In the May issue of HerbalEGram, the American Botanical Council reported on the National Cancer Institute’s new webpage on the medicinal uses of cannabis (Cannabis sativa, Cannabaceae) in cancer treatment—a development ABC described as “the first time a US government agency has acknowledged the herb’s therapeutic benefits.”^1,2* The NCI review summary can be found at www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional.

Many organizations, media outlets, and individuals around the country referred to the NCI cannabis page as a groundbreaking event. “It adds to the growing scientific consensus around the medical efficacy of cannabis and firmly establishes the plant as a [complementary and alternative medicine] treatment alternative,” said Kris Hermes, media specialist for Americans for Safe Access (ASA), an organization promoting safe and legal access to cannabis for medicine and research (e-mail, April 11-June 23, 2011). “And, it further contradicts the federal government’s position, and that of the Department of Health and Human Services (HHS)—which oversees [the National Institutes of Health] and NCI—in particular, that cannabis ‘has no currently accepted medical use in treatment in the United States.’”

“Overall, I’m impressed favorably with the breadth, scope, and details of the summary,” said Dennis McKenna, PhD, a senior lecturer and research associate at the University of Minnesota’s Center for Spirituality & Healing. Dr. McKenna is an ethnobotanist who has extensive research expertise on psychoactive medicinal plants. “Considering this is the NCI, and that the [US Food and Drug Administration]’s official position is that cannabis has no medical use, this is a remarkably honest and objective assessment.”

After the HEG article was published, ABC received an e-mail from Chris Kilham, an ethnobotanist and Fox News herbal medicine correspondent, noting that, though largely unknown, the US government recognized cannabis as medicine in 2003, when the US Department of Health and Human Services (HHS) filed for a patent on using cannabinoids as antioxidants and neuroprotectants (patent no. 6630507).³

“I believe,” wrote Kilham, “that the patent filing, which is very well referenced, was the first actual US government admission of the extraordinary health benefits of cannabis.”

NCI’s Changes to the Initial Review

About 2 weeks after the initial March 17th posting of the NCI cannabis page, the institute made changes to the review due to media and governmental attention.⁴ According to Jeffery White, MD, NCI’s director of the Office of Cancer Complementary and Alternative Medicine, these changes were implemented after NCI noticed that various media outlets, as well as the National Institute on Drug Abuse (NIDA), seemed to be “focusing on and misinterpreting” the following sentence: “In the practice of integrative oncology, the healthcare provider may recommend medicinal Cannabis not only for symptom management but also for its possible direct antitumor effect.”

“The sentence was being interpreted as NCI’s official support for the use of cannabis for the treatment of patients with cancer,” said Dr. White. “It was in the general information section and was only intended to be a factual statement about what is happening in medical practice, at least where marijuana use can be legally recommended according to state or local law. It was never intended to be a statement about the appropriateness of such recommendations (e-mail, April 29 and July 5, 2011).”

“The note from NIDA along with the other media statements were shown to me and I discussed them with Dr. Donald Abrams, who is the lead reviewer for the summary,” said Dr. White. “I recommended changing the sentence to the current wording because I thought it was likely to be the most accurate and supportable statement that could be made about why cannabis was being recommended by healthcare practitioners. We agreed on this wording and the changes were made.”

But new information released in May of 2011 shed more light on the circumstances surrounding NCI’s changes to the cannabis page. Documents obtained through a Freedom of Information Act request by cannabis activist Phil Mocek show that NCI felt pressure to change parts of the review in response to NIDA’s requests, and that Dr. Abrams vehemently disagreed with at least one of the deletions.

