CBD vs. THC - Molecules & More | Cannabinoid Clinical

The Difference Between THC and CBD

Learn more about how CBD and THC affect the endocannabinoid system, and explore the mechanisms of action for cannabinoids.

Endocannabinoid System (ECS)

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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

CBD

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

CBDV

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

It has been investigated in combination with other antiseizure medications in patients with focal seizures and is being investigated for its effects on irritability in children with autism spectrum disorder.^7,8

CBDA

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 suppress vomiting and prevent nausea.⁹

THC

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

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 by acting on CB1 receptors.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.^{10, 11}

THCA

Tetrahydrocannabinolic acid A (how THC naturally occurs in the cannabis plant).¹²

It has been investigated in a limited number of studies.¹²

THCV

Tetrahydrocannabivarin, a lesser-known cannabinoid, is produced from tetrahydrocannabidivaric acid (THCVA).¹³

Studies have been conducted in rodent models of both Parkinson’s disease and insulin sensitivity (a model of diabetes).^14,15

It is under investigation for potential use in type 2 diabetes.¹⁵

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

Medical Marijuana

The term “medical marijuana” refers to using the whole plant or its extracts to treat medical problems.¹⁶

The FDA does not recognize the whole marijuana plant as medicine.¹⁷

Research on extracts from the marijuana plant, called cannabinoids, has led to FDA-recognized medicines, proving this research is possible.¹⁷

Continued research may lead to more FDA-approved medications.¹⁷

The cannabis varieties used for medical or recreational marijuana are generally the same plants, grown in the same conditions, and subjected to the same cannabinoid extraction process.^{16, 18} It is the intent of use that separates these 2 terms legally.

Medical marijuana laws are in constant flux, but as of February 1, 2025, 39 states, the District of Columbia, Guam, Puerto Rico, and the US Virgin Islands have comprehensive programs for access to medical marijuana.¹⁹

Medical marijuana is dispensed for use without any substantial research proving safety or efficacy.¹⁷ In contrast, the FDA requires carefully conducted research (randomized, placebo-controlled clinical trials) in hundreds to thousands of human patients to determine the benefits and risks of a possible medication.²⁰

Many leading national scientific organizations have reported on the lack of appropriate evidence and potential risks for the use of medical marijuana to treat neurological conditions.^{21, 22}

The American Association of Neurology (AAN) position statement noted that “it is not appropriate to extrapolate the results of trials of standardized preparations to other non-standardized, non-regulated medical marijuana products which may be commercially available…”²³

Caution and monitoring are warranted when patients use medical marijuana. Repeated independent research has shown that these products may have inaccurate labels, and unknown constituents can be present in non–FDA-approved products (eg, pesticides, heavy metals, or THC).^{13, 24-27}

Hemp-Derived
Products

Hemp-Derived Products

Hemp and marijuana are both types of cannabis.²⁸

Historically, hemp has been used to produce fibers and seeds for manufacturing, while marijuana has been used for recreational products.²⁸

Because marijuana is federally illegal, retailers became interested in growing hemp for CBD.²⁹ The 2018 Farm Bill descheduled CBD derived from hemp but only if there is no more than 0.3% THC on a dry-weight basis.³⁰ This definition was updated in 2025, effective in 2026, to state that CBD products must contain no more than 0.3% total THC (or other cannabinoids that cause similar intoxication) by dry-weight and imposes a 0.4 mg total THC limit per finished product containter.³¹ FDA-approved drugs are excluded from the revised hemp definition

The FDA notes that these products must not be used as supplements or foods, nor can they be used to treat a medical condition.³²

Changes in the 2014 Agriculture Act and the 2018 Agriculture Improvement Act, also known as the “Farm Bill,” expanded the federal definition of hemp, first specifying it for research (2014) and then for other non-consumed products (2018).^{30, 33} Recent language found in the Continuing Appropriations FY2026 Agricultural Act, narrowed the hemp definition to include no more than 0.3% total THC, including THCA or other cannabinoids that cause similar intoxication, by dry weight. It imposed THC limits on finished products and explicitly excluded synthetic or converted cannabinoids from the hemp definition.³¹

The Food and Drug Administration (FDA) maintains oversight of hemp-derived consumer products, including those used as a food or food ingredient, or as an ingredient in body products, cosmetics, dietary supplements, and therapeutic products.³²

The USDA maintains oversight of program implementation.³⁴ This includes developing regulations and guidance for the commercial production of industrial hemp in the United States, as well as, regulations for individual states or tribes. USDA will not begin reviewing plans until regulations go into effect at the end of 2019 for crop growth in 2020.

