[Editor's Note: Cannabidiol (CBD) is the main non-psychoactive chemical component of marijuana. The US Department of Health and Human Services (HHS) was awarded United States Patent #6,630,507 (185 KB) for CBD and other cannabinoids on Oct. 7, 2003. However, the US Drug Enforcement Agency (DEA) classifies CBD as a Schedule I drug, meaning it is considered to have "no accepted medical use,” "a high potential for abuse,” and "a lack of accepted safety for use of the drug or other substance under medical supervision." Of the 926 medical studies involving CBD (2.08 MB) (as found on PubMed, Sep. 22, 2011), most of them reported positive pharmacological effects although most were also animal or cell studies vs. human studies or clinical trials.
Given the large volume of studies on CBD, the HHS patent of this Schedule I drug, and the growing attention CBD receives, we have compiled the best pro and con arguments that we could find on the subject to help our readers better understand this controversy.]
Antonio W. Zuardi, PhD, Vice Director of the Department of Neurology and Medical Psychology at the University of São Paulo, wrote in his Apr. 17, 2008 paper "Cannabidiol: From an Inactive Cannabinoid to a Drug with Wide Spectrum of Action," in Revista Brasileira de Psiquiatria:
"After the elucidation of the chemical structure of cannabidiol in 1963, the initial studies showed that cannabidiol was unable to mimic the effects of Cannabis. In the 1970's the number of publications on cannabidiol reached a first peak, having the research focused mainly on the interaction with delta9-THC and its antiepileptic and sedative effects. The following two decades showed lower degree of interest, and the potential therapeutic properties of cannabidiol investigated were mainly the anxiolytic, antipsychotic and on motor diseases effects. The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer. Conclusion: In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials.”
The US Department of Health and Human Services (HHS) wrote in its Oct. 7, 2003 United States Patent #6,630,507 "Cannabinoids as Antioxidants and Neuroprotectants" on the website patft.uspto.gov:
"Cannabinoids have been found to have antioxidant properties... This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidiol, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses..."
Raphael Mechoulam, PhD, Lionel Jacobson Professor of Medicinal Chemistry at the Hebrew University of Jerusalem, et al., wrote in their 2007 paper "Cannabidiol - Recent Advances" in Chemistry and Biodiversity:
"CBD... has been shown to produce a plethora of pharmacological effects, many of them associated with both central and peripheral actions... The plethora of positive pharmacological effects observed with Cannabidiol make this compound a highly attractive therapeutic entity in inflammation, diabetes, cancer and affective or neurodegenerative diseases."
Teresa Iuvone, PhD, Professor of Experimental Pharmacology at the University of Naples Federico II, et al., wrote in their Feb. 13, 2009 paper "Cannabidiol: a Promising Drug for Neurodegenerative Disorders," in CNS Neuroscience and Therapeutics:
"The great therapeutic value of CBD, either given alone or in association with THC, derives from the consideration that it represents a rare, if not unique, compound that is capable of affording neuroprotection by the combination of different types of properties (e.g., anti-glutamatergic effects, anti-inflammatory action, and anti-oxidant effects) that almost cover all spectra of neurotoxic mechanisms that operate in neurodegenerative disorders (excitotoxicity, inflammatory events, oxidative injury, etc.).
The reported data here, taken together with the evidence of the CBD's almost absolute absence of side effects, including psychotropicity, suggest its great efficacy and open new horizons for the treatment of the main neurodegenerative disorders!"
The Beckley Foundation, a charitable trust that promotes the scientific investigation of consciousness, wrote in its Oct. 6, 2010 page "Cannabidiol" on beckleyfoundation.org:
"Cannabidiol (CBD), a constituent of herbal cannabis, has attracted much interest recently as a promising medicine. After being discovered in the early 1970s it was quickly established that CBD has anti-convulsant and anxiolytic properties in animal models and in humans... Work in the 1980s and early 1990s suggested CBD had anti-psychotic properties and could be an effective treatment for schizophrenia...
