- CBDa may offer stronger anti-inflammatory and pain-relieving properties than CBD.
- Systemic administration of low-dose CBDa for 14 days helped reduce thermal hyperalgesia in male mice.
- Preliminary studies suggest CBDa may be beneficial for conditions like osteoarthritis and inflammatory bowel disease (IBD).
- CBDa selectively inhibits COX-2, an enzyme linked to inflammation and pain, similar to NSAIDs.
- CBDa activates TRPV1 channels, which help regulate inflammation and pain perception.
- CBDa has a greater affinity for the 5-HT1A receptor than CBD, impacting pain, mood, and anxiety.
- CBDa has shown potential in relieving both neuropathic and inflammatory pain, with stronger effects than CBD alone and enhanced benefits when combined with THC, while also offering significant anti-inflammatory properties.
- CBDa was found to be more potent than CBD at equivalent low doses in reducing hyperalgesia (increased pain sensitivity).
Pain is a natural response, a signal from the body that something needs attention. Whether caused by injury, inflammation, or chronic conditions, pain serves an important purpose. However, when it becomes ongoing, it can severely impact daily life, emotional well-being, and physical health.
In the United States, chronic pain affects an estimated 52 million adults, according to the CDC. Of these, about 20 million experience high-impact chronic pain, meaning it limits their daily activities most days or every day.
While pain is often managed with over-the-counter medications and NSAIDs, or nonsteroidal anti-inflammatory drugs, there has been a growing concern over the widespread issues related to opioid use, including overdose, dependence, and deaths. NSAIDs, such as ibuprofen and naproxen, are commonly used to reduce inflammation, relieve pain, and lower fever. However, long-term use of these medications can lead to serious side effects, including stomach ulcers, kidney damage, and increased risk of heart problems. These alarming trends have paved the way for a greater interest in natural approaches to pain management that offer effective relief with little to no side effects.
People are now moving away from relying solely on NSAIDs and turning toward natural remedies like hemp-based products for pain management. Growing awareness about the risks associated with long-term NSAID and opioid use has led many to seek safer, plant-based alternatives. In fact, a 2017 survey found that nearly 62% of CBD users reported using hemp-derived products specifically to manage pain, and over 50% of them were able to reduce or eliminate their use of prescription pain medications.
Hemp, particularly in its raw form containing compounds like CBDa, offers a promising natural option for addressing inflammation and pain without the serious side effects linked to traditional pharmaceuticals.
In this article, we will explore how CBDa for pain works, why it stands out, and how you can use it safely and effectively as part of your wellness journey.
What is CBDa?
CBDa, short for cannabidiolic acid, is a natural compound found in raw hemp and cannabis plants. It is the precursor to CBD (cannabidiol), meaning CBDa converts into CBD when exposed to heat through a process called decarboxylation. In its raw form, CBDa maintains a unique chemical structure that researchers believe may offer distinct health benefits, particularly for inflammation and pain.
Unlike CBD, which has been widely studied and commercialized, CBDa has only recently begun to attract scientific interest. Early studies suggest that CBDa interacts with the body in different ways, potentially offering even stronger anti-inflammatory, anti-nausea, and pain-relieving effects. One key difference is that CBDa appears to influence serotonin receptors (specifically the 5-HT receptors), which play a role in mood regulation, pain perception, and inflammation control.
Because CBDa is delicate and breaks down easily when heated, it is usually found in products made from raw hemp extracts. These products aim to preserve the plant’s natural state, delivering a broader range of cannabinoids and plant compounds that may work synergistically to enhance therapeutic effects.
How CBDA works for pain?
CBDa has shown promise as a natural alternative for managing pain, particularly due to its anti-inflammatory properties. While scientists are still discovering the possible roles of CBDa for pain, many believe they produce their pain-relieving effects through one of the following mechanisms.
- CBDa Inhibits COX-2 enzyme:
COX-2 (cyclooxygenase-2) is an enzyme that is produced in response to inflammation and is responsible for the production of prostaglandins, which promote inflammation, pain, and fever. COX-2 is often targeted by traditional pain medications like NSAIDs to reduce these symptoms.
