Know Your Medicine: CBD

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CBD, which stands for the phytocannabinoid cannabidiol (not cannabinoids), has exploded on the cannabis scene in a way that no other natural compound has. Although it has received a huge amount of media attention over the past few years, there are so many questions about it. Here is everything you need to know about CBD and more.

Cannabidiol was first discovered in 1940 from the hemp plant by chemist Roger Adams at the University of Illinois. In 1963, Israeli scientists elucidated its exact chemical structure. Subsequent research in the 1970s showed that CBD did not cause intoxication like THC and was thought to be an inactive cannabinoid. Scientific interest in CBD waned until the early 1990s when the important discovery of the endocannabinoid system renewed interest in numerous phytocannabinoids. Over the past decade, hundreds of scientific articles researching how CBD interacts with the human brain and body have been published and the results are astounding!

CBDA, cannabidiolic acid, is the second most common phytocannabinoid produced in the cannabis drug-variety plant — the most common being THC — and the most common phytocannabinoid in the fiber variety plant (hemp). CBDA, found in the raw cannabis flower, is converted to CBD when heated. CBD-rich plants were quite rare in the United States until around 2009, when reports of CBD’s therapeutic value started to appear in the media. Cannabis growers began testing their plants for CBD and made efforts to stabilize CBD-rich varieties.  We now have a number of CBD-rich chemovars such as Charlotte’s Web, AC/DC, Cannatonic, Harlequin, Sour Tsunami, Blue Jay Way, and many others.   

CBD Absorption and Metabolism

The bioavailability of CBD after inhalation is about 31%. CBD is absorbed poorly and erratically when ingested. Sublingual absorption rates are low but less variable than oral ingestion. CBD is metabolized in the liver where it is converted to 7-hydroxy-CBD by enzymes in the P450 system. Most of this breakdown product is excreted in feces, with a small amount excreted in urine.  

CBD Mechanism of Action

CBD does not bind to the cannabinoid receptor the same way that THC does which is why it is not intoxicating. CBD modulates the way that THC binds to the cannabinoid receptor and blocks the conversion of THC to the more psychoactive 11-hydroxy-THC. CBD also inhibits the reuptake of the endocannabinoid anandamide, thus enhancing the endocannabinoid system. CBD works at numerous non-cannabinoid receptors, such as the 5-HT1A (hydroxytryptamine) serotonin receptor, giving an antidepressant effect, the TRPV1 (vanilloid) receptor, giving analgesic and anti-inflammatory effects, and the peroxisome proliferator activated receptors (PPARs) with multiple effects such as anti-proliferation of certain cancer cells, neuroprotection, and cardioprotection. CBD changes the way that GABA, an inhibitory neurotransmitter, binds to the GABA receptor, enhancing the calming, anti-anxiety effects of GABA. CBD has been shown to reduce drug-seeking behavior and can have therapeutic effects on THC withdrawal and nicotine dependence.  

Medicinal Properties of CBD

As you can see, CBD has “multiple targets of action,” meaning that it works at many different places, giving it numerous medicinal properties, which include:

  • Potent anti-inflammatory
  • Antioxidant
  • Neuroprotectant
  • Anticonvulsant
  • Analgesic (pain reliever)
  • Anxiolytic (anti-anxiety)
  • Antidepressant
  • Antipsychotic
  • Antispasmodic
  • Anti-cancer agent

CBD modulates the intoxicating effects of THC and reduces the adverse effects that some people experience with THC, namely rapid heartbeat, anxiety, and short-term memory loss. At the same time, when CBD is taken with THC to treat pain, the combination reduced pain more significantly than THC alone. In low doses, CBD is described as alerting, in high doses (>300 mg) it can be sedating.  Amazingly, CBD has very little side effects even at high doses.  

