05 Feb Should You Try CBDA?
what is cbda?
Cannabidiolic acid (CBDA) is the raw form of cannabidiol (CBD) and, like CBD, is non impairing. CBDA, like other cannabinoids has many wellness benefits. Before we move on to this discussion, however, we want to address the popular headlines that herald in 2022. In January 2022 a study published in the Journal of Natural Products triggered a wave of headlines. They proclaimed that cannabis can prevent or cure COVID. One example was this breathless ditty from Yahoo! Finance: “As Cannabis is Linked to COVID Prevention, How Can You Invest in the Windfall?” The headlines followed the publishing of a study by researchers from Oregon State University and the Oregon Health and Science University. It showed that CBDA and other acidic cannabis compounds can stop the coronavirus from infecting human cells. Wouldn’t this be fantastic!!!
At Blue Lotus Wellness & CBD Boutique we have always been committed to honest, unexaggerated information. Yes, this study is very interesting (to some of us). However, according to an interview by Project CBD with Matt Elmes, PhD, the data comes from samples of cultured cells. Dr. Elmes work has focused on the biochemistry of cannabinoids. “We always need to be careful not to draw clinical conclusions from preclinical experiments like this because nearly every time there will be major caveats when trying to translate them to a real-world setting.”
The experiments provided indication (in conjunction with other proof-of-concept experiments) that CBDA can latch on to COVID virus particles and may hinder its ability to infect new cells. What the sensationalized articles do not want to point out, however, is that most human tissues will not reach anywhere near a concentration-range even when regularly taking large doses of cannabinoids! It is just highly unlikely that the interaction between acidic cannabinoids and COVID will prove to have much, if any, clinical relevance. Dr. Dustin Sulak, cannabis physician and founder of Healer.com, also came to the same conclusion after reviewing the research. It is not that the study is not without merit. Cellular studies are always a great place to start. They give scientists information about how to proceed with more sophisticated studies on living beings. For more information, please see that interview and other articles at ProjectCBD.org
What are the benefits?
The Quick Rundown
If you have been unsatisfied with the results of CBD and are using CBD in high amounts (25-50mg) per dose up to three times a day, CBDA may work better for you and your body chemistry. Unlike CBD, its acidic counterpart will not alter the effects of THC products.
The clinical findings of cannabis physician, Dr. Dustin Sulak, with CBDA and several animal studies show that even small amounts can have significant effects.
CBDA Drops should taste more like a freshly juiced plant because they contain more of the plant’s raw beneficial compounds. They also contain complex terpenes which create a more intense flavor than CBD Drops. Manufacturers make CBDA products by heating CBD cannabis extracts. We recommend unheated CBDA oils, and we advise that you keep them refrigerated for best results.
CBDA SUPPORTS WELLNESS*
- Reduces pain and inflammation after physical activity
- Relieves occasional sleeplessness
- Promotes alertness and clear thinking
- Improves mood, promotes resilience to stress, and relieves irritability
- Enhances performance and recovery from exercise
WHY USE CBDA OIL DROPS?
- You like CBD and want to try adding CBDA to enhance its effects.
- You want to try CBDA’s more powerful benefits or know you respond better to CBDA.
- You’ve tried CBD in the past in moderate to high amounts (25-50mg per does up to 3 times a day) and have been unsatisfied with the results.
- You are using a THC product and you do not want your CBD hemp product to decrease its effects.
How does CBDA work and what does it do?
CBDA does not have activity at the CB1 receptor, or the enzyme (FAAH) that breaks down our endocannabinoid anandamide. CBDA doesn’t seem to have the same ability to modulate the endocannabinoid system like CBD does. It does, however, have several actions in common with CBD, including stimulating the serotonin and capsaicin receptors. We know that CBDA has a higher bioavailability in humans. It has 5-11x better absorption in humans than CBD when taken orally. Scientists found some animal-model evidence that CBDA is stronger and more potent than CBD. Not only do we absorb CBDA better, but CBDA also acts more powerfully. For example, animal studies have found CBDA to be 10 times more potent than CBD in a model of seizures, 100x more potent in a model of inflammatory pain, 10,000x more potent in a model of nausea, and 50,000x more potent in a model of anxiety.
