HerbalEGram: Volume 11, Issue 4, April 2014

In early March, CNN released Weed 2: Cannabis Madness, the second documentary program from its Chief Medical Correspondent Sanjay Gupta, MD, devoted exclusively to the growing interest in and legitimization of medicinal cannabis (Cannabis sativa) in the United States.¹ Dr. Gupta’s initial installment, a documentary titled Weed, was released on CNN in August of 2013. ² The first program signified the highly respected neurosurgeon’s transformation from an opponent to an advocate of medicinal cannabis. The one-hour special was considered a potentially influential accomplishment even as it was met with some criticism from experts in the field of medicinal cannabis research.

Former HerbalGram Associate Editor Lindsay Stafford Mader, who previously covered the cannabis “beat” for the American Botanical Council’s publications, authored a critique last fall in which she evaluated the information presented (or not presented) in Weed.³ The program, according to Mader, had a variety of deficiencies:

1.                   It did not adequately address cannabis’ Schedule I controlled substance classification;

2.                   It oversimplified cannabis chemistry and the effect of cannabis on children’s brains;

3.                   It offered insufficient information on and from cannabis human clinical trials that have been conducted;

4.                   It seemed to misrepresent Colorado’s Stanley Brothers as the first to produce a high-cannabidiol (CBD) variety of cannabis;

5.                   It lacked pushback regarding “stonewalled therapeutic research”;

6.                   And, it possibly alienated viewers with its focus on rare conditions when individuals suffering from a number of more familiar ailments also stand to benefit from medicinal cannabis treatment.³

With Weed 2: Cannabis Madness, Dr. Gupta has not retreated from his stance but “doubled down,” investigating further and filling in some of the gaps left in his first installment. While some critical information in Weed 2 remained underdeveloped or unaddressed altogether, these reports are reflective of the substantial shift in the majority of Americans’ views regarding the legal status of cannabis.⁴

Rare Conditions in the Spotlight

Though Weed 2 features interviews with individuals who have found relief from chronic pain and multiple sclerosis symptoms through medicinal cannabis, the documentary — like its predecessor — centers on a young girl suffering from a rare, severe form of epilepsy that could prove fatal. In Weed, that child was Charlotte Figi, whose Dravet Syndrome caused hundreds of seizures per week. Once virtually catatonic, Charlotte’s life was turned around by a high-CBD, low-tetrahydrocannabinol (THC, the psychoactive compound that causes a “high” in users) medicinal cannabis strain that now bears her name: Charlotte’s Web.²

Similarly, Weed 2 focuses on two-year-old Vivian Wilson and her family, who were residents of New Jersey when Dr. Gupta’s team began documenting their story. Vivian was experiencing up to 75 seizures daily. Her family’s plight for access to medicinal cannabis for her received national attention when Vivian’s father, Brian Wilson, confronted New Jersey Governor Chris Christie about the state medical cannabis program’s constraints regarding minors at a diner during a campaign-related publicity appearance. (Once considered to be the 2016 Republican presidential candidate front-runner, Governor Christie’s already-suffering image was not helped by the footage of his terse exchange with a pleading Brian Wilson that is incorporated into Weed 2: “I know you think it’s simple. It’s simple for you; it’s not simple for me,” interrupted Governor Christie.)¹

Many viewers may find the documentaries’ focus on these very young children to be too exclusive or emotionally manipulative — a valid argument. On the other hand, perhaps Dr. Gupta’s intent is simply to make the most powerful case he believes possible by exposing the experiences of subjects whose existences could be most visibly improved — appropriate to the medium of television — through therapeutic medicinal cannabis treatment, subjects who cannot speak for themselves and whose suffering cannot be ascribed to unhealthful life choices.

“I have now a better appreciation of why he’s choosing to focus on children with an unusual seizure disorder in view of the fact that he himself is a neurosurgeon, so a neurologic condition is probably something that’s compatible with his area of expertise,” said Donald Abrams, MD, an integrative oncologist who studies clinical cannabis at the University of California - San Francisco (personal communication, March 27, 2014). “Also,” Dr. Abrams continued, “I think it’s very compelling to show the immediate and dramatic benefits that these children obtain in using the high-CBD cannabis.”

