Key Takeaways
- CBD+CBDA combinations work because of the entourage effect, where combinations of cannabinoids have greater effects than the sum of their parts.
- Inflammation is the main target for the combination, but it may also help with nausea, getting a restful sleep, and even seizures.
- The company Tanasi is working with Middle Tennessee State University to perform studies, which show a greater benefit from CBD and CBDA in combination than when given individually.
- If you’re interested in trying it, Dr. Benavides recommends 10 mg of each twice per day, increasing from there as needed.
If you’ve been using CBD to manage inflammation or other issues, adding some CBDA to your treatment could improve the outcome dramatically. At least, that’s what brands like Tanasi are saying, based on their research in collaboration with university researchers.
But is it really true? And if it does make a difference, what dose should you take?
We’ve looked into the theory behind 1:1 CBD+CBDA mixtures and how it works in practice.
The Basics of CBDA vs. CBD
Just like THCA is the acidic form of THC which is more abundant in the cannabis plant, CBDA is the acidic form of CBD which is more common in the plant, and is in fact the most common cannabinoid in hemp plants.
RELATED: What Are the Benefits of CBDA?
Dr. Abraham Benavides, an international cannabis consultant and medical cannabis coach, explained to us, “The acidic group on CBDA makes it more reactive with receptors and also makes it more water-loving. This enhances absorption into the body up to three-fold compared to neutral CBD. The increased bioavailability likely also helps improve its effectiveness. However, clinical studies remain to be done.”
Why Mix CBD and CBDA?
If CBDA is beneficial on its own, why mix it with CBD at all?
Dr. Benavides answered, “Currently, data suggests that cannabinoids work best if they work together in the presence of other whole-plant components, a term called the entourage effect.”
He also told us that a 1:1 mixture is a simple and common starting point for brands, adding, “However, we don’t have enough large data yet to know for sure which exact ratios are most therapeutic for people. In the meantime, it’s a reasonable and scientific approach to start empirically with equal parts of each, at least at first in these early stages of cannabis medicine until further discoveries are made.”
What Conditions Are CBD:CBDA Products Useful For?
CBD+CBDA products are usually intended to help with inflammation, but this isn’t the only option, as Dr. Benavides stressed:
“CBDA specifically has dozens of molecular targets in the body, within and outside of the endocannabinoid system, to exert its effects. Most notably, CBDA is estimated to have a thousand times more potent response at the serotonin receptor than CBD. This may lead to enhanced responses in seizures and nausea.”
Jeff Heeren, CEO of Tanasi and Greenway confirmed that reducing inflammation was the main benefit of the combination, but he also emphasized that inflammation involves the interplay of the immune, endocannabinoid, nervous, and autophagy systems:
“These systems work together to control the body’s response to numerous conditions, ranging from pain to being able to relax and sleep. Thus it is not surprising that CBD is being used to treat pain from a number of conditions, including headaches and helping people achieve a more restful sleep.”
What Evidence Do We Have on 1:1 Mixtures of CBD and CBDA?
The theory behind the 1:1 mixture of CBD and CBDA is solid, but is it backed up by science?
Tanasi is working on this as part of their University Grant Partnership agreement with Middle Tennessee State University (MTSU).
The data is available as part of their UK patent, which has been granted for general inflammation and inflammation related to autoimmune diseases. Specifically, this document (or the pending US application) gives details about the experiments.
The studies described in the patent application are either studies of cells in a culture or the effects of the treatments on mice. These types of evidence aren’t perfect – after all, we are not applying CBD and CBDA directly to our cells and we are not large mice – but they both have a crucial role in the development of new treatments.
Dr. Benavides emphasized the value of mouse studies, “Animal studies have been around and validated since the time of the ancient Greeks. Data show that we share 97.5% of our genome with mice, resulting in similar responses to inflammation and infectious disease.”
Adding that, “This doesn’t guarantee that humans will respond in the same way. But it gives us enough information as to whether the compound is safe, effective, and worthy of continuing further study on humans.”
