In recent months, many pundits, skeptics and regulatory bodies have weighed in on what we don’t know when it comes to cannabidiol (CBD) and how it impacts our body.
But what do we know when it comes to CBD and how it acts in various pathways in the human body? And finally, what kind of therapeutic value does the molecule actually hold?
Over the course of my time in the cannabis industry, I’ve been approached by many family members and friends with the same ringing question. With a basic understanding of existing pre-clinical research and the evolving growing CBD market, I’ve decided to dive in deeper and answer this important question.
In my opinion, the adoption of cannabis as a legitimate medical tool depends on the sophistication of consumers and our ability to advocate for new and efficacious treatment using scientific evidence rather than anecdotal claims. Educating ourselves on how CBD works will help drive the industry forward and decrease the prevalence of harmful myths.
CBD Today
Significant research in the space has begun to shed light on the vast therapeutic applications for CBD. Specifically, CBD has been heralded as a key cannabinoid with applications in various therapeutic areas including pain, epilepsy, psychiatry, movement disorders and neurodegenerative disease. CBD does not impart intoxicating psychoactive effects, making the cannabinoid especially attractive to canna-curious consumers turning to cannabis and hemp-derived products for the first time.
While CBD can be derived from the cannabis plant, it is primarily extracted from hemp varieties (C. sativa with <0.3% THC) due to greater CBD abundance (up to 20%) and legal freedom. Last year, the 2018 Farm Bill removed legal restrictions on CBD derived from hemp varieties as opposed to the medically or recreationally grown cannabis plant.
First, we will assess the current state of knowledge on CBD’s mechanism of action in:
The Endocannabinoid System
As you may already know, cannabinoids interact primarily with the body’s endocannabinoid system which has two types of receptors CB1 and CB2. In a study by Laprairie et. al, CBD was found to be a negative allosteric modulator of the CB1 receptor, which means CBD has the power to decrease the activity of THC and limit its psychoactive effects. This explains why - at least anecdotally - strains with higher CBD content tend to have lesser psychoactive effects. It may also explain why those who feel the effects of THC so intensely find that CBD provides calming effects.
You might think this sounds great. But you may also be wondering “what is an allosteric modulator?” and “how does it work?”
Allosteric modulators act on a binding site non-competitively. If you think of a binding molecule or ligand as a key and the lock as a receptor, allosteric modulators change the shape of the lock, thereby affecting the key that fits most closely. Allosteric modulators can enhance or inhibit the strength of a signal, depending on whether they increase the fit of the key or decrease the probability of the key entering the lock (Figure 1).
Other Pathways
However, CBD does not only interact with the endocannabinoid system and its key receptors (CB1 and CB2). Rather, numerous studies in animal models have proven that CBD modulates several other pathways and channels with therapeutic value.
Anticonvulsant Properties
Today, only two CBD-derived drugs have been approved by the FDA; most notably the epilepsy treatment Epidiolex from GW Pharmaceuticals.
While Epidiolex has helped popularize cannabinoids as a treatment, it also embodies the cannabinoid molecule’s most troublesome physical property: hydrophobicity. Cannabinoids are hydrophobic, meaning they hate water and will achieve low bioavailability (or concentration in the blood). This is because hydrophobic molecules are not easily absorbed in aqueous solutions. Therefore, Epidiolex is ingested with sesame oil, a fatty solution that helps the body absorb the critical active ingredient for patients suffering from seizure syndromes like Lennox-Gastaut syndrome (LGS) or Dravet syndrome. Ingesting CBD with sesame oil has its shortcomings. In addition to adverse reactions and a poor taste profile leading to low adherence, sesame is also the ninth most common food allergen.
Due to the limitations of cannabinoids’ hydrophobic properties, cannabis-focused drug development companies are forming superior cannabinoids using enzymatic modifications. These drug candidates may help improve water solubility while maintaining the therapeutic effects of the core CBD molecule. Additionally, these active ingredients could empower Canopy Rivers portfolio companies in the food, beverage, and cosmetics sectors, to have greater bioavailability and purity.
Neuroprotective Properties
Studies have shown that CBD may also be useful in ameliorating symptoms of stress, anxiety, and mental illness. A literature review on CBD by Blessing et al published in Neurotherapeutics found that CBD exhibits anxiogenic effects for conditions such as PTSD, GAD, PD, OCD, and SAD.
There are several proposed mechanisms of action that could support anxiogenic effects. Schier et al. suggests in an oft-cited study that CBD activates the 5-HT1A serotonin receptor thereby activating cascades and pathways similar to serotonin, commonly referred to as the happy chemical. While Schier et al. were able to demonstrate anti-anxiety and antidepressant effects in animal models, translating these studies to clinical trials will help validate this hypothesis.
Full Spectrum vs. Isolate
Many scientists are also proposing that the effects of CBD are often enhanced by the consumption of “full spectrum hemp” or the entire mixture of cannabinoids within the plant, otherwise known as the entourage effect. As data on the efficacy of CBD isolate vs. full-spectrum is explored, companies may create both product types to address divergence in the literature and consumer preference.
Conclusion
According to a Gallup poll published in August, 1 in 7 Americans are already using CBD products for a variety of indications including sleep, anxiety and pain. Still, the shortage of evidence-based research on CBD leaves many unanswered questions on the myriad of uses for CBD and other cannabinoids.
One of the factors currently handicapping research is product standardization. By continuing to increase the quality and consistency of cannabis flower and isolate through plant science and regulatory standardization, clinical research has the opportunity to drive further consumer trust and open up new markets in pharma and biotech for CBD and cannabinoids at large.
Today, CBD is evolving from anecdotal remedy to evidence-based therapeutic and trusted consumer ingredient. Here's to 2020 bringing more high impact studies on CBD efficacy and further solidifying the potential of this small but powerful molecule.
