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.3

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.3

Differentiating Phytocannabinoids


Cannabinoid (CBD) Molecule

Cannabidiol (CBD), the by-product of heating CBDA, is one of the major cannabinoids derived or synthesized from cannabis.2, 4

CBD has very low affinity for cannabinoid receptor CB1 and so is lacking euphoric side effects.1

It is under investigation because of its anticonvulsant properties, as well as other conditions.1

A specific formulation of cannabidiol has been approved by the FDA as a drug for rare, severe forms of epilepsy.5


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

Cannabidivarin (CBDV), a lesser-known cannabinoid, is produced from cannabidivarinic acid (CBDVA).6

Studies have been done in rodent models of epilepsy and autism spectrum disorder.1, 7

It is under investigation for potential anticonvulsant properties.1


Cannabidiolic Acid (CBDA) Molecule

Cannabidiolic acid (CBDA) is how CBD naturally occurs in the plant.4

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.8


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

Tetrahydrocannabinol (THC), most commonly in its delta-9 form, is the by-product of heating THCA.4

It is a major cannabinoid that may be derived from cannabis or synthesized.1

It is primarily responsible for marijuana’s psychotropic properties.1

Recreational and therapeutic uses: FDA-approved synthetic and analogue products, such as dronabinol, are indicated for nausea and vomiting related to chemotherapy and anorexia associated with AIDS.9, 10


Tetrahydrocannabinolic Acid A (THCA) Molecule

Tetrahydrocannabinolic acid A (how THC naturally occurs in the cannabis plant).11

It has been investigated in a limited number of studies.11


Tetrahydrocannabidivaric Acid (THCVA) Molecule

Tetrahydrocannabivarin, a lesser-known cannabinoid, is produced from tetrahydrocannabidivaric acid (THCVA).12

Studies have been conducted in rodent models of both Parkinson’s disease and insulin sensitivity (a model of diabetes).13, 14

It is under investigation for potential use in type 2 diabetes.14

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.



FDA-Approved Cannabinoid Formulations

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

Three tetrahydrocannabinol (THC) and THC analogues (synthetics) - nabilone and 2 formulations of dronabinol - are indicated to treat anorexia associated with weight loss in adult patients with AIDS and nausea and vomiting associated with chemotherapy.9, 10, 37


A plant-derived cannabidiol is indicated for the treatment of seizures associated with rare, severe forms of epilepsy.38


See what really matters when considering cannabis-based treatments.



1. Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and Epilepsy. Neurotherapeutics. Oct 2015;12(4):747-68. doi:10.1007/s13311-015-0375-5

2. ElSohly M, Gul W. Constituents of Cannabis sativa. In: Pertwee R, ed. Handbook of Cannabis. Oxford University Press; 2014:3-22:chap 1.

3. Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav. Dec 2014;41:277-82. doi:10.1016/j.yebeh.2014.08.135

4. Ujvary I, Hanus L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis Cannabinoid Res. 2016;1(1):90-101. doi:10.1089/can.2015.0012

5. US Food and Drug Administration. FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy. 2018.

6. Thomas BF, ElSohly MA. Biosynthesis and Pharmacology of Phytocannabinoids and Related Chemical Constituents. The Analytical Chemistry of Cannabis. Elsevier; 2016:27-41:chap 2.

7. Zamberletti E, Gabaglio M, Woolley-Roberts M, Bingham S, Rubino T, Parolaro D. 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. doi:10.3389/fncel.2019.00367

8. Pertwee RG, Rock EM, Guenther K, et al. Cannabidiolic acid methyl ester, a stable synthetic analogue of cannabidiolic acid, can produce 5-HT1A receptor-mediated suppression of nausea and anxiety in rats. British Journal of Pharmacology. 2018;175(1):100-112. doi:10.1111/bph.14073

9. Marinol® (dronabinol) capsules, for oral use [prescribing information]. North Chicago, IL: AbbVie Inc.

10. Syndros® (dronabinol) oral solution [prescribing information]. Chandler, AZ: Insys Therapeutics Inc.

11. Stone NL, Murphy AJ, England TJ, O'Sullivan SE. A systematic review of minor phytocannabinoids with promising neuroprotective potential. Br J Pharmacol. Oct 2020;177(19):4330-4352. doi:10.1111/bph.15185

12. Sarma ND, Waye A, ElSohly MA, et al. Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes. J Nat Prod. Apr 24 2020;83(4):1334-1351. doi:10.1021/acs.jnatprod.9b01200

13. Espadas I, Keifman E, Palomo-Garo C, et al. Beneficial effects of the phytocannabinoid Delta(9)-THCV in L-DOPA-induced dyskinesia in Parkinson's disease. Neurobiol Dis. Jul 2020;141:104892. doi:10.1016/j.nbd.2020.104892

14. Abioye A, Ayodele O, Marinkovic A, Patidar R, Akinwekomi A, Sanyaolu A. Delta9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. J Cannabis Res. Jan 31 2020;2(1):6. doi:10.1186/s42238-020-0016-7

15. Bostwick JM. Blurred boundaries: the therapeutics and politics of medical marijuana. Mayo Clin Proc. Feb 2012;87(2):172-86. doi:10.1016/j.mayocp.2011.10.003

16. US Food and Drug Administration. FDA and Cannabis: Research and Drug Approval Process. Updated Oct 10, 2020. Accessed Sept 2, 2021.

