Summary
CBDA is the most abundant cannabinoid in Nature – but there’s less than 100 total studies on it. The naturally occurring raw form of CBD that is produced directly in the plant, CBDA was first isolated in 1955. The early research focused on the sedative properties but now it’s been more widely studied for nausea, anxiety, the lowering of inflammation and pain, anti-tumor effects via changes to genetic transcription, and in a model of Alzheimer’s, working with THCA to protect the brain and rescue memory deficits. Well known for its safety, the most common use is now for gut health. The growing trend of juicing the whole cannabis plant and drinking the juice comes from the ability of CBDA to help with gut homeostasis. At the biochemical level, CBDA raises anandamide levels, activates a serotonin receptor, acts as an antioxidant, regulates genetic transcription, and inhibits the COX-1 pathway (a pathway also used by aspirin). Many patents exist for the pharmaceutical uses of CBDA.
Timeline of Research
2023: A look at how CBD & CBDA move through the body & get broken down in humans & domestic animals
A One Health perspective on comparative cannabidiol and cannabidiolic acid pharmacokinetics and biotransformation in humans and domestic animals
https://pubmed.ncbi.nlm.nih.gov/36972696/
2023: A mouse model of Alzheimer's disease, CBDA & THCA rescued memory deficits & reduced the damage by the Aβ plaques & tau proteins
The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer's Disease-like Mouse Model
https://pubmed.ncbi.nlm.nih.gov/37047798/
2022: In humans with obesity, a CBDA analogue helped to improve metabolism, lose weight, reduce appetite, strengthen liver function & improved glycemic & lipid profiles
The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity
https://pubmed.ncbi.nlm.nih.gov/35628417
2022: In a rat model of nausea from chemotherapy, they experienced benefit from THC,CBD & CBD Acid with no detectable differences between the sexes
Evaluation of Sex Differences in the Potential of Δ 9-Tetrahydrocannabinol, Cannabidiol, Cannabidiolic Acid, and Oleoyl Alanine to Reduce Nausea-Induced Conditioned Gaping Reactions in Sprague-Dawley Rats
https://pubmed.ncbi.nlm.nih.gov/35984924
2022: In immune cells, the acid form of the cannabinoids (especially CBDA & CBGA) potently blocked calcium channels to lower T-cell activation & inflammation
Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry
https://pubmed.ncbi.nlm.nih.gov/35910331
2022: In human brain cells, CBDA from hemp seeds (& two other metabolites) altered the microRNAs that regulate gene expression related to important functions such as axon guidance, hippocampal signaling & neurotrophin signaling
Effect of Cannabidiolic Acid, N- Trans-Caffeoyltyramine and Cannabisin B from Hemp Seeds on microRNA Expression in Human Neural Cells
https://pubmed.ncbi.nlm.nih.gov/36286061
2021: CBDA as an antioxidant
Is cannabidiolic acid an overlooked natural antioxidant? – insights from quantum chemistry calculations
https://pubs.rsc.org/en/content/articlelanding/2021/nj/d1nj04771j/unauth
2021: In mice, CBDA reduces thermal pain
Chronic Treatment with Cannabidiolic Acid (CBDA) Reduces Thermal Pain Sensitivity in Male Mice and Rescues the
https://pubmed.ncbi.nlm.nih.gov/33010341/
2020: A review of CBDA
(‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research
https://pubmed.ncbi.nlm.nih.gov/32517131/
2020: In mice, the effects of CBDA
Behavioural and molecular effects of cannabidiolic acid in mice
https://pubmed.ncbi.nlm.nih.gov/32798553/
2020: In rats, CBDA & THCA combine well to reduce nausea
Effect of combined doses of Δ9-tetrahydrocannabinol and cannabidiol or tetrahydrocannabinolic acid and cannabidiolic acid on acute nausea in male Sprague-Dawley rats (Rock)
https://www.ncbi.nlm.nih.gov/pubmed/31897571
2019: Computer simulation identifies CBDA as an agonist of nuclear receptors PPARα & PPARγ (regulators of genetic transcription)
Identification and characterization of phytocannabinoids as novel dual PPARα/γ agonists by a computational and in vitro experimental approach
https://www.ncbi.nlm.nih.gov/pubmed/30611848