But what do we know when it comes to CBD and how it acts in various pathways in the human body? And finally, what kind of therapeutic value does the molecule actually hold?
Over the course of my time in the cannabis industry, I’ve been approached by many family members and friends with the same ringing question. With a basic understanding of existing pre-clinical research and the evolving growing CBD market, I’ve decided to dive in deeper and answer this important question.
In my opinion, the adoption of cannabis as a legitimate medical tool depends on the sophistication of consumers and our ability to advocate for new and efficacious treatment using scientific evidence rather than anecdotal claims. Educating ourselves on how CBD works will help drive the industry forward and decrease the prevalence of harmful myths.
CBD Today
Significant research in the space has begun to shed light on the vast therapeutic applications for CBD. Specifically, CBD has been heralded as a key cannabinoid with applications in various therapeutic areas including pain, epilepsy, psychiatry, movement disorders and neurodegenerative disease. CBD does not impart intoxicating psychoactive effects, making the cannabinoid especially attractive to canna-curious consumers turning to cannabis and hemp-derived products for the first time.
While CBD can be derived from the cannabis plant, it is primarily extracted from hemp varieties (C. sativa with <0.3% THC) due to greater CBD abundance (up to 20%) and legal freedom. Last year, the 2018 Farm Bill removed legal restrictions on CBD derived from hemp varieties as opposed to the medically or recreationally grown cannabis plant.
First, we will assess the current state of knowledge on CBD’s mechanism of action in:
- The endocannabinoid system, and finally;
- Other pathways within the body
The Endocannabinoid System
As you may already know, cannabinoids interact primarily with the body’s endocannabinoid system which has two types of receptors CB1 and CB2. In a study by Laprairie et. al, CBD was found to be a negative allosteric modulator of the CB1 receptor, which means CBD has the power to decrease the activity of THC and limit its psychoactive effects. This explains why - at least anecdotally - strains with higher CBD content tend to have lesser psychoactive effects. It may also explain why those who feel the effects of THC so intensely find that CBD provides calming effects.
You might think this sounds great. But you may also be wondering “what is an allosteric modulator?” and “how does it work?”
Allosteric modulators act on a binding site non-competitively. If you think of a binding molecule or ligand as a key and the lock as a receptor, allosteric modulators change the shape of the lock, thereby affecting the key that fits most closely. Allosteric modulators can enhance or inhibit the strength of a signal, depending on whether they increase the fit of the key or decrease the probability of the key entering the lock (Figure 1).
Other Pathways
However, CBD does not only interact with the endocannabinoid system and its key receptors (CB1 and CB2). Rather, numerous studies in animal models have proven that CBD modulates several other pathways and channels with therapeutic value.
Anticonvulsant Properties
Today, only two CBD-derived drugs have been approved by the FDA; most notably the epilepsy treatment Epidiolex from GW Pharmaceuticals.
While Epidiolex has helped popularize cannabinoids as a treatment, it also embodies the cannabinoid molecule’s most troublesome physical property: hydrophobicity. Cannabinoids are hydrophobic, meaning they hate water and will achieve low bioavailability (or concentration in the blood). This is because hydrophobic molecules are not easily absorbed in aqueous solutions. Therefore, Epidiolex is ingested with sesame oil, a fatty solution that helps the body absorb the critical active ingredient for patients suffering from seizure syndromes like Lennox-Gastaut syndrome (LGS) or Dravet syndrome. Ingesting CBD with sesame oil has its shortcomings. In addition to adverse reactions and a poor taste profile leading to low adherence, sesame is also the ninth most common food allergen.
Due to the limitations of cannabinoids’ hydrophobic properties, cannabis-focused drug development companies are forming superior cannabinoids using enzymatic modifications. These drug candidates may help improve water solubility while maintaining the therapeutic effects of the core CBD molecule. Additionally, these active ingredients could empower Canopy Rivers portfolio companies in the food, beverage, and cosmetics sectors, to have greater bioavailability and purity.
Neuroprotective Properties
Studies have shown that CBD may also be useful in ameliorating symptoms of stress, anxiety, and mental illness. A literature review on CBD by Blessing et al published in Neurotherapeutics found that CBD exhibits anxiogenic effects for conditions such as PTSD, GAD, PD, OCD, and SAD.
There are several proposed mechanisms of action that could support anxiogenic effects. Schier et al. suggests in an oft-cited study that CBD activates the 5-HT1A serotonin receptor thereby activating cascades and pathways similar to serotonin, commonly referred to as the happy chemical. While Schier et al. were able to demonstrate anti-anxiety and antidepressant effects in animal models, translating these studies to clinical trials will help validate this hypothesis.
Full Spectrum vs. Isolate
Many scientists are also proposing that the effects of CBD are often enhanced by the consumption of “full spectrum hemp” or the entire mixture of cannabinoids within the plant, otherwise known as the entourage effect. As data on the efficacy of CBD isolate vs. full-spectrum is explored, companies may create both product types to address divergence in the literature and consumer preference.
Conclusion
According to a Gallup poll published in August, 1 in 7 Americans are already using CBD products for a variety of indications including sleep, anxiety and pain. Still, the shortage of evidence-based research on CBD leaves many unanswered questions on the myriad of uses for CBD and other cannabinoids.
One of the factors currently handicapping research is product standardization. By continuing to increase the quality and consistency of cannabis flower and isolate through plant science and regulatory standardization, clinical research has the opportunity to drive further consumer trust and open up new markets in pharma and biotech for CBD and cannabinoids at large.
Today, CBD is evolving from anecdotal remedy to evidence-based therapeutic and trusted consumer ingredient. Here's to 2020 bringing more high impact studies on CBD efficacy and further solidifying the potential of this small but powerful molecule.