In the last decade or so many other properties of CBD have been characterised... CBD has potent anti-inflammatory properties and is a neuroprotectant... CBD appears to protect, not just neurons, but heart muscle from injury. Several groups in the US and UK are pursuing this line which has massive implications for clinical practice. Perhaps even more dramatic is recent work from Mechoulam's lab which suggests that CBD can restore normal pancreatic functioning in models of type 1 diabetes. The list of putative indications for CBD include…
temporal lobe epilepsy
Type 1 diabetes
Acute myocardial infarction
CBD exhibits an impressive plethora of therapeutic uses, including anticonvulsive, sedative, hypnotic, antipsychotic, anti-inflammatory and neuroprotective properties. CBD is well tolerated in humans, with a profile of very low toxicity, and is devoid of psychoactive and cognitive effects."
Paul Armentano, Deputy Director of the National Organization for the Reform of Marijuana Laws (NORML), wrote in his Oct. 9, 2008 blog post "Is There Anything CBD Can't Do? Then Why Is It Illegal?" on the website blog.norml.org:
"While the prohibition of cannabis is absurd, the ban on the plant's non-psychoactive components is even more mind-boggling — particularly when it's apparent that these compounds possess amazing therapeutic properties. Case in point: cannabidiol (CBD)...
Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer...
[T]he past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.
What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD...? "
Ruth Gallily, PhD, Berthan and Max Densen Professor Emerita of Immunology at the Hebrew University of Jersualem, et al., wrote in their July 20, 2010 approved patent application #7759526 "Pharmaceutical Compositions Comprising Cannabidiol Derivatives" available on the website patentgenius.com:
"The present invention relates to cannabidiol... and to pharmaceutical compositions comprising cannabidiol... being anti-inflammatory agents having analgesic, antianxiety, anticonvulsive, neuroprotective, antipsychotic andanticancer activity...
CBD... has been shown in in vitro assays, in animal tests, as well as in some human, preliminary trials, to produce numerous pharmacological effects... which are of potential therapeutic value... [R]ecent reports describe the in vitro effects of CBD on immune cells... These in vitro studies lend support to earlier reports on analgesic and anti-inflammatory effects in animals...
CBD has been found to produce several, potentially therapeutic, effects in animal models, as well as in patients with neurological diseases... in anxiety... and in psychosis... CBD is a neuroprotective antioxidant."
The US Department of Health and Human Services' (HHS) Office of Public Affairs at the Food and Drug Administration (FDA) wrote in a Sep. 30, 2011 email to ProCon.org:
"It is important to know that the statements in the patent document [United States Patent #6,630,507 Oct 7, 2003] about the purported medical benefits [of cannabidiol] are based on in vitro data (antioxidant properties of this class of molecules, neuroreceptor binding studies, neuronal cell cultures, etc.), and in vivo rat studies. In order to make a determination that these compounds have a role in medical treatments, clinical data would be needed.
'Does this patent indicate the US government's position that cannabidiol has medical value?' 'no,' (since that would be done through the NDA [New Drug Application] process and not the patent application process)...
DEA is responsible for administration of the Controlled Substances Act (CSA). DEA has determined that cannabidiol is a Schedule I substance because it is derived from marijuana... which is also listed in Schedule I. Marijuana is defined under the CSA to mean all parts of the plant, as well as every compound and derivative and preparation, etc. of the plant.
Thus far, an [NDA] for cannabidiol has not been submitted to the FDA that shows that cannabidiol can be used therapeutically. Thus, cannabidiol has no accepted medical use in medical treatment in the United States. Having 'accepted medical use in the United States' of a drug is a necessary finding for drugs that are not in Schedule I, but listed in a less restrictive, Schedules II through V. Thus, currently Schedule I is the only possible CSA schedule where cannabidiol could be listed.
