Cannabinoid Acids: medical benefits of THCa and CBDa
As already explained in many of our articles, cannabinoids are classes of chemical compounds acting on specific receptors in brain and body cells, that alter and/or regulate many physiological functions, modulating signals in the endocannabinoid system. Today we want to talk you about THCa and CBDa, two cannabinoid acids.
Cannabinoids had been classified in endocannabinoids (endogenously produced in animals’ bodies), phytocannabinoids (found in cannabis plants), and synthetic cannabinoids (chemically produced in laboratories). Most of the studies are nowadays focussing on those cannabinoids naturally produced by the plant, such as THC and CBD, but further studies on other less known cannabinoids are increasing in number.
While so far CBD and THC are generally considered as the medical power of the plant, in this article we will make a brief summary of the latest finding on the benefits of two cannabinoids acid: THCa and CBDa.
Phytocannabinoids in the growth of cannabis plant
In 1963 a group of research, led by Dr R. Mechoulam, isolated and reported CBD’s chemical structure. A year later, the same group finally succeeded in isolating also THC and also to elucidate its exact structure.
Few years later, for a better understanding of the biogenesis of cannabinoids, the group figured out to be essential the isolation and classification of all cannabinoid acids. Alongside cannabidiolic acid, the cannabinolic and cannabigerolic acids were identified. Followed have been also classified two ∆⁹-THC acids, A and B, as well as ∆⁸-THC acid and cannabielsoic acid.
After that a possible pathway for the biogenesis of cannabinoids in the plant has been published, the group assumed that it is possible that some of the natural neutral cannabinoids are artefacts formed through different processes: decarboxylation, oxidation (cannabielsoic acid), photochemical cyclization (cannabicyclol), or isomerization (∆⁸-THC and ∆⁸-THC acid) of other constituents.
Cannabinoid Acids: THCa and CBDa
The two main cannabinoids, THC and CBD, don’t exist in their neutral form in the cannabis plant. During the growth of the plant, in fact, they show up in their acid form, as THCa and CBDa. Once these acid cannabinoids are heated, a chemical reaction takes places called “decarboxylation”, commonly known as activation.
As a result of heating, this two cannabinoids change form to become THC and CBD. This heating process can be the result of smoking, vaporizing, heating a mixture of butter and cannabis, but it actually start in a small part during the drying process of the plant, once it is ready.
Regarding THC, the activation of THC-acid in order to obtain decarboxylated form is what makes THC psychoactive. Consuming THC-acid will not provide any “high” feelings since it works on different pathways that not cause any psychotropic effects. When decarboxylated the molecule changes its structure by eliminating a carboxyl group (COOH) from its acid composition. This conversion transforms cannabinoid acids into a neutral state which interacts with CB-1 and CB-2 receptors and provides psychoactive effects, most commonly associated with ingesting or smoking cannabis.
While we understand the psychoactive and therapeutic benefits of neutral cannabinoids, how does the original acid molecule interact with the human body?
THCa and CBDa medical benefits
When talking about such advanced-level physiopathological concepts, it’s better to have a look at how these acid compounds work in nature.
Once cannabis reaches its maturity, THCa accumulates in high concentrations along the flowers and leaves. Its purpose is to induce cellular death, known as necrosis, by creating a pathway through the mitochondrial membrane of cells. This action keeps the mature plant healthy by force eliminating dead, dying or damaged cells.
Humans feature a similar mechanism, referred to programmed cellular death. This term is common when discussing cancer as an error in programmed cell death allows diseased cells to remain active. The proliferation of these diseased cells can then result in cancer. While this is an important finding, it still doesn’t fully answer how these cannabinoids support human health, and further studies on THCa are needed.
So far, we know that cannabinoid acids seem to do not interact with cannabinoid receptors. THCa and CBDa engage with the human endocannabinoid system by altering the efficiency of four primary functions: COX-1 Release, COX-2 Inhibition, TNF-Alpha Inhibition, Interleukin-10 Release. Ultimately, this means these cannabinoids actively support our own body’s ability to reduce inflammation, boost the immune system, performance and significantly lower overall pain levels.
