Key Takeaways
- Research shows that small amounts of CBDa can help calm nausea-related symptoms.
- Cannabinoids like CBDa interact with the endocannabinoid system (ECS) and serotonin (5-HT1A) receptors, both of which play key roles in regulating nausea and vomiting.
- CBDa supports nausea relief by interacting with serotonin receptors.
- CBDa was found to be 1,000 times more potent than CBD at easing nausea.
- Types of nausea reported in CBDa research include toxin and motion-induced nausea and chemotherapy-related nausea.
Introduction
In 2013, scientists made an exciting discovery about cannabidiolic acid (CBDa) and its ability to relieve nausea. It was found to be more effective than CBD and THC in reducing nausea. Until then, most people only knew CBDa as the natural phytocannabinoid compound that turns into CBD when heated. This breakthrough research showed that CBDa has powerful benefits for cancer and other patients suffering from nausea.
The 2013 study found that even tiny amounts of CBDa could calm nausea-related reactions. What’s more, when researchers combined a small dose of CBDa with a standard anti-nausea medication, the results were even stronger, thus paving the way for combined therapies and inspiring further CBDa-centered research. In this brief article, we will examine the anti-nausea effects of CBDa as an effective, non-toxic and natural intervention for nausea relief.
Understanding Nausea and Its Connection to the Endocannabinoid System
Nausea is an unpleasant condition that can be brought on from many different causes, such as motion sickness, certain medications, digestive issues, or even anxiety. It is one of the body’s ways of warning that something is off-balance, often signaling the brain to prepare for vomiting as a protective response.
Underlying this physiologic reaction is a sophisticated communication network between the digestive system and the brain, known as the Gut-Brain Axis. This network constantly transmits signals via the peripheral nervous system, hormones, and chemical signals, to regulate digestion, appetite, and emotional states. The vagus nerve plays a central role in the gut-brain axis, messaging distress signals to the brain, which can trigger feelings of uneasiness or nausea.
One key modulator of the gut-brain communication is the endocannabinoid system (ECS), an innate system with connections to organs and systems throughout the body. The ECS plays a vital role in maintaining internal balance, or homeostasis, influencing mood, appetite, immune response, and the body’s ability to handle discomfort. Within the gut, ECS receptors help regulate gastrointestinal motility, inflammation, and the release of neurotransmitters that play a significant role in nausea.
The ECS helps maintain balance within the body by influencing how the brain and gut communicate, especially during times of stress or discomfort. CBDa and other plant cannabinoids interact with the ECS and specific serotonin receptors (5-HT1A), which play a major role in regulating nausea and vomiting. When activated, ECS receptors can reduce the overactivity of nausea-triggering signals. At the same time, serotonin (5-HT1A) receptors– located in both the brainstem and gastrointestinal tract– help control feelings of queasiness and the urge to vomit. CBDa has been shown to stimulate these receptors indirectly, supporting the body’s ability to calm nausea naturally and at its source.
How CBDa Supports Nausea Relief
- Interaction with Serotonin (5-HT1A) Receptors
Serotonin receptors, especially 5-HT1A receptors, play a key role in controlling nausea and vomiting. These receptors are found in both the brain and the gut, where they help regulate signals that trigger feelings of queasiness. CBDa has shown great potential in reducing nausea that is induced via multiple mechanisms, particularly in its interactions with the body’s serotonin and endocannabinoid systems.
Preclinical studies have demonstrated that CBDa interacts with the serotonin 5-HT1A receptors located in both the brain and the gastrointestinal tract, where they help control the signals that trigger queasiness and vomiting. The molecular mechanism CBDa action works in a similar way to serotonin, stimulating to the, 5-HT1A receptors to work like a natural “brake” to diminish reflex nausea responses.
A landmark 2013 study by Rock and Parker, published in the British Journal of Pharmacology, found that CBDa influence 5-HT1A receptor function. The observed activity led to a measurable reduction in nausea-related reactions. The study highlighted that even very low doses of CBDa could influence the serotonin pathways involved in nausea, indicating its potential as a potent natural alternative for anti-nausea support. Significantly, this mechanism differs from conventional anti-nausea drugs, which typically target dopamine or histamine receptors, with related side-effects.
In 2016, another paper by Rock et al. also reported that CBD and CBDa can reduce acute nausea in animal studies without affecting movement or alertness. Remarkably, the data showed that “CBDA was 1000 times more potent than CBD in reducing acute nausea.” The paper also showed that low doses of CBDa could enhance the effect of standard anti-nausea medications, such as ondansetron, which targets serotonin 5-HT3 receptors.
A 2021 study by Rock et al. found that CBDa is much more effective than CBD at interacting with specific serotonin receptors, which are essential for controlling nausea and vomiting. Even at very low doses, CBDa boosted the activity of these receptors across a wide range of doses.
