By Ginevra Liptan, MD
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With the launch of our new line of CBD and magnesium products, Frida Botanicals, I am getting a lot of great questions about the available research on CBD. So I thought it might be helpful to answer some of them here.
How does CBD interact with the endocannabinoid system? And what the heck is the endocannabinoid system, anyway?
The "endocannabinoid" system is an integral part of our neuro-immuno-endocrine network. This is the system of organ and tissue signaling in the human body that sends and receives chemical messages and is affects for many aspects of human health including mood, pain, inflammation, stress response and immune function.
Our bodies produce their own cannabinoids—endocannabinoids—primarily anandamide, and 2-AG (2-arachidonoylglycerol). A “phytocannabinoid” or plant-derived cannabinoid like CBD or THC can activate the same receptors in the body and have similar or stronger effects than our endocannabinoids. This is similar to how morphine derived from the poppy plant can reduce pain by activating the body’s endorphin receptors.
We know the very specific receptors that THC activates in the body, primarily CB1 and CB2 receptors in the brain, but are still learning all the different rectors CBD interact with- one research article estimated CBD may interact with 65 different receptors in the human body, leading scientists refer to CBD as a “promiscuous” compound.
Szaflarski JP, Bebin EM, Cannabis, cannabidiol, and epilepsy—from receptors to clinical response. Epilepsy Behav. 2014;41:277-82
Miller RJ, Miller RE. Is cannabis an effective treatment for joint pain? Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 107(5):59-67. Epub 2017 Sep 28. Review. PubMed PMID: 28967368
What is CBD?
Cannabidiol, or CBD, is a non-intoxicating component of the cannabis plant with enormous therapeutic potential. Researchers are currently studying the effects of CBD on a wide range of conditions including chronic pain, insomnia, PTSD, anxiety, epilepsy, dementia and more.
Extensive preclinical research and some clinical studies have shown that CBD has strong anti-oxidant, anti-inflammatory, anticonvulsant, anti-depressant, anti-psychotic, anti-tumoral, and neuroprotective qualities.
Fasinu PS, Phillips S, ElSohly MA, Walker LA. Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents. Pharmacotherapy 2016;36(7):781-96.
Campos AC, Fogaça MV, Scarante FF, Joca SRL, Sales AJ, Gomes FV, Sonego AB, Rodrigues NS, Galve-Roperh I, Guimarães FS. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders. Front Pharmacol. 2017 May 23;8:269.
Will CBD make me feel high?
Cannabidiol (CBD) has many health benefits, without producing the psychoactive, "euphoric" effects of THC. “Relaxing but not intoxicating” is how some of my patients have described the effect. That said, I did have one patient that felt that a low dose of CBD did make her feel high. This is why I recommend starting with very low dosages.
Is it safe?
- CBD exhibits no effects on humans indicative of any abuse or dependence potential.
- To date, there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD.
- Chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans.
Source: World Health Organization, WHO Expert Committee on Drug Dependence, Thirty-ninth Meeting Geneva, 6-10 November 2017.
Safety and side effects of cannabidiol (NCBI/NIH). Curr Drug Saf. 2011 Sep 1;6(4):237-49. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Bergamaschi MM(1), Queiroz RH, Zuardi AW, Crippa JA
What are cannabinoids?
Cannabinoids (e.g., THC and CBD) are the chemical compounds secreted by cannabis flowers that can affect the human body. They work by imitating compounds our bodies naturally produce, called endocannabinoids, that affect nerve, brain and immune cell activity.
Currently, there are two known primary cannabinoid receptors: CB1 and CB2 receptors. CB1 receptors are located in the central nervous system, and in some peripheral tissues. They affect appetite, muscle control, pain, cognition, thermoregulation, and our stress response. CB2 receptors are primarily found in immune cells, and at a lower density in the central nervous system. CB2 activation is associated with immune function and immune cell proliferation, inflammation, and pain. Although these two cannabinoid receptors have been studied relatively extensively, there are more cannabinoid receptors being examined.
Source: Szaflarski JP, Bebin EM, Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav. 2014;41:277-82
Are CBD products legal in all 50 states?
Yes, as long as they are derived from hemp, not marijuana, and contain less than 0.3% THC. No medical marijuana card is required to buy or use hemp-derived CBD products.
What is the difference between hemp and marijuana?
Although both hemp and “marijuana” are technically variants of the Cannabis sativa plant, there are significant differences between them. Hemp is considered “industrial” under current regulations, and is defined as having less than 0.3% THC
In the US, the legal definition of “industrial hemp,” (as defined in Section 7606 of the Agricultural Appropriations Act of 2014), is "the plant Cannabis sativa L. and any part of such plant, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis.”
