CannabinoidsCannabisLet’s talk about Cannabinoids (Part 2)

June 27, 2019by Sonal Thakar
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CBD, Cure-All Elixir or Snake Oil?

Almost everywhere you look now, you see products infused with cannabidiol (CBD) including skincare, beverages, tinctures, oils, food, and the list goes on! The once overlooked compound, CBD, is now reaching the mainstream. CBD was discovered by Dr. Roger Adams who isolated CBD for the first time in 19421. In 1963, Dr. Raphael Mechoulam defined the full structure and synthesized CBD in the lab. The 60s and 70s observed an increased use of recreational cannabis and researchers primarily focused on tetrahydrocannabinol (THC) and its psychotropic effects to better understand its pharmacology. While CBD was not initially the focus of researchers, breeders/retailers, or customers due to the lack of psychotropic activity, it is now a dominant interest for the cannabis community and medical researchers.

CBD is growing in popularity due to its characterization as having therapeutic properties without any intoxicating adverse effects. The therapeutic benefits of CBD include relieving symptoms of epilepsy, inflammation, anxiety, schizophrenia, addiction, and possibly even depression; while lacking associated craving and compulsive use2. The adverse side effects, which include tiredness, diarrhea, and changes in appetite/weight, are minimal compared to the medications currently prescribed to relieve these same symptoms. CBD is incorrectly considered as a sedative, and that in low-to-moderate doses, CBD can produce alertness, sleep delay, and counteract the sedative and other adverse effects of THC3. CBD combats insomnia by easing anxiety and stress and creating a chemical balance. Pharmaceutical grade medications, such as Sativex®, which is a 1:1 mixture of THC and CBD, take advantage of this “entourage” interaction to provide robust therapeutic benefits4. The sedative affects associated with cannabis consumption are likely due to other cannabinoids and terpenes, which we will discuss in future posts.

The ability of CBD to moderate some of the psychotropic effects of THC as well as provide therapeutic benefit is due to how it binds to the cannabinoid receptors expressed throughout the body that exist in the endocannabinoid system (ECS), which we covered in Part I of the Cannabinoid Blog Post. While THC strongly binds and activates cannabinoid receptors (CB1 and CB2 receptors), CBD binds more weakly5. At higher doses, CBD can block THC from binding, thereby reducing associated adverse effects like tachycardia, anxiety, and sedation6. CBD reduces CB1 receptor activity and results in decreasing neurotransmission, which is how it can relieve the symptoms of seizures7. Epidiolex®, which is purified 98% oil-based CBD extract, has received FDA approval for treating seizures associated with hard-to-treat forms of epilepsy. The anti-inflammatory effects of CBD are again through binding of the CB2 receptor, which results in reducing the migration of immune cells and accumulation of inflammatory markers. CBD can also moderate symptoms for those suffering from pain, anxiety, addiction, depression, and neuroinflammatory conditions by engaging the CB1 and CB2 receptors as well as other receptors, such as transient potential vanilloid receptor type-1 (TPVR-1), serotonin receptor (5-HT1A), and a G protein-coupled receptor (GPR55)7. Growing interest in CBD for therapeutic purposes is encouraging more research so we can have better understanding of the effective dose of CBD to relieve these symptoms.

CBD can be smoked, vaped, ingested, applied to the skin, or absorbed by an oromucosal (mouth) spray. Each method of consumption differentially affects when CBD peaks in the bloodstream concentration, the time it takes to leave the body, and how much of the CBD is absorbed rather than passed though the gut and liver. Oromucosal sprays like Sativex® are sprayed under the tongue or on the inside of the cheeks to increase direct absorption into the bloodstream. Absorption into the bloodstream can be within 15 minutes and peaks around 1.6-4.2 hours8,9. Oral consumption via oils (like Epidiolex®), tinctures, edibles, and capsules take longer to absorb into the bloodstream due to passing through the gut and liver, but the compound then stays in your system longer. Absorption time in general can be more erratic and variable with peak levels ranging from 60-120 minutes or sometimes even up to 6 hours10. One way to improve absorption is to apply the oil or tincture under the tongue. Inhalation of CBD by smoking and vaporizing allows for rapid absorption into the bloodstream as early as 3 minutes and peaking around 10 minutes8,9. Inhalation is also an effective way to consume CBD since it has a bioavailability (how much of the originally administered compound is actually absorbed) of approximately 31% versus oral consumption, which is 6-15%. Nasal sprays for CBD have the highest bioavailability of 34-46%10. CBD infused in lotions, creams, and balms is absorbed by the skin because it is lipophilic and soluble in fat and can reach the muscles and nerves. Depending on your personal preferences, you can pick the best way to consume CBD for your therapeutic benefit.

How you respond to and metabolize CBD also depends on your personal physiology. Genetic mutations in the CYP3A4 and CYP2C19 enzymes can reduce your metabolism and alter your response. You can learn about how you metabolize CBD as well as your genetic predisposition to other cannabis-related traits. Pathway Genomics has developed a new at-home DNA test, CannabisDNA, to help you understand your predisposition to common cannabis-related traits, metabolism of CBD & THC, and match you to a cannabis strain. Learn more about how this test can help you personalize your cannabis experience and order your $129 test.

 

References

  1. Pertwee, R.G. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147 Suppl 1, S163-71 (2006).
  2. Iffland, K. & Grotenhermen, F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res 2, 139-154 (2017).
  3. Russo, E.B. Cannabidiol Claims and Misconceptions. Trends Pharmacol Sci 38, 198-201 (2017).
  4. Oreja-Guevara, C. Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity. Expert Rev Neurother 12, 3-8 (2012).
  5. Welty, T.E., Luebke, A. & Gidal, B.E. Cannabidiol: promise and pitfalls. Epilepsy Curr 14, 250-2 (2014).
  6. Russo, E. & Guy, G.W. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 66, 234-46 (2006).
  7. Pisanti, S. et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther 175, 133-150 (2017).
  8. Millar, S.A., Stone, N.L., Yates, A.S. & O’Sullivan, S.E. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front Pharmacol 9, 1365 (2018).
  9. Devinsky, O. et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55, 791-802 (2014).
  10. Bruni, N. et al. Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules 23(2018).
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