NEW RESEARCH: CANNABIDIOL (CBD) LOWERS DOPAMINE
Posted on September 27 2019
DOPA RUSH™ COCKTAIL to the Rescue
By Steve Blechman
Cannabidiol (CBD) is the talk of the town! A “miracle cure?” The hottest supplement trend in years and the FDA hasn’t even approved it in food or dietary supplements. It was reported on June 12, 2019 in The New England Journal of Medicine that, “the FDA has taken the position that cannabidiol cannot be legally sold in supplements or food.” The hype for CBD as a “miracle cure” is unknown. We don’t know if cannabidiol can be a “miracle cure” for anything other than epilepsy at this time based on the scientific research! Cannabidiol is sold illegally online and in some retail stores in several dosage forms such as CBD Oil, CBD Candy and CBD Gummy Bears. Sales of CBD are projected to reach $22 billion by 2022.
In an article published Thursday, December 27 in The New York Times, it acknowledges, “In 2017, the National Academies of Sciences, Engineering and Medicine convened a panel of experts to review the health effects of cannabis and cannabinoids. They examined more than 10,000 studies, most of which examined marijuana, not CBD. They found evidence that some cannabinoids — not including CBD — are effective for pain, nausea from chemotherapy and muscle spasms in multiple sclerosis.
“When it comes to CBD, the panel found only a few small randomized clinical trials, and concluded that there was insufficient evidence that CBD was effective in treating conditions like insomnia, addiction to cigarettes and Parkinson’s disease, and limited evidence in its ability to treat anxiety.”
In 2018, the U.S. Food and Drug Administration approved Epidiolex, a CBD concentrate, for two rare and severe forms of epilepsy, on the basis of several clinical trials.” (The New York Times, December 27, 2018). Research has shown that CBD may cause liver toxicity (Molecule, 2019; Healthline, August 20, 2019). More research on long-term safety and efficacy is required, especially for daily use of CBD.
As you can see, the hype on CBD is way ahead of the science! The scientific literature supports CBD for seizures and convulsions. CBD looks promising in the areas of reducing inflammation, relieving pain and anxiety, but much more research is needed. The mechanisms of action for CBD in the scientific literature are not fully understood until recently.
Cannabidiol has little effect on cannabinoid receptors in the brain and in contrast to tetrahydrocannabinol (THC), CBD lacks psychoactive properties or produces euphoric side effects. A most recent study in the journal of Drugs (September 2019) reports: “the most likely mechanism of CBD and seizures includes: (1) antagonism G-protein-coupled-receptor-55 (GPR55) (2) Desensitization of the transient receptor potential of vanilloid-type-1 (TRVP1) (3) Inhibition of adenosine reuptake.”
CBD can raise adenosine levels and can downregulate the release of neurotransmitters such as dopamine. Caffeine is an adenosine inhibitor that raises dopamine! The reduction of dopamine from marijuana abuse and excessive use of CBD is very concerning! It’s concerning because it may cause lasting cognitive impairment! CBD exerts its anti-anxiety effects and anti-inflammatory effects in the body by activating the adenosine receptors and increasing adenosine levels.
The mechanisms of action of CBD as a TRPV1 receptor inhibitor and adenosine reuptake inhibitor may lower dopamine levels in the brain. In my last article I talked about a new study about cannabis abuse and the connection between excessive cannabis use and decreased dopamine release in the brain, which could lead to impaired memory, attention and problem-solving abilities. A new study published in Molecular Psychiatry found evidence of a “compromised dopamine system” in heavy pot smokers, and significantly lower dopamine levels for those heavily dependent on cannabis. MRI and image studies have shown that drug abuses have marked decreases in dopamine release (Neuropharmacology, January 1, 2010).
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two most abundant cannabinoids found in the marijuana plant, with THC containing approximately 12% to 25% and CBD containing 1.4%. People who use THC regularly lower their dopamine levels. CBD is an adenosine activator and doesn’t include the psychoactive effects of THC. Like I said earlier, the latest scientific research has shown that CBD can inhibit dopamine release by inhibiting the TRPV1 receptor in the brain as well as increasing adenosine (Neuropharmacology, 2019, Drugs September 2019). The spice black pepper extract containing piperine has been shown to activate the TRPV1 receptor, and caffeine, which inhibits adenosine and enhances dopamine release. Increasing dopamine has been shown to increase energy, focus, memory, alertness, attention, confidence, mood, motivation, libido, weight control and creativity.
One solution to boost dopamine levels, besides going easier on the weed and THC and CBD, is the breakthrough product Dopa Rush Cocktail™ from Advanced Molecular Labs (AML™). Dopa Rush Cocktail™ is the most potent dopamine-maximizing supplement on the market. Dopa Rush Cocktail™ is a dopamine MAXIMIZER that uses a scientifically backed formula to increase mental alertness, focus, clarity and energy. No crash, no jitters— just enhanced mood, creativity and motivation. Dopa Rush Cocktail™ is designed for students, athletes and motivated professionals for a mental edge in the office, in class or even in the gym.
