CBDa vs. CBD: Which one is better?

by Apoorva Shivankar, M.D

cbda vs. cbd ?

CBDa vs. CBD

The human mind has a natural instinct to explore and sky is the limit for discoveries. Nothing can be proclaimed as an end, the best, the greatest or even the worst eternally. Things come and go, being surpassed/ replaced by others.

The same is true for our master drug cannabidiol CBD. Since 2018, CBD is ruling the world with its magical powers of healing and relaxation. But as we see CBD skyrocketing the marketplace with a vision of $22 billion mark by the year 2022, we can also hear the silent/soft footsteps of a competitor approaching.

Have you also heard the buzz around CBDA or cannabidiolic acid? 

It’s a new cannabis plant product inching towards the central stage. Though the claims are still in the conception, the results of preliminary studies are enough to judge its potential. There are no doubts regarding the exceptional health benefits of cannabidiol but researchers suggest that CBDA can take these CBD benefits to a much superior level. Let’s see how

To begin with let’s brush up our knowledge about CBD

Cannabidiol CBD is a non-psychoactive hemp plant product that interacts with the endocannabinoid system for its never-ending list of health benefits which include

  • An overall sense of well being
  • Food and Drug Administration approved anti-seizure / antiepileptic effects.
  • Freedom from depression, anxiety, pain and inflammation.
  • Apt for treating nausea and vomiting.
  • Immune booster
  • Sleep inducer
  • Warrior against chronic disorders.
  • A cosmetic healer and rejuvenator.

And what not….

All this without any major side-effects.

Can anything beat this?

Introducing CBDA Cannabidiolic acid

Cannabinoid CBDA is a natural acidic form of CBD present in raw hemp and marijuana plants.

The surprising truth is that if you pick up hemp directly from the hemp plant, what you will get is mostly CBDA and very little CBD and that’s because CBDA is the original cannabinoid of hemp which later gets converted to CBD by a process called decarboxylation (removal of an acidic carboxyl group COOH).

This process occurs naturally as the plant ages or dries out or is exposed to heat and light of the sun or processed or cured or even when we smoke/vaporize hemp.  Basically, CBDA is a chemical precursor of CBD.

This CBDA is not an inactive cannabinoid, unlike most other precursor compounds. It has its own magical spell and has just started on its path to charm the world. Research with CBDA has already ignited on a positive note. Who knows it may throw a tough competition to the current elephant of the room, the CBD and why not, in the end, CBDA is the mother of CBD, it should have all the potential.

What are the health benefits of CBDA?

Experts believe that like CBD CBDA also possess almost the same health-promoting properties including anti-inflammatory, antibacterial, anti-depressant, anxiolytic and anti-proliferative effects but exerts these benefits through different mechanism of action.

So far as the research has shown, CBDA unlike CBD doesn’t actually interact with the endocannabinoid system. Instead, it works through other receptor sites and enzymes in our body mainly the

  1. 5HT-1A serotonin receptor (100-fold more affinity than CBD)1,5
  2. COX 2 enzymes. 
  • A rodent study published in 20131 demonstrated that CBDA activates serotonin receptors known to regulate our mood and anxiety essentially controlling an overall sense of well-being.

    This happy hormone serotonin also takes care of total health by regulating bodily essentials such as
    digestion, eating, sleeping, motor skills, and emotions. This makes CBDA a potent anxiolytic, antidepressant, mood elevator and an effective relaxant drug.

  • It was also shown that to combat depression CBDA not only activates 5HT-1A1,4, but also prevents the reabsorption of serotonin3 mimicking the action of the established antidepressants SSRIs.

  • The same study1 also potentiated the role of CBDA in treating nausea and vomiting (especially the chemotherapy induced nausea/vomiting) including anticipatory nausea for which at the moment there is no therapy available. Similarly, the 2016 study2 also highlighted CBDA’s strong influence in treating anticipatory nausea in preclinical models. 
  • With a higher affinity for serotonin receptors that are directly involved in the control of brain seizures, CBDA provides strong anticonvulsive effects too.1,4,5,6 
  • Studies7,8 show that by means of its carboxylic acid group, CBDA selectively inhibits COX-2 enzymes, the key inflammatory mediators responsible for a wide array of inflammatory responses in our body in a way similar to the regular anti-inflammatory drugs NSAIDs. That being said CBDA displays promising potential as a viable drug for inflammation or pain. 
  • Another important health benefit of CBDA is the suppression of breast cancer cells. Theory says, CBDA inhibits cyclooxygenase-2 COX enzyme responsible for inflammation. This COX-2 induced inflammation is the cause of 40% invasive breasts cancers.