In an e-mail dated March 24, 2011, NIDA’s head judge and acting director of the Office of Science Policy and Communications, Susan Weiss, PhD, wrote to NCI: “We just learned about the Cannabis and Cannabinoids PDQ document on NCI’s website. While we agree that there is a substantial literature about the potential therapeutic effects of cannabinoids, we are concerned about the portrayal of the medicinal use of cannabis itself.”⁶

Dr. Weiss then listed the parts of the review that NIDA wished to edit, which included adding a statement that cannabis is not an FDA-approved therapeutic for any medical condition; a brief discussion on non-cancer adverse effects of cannabis, such as addiction, to be accompanied by hyperlinks to corresponding pages of NIDA’s website; and changing the sentence mentioning cannabis’s possible direct anti-tumor effect. Dr. Weiss wrote, “We would be happy to work with you to help make these changes or to review any future changes that might be proposed.”

One day later, Dr. Weiss wrote to NCI again, noting a tweet—a message posted through the social-networking site Twitter—by the executive director of the Drug Policy Alliance. “This is an organization aimed at changing drug policy and promoting the legalization of marijuana—in direct conflict with the administration’s stated policy,” she wrote. “We will be contacting our colleagues at ONDCP (Office of National Drug Control Policy) just to give them a heads up about it. Let us know if you make any changes to the document.” Later that morning, Weiss told others at NIDA in an e-mail, “I just sent the email below to the folks at NCI to make them aware of this (and hopefully get them to modify their website document quickly), but also we think that ONDCP needs to be informed.” (For a discussion on the NIDA’s alleged suppression of clinical cannabis research, please see “The State of Clinical Cannabis Research in the United States” article published in HerbalGram issue 85 at http://cms.herbalgram.org/herbalgram/issue85/article3485.html.)

Those at NCI seemed to feel the pressure from NIDA and were concerned about how the institute might react. “We may be asked to respond sooner rather than later depending on how hard NIDA presses,” wrote Lenora Johnson at NCI. “They have not risen it to the level of NIH.”

Meanwhile, NCI was also receiving e-mails from reporters and one from an FDA press officer. On March 28—4 days after NIDA contacted NCI—the summary was edited to remove mention of physicians who suggest cannabis for its possible anti-tumor effects,4,6 leaving the review’s coverage of anti-tumor effects only in the section on animal and laboratory studies. NCI also clarified that cannabis is not approved by the FDA for any medicinal use and that physicians appear to prescribe cannabis mostly for symptom management (in order to avoid the impression that it recommends the prescribing of cannabis by physicians). It did not, however, add any statements that cannabis was addictive, nor provide links to NIDA’s website.

“NIDA did not make any demands to the NCI or the Board,” said Dr. White. “We reviewed and considered their suggestions as we would anyone’s.”

“This behind-the-scenes debate illustrates the political nature of cannabis and the difficulty of government officials to see this as a public health issue,” said Hermes of ASA. “However, it’s time for the government to put politics aside and let the evidence speak for itself.”

In response to the deletion of some of the review’s anti-tumor information and references, Dr. Abrams sent an e-mail to Dr. White and PDQ CAM board manager Robin Baldwin, writing, “You know, the epidemiological data from Kaiser and Tashkin do possibly support an anti-tumor effect in humans. After reflecting for a few hours, I am not happy that NIDA has been able to impose their agenda on us. The text was vetted by the whole Board. I would ask that we [involve] the whole Editorial Board in the discussion before being bulldogged. I am considering resigning from the Board if we allow politics to trump science!”^5,6

The data Dr. Abrams mentioned in his e-mail were human studies that found smoked cannabis does not affect mortality rates, nor to lead to increased rates of lung cancer. The large 2006 case control study conducted by longtime cannabis researcher Donald Tashkin, MD, of the University of California, Los Angeles, also suggested that cannabis might reduce cancer risks.5 (Dr. Abrams did not wish to comment on the new details released in the FOIA response. As of press time, he was still a member of the PDQ board.)

Additionally, NCI added a statement noting that PDQ, which authored the review, “is editorially independent of the National NCI.”⁴ NCI wrote, “The summary on Cannabis and cannabinoids does not represent a policy statement of NCI or NIH. The summary statement represents an independent review of the literature; that review is not influenced by NCI or any other federal agency.”