Although substantial research on CBDa is lacking, preliminary evidence in the lab suggests that CBDa may help in four distinct therapeutic areas. These include:
- Nausea and vomiting
CBDa against inflammation
Laboratory research in vitro has shown that CBDa has potential anti-inflammatory properties, due to the inhibition of COX-2 (cyclooxygenase) activity. COX-2 is expressed by cells that are involved in inflammation and has emerged as the isoform primarily responsible for the synthesis of prostanoids (PG – a group of complex fatty acids) involved in acute and chronic inflammatory states of pathological processes.
Classical nonsteroidal anti-inflammatory drugs (NSAIDs) have shown to inhibit both COX-1 and COX-2 activities. Inhibition of COX-2-dependent PG synthesis accounts for the anti-inflammatory and analgesic effects of NSAIDs, whereas suppression of COX-1 can lead to many unwanted side effects.
Thus, it has been assumed that specific inhibitors for the COX-2 enzyme might have ideal therapeutic actions, similar to those of classical NSAIDs, without producing any adverse effects, caused by the inhibition of COX-1 activities.
CBDa against Nausea and Vomiting
Several studies have also shown the effect of CBD in reducing nausea and vomiting, through indirect agonism of 5-HT1A receptors located in the brainstem. CBDa inhibits nausea-induced behaviour in rats by somehow enhancing the activation of 5-HT1A receptors, interestingly at a lower concentration than CBD.
It will also be necessary to seek out the mechanisms by which CBDa induces the enhancement of 5-HT1A receptor activation. This could be investigated by carrying out in vitro experiments with 5-HT1A-transfected cells that do not express other types of receptor. Moreover, CBDa has also shown the ability to suppress both toxin- and motion-induced vomiting in shrews.
CBDa as Anti-epileptic Drug
In a patent registered in 2015 by GW Pharma, the anti-seizure effect of CBDa has been studied and explained. Having already a CBD-based drug for treating rare types of epilepsy, such as Dravet Syndrome, the company noticed some limitations, such as the poor bioavailability of the product and its need to be administered at high dosing.
GW Pharma has found that by adding lower amounts of CBDa the therapeutic effect of the drug was more potent, in terms of faster action and stronger effect, and less likely to cause side effects. Moreover, it had a superior bioavailability, which they suggested could mean a quicker onset of the effects. In fact, the company envisage combining both cannabinoids as an anti-epileptic drug, as CBDa may be useful in providing a rapid onset effect, whereas the CBD may be useful in providing an extended effect.
CBDa may help with Anxiety and Depression
CBD’s anti-anxiety effects have been much remarked by many studies on humans with social anxiety and depression. Like CBD, CBDa activates the serotonin 5-HT1A receptor, also known to modulate feelings of well-being and anxiety. In a study, conducted on rats and published on European Neuropsychopharmacology, was shown that CBDa provided antidepressant effects at doses 10-100 times smaller than CBD, but further researches on humans are needed.
Cannabinoid acids (THCa and CBDa) in Cancer treatment
CBDa has lately shown possibilities to inhibit cancer growth. The link between cancer and the acid form of CBD was demonstrated in a study of 2012 on breast cancer cells. In this study was explained that CBDa can be involved somehow in cancer growth through the suppression of COX-2 enzyme, a major instigator of breast cancer metastasis, as well as other forms of tumours.
In similar ways, both THCa and CBDa have shown their anti-inflammatory effects, which make them a potential cancer-killer. A Swedish study of 2011 on the evaluation of six different cannabinoids, including also their acid forms, found that all six of these substances together provided a strong effect on inflammatory processes in laboratory colon cancer cell lines. They have shown that through the interference with the inflammatory process, they are able to inhibit cancer cell proliferation.
While the real effectiveness of THCa and CBDa is still under investigation, the use of these acidic cannabinoids within the modern cannabis industry shows great promise and is worth investigation by researchers and cannabis experts.
The existing research on the medical benefits of both THCa and CBDa, especially regarding inflammation and cancer, already leaves great hopes for those who want to deal with cannabis treatments, without dealing with any psychoactive effects. Hopefully, with more research on the whole cannabis plant, and not just on CBD and THC in neutral form, a better understanding of every existent in nature cannabinoids will permit further and different approaches and methodologies based on medical cannabis.
Did you like the post? Give us some feedback! This post has been done based on existent research to the date of publication of the article. Due to the increase in studies based on medical cannabis, the information provided can vary over time and we’ll keep informing in further writings.