    Take da et al. in their studies published in 2012
    14 and 20149 demonstrated that CBDA not only suppresses these cells but also prevents them from spreading. Subsequent study15 in 2017 discussed the possibility that CBDA could combat the development of highly aggressive breast cancer cells.

Comparing CBDA and CBD

Similarities

  • Both are naturally occurring cannabinoids from cannabis plants.
  • Non-psychoactive, non-intoxicating.
  • Low to nil side-effects.
  • Both effectively treat nausea, vomiting, inflammation and even pain.
  • Both act towards the body’s overall well-being in their own unique ways.

Differences:

 

CBDA

CBD

Molecular structure

Contains carboxylic COOH group

C22H30O4

Carboxylic group removed

C21H30O2

Mechanism of action

CBDA interacts with

  • 5HT-1A serotonin receptor
  • COX-2 enzymes.

 

CBD modulates ECS by inhibiting the breakdown of the endocannabinoid anandamide which then binds to CB1 or CB2 receptors, allowing ECS to restore any imbalances.

 

Form

Raw form

Decarboxylated/Processed

Bioavailability

Comparatively greater

Lower

Potency

Higher

Lower

Products

Limited product types

Variety of products available

Consumption Methods

Juice from plants can be added to foods and drinks or infused into raw extracts, such as live resins and tinctures.

Oils, tinctures capsules, creams, body lotions, vapes, etc.

Stability

Unstable

Much more Stable

Solubility

Water soluble

Water-insoluble

Research work

No extensive scientific research.

Better researched

Trials

No human trials yet.

Approved in humans for epilepsy,

Storage

Being heat-sensitive it needs lower temperatures.

Not temperature sensitive.

  

Which is Better: CBD or CBDA?

Pros of CBD over CBDA

  • Studied and tested far more than for CBDA.
  • Food and Drug Administration approved CBD in humans to treat epilepsy.
  • CBD is more stable.
  • CBD can be cooked with or vaped.
  • CBD is more widely available in commercial products.
  • Better to taste as compared to the raw pungent flavours of CBDA. 

Pros of CBDA over CBD

  • Initial research suggests it could be far superior.
  • Absolutely pure, natural and so lesser toxic or allergic effects. CBD due to processing caries a risk of cross-contamination with allergens. Again, no heating of CBDA means no exposure to toxins released by combustion.

There are many studies suggesting the advantages of CBDA over CBD such as

  • A study in 201312, 13 states that CBDA is a good 1000 times more powerful than CBD in activating serotonin receptors and thereby treating nausea, vomiting, anxiety and even anticipatory nausea. This effect is even more pronounced in chemotherapy patients who are using ondansetron (OND) to treat nausea.

  • Another study11 published in 2018 in the academic journal Frontiers in Integrative Neuroscience impressed on the higher bioavailability of CBDA due to its 100 times more affinity for 5-HT receptors as compared to CBD and thus supported the hypothesis of rapid onset of action and the need of lesser dose than CBD for a similar effect. So affordable and easier to dose too. There are few more studies1,5,8 backing this theory.

  • In a recent study done on rats, CBDA was found to be effective on depression in doses 10-100 times lower than CBD.

  • CBDA can be more effective in seizure management as per the study conducted by GW Pharma limited 10 
  • A study that was published in the European Journal of Clinical Pharmacology showed that CBDA and THCA are more readily absorbed as compared to CBD and THC.

So, is CBDA better than CBD?

Looking at the pros and cons, it’s up to you to select which one is better for you- the one with higher number of scientific evidences or the other with more potent effects. The choice is yours.

But wait,

You can have a 3rd option too which says,

Taking CBDA and CBD together

Yes, you can combine the two together. Actually, the full spectrum or broad-spectrum CBD products in the market already contain some amount of CBDA. The positives of this combo include:

  • You get the best of both compounds.
  • Both are compatible.
  • CBDA contains more terpenes to offer additional benefits.
  • You will enjoy a faster onset of action due to CBDA, and also a long sustained effect due to CBD.
  • CBDA might strengthen CBD effects by inhibiting COX 2 enzyme which further blocks the alternate pathway of anandamide degradation thereby reinforcing the anandamide levels for increased effects.

Takeaway:

Yes, the initial studies point towards a bright future for CBDA but it should always be kept in mind that as of now all research is in the pre-clinical phase with no human studies yet.

So, whether CBDA can establish itself as a proven drug or not depends on further research especially human trials. For now, it’s just wait and watch. Only time will tell whether CBDA may or may not. 

FAQs

Q: How can you consume CBDA?

It’s best to consume it in its natural, pure, unprocessed, unheated, raw form.

