In pharmacology, the term “promiscuous molecule” refers to a molecule that has many different targets within the cellular world. This includes cell receptors, binding proteins, and uptake transporters. CBD, and it’s psychoactive cousin THC, have both been shown to be highly promiscuous molecules, which is beginning to unlock the mystery behind CBD and its overall wellness benefits. 

Through ongoing scientific research, we are learning how promiscuous CBD (and to a lesser extent, THC) actually is. Many people initially were a bit skeptical about some of the incredible claims out there about CBD. How could any one molecule have such a positive impact on so many aspects of human wellness, they asked? While it’s not yet proven by science, there is mounting scientific evidence to support the far-reaching positive effects of CBD (and even THC) may lie in the promiscuity of the molecule itself. 

Molecular promiscuity

Neurons are specialized cells in the brain that are able to communicate through a process of synapses and chemical messenger molecules called neurotransmitters. Each neurotransmitter’s ability to communicate depends on the sensitivity to the cellular receptors on a neuron. Think of unlocking  a smartphone or entering a passcode on a device. If a neurotransmitter “knows” and fits the correct passcode, the neuron will open up and the neurotransmitter can deliver its message to trigger or stop an action. If not, the neuron will remain locked and the message is blocked and ignored. The same basic process occurs at the cellular level. 

Most molecules have a limited ability to interact with various cell receptors. When pharmaceuticals are being designed, different molecules are selected for their specificity, meaning those molecules only have the passcode to specific cell receptors to create a very targeted effect for a drug. 

The body is a complex organism though, and many molecules selected can bind with a few cell receptors, binding proteins, and uptake transporters. This seems to be part of the reason why one pharmaceutical drug designed for one condition may have efficacy for one or more other totally unrelated conditions. 

Truly promiscuous molecules, or ones that have been found to interact with many different cell receptors and other cellular signaling activities, seem to be relatively rare. As additional research comes forward, the promiscuity of phytocannabinoids, including CBD and THC, become increasingly apparent.

The Endocannabinoid System (ECS)

The Endocannabinoid System (ECS) is a biological signaling system typically associated with cannabinoids like CBD and THC. The total scope that ECS has is currently being studied, but it is believed to have modulation impacts on sleep, mood, stress, cardiovascular function, memory, sexual function, and motor control. Endocannabinoids, which are the endogenous (or created within) chemical signalers of all mammals, are produced when certain conditions arise in an attempt to create homeostasis within the organism. Phytocannabinoids are the plant-based versions of endocannabinoids and can interact with the same receptors. 

There are two known primary cell signaling receptors in the ECS: CB1 and CB2. THC (or delta9-Tetrahydrocannabinol) is known to bind directly to CB1, which causes the psychoactive high associated with marijuana. CBD (or Cannabidiol) does not bind with CB1 or CB2 directly, which accounts for why there are no psychoactive effects (like there is with THC) associated with CBD. While the science is still a bit unclear on CBD’s exact role, it is believed that it may work by preventing endocannabinoids from being broken down, allowing them to have a longer and more impactful modulating effect on the body.

Interestingly, CBD also appears to block the ability for THC to bind to CB1. On the medical/recreational cannabis side, that is why there is such an emphasis on THC:CBD ratio. The ratio has a profound effect on the intoxicating properties. 

There is still much debate on the topic in medical research, but it is known that both THC and CBD have profound effects on the ECS, but in very different ways. One which produces intoxicating effects (THC), and the other (CBD) which appears to have a more modulating effect.

Other cell targets of CBD

The Serotonin System. Serotonin is a powerful neurotransmitter and many CNS cells have special receptors for it (one is called 5-HT1A receptors). Serotonin is generally called the bliss molecule as it is generally associated with elevated mood. 5-HT1A receptor activation is also associated with lower blood pressure and decreased heart rate. CBD has been shown to interact with the 5-HT1A receptor as a full agonist (activator). There are other Serotonin receptors that CBD has affinity for as well. A lot more scientific research is needed, but CBD certainly looks promising in its interaction within the Serotonin System.

The Dopamine System. Dopamine is another signaling neurotransmitter in the brain that activates D2 receptors. It is believed to be associated with schizophrenia and other psychotic conditions (that are the result of low dopamine levels). Many antipsychotic medications target the D2 receptor as agonists (activators). CBD has been scientifically demonstrated as a partial agonist, which may explain its suspected antipsychotic properties. Although more research is needed to fully unlock the connection, some of the other documented effects of dopamine on the body (such as drowsiness and decreased appetite) also seem to be associated with CBD.

The Opioid System. This is another very interesting avenue for future scientific study. CBD has been shown to interact with both mu opioid receptors and delta opioid receptors. CBD is a negative allosteric modulator for these receptors, which is to say that it alters the receptor and decreases the effect of other agonists (like opium). This may be why some claim that CBD can reduce cravings associated with opioid addiction. This is again not proven by science, but there is a known interaction between these receptors, so future studies may bear this out. 

Other cellular interactions of CBD. CBD has been shown to interact with glycine receptors, nuclear receptors, and TRP channels, which are all associated with anti-inflammation, pain, pain-blocking, and anti-cancer activities. Interaction with GABA receptors has been shown to have an impact on anti-seizure and epilepsy properties. Other interactions have been shown in the adenosine system, acetylcholine receptors, and atypical cannabinoid receptors.

Final thoughts

As you can see, the sheer volume of CBD’s interactions with so many different neurons, transmitters, and cell receptors within the human body demonstrates its potential for  having a widespread impact. While certainly something that needs to be explored even further through scientific research, the secret of Cannabidiol (CBD) just might lie in its promiscuous nature.