FWD 2 Is CBD the Answer? Analyzing the Role of Cannabidiol in Medicinal Cannabis

HerbalEGram: Volume 9, Number 7, July 2012

Is CBD the Answer?
Analyzing the Role of Cannabidiol in Medicinal Cannabis


In the early summer of 2012, several news outlets reported that scientists in Israel had created a new strain of non-psychoactive medicinal cannabis by reducing levels of the plant’s main active ingredient tetrahydrocannabinol (THC) and increasing another important compound called cannabidiol (CBD).1,2 Israel’s Haaretz Daily Newspaper called the strain a “new breed,” and wrote “nothing quite like this has ever been invented.”2 United States-based news service Reuters picked up on the development, reporting, “Recreational smokers may not see the point, but according to its developers, high-less pot gives people suffering from chronic pain and disease a way to get the all the medical benefits of weed while keeping their senses.”3

Contrary to these news reports, however, high-CBD, low-THC cannabis (Cannabis spp., Cannabaceae) has been produced prior to the Israeli research.

“There is already a great deal of interest in both the scientific community and the ‘user’ community in CBD,” said Michelle Sexton, ND, a clinical cannabis researcher at Bastyr University who owns a cannabis testing business. “There are trends at least in [California] and [Washington] for growers to try to access CBD-rich plant material” (e-mail, July 5, 2012).

In fact, some California parents allegedly prepare tinctures from similar strains for their sick children who are approved to use medicinal cannabis,4 and there is even a Netherlands-based company that developed a CBD chewing gum.5 Additionally, a US nonprofit, Project CBD, is dedicated to encouraging clinical research and disseminating information on the compound.6 While some details are largely inaccurate, the recent Israeli cannabis coverage brings attention to a significant and growing area of medicinal cannabis research.


State of Research

THC is the most active and well known of the more than 100 cannabinoids in cannabis, and it is also responsible for the plant’s psychoactive effects, commonly known as the “high” experienced by people who smoke or ingest cannabis. Because CBD — first elucidated by scientists in 19637 — acts differently than THC within the human endocannabinoid system, it produces no psychoactive effects.8-10 While THC binds to a cannabinoid type one (CB1) receptor in the brain, CBD exerts more activity at the CB2 receptor.11,12 When both THC and CBD are present, CBD can interfere with THC’s binding to the CB1 receptor, possibly neutralizing any psychoactive effects. Additionally, CBD increases the production of an endocannabinoid chemical that occurs naturally in the human body, called anandamide, and also prevents anandamide from being broken down, resulting in an indirect increase in endocannabinoid tone with none of the effects of THC.13

According to a 2008 review of CBD research history, studies on the compound began slowly in the 1970s and waxed and waned until an “explosive increase” in the early 2000s.7 The current body of CBD research, which consists mainly of in vitro and in vivo studies as well as several small human trials and case studies, has shown that it exhibits anti-inflammatory, anti-oxidative, and neuroprotective effects, and also suggests that it might be useful in treating epilepsy, insomnia, anxiety, schizophrenia, Parkinson’s Disease, type 1 diabetes, and nausea in chemotherapy patients.7 In 2000, research into CBD’s effect on cancer cells increased, one of such studies showing it to be the most active of the 5 cannabinoids tested against cancer cell growth. Much of the recent research is examining CBD’s effect on psychiatric disorders and cancer cells, such as a 2010 study by scientists at the California Pacific Medical Center’s (CPMC) Research Institute that showed CBD killed breast cancer cells in mice.14

More human studies on CBD are crucial, and researchers are making progress in this area. The CPMC researchers, for example, are now working on the design of a large-scale clinical trial to test CBD in breast cancer patients (S. McAllister, e-mail, June 20, 2012). A 2012 German study on 39 schizophrenia patients published in Translational Psychiatry found that CBD was an effective treatment and produced far fewer side effects than the traditional pharmaceutical amisulpride.15 Additionally, according to a search on ClinicalTrials.gov, 19 human studies on “cannabidiol” were recently completed and 10 are currently recruiting or active (approximately half of the 30 studies are being conducted on Sativex®, GW Pharmaceuticals, London, England; a whole plant extract oromucosal spray containing predominantly THC and CBD that is in late-stage clinical trials in the United States for treatment of cancer pain).16

The Multidisciplinary Association for Psychedelic Studies (MAPS) hopes to study cannabis with THC and CBD as well as cannabis with varying levels of just THC in veterans with post-traumatic stress disorder (PTSD).17  The MAPS research protocol was first approved by the US Food and Drug Administration. However, the National Institute on Drug Abuse (NIDA) and Public Health Service (PHS) rejected the proposal and refused to sell marijuana to MAPS, preventing the study from taking place. Executive Director Rick Doblin, PhD, said that MAPS is now seeking to have the research supported by the University of Arizona Institutional Review Board, and will then re-try PHS and NIDA. Because MAPS intends to study the whole cannabis plant, and not isolated CBD or THC, it must receive permission from PHS and NIDA to conduct the study. The majority of studies conducted on CBD, including the aforementioned research, have used isolated and extracted CBD.

