The 0.3% THC Rule

Watch as we break down what it really means.

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The Phytocannabinoids Story

Out of more than 100 compounds in the cannabis plant, phytocannabinoids, such as THC, CBD, and cannabinol (CBN), were the first ones to be identified and isolated.1,2

Then in 1988, while scientists were investigating how THC exerted its effects, the endocannabinoid system was discovered within the human body.2

This led to the exploration of how cannabinoids, including both the plant molecules and synthetic versions developed in laboratories that mimic their effects, might be used for therapeutic purposes.

Differentiating Phytocannabinoids

CBD

Cannabidiol (CBD), the by-product of heating CBDA, is one of the major cannabinoids derived or synthesized from cannabis.2,3

CBD has very low affinity for cannabinoid receptor CB1 and so is lacking euphoric side effects.4

It is under investigation because of its anticonvulsant properties, as well as other conditions.5,6

EPIDIOLEX® is a specific formulation approved for specific epilepsies.7

CBDV

Cannabidivarin (CBDV), a lesser-known cannabinoid, is produced from cannabidivaric acid (CBVA).

Studies have been done in rodent models of epilepsy and autism spectrum disorder.7,8

It is under investigation for potential anticonvulsant properties.

CBDA

Cannabidiolic acid (CBDA) is how CBD naturally occurs in the plant.

Testing of CBDA in rodent and rodent-like models illustrates that CBDA works on the serotonin receptor (specifically 5-HT1A) to prevent vomiting and suppress nausea and anxiety.9

THC

Tetrahydrocannabinol (THC), most commonly in its delta-9 form, is the by-product of heating THCA.1,2

It is a major cannabinoid that may be derived from cannabis or synthesized.2

It is primarily responsible for marijuana’s psychotropic properties.2

Recreational and therapeutic uses: FDA-approved synthetic and analogue products, such as Marinol® and Syndros®, are indicated for nausea and vomiting related to chemotherapy and anorexia associated with AIDS.6,7

THCA

Tetrahydrocannabinolic acid A (how THC naturally occurs in the cannabis plant).

Limited study in rodents in nausea.10

THCV

Tetrahydrocannabivarin, a lesser-known cannabinoid, is produced from tetrahydrocannabidivaric acid (THCVA).

Studies have been conducted in rodent models of both Parkinson’s disease and insulin sensitivity (a model of diabetes).11,12

It is under investigation for potential use in type 2 diabetes.13

Not All Cannabinoid Products Are Created Equal

Products that sound similar may not be equivalent for various reasons, including potential differences in development, manufacturing, testing, and approval.

Medical
Marijuana

Hemp-Derived
Products

FDA-Approved Cannabinoid Formulations

FDA has approved 3 synthetic cannabinoids and 1 plant-derived cannabinoid.

Marinol® (dronabinol), Syndros® (dronabinol), and Cesamet® (nabilone) -- tetrahydrocannabinol (THC) and THC analogues (synthetics) are indicated to treat13,14:

• Anorexia associated with weight loss in adult patients with AIDS

• Nausea and vomiting associated with chemotherapy in adult patients who failed conventional antiemetics

 

EPIDIOLEX® is a plant-derived cannabidiol that is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome in patients 2 years of age and older.15

 

See what really matters when considering cannabis-based treatments.

 

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3. Taura F, Sirikantaramas S, Shoyama Y, et al. Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa. FEBS Lett. 2007;581(16):2929-2934. 
4. Amada N, Yamasaki Y, Williams CM, Whalley BJ. Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. Peer J. 2013;1:e214. 
5. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011-2020. 
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7. EPIDIOLEX [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc.; 2018. 
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12. H.R. 5485 – Hemp Farming Act of 2018. https://www.congress.gov/bill/115th-congress/house-bill/5485. Accessed August 20, 2019. 
13. National Institute of Food and Agriculture. Industrial hemp. https://nifa.usda.gov/industrial-hemp. Accessed August 20, 2019. 
14. United States Department of Agriculture. Agricultural Marketing Service. Hemp. https://www.ams.usda.gov/rules-regulations/farmbill-hemp. Accessed August 20, 2019.
15. United States Department of Agriculture. Agricultural Marketing Service. Subtitle G–hemp production. https://www.ams.usda.gov/sites/default/files/media/2018FarmBill.pdf. Accessed August 20, 2019. 
16. Girdhar M, Sharma NR, Rehman H, et al. Comparative assessment for hyperaccumulatory and phytoremediation capability of three wild weeds. 3 Biotech. 2014;4(6):579-589. 
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20. Marinol [package insert]. North Chicago, IL: AbbVie Inc; 2017. 
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22. Syndros [package insert]. Chandler, AZ: Insys Therapeutics, Inc; 2016.
23. U.S. Food and Drug Administration. FDA regulation of cannabis and cannabis-derived products: questions and answers. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-questions-and-answers#farmbill. Updated April 2, 2019. Accessed August 20, 2019. 
24. United States Drug Enforcement Administration. DEA speeds up application process for research on Schedule I drugs. https://www.dea.gov/press-releases/2018/01/18/dea-speeds-application-process-research-schedule-i-drugs. Published January 18, 2018. Accessed August 20, 2019. 
25. U.S. Food and Drug Administration. Marijuana research with human subjects. https://www.fda.gov/news-events/public-health-focus/marijuana-research-human-subjects. Updated April 2, 2019. Accessed August 20, 2019. 
26. U.S. Food and Drug Administration. Warning letters and test results for cannabidiol-related products. https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products. Updated July 24, 2019. Accessed August 20, 2019. 
27. SATIVEX [product monograph]. Mississauga, Ontario: Bayer Inc; 2015. 
28. Iannotti FA, Hill CL, Leo A, et al. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-1141. 
29. Zamberletti E, Gabaglio M, Woolley-Roberts M, et al. Cannabidivarin treatment ameliorates autism-like behaviors and restores hippocampal endocannabinoid system and glia alterations induced by prenatal valproic acid exposure in rats. Front Cell Neurosci. 2019;13(367):1-15. 
30. Bolognini D, Rock EM, Cluny NL, et al. Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Brit J Pharmacol. 2013;168:1456-1470. 
31. Rock EM, Kopstick RL, Limebeer CL, Parker LA. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Brit J Pharmacol. 2013;170:641-648. 
32. García C, Palomo-Garo C, García-Arencibia M, Ramos JA, Pertwee RG, Fernández-Ruiz J. Symptom-relieving and neuroprotective effects of the phytocannabinoid ∆9-THCV in animal models of Parkinson’s disease. Brit J Pharmacol. 2011;163:1495-1506. 
33. Wargent ET, Zaibi MS, Silvestri C, et al. The cannabinoid ∆9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutr Diabetes. 2013;3:e68. 
34. Jadoon KA, Ratcliffe SH, Barrett DA, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016;39(10):1777-1786. 
35. U.S. Food and Drug Administration. What We Do. https://www.fda.gov/about-fda/what-we-do. Accessed on August 20, 2019. 
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39. Jikomes N, Zoorob M. The cannabinoid content of legal cannabis in Washington State varies systematically across testing facilities and popular consumer products. Scientific Reports. 2018;8:4519.