While the 2018 Agriculture Improvement Act stipulated that hemp-derived products can have no more than 0.3% delta-9 THC by dry weight, some purveyors interpreted this to apply to finished product.³⁰ This misinterpretation led to products being sold with high levels of THC.³⁵ This loophole in the 2018 Agriculture Improvement Act has been addressed in the Continuing Appropriations FY2026 Agricultural Act by narrowing the definition of hemp to no more than 0.3% total THC by dry weight and imposing a 0.4 mg total THC limit on finished products.³¹

Hemp-derived products may pose a risk to the public with unintended high dose exposure to THC.³⁶ Moreover, hemp plants are soil remediators that absorb toxic chemicals from the soil they are grown in.³⁷

When phytocannabinoids are extracted from these plants, toxic chemicals from the soil can also be in the extraction.³⁸ Rigorous growing, harvesting, extraction, manufacturing, and testing practices must be performed to ensure safe products for consumption.¹³ Even products undergoing state testing may have inaccurate labels due either to lab quality issues or the post-testing degradation of cannabinoid content.^39,40

FDA-Approved Cannabinoid Formulations

The U.S. Food and Drug Administration (FDA) is responsible for protecting public health by regulating products such as medical drugs, medical devices, tobacco products, food, and cosmetics.⁴¹

When a product is “FDA-approved,” that means it has gone through a series of rigorous tests to assess safety and efficacy.¹⁷

With growing interest in the development of medicines from cannabis, the FDA is concerned that non–FDA-approved products can put the health and safety of consumers at risk.¹⁷

The FDA requires carefully conducted research studies (randomized, placebo-controlled clinical trials) in hundreds to thousands of patients to determine the benefits and risks of a possible medication before it can be marketed to the public or physicians.^{17, 20}

The FDA has approved 4 cannabinoid products: a plant-derived cannabidiol oral solution for the treatment of seizures associated with rare, severe forms of epilepsy; and 3 formulations of synthetic THC cannabinoid products, dronabinol and nabilone for the treatment of nausea and vomiting associated with cancer chemotherapy or loss of appetite and weight loss in people with AIDS.^{5, 10, 11, 42}

The FDA has not approved any marijuana or hemp products purchased at dispensaries, retail shops, or online for treating any medical conditions or as dietary supplements.¹⁷ It is also not legal to sell foods containing THC or CBD in interstate commerce.³⁰

As patient and consumer demand increases, so does the need for greater scientific understanding of cannabis and cannabinoids.¹⁷ Clinical trials to examine the medical validity and safety of these dispensary and retail products have not been conducted, thus they are not FDA-approved.

Testing of Schedule I products can seem daunting, but there are paths through the FDA and DEA to perform research on these restricted products.^{17, 43}

Without FDA approval and oversight, products are susceptible to error or corruption in production and marketing. Patients are left on their own to guess at the content and quality of non–FDA-approved cannabinoid products.^24-26

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 patients with AIDS and nausea and vomiting associated with chemotherapy.^{10, 11, 42}

A plant-derived cannabidiol is indicated for the treatment of seizures associated with rare, severe forms of epilepsy.⁵

See what really matters when considering cannabis-based treatments.

References

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. Epidiolex® (cannabidiol) oral solution [prescribing information]. Carlsbad, CA: Jazz Pharmaceuticals, Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec

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

7. Brodie MJ, Czapinski P, Pazdera L, et al. A Phase 2 Randomized Controlled Trial of the Efficacy and Safety of Cannabidivarin as Add-on Therapy in Participants with Inadequately Controlled Focal Seizures. Cannabis Cannabinoid Res. Dec 2021;6(6):528-536. doi:10.1089/can.2020.0075

8. Cannabidivarin (CBDV) vs. Placebo in Children with Autism Spectrum Disorder (ASD). ClinicalTrials.gov Identifier: NCT03202303. Updated Oct 22, 2025. Accessed Apr 24, 2026. https://clinicaltrials.gov/study/NCT03202303?tab=study

9. 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. Br J Pharmacol. Mar 2013;168(6):1456-70. doi:10.1111/bph.12043

10. Marinol® (dronabinol) capsules, for oral use [prescribing information]. North Chicago, IL: AbbVie Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0efeeec-640d-43c3-8f0a-d31324a11c68

11. Syndros® (dronabinol) oral solution [prescribing information]. Chandler, AZ: Benuvia Therapeutics Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a7801c70-995d-46a2-91ee-141ef427c6b5

12. 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

13. 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

14. 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

15. 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

16. 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

17. US Food and Drug Administration. FDA and Cannabis: Research and Drug Approval Process. Updated Feb 24, 2023, Accessed Sep 2, 2024. https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process

18. 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

19. National Conference of State Legislatures. State medical marijuana laws. 2025. Accessed Mar 25, 2025. https://www.ncsl.org/health/state-medical-cannabis-laws

20. Rados C. Inside clinical trials: testing medical products in people. FDA Consum. Sep-Oct 2003;37(5):30-5. https://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/2003/503_trial.html

21. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 10.17226/24625The National Academies Press; 2017:486.

