The Decarboxylation of Cannabinoids
Decarboxylation of cannabinoids is crucial to understanding cannabis as medicine. Each cannabinoid acid decarboxylates into its corresponding free cannabinoid, such as THCA decarboxylating into THC and CBDA decarboxylating into CBD. Although the body is capable of converting cannabinoids into a variety of metabolites, once a cannabinoid acid enters the body it is generally not converted to its free cannabinoid form. This means that administering THCA and THC will have different effects on the human mind and body, and this essential difference can be found among all cannabinoids. Below is an overview of the major cannabinoids and the pharmacological and medical differences between their acids and their free forms.
THC / THCA
Tetrahydrocannabinol (THC) is a well-known cannabinoid that acts as the primary intoxicant and euphoriant of cannabis. THC is also one of the most practical and safe treatments for neuropathic, chronic, and other types of pain(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). THC is effective in addressing both the immunological and symptom component of Multiple Sclerosis (MS)(5, 6, 13, 14, 15, 16).
Despite the fact that THCA is not an intoxicant, it is a powerful medicine. THCA is one of the strongest anti-inflammatory agents in cannabis(7, 17, 18). Smokers receive very little to none of this cannabinoid, due to its decomposition in the smoking process. THCA is an anti-inflammatory agent, and according to one study, a more powerful neuroprotective agent than THC(19). THCA is a powerful COX-1 and COX-2 antagonist, similar to aspirin and ibuprofen, but with far less toxicity to the liver(17).
The effects of THCA and THC reflect the diversity of action on the human body a cannabinoid and its precursor acid can have. The other cannabinoids, CBD, CBG, CBC, and THCV all have acid forms which have distinct effects on human health.
CBD / CBDA
Cannabidiol (CBD) has been shown to be an effective medicine for people suffering from anxiety(5, 7, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28). CBD has also been shown to be effective at fighting breast cancer cells(29, 30). Many studies find that CBD promotes apoptosis, or cell suicide, in breast cancer cells while leaving the healthy cells unaffected.
Cannabidiolic acid (CBDA) is CBD’s acid precursor from raw cannabis flower. CBDA has also been shown to fight human breast cancer, but in a different way. Whereas CBD causes apoptosis in breast cancer cells, CBDA has been shown to slow or stop metastasis of breast cancer cells by arresting their motility, or ability to move throughout the body(31). This evidence would indicate that a breast cancer patient may want to talk to their doctor about dual CBD/CBDA therapy, taking both decarboxylated CBD and raw CBDA together.
CBG / CBGA
Cannabigerol (CBG) has been shown to have some potent anti-inflammatory properties that are particularly applicable in inflammatory bowel disease (IBS)(32). Additionally, CBG has been shown to have some properties not known among many other cannabinoids, such as an ability to interact with human adrenal receptors and serotonin receptors(33). Currently, more studies need to be done on Cannabigerolic Acid (CBGA) in isolation from CBG to learn what, if any, differences there are between the cannabinoid and its precursor acid on human health.
- Burns, Tammy L., and Joseph R. Ineck. “Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.” Annals of Pharmacotherapy 40.2 (2006): 251-260.
- De Petrocellis, Luciano, et al. “Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.” Journal of Pharmacology and Experimental Therapeutics 325.3 (2008): 1007-1015.
- Fine, Perry G., and Mark J. Rosenfeld. “The endocannabinoid system, cannabinoids, and pain.” Rambam Maimonides medical journal 4.4 (2013).
- Fine, Perry G., and Mark J. Rosenfeld. “Cannabinoids for neuropathic pain.” Current pain and headache reports 18.10 (2014): 451.
- Kogan, Natalya M., and Raphael Mechoulam. “Cannabinoids in health and disease.” Dialogues in clinical neuroscience 9.4 (2007): 413.
- Russo, Ethan B. “Cannabinoids in the management of difficult to treat pain.” Therapeutics and Clinical Risk Management 4.1 (2008): 245.
- Russo, Ethan B. “Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects.” British journal of pharmacology 163.7 (2011): 1344-1364.
- Mechoulam, Raphael, and Shimon Ben-Shabat. “From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis.” Natural product reports 16.2 (1999): 131-143.
- Wilson-Poe, Adrianne R., et al. “The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids.” Pharmacology Biochemistry and Behavior 103.3 (2013): 444-449.
- Ware, Mark A., et al. “Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.” Canadian Medical Association Journal 182.14 (2010): E694-E701.
- Nurmikko, Turo J., et al. “Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.” Pain® 133.1 (2007): 210-220.
- Johnson, Jeremy R., et al. “Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain.” Journal of pain and symptom management 39.2 (2010): 167-179.
- Koppel, Barbara S., et al. “Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders Report of the Guideline Development Subcommittee of the American Academy of Neurology.” Neurology 82.17 (2014): 1556-1563.
