• Compared to cannabidiol (CBD), cannabidiolic acid (CBDA) may be less potent in activating the TRPM8 receptors involved in pain and inflammatory processes(1). This finding suggests that CBDA may have less pain-relieving and anti-inflammatory potential than CBD.
  • One study suggested that CBDA may have anti-inflammatory, anticonvulsant, antiemetic (antinausea), and anticancerogenic (anticancer) properties(2).
  • In comparison, CBD may have analgesic (pain-relieving), antioxidant, anticonvulsant, anxiolytic (antianxiety), and anti-inflammatory effects(3).
  • Researchers mentioned that scientific interest in CBD may have masked CBDA’s potential health benefits for years(4).

CBDA vs CBD: Medical Uses and Benefits

CBDA and CBD appear to share the ability to antagonize the transient receptor potential cation channel subfamily M member 8 (TRPM8) receptors(5). These receptors activate during cold sensitization and painful, inflammatory processes.

However, CBDA may have less potency in activating the TRPM8 receptors than CBD(6). This finding suggests that CBDA may have less pain-relieving and anti-inflammatory potential than CBD.

Despite this result, researchers must conduct further studies to support this finding and whether CBDA’s potential to help alleviate pain and inflammation is substantiated.

One study suggested that the benefits of CBDA include anticonvulsant, antiemetic (antinausea), anti-inflammatory, and anticancerogenic (anticancer) effects(7).

Meanwhile, the benefits of CBD, a phytocannabinoid extracted from the cannabis plant, may include anticonvulsant, antioxidant, anxiolytic, analgesic, and anti-inflammatory effects(8).

CBD may be obtained from hemp or marijuana, which are varieties of the cannabis plant. However, hemp is the CBD-rich variety and contains less than 0.3% tetrahydrocannabinol (THC).

THC is a substance that may possess anti-inflammatory, analgesic, and antioxidant properties(9). The substance is also known for its psychoactive effects or a “high” feeling typically linked to marijuana use(10).

CBDA Usage vs. CBD Usage

Cannabinoids in the cannabis plant are almost exclusively present in their acidic forms, such as CBDA, tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA), and cannabigerolic acid (CBGA).

These cannabinoids must undergo decarboxylation, which removes a carboxyl group within the compound, to transform them into neutral forms, such as CBD, THC, CBD, and CBG.

Depending on the product type manufacturers desire to produce, they may include a decarboxylation process during extraction to obtain neutral cannabinoids for products such as CBD oil or skip this step to retain the cannabinoidsacidic form.

Methods to extract CBD or CBDA include the following:

  • CO2 extraction: Manufacturers utilizing this extraction method use highly pressurized carbon dioxide to obtain CBD oil from hemp.

Carbon dioxide is an odorless, colorless, and noncombustible gas. The U.S. Food and Drug Administration (FDA) affirms CO2 to be “generally recognized as safe” (GRAS) for food use(11).

  • Hydrocarbon extraction: In the hydrocarbon technique, CBD manufacturers use hydrocarbons such as propane or butane as solvents for CBD extraction.

However, hydrocarbons are neurotoxic and flammable, making handling these compounds a significant safety issue. Hydrocarbons can pose a health risk if not wholly removed from the CBD extract.

  • Ethanol extraction: In this method, manufacturers use ethyl alcohol, also called ethanol, as a solvent to extract CBDA and CBD from the cannabis plant.

Ethanol may be a safer compound to work with than butane and a more efficient alternative than CO2(12). However, ethanol is an “exhaustive” solvent, requiring extra refinement to remove unwanted compounds, which may reduce the final product’s potency.

After extraction, CBDA and CBD are categorized into full-spectrum, broad-spectrum, or isolate products and processed into different commercial products, such as CBD oil or raw hemp oil, administered through varying delivery routes.

Full-spectrum products contain all the cannabinoids and compounds in the cannabis plant.

Meanwhile, broad-spectrum products are similar to full-spectrum products, except broad-spectrum are THC-free.

Lastly, isolates are cannabis products typically containing only one ingredient or compound, such as CBD.

Delivery routes and product types for each route include the following:

  • Ingestion: This method involves taking CBD or CBDA orally or through the mouth. Oral products include capsules or edibles like chews, gummies, candies, or cookies.
  • Sublingual administration: The sublingual method involves applying the drug under the tongue to allow the compound to enter the bloodstream directly.

Sublingual CBDA or CBD products include tinctures, high-potency oils, and oromucosal sprays. Individuals may administer tinctures using calibrated droppers for accurate dosing.

CBDA or CBD oil tinctures may have a grassy or earthy taste. Consumers may consider mixing food or drinks with these products(13).

  • Topical application: In the topical route, individuals apply CBDA or CBD products to the skin. CBDA and CBD topicals do not get absorbed into the bloodstream in this method.

Topical products include creams, ointments, lotions, lip balms, salves, and roll-on sticks.

  • Inhalation: This delivery route allows individuals to inhale the drug through vaping or smoking(14).

It is crucial to note that individuals should take precautions before using vapes because these products can lead to health hazards associated with lung disease(15).

If one has an existing medical condition, they should consult a doctor or healthcare professional for a diagnosis and effective treatment before using any CBD products.