22. Testai FD, Gorelick PB, Aparicio HJ, et al. Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association. Stroke. Apr 2022;53(4):e176-e187. doi:10.1161/STR.0000000000000396

23. American Academy of Neurology. AAN POSITION: USE OF MEDICAL CANNABIS FOR NEUROLOGIC DISORDERS. Updated Sept, 2020. Accessed Dec 2, 2021. https://www.aan.com/policy-and-guidelines/policy/position-statements/medical-cannabis/

24. 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

25. 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

26. US Food and Drug Administration. Warning Letters and Test Results for Cannabidiol-Related Products. FDA.gov. Updated Sept 3, 2025, 2025. Accessed Feb 21, 2025. https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products

27. Gardener H, Wallin C, Bowen J. Heavy metal and phthalate contamination and labeling integrity in a large sample of US commercially available cannabidiol (CBD) products. Sci Total Environ. Dec 10 2022;851(Pt 1):158110. doi:10.1016/j.scitotenv.2022.158110

28. 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

29. 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

30. House of Representatives. (2018) Agriculture Improvement Act of 2018. https://www.congress.gov/bill/115th-congress/house-bill/2/text

31. House of Representatives. (2025) Continuing Appropriations, Agriculture, Legislative Branch, Military Construction and Veterans Affairs, and Extensions Act, 2026. https://www.congress.gov/bill/119th-congress/house-bill/5371/text/eas

32. US Food and Drug Administration. Hemp Production and the 2018 Farm Bill. 2019. Accessed Dec 2, 2021. https://www.fda.gov/news-events/congressional-testimony/hemp-production-and-2018-farm-bill-07252019

33. House of Representatives. (2014) Agriculture Reform, Food, and Jobs Act of 2013. https://www.congress.gov/bill/113th-congress/house-bill/2642/text

34. Establishment of a Domestic Hemp Production Program, Department of Agriculture (USDA). 7 CFR §990 (2021). Accessed 3 Dec 2021. https://www.federalregister.gov/documents/2021/01/19/2021-00967/establishment-of-a-domestic-hemp-production-program

35. Johnson E, Kilgore M, Babalonis S. Cannabidiol (CBD) product contamination: Quantitative analysis of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) concentrations found in commercially available CBD products. Drug Alcohol Depend. Aug 1 2022;237:109522. doi:10.1016/j.drugalcdep.2022.109522

36. 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

37. 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

38. 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.

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. 2018/03/14 2018;8(1):4519. doi:10.1038/s41598-018-22755-2

40. 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

41. US Food and Drug Administration. What We Do. FDA.gov. 2018. Accessed Dec 3, 2021. https://www.fda.gov/about-fda/what-we-do

42. Cesamet® (nabilone) capsules [prescribing information]. Bridgewater, NJ: Bausch Health US LLC. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=83c7ac15-ece9-47de-b83c-d575544fa449

43. US Food and Drug Administration. Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry. 2020. Accessed Feb 9, 2026. https://www.fda.gov/media/140319/download

Title	Content
Agricultural Improvement Act of 2018
Bioaccessibility
Bioaccumulation
Botanical Drug Product
Broad Spectrum*
Cannabinoid
Cannabinoid Receptors
Cannabis
Cannabis Halo Effect
Cannabis sativa L.
CBC
CBD
CBD Oil/Hemp CBD Oil*
CBDA
CBDV
CBG
CBGA
CBN
DEA Drug Scheduling
Dietary Supplement
Endocannabinoid System
Endocannabinoids
Entourage Effect*
FDA-Approved Cannabinoid Medicine
Full Spectrum*
Hemp
Hemp Oil/Hempseed Oil*
Isolate*
Marijuana
Medical Cannabis*
Nutraceutical*
Phytocannabinoids
Phytoremediation
Pyramid of Evidence
Real-World Data
Real-World Evidence
Recreational Marijuana*
Synthetic Cannabinoids
Terpenes/Terpenoids
Δ⁸-THC
Δ⁹-THC
THCA
THCV
Trichomes

THC vs. CBD

The Difference Between THC and CBD

Test your knowledge

The Phytocannabinoids Story

Differentiating Phytocannabinoids

CBD

CBDV

CBDA

THC

THCA

THCV

Not All Cannabinoid Products Are Created Equal

Medical Marijuana

Medical Marijuana

Hemp-Derived Products

Hemp-Derived Products

FDA-Approved Cannabinoid Formulations

FDA-Approved Cannabinoid Formulations

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

References

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Medical
Marijuana

Hemp-Derived
Products