2019: In mice, CBDA helpful against model of Dravet Syndrome – examination of pharmacokinetics
Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome
https://pubs.acs.org/doi/full/10.1021/acs.jnatprod.9b00600
2018: In rats, CBDA has anti-inflammatory and anti-hyperalgesia effects in this model of inflammatory pain
Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain
https://www.ncbi.nlm.nih.gov/pubmed/30225659
2018: A review of the nonpsychoactive cannabinoids
Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer
https://www.ncbi.nlm.nih.gov/pubmed/30627539
2017: In rats, CBDA didn’t affect anxiety in low stress situations - but helped to reduce anxiety in previously stressed animals
Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats
https://www.ncbi.nlm.nih.gov/pubmed/28424834
2017: In neuronal cells, CBDA found to be a PPARγ agonist (regulator of genetic transcription)
Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14019
2017: A patent for use of CBDA in pet food
Pet food including cannabidiolic acid
https://patents.google.com/patent/AU2018239222A1
2016: A review of cannabinoids for nausea
Cannabinoid Regulation of Acute and Anticipatory Nausea (Rock)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576606/
2016: GW’s patent for CBDA for autism
Use of cannabidiolic acid in the treatment of autism spectrum disorder and associated disorders
https://patents.google.com/patent/US20190117619A1/en
2016: Important set of tests (paid for by GW) on the neuromotor effects of CBDA – they found it well tolerated and devoid of neuromotor side effects
Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea (Brierley)
http://centaur.reading.ac.uk/46344/
2016: In rats, combination of THC & CBDA increased hedonic experience of food and anti-nausea effects
Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models (Rock)
https://www.ncbi.nlm.nih.gov/pubmed/27438607
2016: GW patent on CBDA for inflammatory skin conditions
Use of cannabinoids in the treatment of inflammatory skin conditions
https://patents.justia.com/patent/20180263952
2015: In shrews, additive effect from combination of CBDA & THC for both lithium-chloride-induced vomiting and abdominal retching
Synergy between cannabidiol, cannabidiolic acid, and Δ⁹-tetrahydrocannabinol in the regulation of emesis in the Suncus murinus (house musk shrew)
https://www.ncbi.nlm.nih.gov/pubmed/26030435
2015: A combination of THC & CBDA reduced acute nausea – CBDA did not impair locomotor activity at any level
Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping (Rock)
https://www.ncbi.nlm.nih.gov/pubmed/26381155
2014: In rats, CBDA suppressed nausea as well as the anticipation of nausea – effect blocked by CB1 antagonists & 5-HT1A antagonists
A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping
https://www.ncbi.nlm.nih.gov/pubmed/24595502
2013: CBDA better than CBD at reducing vomiting in shrews and nausea in rats – works by enhancing the 5-HT1A receptor
Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation
https://www.ncbi.nlm.nih.gov/pubmed/23121618
2013: The anti-nausea medication metoclopramide (MCP) is significantly enhanced by CBDA – doses of each which are so low as to be ineffective, work well when combined
Suppression of lithium chloride-induced conditioned gaping (a model of nausea-induced behaviour) in rats (using the taste reactivity test) with metoclopramide is enhanced by cannabidiolic acid
https://www.ncbi.nlm.nih.gov/pubmed/24012649
2013: CBDA was 1000 times more potent than CBD in reducing acute nausea – suggested use for cancer chemotherapy
Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats
https://www.ncbi.nlm.nih.gov/pubmed/23488964
2011: First CBDA gut study: In the shrew, CBDA reduces intestinal contractions & tension in GI tract – the mechanisms did not involve CB1, CB2, or the brain
The effects of cannabidiolic acid and cannabidiol on contractility of the gastrointestinal tract of Suncus murinus (Cluny)
https://www.ncbi.nlm.nih.gov/pubmed/21975813
2011: CBDA inhibits NAAA – potent at inhibiting AEA reuptake – inhibits DAGLα – agonist at TRPA1 channels – binds to TRPM8
