CBD: Uses and What the Research Says

Overview

Cannabidiol (CBD) is a non-intoxicating cannabinoid found in cannabis plants. Unlike THC, CBD does not produce a "high." It has become widely available in various product forms including oils, capsules, edibles, and topicals. This guide examines what CBD is, what the current research shows, and what remains uncertain.

What is CBD?

CBD is one of over 100 cannabinoids identified in the cannabis plant. It was first isolated in 1940 by American chemist Roger Adams, and its structure was determined in 1963 by Raphael Mechoulam [1].

CBD can be derived from both marijuana and hemp plants. Under U.S. federal law, CBD products derived from hemp (containing less than 0.3% Delta-9 THC) are legal, while marijuana-derived CBD remains federally controlled [2].

How CBD Works

CBD interacts with the body differently than THC. Rather than binding directly to CB1 receptors (which produces THC's intoxicating effects), CBD has a more complex mechanism of action that researchers are still working to fully understand.

Known Mechanisms

Research has identified several ways CBD interacts with biological systems:

• Modulation of endocannabinoid signaling: CBD may inhibit the enzyme FAAH, which breaks down the endocannabinoid anandamide. This could increase anandamide levels in the body [3].

• Serotonin receptors: CBD has been shown to activate 5-HT1A serotonin receptors, which may relate to its effects on anxiety in some studies [4].

• TRPV1 receptors: CBD activates these receptors, which are involved in pain perception and inflammation [5].

• GPR55 receptors: CBD may act as an antagonist at these receptors, which has implications for bone health and blood pressure regulation [6].

What Research Shows

FDA-Authorized Uses

The FDA has approved one CBD-based medication: Epidiolex (cannabidiol oral solution). It is approved for treating seizures associated with:

• Lennox-Gastaut syndrome
• Dravet syndrome
• Tuberous sclerosis complex

These are severe forms of epilepsy that are often resistant to other treatments. Clinical trials showed significant reductions in seizure frequency compared to placebo [7].

Research on Other Conditions

Studies have investigated CBD for various other conditions. Results are mixed, and most research is preliminary.

Anxiety

Several small studies have found that CBD may reduce anxiety in specific contexts. A 2019 study of 57 men found that 300mg of CBD reduced anxiety during a simulated public speaking test compared to placebo [8]. However, larger, long-term studies are needed to confirm these findings.

Pain

Research on CBD for pain has produced mixed results. A 2020 review noted that while some studies show potential benefits, many studies use CBD combined with THC, making it difficult to isolate CBD's effects. The review concluded that evidence for CBD alone treating chronic pain is currently insufficient [9].

Sleep

Some studies suggest CBD may help with sleep, but findings are inconsistent. A 2019 case series found that sleep scores improved in 66.7% of patients during the first month of CBD treatment, but fluctuated over time [10]. More controlled research is needed.

Inflammation

Preclinical studies (cell cultures and animal models) have shown inflammation-related properties of CBD. However, translating these findings to humans requires clinical trials, which are still limited [11].

Product Types

CBD products come in several forms, each with different characteristics:

Full-Spectrum CBD

Contains CBD along with other cannabinoids (including up to 0.3% THC), terpenes, and plant compounds naturally present in hemp. Some researchers theorize these compounds may work together synergistically—a concept called the "entourage effect"—though clinical evidence for this is limited [12].

Broad-Spectrum CBD

Contains CBD and other cannabinoids/terpenes, but with THC removed or reduced to non-detectable levels.

CBD Isolate

Pure CBD with no other cannabinoids or plant compounds. Typically 99%+ pure cannabidiol.

Delivery Methods

Bioavailability data from Millar et al., 2018 [13].

Dosing

There is no standard CBD dose. The FDA-authorized medication Epidiolex uses doses of 5-20 mg/kg/day for seizure disorders. For general wellness products, doses in studies have ranged widely, from 15mg to several hundred milligrams daily.

Factors affecting appropriate dosing include:

• Body weight
• Individual metabolism
• The condition being addressed
• Product type and bioavailability
• Presence of other medications

Most sources recommend starting with a low dose (10-20mg) and adjusting based on effects [14].

Safety and Side Effects

CBD is generally considered well-tolerated. In clinical trials for Epidiolex, the most common side effects included:

• Drowsiness
• Decreased appetite
• Diarrhea
• Fatigue
• Elevated liver enzymes (at high doses) [15]

Drug Interactions

CBD is metabolized by cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19. This means it can interact with medications that use these same pathways. Anyone taking prescription medications should consult their healthcare provider before using CBD [16].

Product Quality Concerns

The CBD market is largely unregulated. Studies have found that many products contain different amounts of CBD than labeled, and some contain contaminants. A 2017 study found that only 31% of CBD products tested had accurate labeling [17].

To assess product quality, look for:

• Third-party lab testing (Certificate of Analysis)
• Clear labeling of CBD content per serving
• Information about the source of hemp
• Testing for contaminants (pesticides, heavy metals, solvents)

What Remains Unknown

Despite widespread use, significant gaps remain in CBD research:

• Optimal dosing for various conditions
• Long-term safety with daily use
• Efficacy for most conditions people use it for
• How different product types compare in effectiveness
• Individual variation in response

Summary

CBD is a non-intoxicating cannabinoid with one FDA-authorized use for certain seizure disorders. Research on other uses is ongoing but largely preliminary. While CBD appears generally well-tolerated, product quality varies significantly in the unregulated market. Consumers should look for third-party tested products and consult healthcare providers, especially if taking other medications.

References

1. Mechoulam R, Shvo Y. Hashish. I. The structure of cannabidiol. Tetrahedron. 1963;19(12):2073-2078.

1. Agriculture Improvement Act of 2018, Pub. L. No. 115-334, 132 Stat. 4490.

1. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2(3):e94.

1. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037-1043.

1. Bisogno T, Hanuš L, De Petrocellis L, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001;134(4):845-852.

1. Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092-1101.

1. 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.

1. Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry. 2019;41(1):9-14.

1. Vela J, Dreyer L, Petersen KK, et al. Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. Pain. 2022;163(6):1206-1214.

1. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18-041.

1. Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and Inflammation-Related Properties of Cannabidiol. Antioxidants (Basel). 2019;9(1):21.

1. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

1. Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front Pharmacol. 2018;9:1365.

1. MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-19.

1. U.S. Food and Drug Administration. Epidiolex Prescribing Information. https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf

1. Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019;8(7):989.

1. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017;318(17):1708-1709.