The Data on CBD and CBDA for Inflammation
While the research also looked into cannabinoids as antioxidants and autophagy, here we will focus on the results on inflammation and cytokines.
Dr. Benavides explained to us that cytokines are “chemical messengers,” which are released in response to bacteria, cell damage or other triggers, with the external cytokine response “recruiting” immune cells, and the internal response causing an inflammatory cascade.
He described how this process can cause problems:
“Inflammatory responses can sometimes be activated inappropriately, without the presence of any real damage or foreign pathogen (e.g., sterile inflammation, autoimmune disease, etc). If this goes on, many chronic diseases can occur. A large family of cytokines called interleukins (abbreviated with the prefix ‘IL’) are implicated in many diseases related to aging, cancer, cardiovascular disease, gout, chronic liver disease, diabetes, arthritis, inflammatory bowel disease, severe COVID-19, and many more.”
The studies from MTSU and Tanasi looked at the impact of cannabinoids on IL cytokines and other important parts of this system.
In both cell culture tests and animal studies, the combination of CBD and CBDA was more effective at suppressing cytokines than either cannabinoid alone.
In the mouse model, CBD suppressed cytokines by an average of 12.9%, CBDA by 13.7% and the combination by 21%.
While there are both pro-inflammatory and anti-inflammatory cytokines, the document explains that 7 out of 8 pro-inflammatory cytokines tested were suppressed, while only 1 out of 3 anti-inflammatory cytokines were suppressed.
They point out that the “cannabinoids preferentially targeted the suppression of inflammatory cytokines as opposed to anti-inflammatory cytokines.”
Overall, the initial research looks positive, and Jeff Heeren told us, “When the patent issues we plan to perform human trials to examine the 1:1 CBD:CBDA formulation versus CBD alone.”
Does This Get the Most Out of the Entourage Effect?
While the initial research seems very positive, Dr. Benavides made an important point:
“However, a really important note is that Tanasi uses what they call a ‘defined spectrum’ formulation of 1:1 CBD:CBDA. This means their products are THC-free and devoid of all other whole-plant components, acting more like an isolate. While isolates have some activity on their own, entourage effect data suggests that it would be more effective with natural, whole-plant components present. This is why I steered more towards the brand Myriam’s hemp, which uses full spectrum hemp oil as the base.”
And the data supports his point, with many of the cannabinoids tested showing just as much cytokine suppression as CBD and CBDA. Jeff explained that the final decision was partially an economic one:
“The combination of CBD and CBDA was the most promising, so we focused on CBD and CBDA which would lead to a more affordable product for the consumer. Even a CBC:CBCA or CBG:CBGA product would be a lot more costly to the consumer than CBD:CBDA.”
So on balance, the decision was made to focus on CBD:CBDA blends to maximize both efficacy and cost-effectiveness.
How to Use CBD and CBDA Combinations
If the initial results sound positive, Dr. Benavides recommends starting at 10 mg of each (in equal amounts) twice per day to maximize effectiveness while still getting the best bang for your buck, and increasing gradually as needed.
Tanasi has a range of high-quality CBD and CBDA products, and Myriam’s has a full spectrum CBD and CBDA oil if you want other beneficial cannabinoids and terpenes in there too.
From their side, Tanasi sees a lot of positive feedback from customers. Jeff told us, “It amazes me when customers provide their feedback. Many times we read, ‘I’ve tried CBD before, but when I take Tanasi I really understand the benefits that I’m seeking.’”
Conclusion – CBD:CBDA Is a Promising Combination
CBD and CBDA seem to work better in combination than either do individually, based on the data we have so far.
However, it’s important to remember that the evidence right now is very limited, and even though we can make valid assumptions based on animal studies, we’ll need to see the results of the human trials before we can reach a solid conclusion.
In the meantime, if you find that CBD doesn’t quite do the trick on its own, you should definitely consider a combination with CBDA.