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
https://www.ncbi.nlm.nih.gov/pubmed/21175579
2011: CBDA found to inhibit COX1 – but not COX2 (contradicts Takeda (2008) where it was found to be a COX 2 inhibitor)
Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa (Ruhaak)
https://www.ncbi.nlm.nih.gov/pubmed/21532172
2008: CBDA is even more efficient than CBD at blocking the COX-2 inflammatory enzyme (similar to aspirin)
Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis (Takeda)
https://www.ncbi.nlm.nih.gov/pubmed/18556441
2008: In cells, CBDA was least potent at TRPA1 activation (partial agonists) – antagonized the TRPM8 activation by icilin & menthol
Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8
https://www.ncbi.nlm.nih.gov/pubmed/18354058
2008: CBDA, THCA, & CBGA all cause mitochondrial permeability transition (MPT) – a process to cause necrosis (induced cell death) in cells
Cannabinoids act as necrosis-inducing factors in Cannabis sativa (Shoyama)
https://www.ncbi.nlm.nih.gov/pubmed/19704450
2002: GW’s patent for CBDA for nausea
Compositions comprising cannabidiolic acid for treatment of nausea, vomiting, emesis, motion sickness or like conditions
https://patents.google.com/patent/EP1482917B1/
1991: A comparison of the differences when you give high THCA or high CBDA extracts to mice: CBDA was better at causing hypothermia, inducing sleep, decreasing horizontal and vertical motion & inducing catalepsy
Comparison of Pharmacological Activity in Mice of Different Cannabis Extracts from CBDA and THCA Strains
https://www.jstage.jst.go.jp/article/jhs1956/37/6/37_6_507/_pdf
1976: CBDA highly effective at inhibiting spore growth of Bacillus cereus
The sporostatic effect of cannabidiolic acid (Farkas)
https://inis.iaea.org/search/search.aspx?orig_q=RN:8301251
1972: Chilean analysis shows CBDA relaxes a rabbit’s small intestine
[Chilean marihuana: chemical analysis and pharmacological aspects]
https://europepmc.org/article/med/5016759
1969: First synthesis of CBDA and other cannabinoid acids
Carboxylation of resorcinols with methylmagnesium carbonate. Synthesis of cannabinoid acids (Mechoulam)
https://pubs.rsc.org/en/content/articlelanding/1969/c2/c29690000343#!divAbstract
1969: CBDA is effective against lactic acid bacteria in finished fruit juice products
Investigation of certain properties of cannabidiolic acid from the aspect of food preservation (Gal)
http://agris.fao.org/agris-search/search.do?recordID=US201301171441
1965: Original structural elucidation paper by Mechoulam & Gaoni
Hashish. IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids
https://www.ncbi.nlm.nih.gov/pubmed/5879350
1960: Very early review finds CBDA to be strongly antibiotic – links to early work on CBDA
Cannabis as a medicament (J. Kabelik,, Z. Krejci,, F. Santavy)
https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1960-01-01_3_page003.html
1960: Schultz & Haffner conclude that the cannabinoids occur because of decarboxylation of their acid forms
[On the question of the biosynthesis of cannabinol. Part III].
https://www.ncbi.nlm.nih.gov/pubmed/14443791
1959: Schultz & Haffner find CBDA to be antibiotic & sedative
[A sedative and antibacterial active agent from the German hemp (Cannabis sativa)]
https://europepmc.org/article/med/13648646
1959: Early work on structure and antibiotic properties by Krejci, Horak, & Santavy
[Hemp (Cannabis sativa)-an antibiotic drug. 3. Isolation and constitution of two acids from Cannabis sativa]
https://www.ncbi.nlm.nih.gov/pubmed/14411912
1958: An independent isolation of CBDA by Schultz & Haffner
[A sedative active principle from the German common hemp (Cannabis sativa). I]
https://www.ncbi.nlm.nih.gov/pubmed/13583964
1955: First isolation of CBDA by Z Krejci & F Santavy
The isolation of further substances from the leaves of Indian hemp (Cannabis sativa L. var. indica)
(Not available online)
1945: It’s guessed here that the cannabis extract studied by Todd et al contained CBDA
131. Cannabis indica. Part XI. An examination of the alkali-soluble portion of American hemp resin
https://pubs.rsc.org/en/content/articlelanding/1942/jr/jr9420000628/unauth#!divAbstract