CBDa selectively inhibits the COX-2 enzyme, reducing the production of prostaglandins and, in turn, helping to decrease inflammation and pain. This action is similar to how NSAIDs work but without many of their harmful side effects.
- Activates TRPV1 channels:
TRPV1 channels (transient receptor potential vanilloid channels) are involved in the sensation of pain, particularly in response to heat and inflammatory substances. These channels play a role in mediating pain perception and the body’s response to injury.
CBDa activates TRPV1 channels, which helps regulate pain signals and reduces the overall perception of pain. This interaction helps alleviate discomfort caused by both acute and chronic pain conditions.
- Interacts with the 5-HT1A receptor
The 5-HT1A receptor is a type of serotonin receptor involved in regulating mood, anxiety, and pain perception. It is critical for controlling emotional responses to pain, as well as modulating the intensity of pain signals in the brain.
CBDa has a greater affinity for the 5-HT1A receptor than CBD. This means it may help reduce pain by influencing mood and emotional stress related to chronic pain, potentially offering not just pain relief, but also emotional support for those living with discomfort.
What does research say about CBDa for pain
Research into CBDa suggests it may be a potent natural alternative for pain relief. Early studies show that CBDa has promising effects in reducing pain and inflammation, and it may even outperform CBD in some cases. Here’s what the current research reveals:
A 2018 study found that CBDa significantly reduced hyperalgesia (heightened pain sensitivity) in an inflammatory pain model. This suggests that CBDa may be more potent than CBD for managing certain types of pain. Interestingly, when doses of CBDA or THC that were ineffective on their own were combined, they produced a notable anti-hyperalgesic effect and reduced inflammation, further highlighting the potential synergistic properties of CBDa.
Another 2018 study revealed that CBDa was more effective than CBD alone in reducing inflammation and pain sensitivity in mice. This reinforces the idea that CBDa may be a more potent compound for managing certain types of pain.
CBDa may exhibit sex-dependent effect on users. One study on CBDa's effect on chronic pain revealed that in males, CBDa-ME (a form of CBDa) produced a significant, concentration-dependent anti-hyperalgesic effect, influencing both nociceptive (pain-related) and non-nociceptive mechanoreceptors. Interestingly, these effects were not observed in females at any of the concentrations tested.
In a study of horses with chronic osteoarthritis, oral administration of CBDa combined with CBG/CBD oil showed promising results in reducing pain. This suggests that CBDa could potentially benefit not just humans, but animals as well.
Research involving a mouse model of Rett syndrome, a neurological disorder known for heightened pain sensitivity, showed that systemic administration of low-dose CBDa for 14 days helped reduce thermal hyperalgesia in male mice. This finding supports CBDa’s potential in modulating abnormal pain perceptions in genetically predisposed conditions.
Another study demonstrated that chronic treatment with CBDa significantly reduced pain sensitivity in wild-type mice, further suggesting that CBDa may provide lasting pain relief.
Types of pain CBDa may assist with
CBDa has shown promise for alleviating various types of pain, including neuropathic pain and inflammatory pain. Below are some key studies that demonstrate CBDa's potential in treating these conditions:
1. Neuropathic Pain
Neuropathic pain, caused by nerve damage, can be difficult to treat with traditional medications. A study published in the British Journal of Pharmacology examined the effects of a stabilized form of CBDa, known as CBDA-Methyl Ester (CBDA-ME), in a rat model of peripheral neuropathic pain. The research found that CBDA-ME significantly reduced mechanical hypersensitivity (increased sensitivity to touch or pressure) in male rats when administered intraperitoneally over 14 days. However, this effect was not observed in female rats, suggesting that CBDa’s analgesic effects may be sex-dependent. These effects were attributed to changes in the excitability of primary sensory neurons.
2. Inflammatory Pain
Inflammatory pain, such as that caused by conditions like arthritis, can often be managed with anti-inflammatory medications. In a rodent model of carrageenan-induced acute inflammation, CBDa demonstrated dose-dependent anti-hyperalgesic (pain-reducing) and anti-inflammatory effects when administered 60 minutes before inflammation was induced. Notably, CBDa was found to be more potent than CBD at equivalent low doses in reducing hyperalgesia (increased pain sensitivity).