“There is a lot of suggestive evidence that a combination of THC and CBD will be effective with anxiety disorders, and in particular with PTSD,” said Dr. Doblin. “One of the main purposes of that protocol is to evaluate the role of CBD” (oral communication, June 26, 2012).  

According to Sarah Russo, former outreach coordinator of Project CBD who recently joined the staff of the Society for Cannabis Clinicians (SCC), SCC is currently conducting a physician-analyzed survey on how lab-verified cannabis containing CBD is affecting patients (e-mail, June 26, 2012).

“They hope to eventually have enough data that they can use to create a peer review journal article about the effects of CBD as medicine,” she said. 


Implications for Medicinal Cannabis

The results of CBD research thus far — and that the compound is non-psychoactive — will likely lead some to wonder if researchers and activists should focus more on CBD and CBD-rich cannabis than on THC and other cannabinoids. After all, if CBD is medicinal and doesn’t get its users high, why would the federal government have a problem with it?

Actually, the federal government has already made CBD illegal by placing it on the List of Controlled Substances as a Schedule I drug — a classification reserved for substances with the highest potential for abuse, least evidence of medical value, and concerns for safety, e.g., heroin.18 All of the sources interviewed for this HerbalEGram story said that they think CBD’s non-psychoactive properties will have no affect on federal regulations.

“In the eyes of the federal government,” said Russo, “any component in cannabis is regulated, whether or not it is psychoactive. CBD is, however, a ‘myth buster’ (according to Martin Lee, co-founder of Project CBD) because it refutes the idea that medical cannabis is an excuse for people to get high. Now people can use a lesser psychoactive type of cannabis (or not if they wish).”

Many sources also expressed that focusing on CBD or CBD cannabis is not a smart medical strategy.  The “high” produced by cannabis containing THC, for example, serves a medicinal purpose for patients with certain conditions.

“I always say that for patients I deal with [who have] cancer,” said Donald Abrams, MD, an integrative oncologist who studies clinical cannabis at the University of California - San Francisco. “I don’t think euphoria is an adverse experience. It depends on the condition being treated. Some of my patients don’t like being high, that’s not what they want. Some welcome it. I don’t think it should be an unwelcome side effect unless it is unwelcome to those who use it.”

 Dr. Doblin explained the effect that cannabis has in some PTSD patients. “[Marijuana] helps them sleep better, and they don’t have the nightmares,” he said. “The high is part of the therapeutic effect for some of the patients because it gets them more ‘present-focused’ and it elevates their mood."

An additional reason that discounts a sole focus on CBD is that THC and cannabis with THC are active, useful medicines.19 Synthetic THC in the form of Marinol® (Dronabinol) is an approved medicine for nausea associated with chemotherapy and AIDS-wasting syndrome (despite its shortcomings when compared to smoking whole cannabis). Additionally, the University of California – San Diego’s Center for Medicinal Cannabis Research studied cannabis for 10 years using cannabis from NIDA — which had very little CBD in it, about 0.2-0.4% (M. ElSohly, e-mail, July 2, 2012) — and found it to be effective for treating multiple sclerosis, spasticity, pain, and nausea in cancer patients undergoing chemotherapy.16

“There’s a lot of evidence to suggest that THC itself has substantial therapeutic benefits,” said Dr. Doblin. “The whole field of cannabinoid research should be enlarged because of the great potential that there is. Yes, we should bring in more people to study CBD, but I don’t think that means that research on THC should be de-emphasized.”

Dr. Sexton of Bastyr noted that most cannabis currently available in the United States has been bred to contain very high levels of THC, and that cannabis with lower THC levels — to which patients can develop a tolerance of psychoactive effects — as well as CBD and other compounds is essential.

“It is my hope that through education about the value of less THC and restoring the full spectrum of cannabinoids to the plant, there will be more value of [cannabis’s] ‘medicinal’ effects.”