THCa is another natural phytocannabinoid (like CBDa) and has been shown to possess anti-nausea and anti-emetic properties that appear more potent than THC, yet without inducing any of the undesirable intoxicating effects caused by THC. CBDa and THCa work through complementary pathways to reduce nausea without impairing cognitive function; this is of paramount importance for most patients seeking relief.
Types of Nausea Reported in CBDa Research
- Toxin- and Motion-Induced Nausea
Toxin-induced nausea occurs when the body reacts to harmful substances, such as poisons or certain chemicals, by triggering queasiness and the urge to vomit. According to a 2013 study published by Bolognini et al., CBDa has strong potential to reduce nausea and vomiting caused by toxins and motion sickness.
Chemotherapy-Related Nausea
Chemotherapy-induced nausea and vomiting (CINV) is among the most prevalent and distressing side effects experienced by patients undergoing cancer treatments. Data from the Cancer Center indicate that up to 80% of patients receiving chemotherapy experience some form of nausea or vomiting. This can severely affect a patient's quality of life, leading to dehydration, weight loss, depression, and even reluctance to continue treatment. A 2024 study by Bathula and Maciver highlighted the role of major cannabinoids in reducing these symptoms in cancer patients. CBDa is able to interact more effectively with serotonin receptors with therapeutic effects that can be 1,000 times more potent than CBD, suggesting it may offer even stronger anti-nausea effects. While research on CBDa for chemotherapy-induced nausea and vomiting is still limited, many patients are succeeding in finding much-needed relief.
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FAQ
How does CBDa help with nausea?
CBDa works by supporting serotonin 5-HT1A receptors, which act like a natural “brake” for nausea signals. By enhancing serotonin’s binding to these receptors, CBDa may help reduce nausea without affecting movement or alertness.
Can CBDa help with chemotherapy-induced nausea?
Preclinical studies suggest that CBDa may reduce chemotherapy-induced nausea and vomiting. CBDa has also been shown to enhance the effectiveness of conventional anti-nausea medications, such as ondansetron, indicating potential as an adjuvant cancer therapy.
Is CBDa stronger than CBD for nausea relief?
Yes. Research shows that CBDa can be up to 1,000 times more potent than CBD in activating serotonin 5-HT1A receptors, qualifying it as a natural anti-nausea agent of significant clinical interest.
Does CBDa cause the “high” like THC?
No. CBDa does not produce the cognitive impairment and intoxicating effects associated with THC. CBDa provides nausea relief via its network of physiological system effects, restoring the balance of homeostasis in ways that benefit both body and mind.
Has CBDa been tested in humans for nausea?
The most promising results have been seen in direct patient care rather than clinical trials. Definitive studies are of importance, as they serve to build awareness and confidence among health professionals; hence there is an urgent need for large-scale, controlled trials in order CBDa to be made more widely available to patients as a non-toxic, anti-nausea and vomiting agent of superior effectiveness.
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References
Bathula, P. P., & Maciver, M. B. (2024). Cannabinoids in Treating Chemotherapy-Induced Nausea and Vomiting, Cancer-Associated Pain, and Tumor Growth. International Journal of Molecular Sciences, 25(1), 74. https://doi.org/10.3390/ijms25010074
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.
Charnay Y, Léger L. Brain serotonergic circuitries. Dialogues Clin Neurosci. 2010;12(4):471-87. PMID: 21319493; PMCID: PMC3181988. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181988/pdf/DialoguesClin Neurosci-12-471.pdf
Why chemotherapy may cause nausea and vomiting. Cancer Center, City of Hope. https://www.cancercenter.com/community/blog/2020/12/chemotherapy-nausea-vomiting
Rock EM, Kopstick RL, Limebeer CL, Parker LA. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Br J Pharmacol. 2013 Oct;170(3):641-8. doi: 10.1111/bph.12316. PMID: 23889598; PMCID: PMC3792001. https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.12316
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.
Rock EM, Sticht MA, Limebeer CL, Parker LA. Cannabinoid Regulation of Acute and Anticipatory Nausea. Cannabis Cannabinoid Res. 2016 Apr 1;1(1):113-121. doi: 10.1089/can.2016.0006. PMID: 28861486; PMCID: PMC5576606.
Rock, EM, Parker, LA. The Role of 5-HT 1A Receptor, and Nausea and Vomiting Relief by Cannabidiol (CBD), Cannabidiolic Acid (CBDA), and Cannabigerol (CBG). In Handbook of Cannabis and Related Pathologies. 2017; Ch. 72:703–712. Elsevier. doi: 10.1016/B978-0-12- 800756-3.00083-1
Rock EM, Limebeer CL, Pertwee RG, Mechoulam R, Parker LA. Therapeutic Potential of Cannabidiol, Cannabidiolic Acid, and Cannabidiolic Acid Methyl Ester as Treatments for Nausea and Vomiting. Cannabis Cannabinoid Res. 2021 Aug;6(4):266-274. doi: 10.1089/can.2021.0041. Epub 2021 Jun 11. PMID: 34115951; PMCID: PMC8380783.