For more information on Dopa Rush Cocktail™ go to www.advancedmolecularlabs.com
- Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy. Franco, V. & Perucca, E. Drugs (2019) 79: 1435. https://doi.org/10.1007/s40265-019-01171-4
- Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH1A and TRPV1 receptor mechanisms. Ewa Galaj Guo, HuaBiHong-JuYang, Zheng-XiongXi
- The New York Times. Is CBD Helpful, or Just Hype? Richard A. Friedman. December 27, 2018.
- Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH and TRPV1 receptor mechanisms. Neuropharmacology. DOI 10.1016/j.neuropharm.2019.107740
- Evan de Giessen, J J Weinstein, C M Cassidy, M Haney, Z Dong, R Ghazzaoui, N Ojeil, LS Kegeles, X Xu, NP Vadhan, ND Volkow, M Slifstein, A Abi-Dargham. Deficits in striatal dopamine release in cannabis dependence. Molecular Psychiatry, 2016; DOI: 10.1038/mp.2016.21
- Tobias U Hauser, Eran Eldar, Nina Purg, Michael Moutoussis, Raymond J Dolan. Distinct roles of dopamine and noradrenaline in incidental memory. Journal of Neuroscience 12 August 2019, 0401-19; DOI: 10.1523/JNEUROSCI.0401-19.2019
- The Opportunity of CBD – Reforming the Law. Pieter A. Cohen, M.D., and Joshua Sharfstein, M.D. July 25, 2019 N Engl J Med 2019; 381:297-299
- Hope for cannabis as treatment for opioid addiction by Steven Laviolette, The Conversation. Medical Express.com November 22, 2018
- Shi QX, Yang LK, Shi WL, et al. The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress. Mol Brain. 2017;10(1):38. Published 2017 Aug 11. doi:10.1186/s13041-017-0318-7
- 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. 2017;2(1):139-154. Published 2017 Jun 1. doi:10.1089/can.2016.0034
- Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial.Yasmin L. Hurd, Sharron Spriggs, Julia Alishayev, Gary Winkel, Kristina Gurgov, Chris Kudrich, Anna M. Oprescu, and Edwin Salsitz. American Journal of Psychiatry 0 0:0
- Worried About CBD Hurting Your Liver? Here’s What the Experts Have to Say. Christopher Curley. Heathline. August 20, 2019 https://www.healthline.com/health-news/can-cbd-hurt-your-liver-what-to-know-about-a-new-study
- Ewing, L.E.; Skinner, C.M.; Quick, C.M.; Kennon-McGill, S.; McGill, M.R.; Walker, L.A.; ElSohly, M.A.; Gurley, B.J.; Koturbash, I. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules 2019, 24, 1694.
- Wiley. Cannabis' effects on brain neurochemistry. ScienceDaily, 7 August 2019. www.sciencedaily.com/releases/2019/08/190807092348.htm
- Columbia University Medical Center. Heavy cannabis use associated with reduced dopamine release in brain: Effect similar to other addictions. ScienceDaily, 14 April 2016. www.sciencedaily.com/releases/2016/04/160414214826.htm
- Honor Whiteman. Medical News Today.com Marijuana and mental illness low dopamine levels may play a role. Monday, November 21, 2016.
- GWPharmaceuticals. Press release: GW Pharmaceuticals reports positive Phase 3 pivotal trial results for EPIDIOLEX (cannabidiol) oral solution in patients with seizures associated with tuberous sclerosis complex. Carlsbad, USA, May 6, 2019 http://ir.gwpharm.com/news-releases/news-release-details/gw-pharmaceuticals-reports-positive-phase-3-pivotal-trial. Accessed 25 June 2019.
- Friedman D, French JA, Maccarrone M. Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders. Lancet Neurol. 2019;18(5):504-12.
- Nichol K, Stott C, Jones N, Bazelot M, Whalley BJ. The proposed multimodal mechanism of action of cannabidiol in epilepsy: Modulation of intracellular calcium and adenosine-mediated signaling. [abstract] American Epilepsy Society Annual Meeting, New Orleans, LA, November 30–December 4, 2018.
- Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, 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):845-52.
- De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479-94.
- Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, et al. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci. 2014;5(11):1131-41.
- Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects. CNS Drugs. 2018;32(11):1053-67.
- Ahn Y, Drummond-Main C, Kiroski I, Rho JM. Cannabidiol impairs mitochondrial function independent of CB1 and GPR55 receptors [abstract]. American Epilepsy Society Annual Meeting, New Orleans, LA, November 30-December 4, 2018. https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/500201. Accessed 10 Feb 2019.
- McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, et al. A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol. 2018;5(9):1077–88.
- Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085–96.