Early research supports the suggestion that CBD and THC are more effective when used together.20 A 2010 study on THC and CBD in glioblastoma cells, for example, found that treatment with both compounds was much more successful than when just THC was employed. Additionally, Sativex is a combination of THC, CBD, and other cannabinoid and terpenoid components because, according to manufacturer GW Pharmaceuticals, CBD “is believed to enhance the therapeutic benefits of THC while modulating the unwanted psychotropic and other THC-related side effects.”21 Russo of SCC, however, pointed out that further research on humans is needed to confirm the relationship between CBD and THC.

Synergy between CBD and THC might not always be the case, however, as Sean McAllister, PhD, lead researcher of the CBD breast cancer study in mice, said, “There may be tumor-specific sensitivity, i.e., some may respond well to CBD but not to THC and visa versa.”

“There are increasingly more options for patients to choose what type of cannabis they want to use, which is extremely important,” said Russo. “I do not feel that putting CBD cannabis on a pedestal is a good idea. Cannabis is a plant, and it should not be illegal, no matter the [content of] CBD or THC or other compounds.” 


—Lindsay Stafford Mader


References

  1. Collier M. Cannabis without ‘high’ developed by Israeli scientists. The Christian Post. June 1, 2012. Available at: www.christianpost.com/news/cannabis-without-high-developed-by-israeli-scientists-75900/. Accessed June 26, 2012.

  2. Levin L. Israeli scientists take the high out of weed. Haaretz Daily Newspaper. June 4, 2012. Available at: www.haaretz.com/news/national/israeli-scientists-take-the-high-out-of-weed-1.434387. Accessed June 27, 2012.

  3. Cleary T. What a drag, Israeli team grows "highless" marijuana [video]. Reuters. June 27, 2012. Available at: www.reuters.com/video/2012/06/27/what-a-drag-israeli-team-grows-highless?videoId=236214479&videoChannel=6. Accessed June 27, 2012.

  4. Egan P. Medical marijuana brings relief to sick kids; treatment is controversial. Gannett News Service. May 28, 2012. Available at: http://www.livingstondaily.com/article/20120528/NEWS01/205280301/Medical-marijuana-brings-relief-sick-kids-treatment-controversial. Accessed June 26, 2012.

  5. Home. CanChew Biotechnologies website. Available at: http://canchewbiotech.com/. Accessed June 26, 2012.

  6. Project CBD homepage. Project CBD website. Available at: http://projectcbd.org/. Accessed July 2, 2012. 

  7. Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr. 2008;30(3):271-80.

  8. 11. Showalter VM, Compton DR, Martin BR, Abood ME. Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther. 1996;278:989–999.

  9. Alozie SO, Martin BR, Harris LS, Dewey WL. 3H-delta 9-Tetrahydrocannabinol, 3H-cannabinol and 3H-cannabidiol: penetration and regional distribution in rat brain. Pharmacol Biochem Behav. 1980;12(2):217–218.

  10. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci. 2003;23(4): 1398–1405.
  11. Russo E. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Brit J Pharmacology. 2011;163:1344–1364.

  12. Russo E, Guy G. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Medical Hypotheses. 2006;66:234–246.

  13. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, 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. Brit J Pharmacology. 2001;134:845-852.

  14. McAllister SD, Murase R, Christian RT, Lau D, et al. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res Treat. 2010; DOI 10.1007/s10549-010-1177-4.

  15. Pedersen T. Marijuana Compound May Beat Antipsychotics at Treating Schizophrenia. Psych Central News. June 7, 2012. Available at: http://psychcentral.com/news/2012/06/07/marijuana-compound-may-beat-antipsychotics-at-treating-schizophrenia/39803.html. Accessed July 2, 2012.

  16. Search: cannabidiol. June 28, 2012. ClinicalTrials.gov website. Available at: http://clinicaltrials.gov/ct2/results?term=cannabidiol&pg=1. Accessed June 28, 2012.

  17. Medical marijuana: marijuana for PTSD study. Multidisciplinary Association for Psychedelic Studies website. Available at: www.maps.org/research/mmj/. Accessed July 2, 2012.

  18. Lists of: Scheduling Actions, Controlled Substances, Regulated Chemicals. US Department of Justice, Drug Enforcement Administration, Office of Diversion Control. April 2012. Available at: www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf. Accessed July 2, 2012.

  19. Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical marijuana: clearing away the smoke. The Open Neurology Journal. 2012;6:18-25.

  20. Marcu JP, Christian RT, Lau D, Zielinski AJ, et al. Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther. 2010;9(1):180-189.

  21. Sativex: FAQs. GW Pharmaceuticals website. Available at: www.gwpharm.com/sativex-faqs.aspx. Accessed June 18, 2012.