, CBD has a variety of targets that are receptors. These receptors are proteins that reside on the membrane of the cell and convey information from the outside of the cell to the inside of the cell. While the cannabinoid receptors are the most widely known targets, as noted, CBD is capable of interacting with a variety of other receptor types as well.
Also, receptors are not the only cellular targets that CBD is able to interact with. CBD can interact with non-receptor proteins as well. A specific example of this is the protein FAAH (fatty acid amide hydrolase). FAAH in the cell will normally break down the endocannabinoid anandamide. CBD interacts with FAAH to slow down the degradation of anandamide. In this way, CBD works to increase the base level of natural endocannabinoids within the system, often referred to as endocannabinoid tone.
Biochemistry is Tricky
So why do some people say that CBD is non-psychoactive? Well in short, biochemistry is tricky. There are a large number of details that can really complicate the picture. Many in the young CBD industry believed that non-intoxicating and non-psychoactive were synonymous. THC is a strong CB1 agonist which is the reason for the intoxicating effects, while CBD does not bind to the CB1 receptor in such a way as to provoke the same effect.
This is the reason that so many suggest CBD is non-psychoactive. In truth, however, CBD has many other important interactions that have an effect on the chemistry taking place in the brain. These interactions are important to many of the stress reducing, antidepressant effects that CBD is known for.
How CBD Assists THC
CBD is the natural assistant to THC. It is the reason why they are produced by the same plant. Instead of two peas in a pod, these are two cannabinoids in a trichome. But the mutual love is still the same. This is the core duo when talking about the entourage effect. While terpenes have important entourage effects at other receptors, terpenes don’t typically have any entourage effects with THC at the cannabinoid receptors. That’s where CBD comes in.
CBD is able to act as an allosteric modulator at the CB1 receptors in low doses. This means that CBD hangs around the receptor enough to slightly alter the effect that THC has when it binds to the same receptor. Since CBD also has the effect of increasing endocannabinoid levels, in higher ratios of CBD, THC can actually be blocked from binding.
This is done through the endocannabinoids themselves. The increase in endocannabinoids act to compete with THC for the ability to bind at the receptors. This can decrease the feelings of anxiety and paranoia that are associated with too high of dosage of THC. An important outcome of this is that CBD has been used to counteract some of the negative feelings associated with getting “too” high.
CBD, THC And Tolerance
In addition to being able to pull THC users from the grips of anxiety and paranoia, CBD can provide other big saves for recreational THC users. Literally. Every long term THC consumer knows that tolerance is real. Over a long period of time, tolerance can also be costly!
THC tolerance develops after prolonged exposure to high doses of THC. The cannabinoid receptors that sit on the outside of the cell membrane to interact with THC and endocannabinoids, can be flipped to the inside of the cell membrane. This reduces the number of receptors on the outside of the cell capable of binding to cannabinoids. The reduction in receptors means a reduced effect within the cell.
In order to maintain the same level of high, all of the receptors must be interacting with THC, this requires large amounts of THC in the bloodstream at a constant basis. This is why THC users find that over time they may need larger or more frequent doses to sustain the same effect.
CBD With The Save
Here again, CBD helps. One of the entourage benefits associated with CBD is a reduction in tolerance development over time. When CBD supplementation is added to THC use along with the occasional “tolerance” day, THC tolerance can be minimized. This means a reduction in the amount of THC needed to have the same effect, and for many recreational THC users, a huge financial savings.
As any recreational THC user can tell you, cannabis products can be costly. This is true regardless of the chosen method of consumption. Supplementing these high cost THC products with CBD can not only improve the quality of the experience enjoyed by the consumer, but also reduce the amount and therefore the cost needed for that experience. That is a cost that can really add up.
CBD supplementation can be particularly helpful for those that regularly consume high THC dabs. High concentration dab products regularly meet or exceed 80% THC with little to no other cannabinoids or terpenes. These products when dabbed can lead to really intense feelings of euphoria. As such this has become a highly desired means of consuming THC for the recreational user.