- M Saito, Viviane, Rafael M Rezende, and Antonio L Teixeira. “Cannabinoid modulation of neuroinflammatory disorders.” Current neuropharmacology 10.2 (2012): 159-166.
- Russo, Ethan, et al. “Chronic cannabis use in the Compassionate Investigational New Drug Program: An examination of benefits and adverse effects of legal clinical cannabis.” Journal of Cannabis Therapeutics 2.1 (2002): 3-57.
- Zajicek, J. P., et al. “Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.” Journal of Neurology, Neurosurgery & Psychiatry 76.12 (2005): 1664-1669.
- Ruhaak, Lucia Renee, et al. “Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa.” Biological and Pharmaceutical Bulletin 34.5 (2011): 774-778.
- Izzo, Angelo A., et al. “Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.” Trends in pharmacological sciences 30.10 (2009): 515-527.
- Moldzio, Rudolf, et al. “Effects of cannabinoids Δ (9)-tetrahydrocannabinol, Δ (9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.” Phytomedicine 19.8 (2012): 819-824.
- Bergamaschi, Mateus M., et al. “Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients.” Neuropsychopharmacology 36.6 (2011): 1219-1226.
- Bergamaschi, Mateus Machado. Subjecffve effects of cannabidiol in anxiety disorder and canabinoid excretion in chronic daily cannabis smokers during sustained abstinence. Diss. Universidade de São Paulo.
- Campos, Alline Cristina, et al. “Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.” Phil. Trans. R. Soc. B 367.1607 (2012): 3364-3378.
- Gururajan, Anand. “Comment on:“Anxiogenic-like effects of chronic cannabidiol administration in rats”(Elbatsh MM, Assareh N, Marsden CA, Kendall DA, Psychopharmacology 2012).” Psychopharmacology (2012): 1-2.
- Malone, Daniel Thomas, Dennis Jongejan, and David Alan Taylor. “Cannabidiol reverses the reduction in social interaction produced by low dose Δ 9-tetrahydrocannabinol in rats.” Pharmacology Biochemistry and Behavior 93.2 (2009): 91-96.
- Hill, Andrew J., et al. “Phytocannabinoids as novel therapeutic agents in CNS disorders.” Pharmacology & therapeutics 133.1 (2012): 79-97.
- Sarris, Jerome, Erica McIntyre, and David A. Camfield. “Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.” CNS drugs 27.4 (2013): 301-319.
- Khanum, Farhath, and Sakina Razack. “Anxiety–Herbal treatment: A review.” Res Rev Biomed Biotech 1.2 (2010): 83-89.
- Fusar-Poli, Paolo, et al. “Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol.” International journal of neuropsychopharmacology 13.4 (2010): 421-432.
- Ligresti, Alessia, et al. “Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma.” Journal of Pharmacology and Experimental Therapeutics 318.3 (2006): 1375-1387.
- Caffarel, María M., et al. “Cannabinoids: a new hope for breast cancer therapy?.” Cancer treatment reviews 38.7 (2012): 911-918.
- Takeda, Shuso, et al. “Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration.” Toxicology letters 214.3 (2012): 314-319.
- Borrelli, Francesca, et al. “Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.” Biochemical pharmacology 85.9 (2013): 1306-1316.
- Cascio, M. G., et al. “Evidence that the plant cannabinoid cannabigerol is a highly potent α2‐adrenoceptor agonist and moderately potent 5HT1A receptor antagonist.” British journal of pharmacology 159.1 (2010): 129-141.
- Dussy, Franz E., et al. “Isolation of Δ 9-THCA-A from hemp and analytical aspects concerning the determination of Δ 9-THC in cannabis products.” Forensic science international 149.1 (2005): 3-10.
Cannabis Tissue Culture Master Class (Canna Cribs Podcast 11)March 12, 2021
Canna Cribs Podcast Episode 10: Graham Farrar of GlassHouse FarmsMarch 3, 2021
Canna Cribs Podcast Episode 9: Kevin Ahaesy of ECO CannabisFebruary 18, 2021
Canna Cribs Podcast Episode 8: Jarret Ricci from Next Big CropFebruary 2, 2021
Do you want to receive the next Grower’s Spotlight as soon as it’s available? Sign up below!
Want to get in touch with Marco? He can be reached via the following methods:
- Email: [email protected]
Do you have any questions or comments?
About the Author
Marco Troiani is one of the founding members of Digamma Consulting and the laboratory manager. He was also the laboratory manager of DB Labs from its founding 2015-2016. His responsibilities included developing detection methods for terpenes and solvents (GC-MS), metals (ICP-MS), pesticides (GC-MS-MS), and Total Yeast and Mold, Total Aerobic Bacteria, Total Coliform Bacteria, and Salmonella spp. in cannabis and associated products.