CBD AND CBDA – WHAT’S THE DIFFERENCE?
Cannabidiol (CBD) is a well-known component of hemp (cannabis with less than .3% delta-9 THC) with diverse health benefits. Many people are surprised to learn that the hemp plant does not directly produce CBD. The plant actually produces cannabidiolic acid (CBDA) which converts to CBD slowly at room temperature, or rapidly when exposed to high temperatures.
CBD and its acidic counterpart share many physiologic properties, but also have some important differences:
- CBDA is more easily absorbed (up to 11 times) when taken by mouth, compared to CBD. (1)
- CBDA and CBD both have anti-inflammatory properties but may act via different mechanisms in the body. For example, unlike CBD, CBDA has been shown to decrease the activity of the COX-2 enzyme. This enzyme is responsible for increasing inflammation. (2)
- CBDA may be more potent than CBD for some applications based on studies of rodent models of nausea (3), stress-induced anxiety (4), pain and inflammation, and seizures (5). We don’t know if similar results translate to humans yet. It is possible, however, that CBDA may be more effective than CBD at lower doses.
- CBDA is unlikely to mitigate the adverse effects of THC, a common usage of CBD. Many people appreciate the combined effects of CBD and THC. Some find, however, that CBD weakens the beneficial effects of THC and may prefer CBDA.
Which cannabinoid is best for me?
Dr. Sulak generally recommends starting with a trusted CBD product that contains the widest spectrum of naturally occurring terpenes, flavonoids, and at least a small amount of CBDA. If this does not work for you at a moderate to high dose, then try CBDA. You can try adding CBDA to your CBD dose, or try changing to CBDA.
How about Pain?
Here’s the bottom line regarding CBD formulations and pain:
- Higher doses of CBD are often necessary to effectively address pain but can be too costly to sustain.
- CBD formulations that include the legally allowed amount of THC are more effective and often require lower doses than purified CBD.
- CBD formulations that include CBDA –with or without THC– are usually more potent and effective than products with no CBDA.
What about Anxiety
Here’s the bottom line regarding CBD formulations and anxiety:
- CBD formulations that include the legally allowed amount of THC are more effective and at lower doses.
- CBD formulations that include CBDA –with or without THC– may be more potent and effective as well.
In conclusion, CBDA, the often-overlooked precursor to CBD, has incredible therapeutic potential, gaining the attention of researchers and consumers alike. While we do not expect CBDA to completely replace CBD in our cannabis repertory, we do expect CBD users to find products containing CBDA much more potent, and some to find switching to CBDA altogether more effective for relieving their symptoms and promoting health.
The Science and the Nitty Gritty
What is CBDA?
Cannabidiolic acid was first isolated by Israeli scientist Raphael Mechoulam in 1965 (6). Through exposure to sufficient heat or sunlight, CBDA changes into CBD by going through a chemical process called decarboxylation in which the carboxyl group is lost.
While many of us associate decarboxylation with cannabis, the same chemical reaction occurs in cellular respiration. It’s the reason we all exhale CO2 as a byproduct of metabolism.
For many years, scientists considered decarboxylated cannabinoids the ‘activated’ compounds, producing more potent therapeutic effects in our bodies. However, this assumption has recently been turned upside down with studies showing CBDA’s activation of 5-HT1A serotonin receptors to be significantly more potent than CBD. And CBDA was also shown to have a stronger binding affinity than CBD as an antagonist at another important receptor known as GPR55.
These discoveries suggested that CBDA could indeed have an important place at the therapeutic table for conditions as varied as cancer, anxiety, epilepsy, and treatment-resistant nausea and vomiting.