Hemp CBD vs. Marijuana CBD

CBD is produced in both hemp/fiber variety and drug variety cannabis plants. Are they the same compound? Yes, but we know from numerous studies that cannabinoids such as CBD work best when other cannabinoids and terpenoids are present, a synergy termed “the entourage effect.”  Hemp is virtually devoid of other cannabinoids and terpenoids. Also, industrial hemp contains very little CBD, necessitating a large number of hemp plants to obtain what can be obtained from one CBD-rich drug variety plant. The use of a large number of hemp plants also increases the risk of toxin contamination as hemp is a bio-accumulator, drawing up toxins from soil. (Fun fact: industrial hemp was planted around the Chernobyl nuclear power plant after the nuclear explosion in 1986). Most importantly, an excellent study from Israel in 2015 showed that whole-plant CBD, containing cannabinoids and terpenoids, was superior to single molecule CBD, with whole plant extract having a wider therapeutic window and better efficacy at lower doses. My clinical experience with thousands of patients confirms that whole plant CBD-rich cannabis is more efficacious than hemp-based single molecule CBD.  

How Should Patients Choose CBD Products?

Be aware that there are a small number of hemp products on the market that are labeled “hemp” to comply with governmental regulations that require these products to have less than 0.3% THC, but they are robust with cannabinoids and terpenoids. Other products are devoid of all cannabinoids including CBD, despite the manufacturers’ claims. In 2015 and 2016, the FDA purchased a number of CBD products online and tested them for the presence of CBD and other cannabinoids, finding that the amount of CBD claimed on the labels was markedly inaccurate — some products did not contain any CBD. In states that have medical cannabis laws, it’s best to obtain products from licensed suppliers who share their test results, which should validate the product’s robust cannabinoid and terpenoid profiles.  If you are obtaining hemp through online outlets, thorough research is required as there are many bogus claims being made.

CBD is truly an amazing compound. There are very few medicines that have such a long list of beneficial properties with little to no side effect and are completely natural. Many patients using CBD as medicine experience life-changing relief of symptoms and are able to discontinue ineffective and toxic medications. Unfortunately, CBD is still classified as a Schedule I federally illegal substance that is still prohibited from being thoroughly researched. We must be free to study this plant’s medicinal benefits to fully understand its impact on human health.  


Sources

Devinsky, Orrin, et al. “Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.” Epilepsia 55.6 (2014): 791-802.

Gallily, Ruth, Zhannah Yekhtin, and Lumír Ondřej Hanuš. “Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol.” Pharmacol Pharm 6 (2015): 75-85.

Karniol, I. G., and E. A. Carlini. “Pharmacological interaction between cannabidiol and Δ 9-tetrahydrocannabinol.” Psychopharmacology 33.1 (1973): 53-70.

Karniol, Isac G., et al. “Cannabidiol interferes with the effects of Δ9-tetrahydrocannabinol in man.” European journal of pharmacology 28.1 (1974): 172-177.

Russo, Ethan B., et al. “Agonistic properties of cannabidiol at 5-HT1a receptors.” Neurochemical research 30.8 (2005): 1037-1043.

Russo, Ethan, and Geoffrey W. Guy. “A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol.” Medical hypotheses 66.2 (2006): 234-246.

Russo, Ethan B., Geoffrey W. Guy, and Philip J. Robson. “Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis‐Based Medicine.” Chemistry & biodiversity 4.8 (2007): 1729-1743.

Zuardi, Antonio Waldo. “Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action.” Revista brasileira de psiquiatria 30.3 (2008): 271-280.

About Author

Bonni Goldstein, M.D. is a physician who specializes in cannabis medicine in Los Angeles, California. She specialized in Pediatric Emergency medicine for years before witnessing the amazing benefits of this treatment in an ill loved one. Since then, she has successfully treated thousands of adult and pediatric patients with cannabis. She regularly speaks about cannabis medicine at conferences and patient groups around the world. She is the owner and medical director of CannaCenters and medical advisor to Weedmaps.com. She is the author of the recently published book, Cannabis Revealed.

1 Comment

  1. I’m interested in how the low uptake of orally (or sublingually) administered CBD squares with its usage to treat Dravet syndrome and other types of epilepsy. Is it simply a matter of scaling the dose or are there ways to make oral CBD more bioavailable?

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