For these consumers, the intense feelings of paranoia and anxiety can also come from the high doses of THC. Similarly, the high doses of THC can lead to a more rapid development of THC tolerance. These are both drawbacks that can be alleviated with CBD supplementation. Adding a daily CBD supplement can be of great value to someone that regularly consumes high THC dabs.
CBD At The Molecular Level
CBD doesn’t have to play a supporting role to THC however. CBD supplementation has enough benefits for any health conscious person, to be the star in a leading character role of its own. There is a key structural difference between THC and CBD that has important implications in regards to how these chemicals behave at the molecular level. CBD has a second alcohol group coming off the benzene ring, which in THC is locked into a cyclic ring structure containing the alcohol’s oxygen atom.
This means that while THC is locked into this flat three ring structure, CBD contains a single bond between the two rings that allows for complete rotation between the two different rings. All of this means that CBD has a great deal more movement available within the bonds of the chemical structure. This allows CBD to have “promiscuity” among the receptors of different systems.
This “promiscuity” means that CBD has the ability to act in antagonistic, agonistic, and allosterically modulating ways at a variety of receptors. The receptor types that CBD interacts with include cannabinoid, opioid, adrenergic, and serotonin receptors among others. While it’s impossible to completely sum up the net effects of CBD on the body, many of the interactions that CBD has, ultimately act to regulate the homeostasis of the body. This is carried out mostly via interactions in the nervous system, the immune system and the digestive system. This provides many different routes for CBD to ensure that your natural regulatory responses are taken care of.
CBD For The Day To Day Struggles
Most people tend to think of CBD as a medicine that someone might turn to when they are experiencing certain effects. While that may be true, for a number of other people, CBD is much more like a daily vitamin or supplement. The purpose of taking CBD for those individuals isn’t to start feeling better after they have started to feel bad, but to actually prevent negative side effects from an imbalance in the endocannabinoid system. This can be of particular assistance to cannabis consumers that are already consuming high doses of THC.
The Sum of Many Parts
Obviously CBD has a great deal of utility in a wide variety of settings. That is precisely why it can be so difficult to explain “why” CBD. The answers are pretty straightforward with THC, it gets you high, and relieves pain. With CBD however, things are not as easy to decipher. Being the promiscuous molecule that it is, CBD interacts with a number of different physiological processes. All of these of course vary by the individual as well. This makes the answer of “why” CBD, even more difficult.
For some CBD may be used for pain management, for others anxiety and depression. These may be the most common answers heard when asking people why they have tried CBD. They are definitely not the only answers though. Regulation of homeostasis processes or maintenance of endocannabinoid tone, and reduction in THC tolerance dependence are shown to be just as important.
Breaking The Taboo
There was once a thought of a divided cannabis world. This dates back to the naming of hemp strains in Europe as Cannabis Sativa, while the high THC strains in central Asia were named Cannabis Sativa ssp. Indica. More commonly the divide has been in how the different varieties are regulated, and the taboos placed on them in our society.
These days, it is often the stereotype that younger people and old hippies want to get stoned and use high THC strains of cannabis. Conversely an elderly generation that isn’t interested in any of the intoxicating effects of THC, turn to CBD found in hemp cannabis strains, for the therapeutic value.
This is an outdated taboo! In fact, both groups can benefit from a combined approach that builds off the synergy of the entourage effect. Study after study has consistently shown that whether you are trying to have an enjoyable time, or seeking pain management solutions, cannabinoids work better together. So let your cannabinoids be like the Beatles, and come together… over weed!
- Goldstein, Bonni. Cannabis Is Medicine: How Medical Cannabis and CBD Are Healing Everything from Anxiety to Chronic Pain. Hachette UK, 2020.
- de Almeida, Douglas L., and Lakshmi A. Devi. “Diversity of molecular targets and signaling pathways for CBD.” Pharmacology research & perspectives 8.6 (2020): e00682.