  • Eat directly.
  • Make a juice.
  • Garnish your food, salad, pasta, pizza or sandwiches with generous amounts of raw cannabis leaves.
  • Now a days CBDA is also available as raw hemp oil, topicals, pills, capsules, etc in the market.

Q. What is CBGA?

Cannabigerolic acid (CBGA) is the ‘Mother of all cannabinoids’ present in raw cannabis plants. In presence of suitable plant enzymes, it can be converted to three major cannabinoids THCA (Tetrahydrocannabinolic acid), Cannabidiolic acid CBDA or CBCA which on decarboxylation converts to CBD, THC and CBC respectively. 

References:

  1. Bolognini D, Rock EM, Cluny NL, Cascio MG, Limebeer CL, Duncan M, Stott CG, Javid FA, Parker LA, Pertwee RG. Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br J Pharmacol. 2013 Mar;168(6):1456-70. doi: 10.1111/bph.12043. PMID: 23121618; PMCID: PMC3596650.

  2. Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea. Psychopharmacology (Berl).2016;233(2):243-254.doi:10.1007/s00213-015-4100-1 

  3. Hen-Shoval D, Amar S, Shbiro L, Smoum R, Haj CG, Mechoulam R, Zalsman G, Weller A, Shoval G. Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression. Behav Brain Res. 2018 Oct 1;351:1-3. doi: 10.1016/j.bbr.2018.05.027. Epub 2018 May 31. PMID: 29860002.

  4. Pertwee, R. G., Rock, E. M., Guenther, K., Limebeer, C. L., Stevenson, L. A., Haj, C., Smoum, R., Parker, L. A., and Mechoulam, R. (2018) Cannabidiolic acid methyl ester, a stable synthetic analog of cannabidiolic acid, can produce 5‐HT1A receptor‐mediated suppression of nausea and anxiety in rats. British Journal of Pharmacology, 175: 100– 112. doi: 10.1111/bph.14073 

  5. Russo E. B., Burnett A., Hall B., Parker K. K. (2005). Agonistic properties of cannabidiol at 5-HT-1a receptors. Neurochem. Res. 30, 1037–1043. 10.1007/s11064-005-6978-1 [PubMed] [CrossRef] [Google Scholar]

  6. Bagdy G., Kecskemeti V., Riba P., Jakus R. (2007). Serotonin and epilepsy. J. Neurochem. 100, 857–873. 10.1111/j.1471-4159.2006.04277.x [PubMed] [CrossRef] [Google Scholar]

  7. Takeda S, Misawa K, Yamamoto I, Watanabe K. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos. 2008 Sep;36(9):1917-21. doi: 10.1124/dmd.108.020909. Epub 2008 Jun 12. PMID: 18556441.

  8. Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009 Jan;156(1):181-8. doi: 10.1111/j.1476-5381.2008.00046.x. PMID: 19133999; PMCID: PMC2697769.

  9. Takeda S, Okazaki H, Ikeda E, Abe S, Yoshioka Y, Watanabe K, Aramaki H. Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. J Toxicol Sci. 2014;39(5):711-6. doi: 10.2131/jts.39.711. PMID: 25242400.

  10. USE OF CANNABINOIDS IN THE TREATMENT OF EPILEPSY. Published by GW Pharma Limited INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT).World Intellectual Property Organization International Bureau. International Publication Date 16 February 2017 (16.02.2017). International Publication Number (43) WO 2017/025712 Al. https://patents.google.com/patent/WO2017025712A1/en

  11. Russo EB. Cannabis Therapeutics and the Future of Neurology. Front Integr Neurosci. 2018 Oct 18;12:51. doi: 10.3389/fnint.2018.00051. PMID: 30405366; PMCID: PMC6200872.

  12. Rock EM, Parker LA. Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats. Br J Pharmacol. 2013 Jun;169(3):685-92. doi: 10.1111/bph.12162. PMID: 23488964; PMCID: PMC3682714.

  13. Rock, E.M., Sullivan, M.T., Collins, S.A. et al. Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews. Psychopharmacology 237, 2621–2631 (2020). https://doi.org/10.1007/s00213-020-05559-z

  14. Takeda S, Okajima S, Miyoshi H, Yoshida K, Okamoto Y, Okada T, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H. Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicol Lett. 2012 Nov 15;214(3):314-9. doi: 10.1016/j.toxlet.2012.08.029. Epub 2012 Sep 8. PMID: 22963825; PMCID: PMC4009504.

  15. Takeda S, Himeno T, Kakizoe K, Okazaki H, Okada T, Watanabe K, Aramaki H. Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness. J Nat Med. 2017 Jan;71(1):286-291. doi: 10.1007/s11418-016-1030-0. Epub 2016 Aug 16. PMID: 27530354.

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