Marijuana generally refers to Cannabis sativa plants that have a high concentration of THC, and the word stems from the recreational use of THC rich cannabis for the purpose of getting “high.” Hemp plants possess a high concentration of CBD, with only traces of THC, and hemp extracts are associated with medicinal use.
How to choose a CBD product?
Make sure the product you buy has been third party lab tested for the 3 P’sPotency (how much CBD is in it), Purity (any residual solvents from extraction process) and Pesticides. Third party lab testing should be available on the product website.
Unfortunately, CBD labels on products are often inaccurate and unreliable as far as their CBD content. A JAMA 2017 study found that nearly 70% of all products sold online made from cannabidiol—an extract of the marijuana plant also known as CBD—contained either higher or lower concentrations of the drug than indicated on the label. (The Real Risk of Buying Medical Marijuana Online by Amanda MacMillan Nov. 7, 2017 TIME Health)
CBD-rich products should be lab tested to verify they are free of pesticides, and other contaminants. Best to avoid products extracted with toxic solvents like BHO, propane, hexane or other hydrocarbons. Opt for products that utilize cleaner extraction methods such as supercritical CO2.
Beware of CBD vape pen oil that contains propylene glycol. When overheated, this chemical additive produces formaldehyde, a carcinogen, as a byproduct, according to a 2015 report in the New England Journal of Medicine.
Are whole plant extracts better than CBD isolate?
Products infused with a crystalline CBD isolate, derived and extensively refined from industrial hemp, are available. But single-molecule CBD is thought to be less effective therapeutically than whole plant CBD-rich oil extract. The rich recipe of compounds in medicinal plants exerts healing effects through complementary action. This supports the idea of the "entourage effect", where mixtures of cannabinoids, their co-occurring terpenes, and perhaps other molecules such as flavonoids and stilbenoids, have a greater positive effect than just CBD or THC alone.
Sources: Spelman K. “Silver Bullet” Drugs vs. Traditional Herbal Remedies: Perspectives on Malaria. HG J Am Bot Coun 84:44-55.
Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug;163(7):1344-64.
Shimon Ben-Shabat S, Fride E, Sheskin T,Tamiri T, Rhee MH, Vogel Z. Bisogno T,De Petrocellis LD, Di Marzo V, Mechoulam R. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Euro J Pharmacol. 1998;353:23–31.
Is water soluble CBD better?
Water-soluble forms of CBD are not naturally occurring products. The process of making a fat-soluble compound, such as CBD, soluble in water, involves a process called nano-emulsion. Nano-emulsion uses high frequency ultrasound to induce a process called cavitation, in which small, water soluble spheres (called liposomes) are formed. The CBD molecules are suspended in the liposomes which float in the water. Although some manufacturers make claims about how this form of CBD is "enhanced", there is no data confirming this claim. I have not yet found a water-soluble CBD product that provides as much benefits as lipid-soluble CBD.
Will CBD extract influence results of a drug test?
Most drug tests screen for the psychoactive compound THC, not cannabidiol (CBD). However, full-spectrum hemp extracts may contain trace amounts of THC, so could cause a positive result when screening urine and blood specimens, especially when taken at high doses. I recommend a prudent and cautious approach to taking CBD rich hemp extracts in the context of urine drug screens.
Will CBD interact with my other medications?
At low doses of CBD, less than 150mg total per day, it is unlikely that significant drug-herb interactions will occur. However it is always possible that drug-herb interactions can occur, and this is more likely the higher the dose. CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes. If you are taking a medication where maintaining a certain blood level is critical- such as anti-seizure, anti-viral, blood-thinning medications- talk with your health care provider or pharmacist before trying CBD.
Does CBD affect appetite?
Unlike THC, CBD has negligible effects on appetite and satiety.
Does CBD cause side effects?
Typically CBD is not associated with many side effects but these have all been reported:
- Dry mouth
- Rarely can cause feelings of mild intoxication
What is the right dosage of CBD?
An effective dosage can range from as little as a 5mg of CBD per day up to 150mg per day. Make sure to start low and go slow. Take a few small doses over the course of the day rather than one big dose. Use the same dose for several days. Observe the effects and if necessary adjust the amount. Don’t overdo it.
Author Bio: Ginevra Liptan, MD, developed fibromyalgia while in medical school. She is a graduate of Tufts University School of Medicine and board-certified in internal medicine. Dr. Liptan is the founder and medical director of The Frida Center for Fibromyalgia and the author of The FibroManual: A Complete Fibromyalgia Treatment Guide For You...And Your Doctor and The Fibro Food Formula: A Real-Life Approach to Fibromyalgia Relief.