 Mechoulam R, Gaoni Y. The isolation and structure of cannabinolic, cannabidiolic and cannabigerolic acids. Tetrahedron. 1965;21:1223–1229. [PubMed]
 Gaoni Y., Mechoulam R. (1964) Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 86: 1646–1647 [Ref list]
 ElSohly, M. A., and Slade, D. (2005). Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci. 78, 539–548. doi: 10.1016/j.lfs.2005.09.011 [PubMed Abstract]
 Guillermo Moreno-Sanz (2016). Cannabis and Cannabinoid Research. Volume 1, issue 1 https://doi.org/10.1089/can.2016.0008
 Sirikantaramas, S., Taura, F., Morimoto, S., and Shoyama, Y. (2007). Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology. Curr. Pharm. Biotechnol. 8, 237–243. doi: 10.2174/138920107781387456 [PubMed Abstract]
 Kerstin Iffland, Michael Carus and Dr. med. Franjo Grotenhermen (2016). Decarboxylation of Tetrahydrocannabinolic acid (THCA) to active THC. European Industrial Hemp Association (EIHA).
 Guillermo Moreno-Sanz (2016). Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A. Cannabis and Cannabinoids Research, Volume 1 issue 1 https://doi.org/10.1089/can.2016.0008
 Angelo A. Izzo, Francesca Borrelli, Raffaele Capasso, Vincenzo Di Marzo and Raphael Mechoulam. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. https://doi:10.1016/j.tips.2009.07.006
 Shuso Takeda, Koichiro Misawa, Ikuo Yamamoto, and Kazuhito Watanabe (2008). Cannabidiolic Acid as a Selective Cyclooxygenase-2 Inhibitory Component in Cannabis. Vol. 36, No. 9 The American Society for Pharmacology and Experimental Therapeutics 20909/3374428. DMD 36:1917–1921, 2008
 Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–182. [PubMed]
 Cluny NL, Naylor RJ, Whittle BA, Javid FA. The effects of cannabidiol and tetrahydrocannabinol on motion-induced emesis in Suncus murinus. Basic Clin Pharmacol Toxicol. 2008;103:150–156.[PubMed]
 Colin Stott, Nicholas Jones, Robin Williams, Benjamin Whalley (2017). Use of cannabinoids in the treatment of epilepsy. International Publication Number: WO 2017/025712
 L. Shbiro, D. Hen-Shoval, N. Hazut, G. Zalsman, R. Mechoulam, A. Weller, G. Shoval (2017). Anti-depressant-like effects of cannabidiol and cannabidiolic acid in genetic rat models of depression. European Neuropsychopharmacology, Volume 27, Supplement 4, pages S783-S784, DOI: https://doi.org/10.1016/S0924-977X(17)31426-8
 Takeda S, Okajima S, Miyoshi H, Yoshida K, et alt. (2012). Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicology Letters, 214(3): 314-9. DOI: 10.1016/j.toxlet.2012.08.029
 Takeda S, Okajima S, Miyoshi H, Yoshida K, Okamoto Y (2012). Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. DOI: 10.1016/j.toxlet.2012.08.029.
Graduado en Lenguas y Culturas Modernas, Después de varios años de investigación personal y de participar en conferencias sobre el mundo del cáñamo industrial, me he unido a la redacción de Kalapa Clinic, donde he recibido formación directa de los médicos especializados de la clínica; esto me ha brindado la oportunidad de convertirme en un experto en las aplicaciones terapéuticas de los cannabinoides.
Es de esta manera donde mi pasión por el debate intercultural, las ganas de eliminar los perjuicios y conociendo el potencial terapéutico de la planta, se conjugan bajo un único objetivo: explicar a la mayor cantidad personas, los beneficios de los cannabinoides y como la planta de cannabis puede mejorar la vida de muchas personas.
Cannabinoid acids (THCa and CBDa) are showing many medical benefits as treatments for inflammation, epilepsy, nausea and vomiting.
Benefits of cbda
Reading Time: 7 minutes
When you first think about cannabis derivatives, you probably think of two different components: THC and CBD. Most people are familiar with how both of these substances work. THC is what produces the “high” associated with cannabis use, although it also has some therapeutic applications. CBD, on the other hand, produces no “high,” and has its own separate benefits.
What you might not be aware of is that there are more than a hundred other compounds in the cannabis plant. One of these is Cannabidiolic acid, also known as CBDA. So, what’s the difference between CBDA vs CBD? Like CBD, CBDA is found naturally in the cannabis plant, both in its hemp and marijuana variations. In fact, CBDA is the precursor chemical that produces CBD.
