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,
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
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
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
—Lindsay Stafford Mader
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- Home. CanChew Biotechnologies website. Available at:
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- Project CBD homepage. Project CBD website. Available at: http://projectcbd.org/. Accessed July 2, 2012.
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- Pedersen T. Marijuana Compound May Beat Antipsychotics at Treating
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