17. Cash MC, Cunnane K, Fan C, Romero-Sandoval EA. Mapping cannabis potency in medical and recreational programs in the United States. PloS one. 2020;15(3):e0230167-e0230167. doi:10.1371/journal.pone.0230167

18. National Conference of State Legislatures. State medical marijuana laws. 2021. Accessed Dec 6, 2021.

19. US Food and Drug Administration. Inside Clinical Trials: Testing Medical Products in People. 2014. Accessed Feb 18, 2022.

20. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. The National Academies Press; 2017:486.

21. American Academy of Neurology. AAN POSITION: USE OF MEDICAL CANNABIS FOR NEUROLOGIC DISORDERS. Updated Sept 2020. Accessed Dec 2, 2021.

22. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. Nov 7 2017;318(17):1708-1709. doi:10.1001/jama.2017.11909

23. Vandrey R, Raber JC, Raber ME, Douglass B, Miller C, Bonn-Miller MO. Cannabinoid Dose and Label Accuracy in Edible Medical Cannabis Products. JAMA. Jun 23-30 2015;313(24):2491-3. doi:10.1001/jama.2015.6613

24. US Food and Drug Administration. Warning Letters and Test Results for Cannabidiol-Related Products. 2020. Accessed Feb 23, 2021.

25. Clean Label Project. Hemp Study Infographic. 2019. Accessed Dec 2, 2021.

26. Small E. Evolution and Classification of Cannabis sativa (Marijuana, Hemp) in Relation to Human Utilization. Bot Rev. Sept 1 2015;81(3):189-294. doi:10.1007/s12229-015-9157-3

27. VanDolah HJ, Bauer BA, Mauck KF. Clinicians' Guide to Cannabidiol and Hemp Oils. Mayo Clin Proc. Sep 2019;94(9):1840-1851. doi:10.1016/j.mayocp.2019.01.003

28. US Food and Drug Administration. Hemp Production and the 2018 Farm Bill. 2019. Accessed Dec 2, 2021.

29. Establishment of a Domestic Hemp Production Program, Department of Agriculture (USDA) 7 CFR §990 (2021). Accessed 3 Dec 2021.

30. Cannabinoid Clinical. Creating Confusion: The THC 0.3% Threshold. 2020. Accessed Dec 6, 2021.

31. Yang Y, Lewis MM, Bello AM, Wasilewski E, Clarke HA, Kotra LP. Cannabis sativa (Hemp) Seeds, Delta(9)-Tetrahydrocannabinol, and Potential Overdose. Cannabis Cannabinoid Res. 2017;2(1):274-281. doi:10.1089/can.2017.0040

32. Rheay HT, Omondi EC, Brewer CE. Potential of hemp (Cannabis sativa L.) for paired phytoremediation and bioenergy production. GCB Bioenergy. 2020;13(4):525-536. doi:10.1111/gcbb.12782

33. McPartland JM, McKernan KJ. Contaminants of Concern in Cannabis: Microbes, Heavy Metals and Pesticides. In: Chandra S, Lata H, ElSohly MA, eds. Cannabis sativa L - Botany and Biotechnology. Springer International Publishing; 2017:457-474:chap 22.

34. Jikomes N, Zoorob M. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products. Scientific Reports. 2018/03/14 2018;8(1):4519. doi:10.1038/s41598-018-22755-2

35. Micalizzi G, Vento F, Alibrando F, Donnarumma D, Dugo P, Mondello L. Cannabis Sativa L.: a comprehensive review on the analytical methodologies for cannabinoids and terpenes characterization. J Chromatogr A. Jan 25 2021;1637:461864. doi:10.1016/j.chroma.2020.461864

36. US Food and Drug Administration. What We Do. 2018. Accessed Dec 3, 2021.

37. Cesamet® (nabilone) capsules, for oral administration [prescribing information]. Costa Mesa, CA: Valeant Pharmaceuticals International.

38. Epidiolex® (cannabidiol) oral solution [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

39. Gottlieb S. Statement from FDA Commissioner Scott Gottlieb, M.D., on signing of the Agriculture Improvement Act and the agency’s regulation of products containing cannabis and cannabis-derived compounds. 2018.

40. US Food and Drug Administration. Center for Drug Evaluation and Research. Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry. 2020.