PDQ, or Physician Data Query, serves as NCI’s database of information on cancer topics and research.⁷ Several PDQ editorial boards, such as the Complementary and Alternative Medicine (CAM) editorial board of PDQ—which authored the NCI cannabis page—regularly review new cancer-related research and information in consideration for adding to NCI’s website.

“The NCI only establishes and financially and administratively supports the PDQ Editorial Boards,” said Dr. White. “Therefore the posting of the PDQ Summary on Cannabis and Cannabinoids does not signal any official NCI opinion on this topic” (e-mail, April 29, 2011).

However, possibly compromising NCI’s statement on the unquestionable, clear separation between NCI and PDQ is the fact that Dr. White also serves as the editor-in-chief of the PDQ CAM board.

“Saying that NCI didn’t say this, [that] PDQ said it, is a bit disingenuous,” said Dr. McKenna. “[NCI] contracted the study and paid for it. It went through several levels of peer review by qualified experts; they put it on their website. That’s a sign that they believe the information is accurate, at least enough to put [it] out to clinicians and others.”

Possible Shortcomings of the Review

Though the review has maintained its laboratory and animal data on cannabis’s anti-tumor effects,8 the PDQ review omits what some might consider evidence that is just as—if not more—compelling. In addition to the Tashkin research and Kaiser Permanente Medical Care Program study mentioned by Dr. Abrams, a 2006 study published in The Journal of Pharmacology and Experimental Therapeutics, for example, showed that cannabidiol (CBD) was the “most potent inhibitor of cancer cell growth” in mice injected with human breast carcinoma cells” (compared with cannabigerol, cannabichromene, cannabidiol acid and THC acid).⁹

Additionally, in a 2006 study, Spanish researchers conducted a pilot phase I clinical trial on 9 patients with recurrent glioblastoma multiforme. After being administered THC, two patients experienced “inhibited tumor cell proliferation” and “decreased tumor cell Ki67 immunostaining.”¹⁰ Furthermore, a January 2011 study in Molecular Cancer Therapeutics—published 3 months before the NCI cannabis review was posted—found that THC, CBD, and temozolomide exerted “strong antitumoral action” in cultures of human glioma cells.¹¹ Also of interest yet excluded by the NCI review, was an in vitro study conducted in 2010 by researchers in California reporting that CBD “inhibits human breast cancer cell proliferation and invasion,” and “significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis.”¹²

[Editor’s note: Since ABC published its original article in HEG and very near HG 91 press time, the PDQ board has added to its cannabis summary the aforementioned 2011 glioma study and 2006 study showing inhibited tumor cell proliferation in recurrent glioblastoma patients. It also made additional changes to the summary.]

Impact on Cannabis’s Schedule I Status

NCI’s new cannabis page has spurred much discussion over its impact on the movement to have cannabis rescheduled. Cannabis is currently listed by the US Drug Enforcement Agency (DEA) as a Schedule I drug, a classification that prohibits cannabis use for anything other than research. Cannabis shares this status with drugs like heroin and LSD. According to the Controlled Substances Act, Schedule I drugs meet 3 criteria: (1): having a high potential for abuse; (2) having no currently accepted medical use in treatment in the United States; and (3) having a lack of accepted safety for use of the drug or other substance under medical supervision.¹³ Some say that NCI’s addition of information on cannabis’s medicinal uses in cancer treatment to its website further challenges the validity of this Schedule I status, particularly with regard to the second criterion.¹⁴

The rescheduling movement aims to have cannabis downgraded to a Schedule III or lower classification. Schedule III drugs are considered to have a less significant potential for abuse than Schedule I and II drugs, as well as a currently accepted medical use in treatment in the United States.¹³ They are available through prescriptions, are permitted to have 5 refills in 6 months, and may be ordered orally.¹⁵ Dronabinol (brand name Marinol^®), a synthetic drug containing tetrahydrocannabinols (THC), is currently a Schedule III drug. A federal petition to reschedule cannabis, which was filed in 2002 by the multi-organizational Coalition for Rescheduling Cannabis, went unanswered by the US government for almost 10 years.¹⁶ Two months after, the Coalition sued the federal government for the lengthy and “unreasonable” delay, the DEA announced that it was denying the petition in July of 2011. The Coalition has filed an appeal challenging this decision.