NAUSEA & VOMITING
Serotonin is perhaps the most widely known class of neurotransmitter due to its role in mood regulation. However, serotonin’s biological reach extends far beyond just keeping us happy. It is involved in such diverse physiological functions as nausea, vomiting, and intestinal movements.
Much of what we know about CBDA’s activation of 5-HT1A serotonin receptors is thanks to research by Erin Rock and her team at Guelph University in Ontario, led by neuroscientist Linda Parker. Rock examined the therapeutic application of both CBD and CBDA for different types of nausea and vomiting. (7) She showed that by binding with 5-HT1A receptors in a more potent fashion than CBD, CBDA suppressed nausea and vomiting caused by toxins and motion sickness.
Perhaps the most exciting breakthrough relates to CBDA’s remarkable success in reducing anticipatory nausea. The type of intense nausea one experiences prior to chemotherapy when patients feel horrible before treatment has even begun. Anticipatory nausea, we should note, has no effective pharmaceutical treatment.
In a different study examining the efficacy of combining CBDA with ondansetron, a standard antiemetic drug, Rock’s team found that even at very low doses CBDA enhanced the pharmaceutical drug’s anti-nausea effect. (3) In fact, Rock goes on to assert that the amount of CBDA needed to reduce nausea was a staggering 1000 times less than required by CBD to have the same effect.
Furthermore, the Canadian scientists confirmed that CBDA is not intoxicating or impairing as it does not interact with CB1 cannabinoid receptors. This makes CBDA potentially a better option for patients who struggle with the mood-altering effects of THC-rich cannabis or dronabinol (FDA-approved synthetic THC).
CBD burst into the mainstream largely because of its celebrated anti-seizure effects. To date, the only approved CBD pharmaceutical in the United States is the purified CBD tincture, Epidiolex. It is approved for three types of drug-resistant epilepsy.
It’s not surprising that GW Pharma, the company behind Epidiolex, is looking closely at CBDA’s therapeutic potential. In pharmacokinetic studies comparing CBDA with CBD, GW scientists found CBDA to have superior bioavailability and faster onset than CBD – properties that make CBDA a very attractive option for drug development.
Not only did it require lower doses (thus reducing the chance of side effects), but CBDA was more effective in seizure reduction in certain parameters. Some of this data appears in GW’s patent application (8) for the ‘Use of cannabinoids in the treatment of epilepsy,’ rather than in a peer reviewed study. But it certainly backs up Rock’s findings, as well as anecdotal reports coming from U.S. cannabis clinicians such as Dr. Bonni Goldstein and Dr. Dustin Sulak, who’ve had great success when treating patients with CBDA.
A CASE HISTORY
Peruvian physician Max Alzamora shared a compelling case study involving CBDA in a recent Society of Cannabis Clinicians webinar.
14-year-old Glendy came into his office having 10 seizures a day due to autoimmune encephalitis. Prior to seeing Dr. Alzamora, she had at one point been in a medical coma for 45 days. She also contracted drug-induced hepatitis, which medication she her doctor prescribed caused.
Glendy’s parents acquired CBD oil from the United States, which brought about some seizure reduction. However, buying imported CBD oil wasn’t financially viable for the family, so Dr. Alzamora found a local source of CBD oil. Or so he thought.
It turns out, the CBD oil hadn’t been decarboxylated, and Glendy was in fact taking CBDA. California lab tests later confirmed the oil primarily contained CBDA rather than CBD. And guess what – her seizures reduced even further. In fact, at latest count, Glendy, now 16, only has ten seizures a year and no longer takes any pharmaceutical anti-epileptic drugs. Her cognitive development, anxiety, autistic-like behavior, and overall quality of life have all markedly improved since switching to the CBDA oil.
“While I was already getting good results in my patients with cannabinoid treatments containing THC and CBD,” says Dr. Alzamora, “CBDA has been especially effective in treating epilepsy, Parkinson’s, and inflammatory conditions. For me, the acidic cannabinoids open a whole spectrum of therapeutic possibilities.”
