Learn About Cannabidiolic Acid CBDa
Cannabidiolic Acid (CBDa), is a cannabinoid found in cannabis plants. It is most abundant in the glandular trichomes on the female seedless flowers or more accurately infructescence often colloquially referred to as buds. CBDa is the chemical precursor to cannabidiol (CBD). Through the process of decarboxylation cannabidol is derived via a loss of a carbon and two oxygen atoms from the 1 position of the benzoic acid ring. (Heating or catalyzing CBDa transforms it into CBD, thereby increasing the total CBD level.)
Cannabis flowers go through major transformations as they dry. In fresh flowers, the active components are found as acids. When cannabis is dried and heated, these acids break down into more famous compounds like THC and CBD. THC is the primary psychoactive in the cannabis plant. Cannabinoids like THC and CBD, which have been studied over the past four decades, have long been thought of as the main therapeutic compounds in the cannabis plant. However, emerging preclinical evidence suggests that there may be some benefit to keeping the plant raw. "Raw" meaning fresh leaves and flowers that have not been dried, cured, or heated.
High levels of CBDa can be found in raw materials taken from high-CBD cultivars. This includes hemp cultivars as well as CBD-dominant plants sold in medical and legal cannabis dispensaries. CBDa can be incorporated into one's diet in tinctures, juices, smoothies, salads and practically any preparation that does not involve high heat.
Clinical research reveals that higher concentrations of CBDA displayed more pronounced antimicrobial activity than CBD alone. Unfortunately, the majority of cannabis research has focused on psychoactive THC or activated CBD, not CBDa. This means that the little information that is available is subject to change and is considered preliminary evidence at best. Existing research does show promise for CBDa to potentially benefit patients with inflammation, nausea and vomiting, psychosis, and cancer.
New research published in January 2022 suggests that CBDa (in addition to CBGa) may prevent aggressive viruses, such as COVID-19, from entering human cells in vitro. While high quality human studies are needed to confirm this preliminary research, the potential for use of cannabidiolic and cannabigerolic acids in this arena is creating much excitement in the hemp industry for certain.
CBDa Clinical Research
Cannabinoids Block Cellular Entry of SARS-CoV‑2 and the Emerging Variants
Richard B. van Breemen, Ruth N. Muchiri, Timothy A. Bates, Jules B. Weinstein, Hans C. Leier, Scotland Farley, and Fikadu G. Tafesse | Journal of Natural Products 2022 85 (1), 176-184 | Full Text Article
As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)and its variants, which cause COVID-19. Affinity selection−mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.
Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression
D. Hen-Shovala, S. Amarc, L. Shbirob, R. Smoumd, Christeene G. Hajd, R. Mechoulamd, G. Zalsmane, A. Wellera, G. Shovale | Behavioral Brain Research 351 (2018) | Full Text Article
Cannabidiolic acid methyl ester (HU-580) was recently shown to reduce stress-induced anxiety-like behavior in rats. The aim of this study was to examine the antidepressant effect of HU-580 in two different rat models of depression. Using the forced swim test (FST), we evaluated the effect of HU-580 in 43 Wistar–Kyoto (WKY) and 23 Flinders Sensitive Line (FSL) adult male rats. Key results: 1 mg/kg HU-580 reduced immobility and increased swimming in WKY rats, compared to vehicle- treated controls (p less than 0.05). This dose exerted similar effects in FSL rats (p less than 0.05). Conclusion and implications: This is the first report of antidepressant efficacy of HU-580. These findings expand the very limited existent results, suggesting that HU-580 is a potent anxiolytic agent. Taken together with its chemical stability, HU-580 emerges as a candidate for a future antidepressant medication.
An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain
Yong Fang Zhu, Katja Linher-Melville, Mohammad Javad Niazmand, Manu Sharma, Ayesha Shahid, Kan Lun Zhu, Natalka Parzei, Jesse Sidhu, Christeene Haj, Raphael Mechoulam, Gurmit Singh | January 24, 2020 | British Journal of Pharmacology | Full Text Article
Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid CBDA, are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable. After 14 consecutive days of intraperitoneal CBDA-ME administration at 0.01, 0.1 and 1 μg·kg−1, commencing 1 day after surgically implanting a sciatic nerve-constricting cuff to induce NEP, the anti-nociceptive efficacy of this cannabinoid was assessed in male and female Sprague–Dawley rats relative to vehicle-treated counterparts. In females, 2 and 4 μg·kg−1 daily doses of CBDA-ME were also evaluated. Behavioural tests were performed for hind paw mechanical and thermal withdrawal thresholds once a week for 8 weeks. At endpoint, in vivo electrophysiological recordings were obtained to characterize soma threshold changes in primary sensory neurons.
Effect of cannabidiolic acid and Δ9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain
Erin M. Rock, Cheryl L. Limebeer, Linda A. Parker | September 17, 2018 | Psychopharmacology(2018) 235:3259–3271 | Full Text Article
Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ⁹-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties. Objectives The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD’s potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA. Results CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA’s effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation. Conclusion CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.
Therapeutic Potential of Cannabidiol, Cannabidiolic Acid, and Cannabidiolic Acid Methyl Ester as Treatments for Nausea and Vomiting
Erin M. Rock, Cheryl L. Limebeer, Roger G. Pertwee, Raphael Mechoulam, and Linda A. Parker | August 5, 2021 | Cannabis and Cannabinoid Research, Volume 6, No 4 | Full Text Article
Nausea and vomiting are the most distressing symptoms reported by oncology patients undergoing anticancer treatment. With the currently available treatments, vomiting and especially nausea remain problematic, highlighting the need for alternative treatments. Here we review in vitro and in vivo evidence for the effectiveness of the nonpsychoactive cannabinoid cannabidiol (CBD) in managing nausea and vomiting. In addition, we also review the evidence for CBD's acidic precursor, cannabidiolic acid (CBDA), and a methylated version of CBDA (CBDA-ME) in these phenomena. Finally, we explore the potential role of CBD in the treatment of cannabinoid hyperemesis syndrome. CBD has demonstrated efficacy in reducing nausea and vomiting, with CBDA and CBDA-ME being more potent. The data suggest a need for these compounds to be evaluated in clinical trials for their ability to reduce nausea and/or vomiting.