Furthermore, the study revealed that combining sub-effective doses of CBDa and THC resulted in a significant synergistic effect, providing enhanced analgesic and anti-inflammatory outcomes.
3. General Pain and Inflammation Relief
Both CBD and CBDa have been shown to have potent anti-inflammatory effects, making them effective in addressing pain caused by inflammation. For example, a 2018 study found that CBDa and THC were more effective than CBD in treating inflammatory pain, further supporting CBDa’s ability to manage pain and its underlying causes.
Safety and Side Effects of CBDa
CBDa is considered to be a safe and well-tolerated compound, especially compared to traditional pain management options like NSAIDs and opioids. However, as with any supplement or natural remedy, it’s important to understand its safety profile and any potential side effects before incorporating it into your routine.
- Mild Side Effects
Most users of CBDa report minimal side effects, especially when taken at appropriate doses. Some common mild side effects can include drowsiness, dry mouth, gastrointestinal distress. However, these side effects are typically temporary and subside after the body adjusts to the compound.
- Drug Interactions
CBDa can interact with certain medications, especially those that are metabolized by the liver enzymes, such as CYP450 enzymes. This can affect how your body processes other drugs. Medications that may interact with CBDa include: Blood thinners (e.g., warfarin), sedatives or anti-anxiety medications (e.g., benzodiazepines), and antidepressants. If you are taking any of these or other prescription medications, it’s essential to consult with your healthcare provider before using CBDa to avoid potential interactions.
- Pregnancy and Breastfeeding
While there is no conclusive research on the safety of CBDa during pregnancy or breastfeeding, it is generally advised to err on the side of caution and avoid using CBDa during these times. The effects of cannabinoids on fetal development and infants are still under study, and caution is recommended.
- How to Minimize Risks
To ensure safe use of CBDa:
- Start with a low dose: Begin with a small amount and gradually increase the dose if needed. This allows you to monitor how your body responds.
- Consult a healthcare professional: Particularly if you are pregnant, breastfeeding, or taking medications that might interact with CBDa.
- Choose high-quality products: Look for third-party lab-tested products to ensure the CBDa is free of contaminants like pesticides, heavy metals, and solvents.
References
Centers for Disease Control and Prevention (CDC). (2023). Understanding the impact of chronic pain on individuals and healthcare systems. MMWR Morbidity and Mortality Weekly Report, 72, 15-18. Retrieved from https://www.cdc.gov/mmwr/volumes/72/wr/mm7215a1.htm
National Center for Biotechnology Information (NCBI). (n.d.). Oral cannabinoids for chronic pain in adults: A systematic review. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK425767/.
Gamage, P. P., McDougall, J. J., & Kremlev, S. (2018). Cannabidiolic acid (CBDA) alleviates hyperalgesia in a rat model of inflammatory pain. Psychopharmacology, 235(10), 3067-3075. https://link.springer.com/article/10.1007/s00213-018-5034-1
Matuszczak, L., & Szymczak, G. (2020). Pharmacological properties of CBDA: Potential clinical applications. PubMed Central (PMC). Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC7236066/
Bishara, D., et al. (2022). Effect of cannabinoids on osteoarthritis pain in horses: A pilot study. PubMed Central (PMC). Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11668182/
Andersen, S. L., et al. (2020). The role of CBDA in modulating pain sensitivity in Rett syndrome. PubMed Central (PMC). Retrieved from https://pubmed.ncbi.nlm.nih.gov/33010341/
Gamage, P. P., et al. (2021). Chronic pain management: The efficacy of CBDA in animal models. ScienceDirect. https://www.sciencedirect.com/science/article/abs/pii/S0306452220306254
Dvorak, A., et al. (2018). Cannabidiol and its derivatives: Clinical research and findings on pain management. PubMed. https://pubmed.ncbi.nlm.nih.gov/30225659/