This is not to say that cannabidiol cannot be studied for development or to support rescheduling. Delta-9-tetrahydrocannabinol (THC, dronabinol) was developed as an antiemetic and treatment for AIDS wasting and approved for marketing under the trade name Marinol. Marinol is listed in Schedule III. All research on cannabidiol would need to be conducted under a Schedule I license issued by the DEA.
An investigator wishing to remove cannabidiol from Schedule I would have to demonstrate that cannabidiol has NO abuse potential in order for it to be decontrolled. This would probably necessitate conducting studies to demonstrate that its pharmacology differs from other substances that have high abuse potential and that cannabidiol is not being abused by individuals...
Consideration of rescheduling or decontrol could be initiated by petitioning the DEA and providing all available and relevant data in the petition."
[Editor's Note: ProCon.org also emailed two additional questions below to HHS on Oct. 6, 2011. As of May 29, 2012, we have not yet received a response.
"1. Has HHS allowed other government agencies or private parties to use its patent?
2. Has HHS filed other patents regarding substances between drug code #7350 and drug code #7380? If so, could you please provide a list or direct us to where we could obtain such a list?"]
The Drug Enforcement Administration's (DEA) Office of Congressional and Public Affairs wrote in a Sep. 27, 2011 email to procon.org:
"Cannabidiol is currently controlled in schedule I under the drug code for marijuana, 7360. The drug code 7372 for cannabidiol is used by DEA only for internal record-keeping purposes. DEA is currently working on a Final Rule to establish the drug code for marihuana extract as 7350.
In July 2011, DEA published a Notice of Proposed Rulemaking (NPRM) in the Federal Register. The NPRM proposes the establishment of a new drug code for marijuana extract independent of the drug code for marijuana and tetrahydrocannabinols. Drug codes are linked to DEA registrations and provide specificity as to the substance/drug/or chemical each registrant canpossess under their registration. The codes are also used for internal tracking purposes.
The Single Convention on Narcotic Drugs, 1961, requires statistical reporting to the United Nations on the use and production of marijuana and marijuana extract for the medical and scientific needs of each party of the treaty. The statistical reports for marijuana and marijuana extract have to be reported separately for the U.S. to be in compliance with this treaty...
Cannabidiol has always been a schedule I controlled substance listed under marijuana...
The Department of Health and Human Services (DHHS) is the U.S. competent authority for determining whether a substance is safe and effective for medical use and for approving a drug product for marketing in the United States. DEA would therefore defer to DHHS for any related questions...
The Federal Register notice published in FR Vol 57 10499-10508, 1992, details the issues and criteria for determining accepted medical use...
DEA performed an outreach to the scientific community to obtain data on the current state of research and abuse potential of cannabidiol. DEA's scientific review involving cannabidiol depends upon reliable and peer-reviewed scientific studies which are still being gathered as they become available."
[Editor's Note: ProCon.org also emailed five additional questions below to the DEA on Oct. 5, 2011 and received confirmation on Oct. 6, 2011 that they were forwarded to the appropriate DEA Section Chief for comment. As of May 29, 2012, we have not yet received a response.
"1. Since drug code 7372 is used by DEA only for internal record-keeping purposes, could you please provide all the internal drug codes between 7350 and 7380 along with which substance they correspond to? Since we had seen the drug code 7372 on DEA Form 225 on the DEA website we did not realize that internal codes existed.
2. When do you expect that DEA will complete its work on a Final Rule establishing the drug code for marijuana extract as 7350? A specific deadline would be ideal, but a ballpark estimate would also be useful.
3. Which substances would be classified under the new drug code 7350?
4. Will cannabidiol itself be classified under 7350 since it does not contain 'cannabidinols AND cannabidiols' as specified in the proposed drug code?
5. How will the new 7350 classification affect the DHHS patent [United States Patent #6,630,507 (185 KB) Oct 7, 2003] on cannabinoids and cannabidiol if at all?"]