Even though these are two very similar compounds, there are important differences between them that need to be discussed. Here, we’ll explain why you might want to use CBDA vs CBD, as well as what benefits you can gain from both compounds. Let’s take a closer look!
What is CBDA?
Cannabidiolic acid, or CBDA for short, is a natural compound that’s produced by the cannabis plant. CBDA is a relatively recent discovery, and was not even isolated until 1996. It’s primarily found in raw, unprocessed cannabis plants.
The main difference between CBDA vs CBD is that CBDA is a precursor chemical to Cannabidiol (CBD), which is a similar but not acidic. What that means is that it’s a natural compound found in the raw plant. As with many other cannabinoids, CBDA undergoes a transformation when cannabis is processed. When the plant is heated, cured, or dried, acidic compounds break down into new chemicals. This is the process that produces large amounts of CBD from CBDA.
In raw cannabis, by contrast, you’ll find a large quantity of CBDA. You can also find it in most raw, unprocessed cannabis products. For instance, raw hemp oil is rich in CBDA. This is also true for regular CBD oils that haven’t been filtered or otherwise processed.
Is CBDA the Same as CBD?
CBD and CBDA are both cannabinoids. This is a class of chemicals that are found in the cannabis plant. In fact, they’re also found in the human body, and are used by the endocrine system to regulate normal bodily functions. This is why cannabinoids are often considered healthy dietary supplements. In total, the cannabis plant contains at least 113 cannabinoids. However, the exact concentration will depend on the type of plant and whether or not the plant has been decarboxylated.
Decarboxylation sounds like a complex process, so let’s break it down as simply as possible. As we mentioned, a major difference between CBDA vs CBD is that CBDA is an acid. This is because there’s a chemical chain called “carboxyl” attached to the molecule. When the cannabis is left to cure, the carboxyl chain will slowly break down. When this happens, CBDA and other acidic cannabinoids lose their acidity. They also become more active. Decarboxylation can be accelerated by other processes, like heating in particular.
In live, growing cannabis plants, CBD is only found in relatively small quantities. By drying or heating the plant, producers can convert the CBDA into CBD. However, one thing is the same between these two compounds: both of them are non-intoxicating. Neither one of them will get you “high”, which means they’re safe to take before work, or even before driving.
Cannabinoids all affect your body through your natural endocannabinoid system. This system activates neurotransmitters, which can help moderate your brain function. It also helps regulate many other bodily systems. However, the effects of CBDA vs CBD are different, since CBD is active and CBDA is not.
What Benefits Does CBDA Offer?
Okay, we’ve talked a bit about the science between how CBDA works. But what does it actually do when you ingest it? The short answer is that we know a lot less about the effects of CBDA compared to the effects of CBD. The reason is that CBD has been studied for many years, while scientists are only just beginning to study the effects of CBDA.
Why the lack of study? The simple answer is that until very recently, scientists didn’t think that cannabinoids had any effect in their acidic, non-active form. As a result, they didn’t bother to run many studies on CBDA and other inactive cannabinoids.
All of this started to change in 2008. That year, some researchers noticed that CBDA had a very similar structure to commonly-used non-steroidal anti-inflammatory drugs (NSAIDs). This class of drugs includes everyday painkillers such as acetaminophen and ibuprofen. These researchers followed up on their discoveries by investigating whether CBDA actually worked the same way as common NSAIDs. Amazingly, they found that CBDA inhibits COX-2, the same body chemical that’s inhibited by NSAIDs.
However, CBDA isn’t just used to reduce inflammation. It can also be used to treat nausea and anxiety. In this case, there’s a strong similarity between CBDA vs CBD. In fact, CBDA is actually more effective . It’s more than a thousand times more effective than CBD in activating a serotonin receptor that reduces nausea and anxiety. This effect is even more pronounced in chemotherapy patients who are using ondansetron (OND) to treat nausea.
Furthermore, CBDA doesn’t act directly on the endocannabinoid system. Instead, by inhibiting COX-2 activity, it has an indirect effect. It also acts on 5-HT receptors, which influence serotonin production. Serotonin production is essential to overall health, including reduced anxiety and general well-being.
What’s the difference between CBDA vs CBD oil? We’ll explain everything you need to know about the difference between these two supplements.