What Is CBDA?

Cannabidiolic acid (CBDA) is a phytocannabinoid (plant-based cannabinoid) derived from the hemp plant, a variety of Cannabis sativa(16).

Manufacturers may convert CBDA to its neutral form, CBD, through heat- or light-induced decarboxylation(17).

However, researchers mentioned that these health benefits may have been overlooked since most scientific interests focused on CBD(18).

Thus, researchers need to investigate CBDA through more extensive studies to conclusively determine its potential therapeutic benefits.

Role of CBDA in the Endocannabinoid System

One study in Frontiers in Physiology showed that CBDA may inhibit the cyclooxygenase-2 (COX-2) enzymes(19).

Inhibiting COX-2 may help increase anandamide (AEA) levels(20). AEA, an endogenous cannabinoid (endocannabinoid) found in the body’s endocannabinoid system (ECS), may produce a modulatory effect on an individual’s brain reward circuitry(21).

Drugs that block COX-2 enzymes are called COX-2 inhibitors, which are nonsteroidal anti-inflammatory drugs (NSAIDs) that may help reduce inflammation and relieve pain(22).

The endocannabinoid system (ECS) comprises chemical signals and receptors within the body and the brain(23). The ECS’ role is to regulate and control many of the body’s crucial functions, including:

  • Learning
  • Memory
  • Sleep
  • Eating
  • Emotional processing
  • Pain control
  • Immune and inflammatory responses

The brain reward circuitry links several brain structures that help regulate or control the individual’s ability to feel pleasure, which may motivate individuals to repeat behaviors(24).

Thus, CBDA, if proven to have an inhibitory effect on COX-2 enzymes, may potentially affect an individual’s reward system through AEA.

Research and Studies on CBDA

Various studies using animal models, such as rats, showed that CBDA may help inhibit vomiting caused by motion sickness or toxins(25). CBDA may also improve the activation of 5-HT receptors, specifically the 5HT1A subtype, in the brain stem membrane.

5HT1A is a serotonin receptor that may help manage anxiety and depression(26). This receptor is typically involved in the activity of antidepressant drugs and controlling mood disorders.

Additionally, the 5HT1A receptors mediate the antinausea effects of CBD and CBDA(27).

Another animal study suggested that CBDA, taken alone or at low doses of combined CBDA and THC, may have anti-inflammatory and antihyperalgesic effects(28).

Hyperalgesia is increased pain sensitivity and extreme pain response(29).

While animal studies on CBDA do not immediately correlate to similar effects of the compound in humans, researchers may use such studies as a reference for more extensive and well designed human clinical studies.

CBDA Side Effects

Studies have not entirely determined the side effects of CBDA. However, because CBD is the decarboxylated form of CBDA, some manufacturers claim CBDA may have similar side effects as CBD.

These side effects may include dry mouth, reduced appetite, diarrhea, fatigue, and drowsiness(30).

CBDA Legality

The 2018 Farm Bill excludes hemp and hemp-derived products containing less than 0.3% THC from the “marijuana” definition under the Controlled Substances Act (CSA)(31).

Therefore, cannabis products with THC content higher than 0.3% are considered illegal under United States federal law(32). In other words, products containing CBDA are not prohibited, provided their THC content is within legal limits.

Despite this law, the legal implementation and regulation of medical marijuana or cannabis products vary from one state to another.

As of February 3, 2022, 37 U.S. states have allowed the use of cannabis products for medical purposes(33). States with regulated cannabis programs include Washington, Colorado, California, Virginia, and New York.

Therefore, consumers must review and understand their state’s laws before purchasing cannabis products, such as those containing CBDA or CBD.

  1. Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
  2. Ibid.
  3. Cannabidiol Primer for Healthcare Professionals
  4. Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
  5. Ibid.
  6. Ibid.
  7. Ibid.
  8. Cannabidiol Primer for Healthcare Professionals
  9. Ibid.
  10. Tetrahydrocannabinol
  11. CFR – Code of Federal Regulations Title 21
  12. Page 243 of Healing With CBD
  13. Page 208 of Healing With CBD
  14. Best Way to Take CBD
  15. Can Vaping Damage Your Lungs? What We Do (and Don’t) Know
  16. Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
  17. Ibid.
  18. Ibid.
  19. Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment
  20. An Introduction to the Endogenous Cannabinoid System
  21. Brain Activity of Anandamide: A Rewarding Bliss?
  22. COX-2 Inhibitors
  23. The Endocannabinoid System: Essential and Mysterious
  24. The Reward Circuit: How the Brain Responds to Natural Rewards and Drugs
  25. Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
  26. 5-HT1A Receptors in Mood and Anxiety: Recent Insights Into Autoreceptor Versus Heteroreceptor Function
  27. Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
  28. Effect of Cannabidiolic Acid and ∆ 9-Tetrahydrocannabinol on Carrageenan-Induced Hyperalgesia and Edema in a Rodent Model of Inflammatory Pain
  29. Hyperalgesia
  30. What Are the Benefits of CBD — And Is It Safe to Use?
  31. Hemp Production and the 2018 Farm Bill
  32. CBD & THC: Myths and Misconceptions
  33. State Medical Cannabis Laws
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