But medical scientists still have much to learn about CBDA’s multiple mechanisms of action with respect to epilepsy and other conditions. “I personally will be gathering more evidence that I hope will benefit patients,” Alzamora asserts.
With Glendy’s epilepsy caused by an autoimmune condition, it’s possible her positive response to CBDA in part could be attributable to the acid cannabinoid’s anti-inflammatory action, which may occur because of its role as a selective Cox-2 inhibitor. (2)
There are two types of Cyclooxygenase (Cox) enzymes: Cox-1 maintains the normal lining of the stomach and intestines, and Cox-2 has a pro-inflammatory effect. Non-steroidal anti-inflammatory drugs, such as aspirin and ibuprofen, inhibit both Cox-1 and Cox-2 enzymes. By inhibiting Cox-1, long-term use of these over-the-counter drugs can cause major gastrointestinal complications.
It’s therefore of therapeutic interest to develop selective Cox-2 inhibitors that bypass Cox-1 and relieve patients’ inflammation-related symptoms, while sparing them of any dangerous long term consequences. As a Cox-2 inhibitor, CBDA shows potential as a safer non-steroidal anti-inflammatory drug. Researchers, However, have not yet carried out studies on humans.
One preclinical study (9) also found that CBDA’s downregulation of Cox-2 enzymes may help prevent the spread of a certain type of invasive breast cancer typified by higher than normal levels of Cox-2. When the breast cancer cells were treated with CBDA over 48 hours, both Cox-2 and Id-1, a protein associated with the aggressive spread of breast cancer cells, were down-regulated, while Sharp-1 expression, a suppressor of breast cancer metastasis, increased. Although this is very much preliminary data, it suggests that for certain types of breast cancer, CBDA may halt the spread of malignant cells to other parts of the body.
A SYNTHETIC CBDA COMPOUND
Professor Mechoulam generated headlines with the launch of a patented synthetic CBDA methyl ester. He subtly altered the chemical structure to make the methyl ester compound more stable than CBDA. Mechoulam and his team have begun to investigate the compound’s therapeutic use in conditions such as anxiety, depression, (10) inflammatory bowel disease, nausea and vomiting, and as an alternative to steroids.
This stabilized version of CBDA may be easier to work within the lab for the development of pharmaceuticals. It is not, however, at all clear that it represents a significant improvement as a therapeutic modality compared to artisanal cannabis or hemp products containing CBDA.
When stored appropriately in a cool, dark cupboard away from sunlight (or even the refrigerator in hot climates), CBDA does not tend to degrade if we consume it within a few months. However, if you’ve got an opened CBDA bottle that’s been hanging around for a couple of years in direct sunlight, it probably won’t have the same cannabinoid profile it once had – and your carrier oil may have gone rancid.
GET SOME CBDA IN YOUR LIFE
For the conscious consumer trying to navigate today’s largely unregulated market, the presence of CBDA in a cannabis oil extract suggests that it’s likely a true full-spectrum product, rather than a formulation made from CBD isolate or distillate, both of which require heat to decarboxylate.
You can add a few fresh cannabis leaves or flower tops to a salad or smoothie. It’s an easy way to get acidic cannabinoids into your system. As recommended by Dr. Dustin Sulak, you can try putting a small amount of raw CBDA-rich bud into a cup of steeping tea. The heat won’t be sufficient for decarbing, and you will get the benefits of this often neglected cannabis compound.
Indeed, it seems that after all these years of living in CBD’s shadow, CBDA is finally gaining recognition as a safe, and in some ways more potent, alternative to its famous cannabinoid relative. For those who are already taking CBD oil, or for those who are thinking about it, small doses of a CBDA-rich product may be worth considering. Let us know if and how CBDA works for you. We always like to hear from our clients and readers.