Despite stating that the US government’s opposition to cannabis as a medicine is “not a consistent position,” and “does not make scientific sense,” Dr. McKenna said he thinks the NCI review will probably, and “unfortunately,” have very little impact on the scheduling of cannabis. “These decisions are made by politicians, who as a rule are not scientists or clinicians and are quite happy to ignore scientific evidence when it’s inconvenient,” he said, noting mounting scientific concerns about climate change as an example. “Only when this information becomes widespread enough in the public domain, and is understood by sufficient numbers of people, who then demand changes in the scheduling, will this information make a difference. What will or may also make a difference is when a politician, or a close relative of one, receives significant benefits from cannabis as an adjunct treatment in cancer therapy. Then, and only then, will you see a change.”

According to Hermes of ASA, the medical cannabis access organization, the NCI cannabis review does not necessarily indicate a broader shift by larger US governmental entities, such as HHS. Instead, he said, it might signal a general inability of the federal government to maintain its long-held position against public opinion and science.

“Certain agencies are reviewing their policies and changing them slightly enough to give the impression of meaningful change,” he said, noting the US Department of Veterans Affairs’ July 2010 decision to allow patients to use cannabis as prescribed by outside physicians without risking denial of VA services and benefits.¹⁷ “These policy changes are by no means comprehensive or adequate to solving this public health issue at the federal level, but it indicates that pressure on the government is working.”

*Both the Institute of Medicine (IOM) and a panel of experts convened by the NIH have previously recognized that cannabis can be medicinally beneficial to some patients.¹⁸ But the IOM is “an independent, nonprofit organization that works outside of government to provide unbiased and authoritative advice to decision makers and the public.”¹⁹ Additionally, NIH expert panels are independent bodies and usually consist of both governmental and non-governmental scientists who are called upon to make recommendations to policymakers. Neither of these entities are official bodies of the federal government.

—Lindsay Stafford

References

1. Cannabis and Cannabinoids (PDQ): Overview. National Cancer Institute website. Available at: www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page1. Accessed April 17, 2011
2. Stafford L. US government institution acknowledges medicinal uses of cannabis. HerbalEGram, March 2011. Available at: http://cms.herbalgram.org/heg/volume8/05May/NCI_CannabisPage.html?t=1304368249.
3. United States Patent 6,630,507 Hampson, et al. October 7, 2003. Cannabinoids as antioxidants and neuroprotectants. USPTO Patent Full-Text and Image Database. Available at: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=6630507.PN.&OS=PN/6630507&RS=PN/6630507. Accessed June 27, 2011.
4. Cannabis and cannabinoids (PDQ®): Changes to this summary (3/30/2011). National Cancer Institute website. Available at: www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page8. Accessed April 26, 2011.
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6. FOI request: National Cancer Institute’s cannabis and cannabinoids PDQ. Requested by pmocek on March 30, 2011, for the Department of Health and Human Services of United States of America and fulfilled on May 4, 2011. MuckRock.com. Available at: www.muckrock.com/foi/view/united-states-of-america/national-cancer-institutes-cannabis-and-cannabinoids-pdq/502/.
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15. Commonly Abused Drugs. National Institute of Drug Abuse website. Available at: www.drugabuse.gov/DrugPages/DrugsofAbuse.html. Accessed April 27, 2010.
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17. Yen H. Medicinal marijuana in VA clinics OK’d in states where it’s legal. Huffington Post: Politics. July 15, 2010. Available at: www.huffingtonpost.com/2010/07/27/medical-marijuana-in-va-c_n_660449.html. Accessed April 17, 2011.
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19. About the IOM. Institute of Medicine website. Available at: www.iom.edu/About-IOM.aspx. Accessed April 10, 2011.