“Medical Marijuana Refugees”

In telling the Wilsons’ story, Dr. Gupta highlights the tragic phenomenon of so-called “medical marijuana refugees” — families who have left their home states, jobs, friends, and extended families behind in order to obtain medicinal cannabis treatment for their children in more permissive states, Colorado in particular.¹

Because cannabis is still illegal on a federal level, most people cannot bring this medicine across state lines, if it is legal for children in their state at all. In order to see if Vivian responds to medicinal cannabis — specifically to an oil made from Charlotte’s Web — Brian takes his two-year-old daughter to Colorado to establish residency, leaving Vivian’s mother and sister (Meghan and Adele Wilson, respectively) back in New Jersey.¹

In December of 2013, the New York Times reported on a community of approximately 100 families of myriad political and religious persuasions from around the country who relocated to the state of Colorado in a desperate attempt to deliver their children from unrelenting seizures.⁵ In Weed 2, Dr. Gupta makes a visit to a gathering of such medical marijuana refugees in Colorado — speaking to parents from Ohio, Alabama, and Florida — and emerges heartbroken for these “trapped” families, unable to transport their children’s medicines home; they could be charged with drug trafficking and risk losing custody of their children.⁵

“This is the problem I’m talking about between the federal and the state level,” said neurologist and Denver Health Comprehensive Epilepsy Program Chief Edward Maa, MD, interviewed in Weed 2. He continued: “This conflict is really driving families apart.” “That’s just crazy,” responded Dr. Gupta.¹

The Problem of Schedule I Classification

As in Weed, Weed 2 fails to place cannabis’ Schedule I designation by the US Drug Enforcement Agency (DEA) into context by providing examples of other drugs in the category, such as heroin and LSD.^1,2 Dr. Gupta better elucidated in a CNN.com editorial published in anticipation of the sequel:⁶

“Marijuana is classified as a Schedule I substance, defined as ‘the most dangerous’ drugs ‘with no currently accepted medical use,’” wrote Dr. Gupta. “Neither of those statements has ever been factual. Even many of the most ardent critics of medical marijuana don't agree with the Schedule I classification, knowing how it's impeded the ability to conduct needed research on the plant.”

“[C]ocaine and methamphetamine are actually more available than marijuana to patients, physicians and medical researchers,” he continued. “They are Schedule II drugs, with recognized medical uses.”

To his credit, in Weed 2, Dr. Gupta does call attention to the seeming hypocrisy of cannabis’ scheduling by pointing out that since October of 2003, the federal government has held a patent on use of cannabinoids for two medicinal purposes.¹

Patent No. 6630507 is titled “Cannabinoids as Antioxidants and Neuroprotectants.”⁷ The patent’s “assignee” is the United States “as represented by the Department of Health and Human Services.” According to the patent abstract, the antioxidant properties of cannabinoids make them “useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases,” and their function as neuroprotectants may serve to “[limit] 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.”⁷

Regulation and Research

As documented in Weed 2, Vivian Wilson’s seizures dropped to only 10 per day following regular administration of Charlotte’s Web oil (as a result, the whole family ultimately relocates to Colorado).¹ Viewers also witness the contrast between Vivian’s seemingly decreased level of consciousness, plus poor mobility and lack of balance after receiving a dose of her pharmaceutical anti-seizure medication versus her unchanged state after being administered high-CBD cannabis oil.

Coupled with an interview with Frank Bianco, who suffers from chronic pain and turned to medicinal cannabis after his prescribed pain medication made him feel sick, Weed 2 suggests, at the very least, that its viewers should consider the intensity of the side effects of pharmaceutical drugs used to treat many of the same conditions and/or symptoms that cannabis therapy may benefit or improve with fewer unwanted or dangerous side effects. Again, Dr. Gupta’s CNN editorial takes this idea further. “[O]n average, a person dies every 19 minutes in this country from a legal prescription drug overdose,” he wrote, “while it is virtually unheard-of to die from a marijuana overdose.”⁶

“In general, cannabis is very non-toxic. Unlike opiates, there is no dose of cannabis that arrests breathing, and there is a reason for this,” said Ethan Russo, MD, president of the International Cannabinoid Research Society and a senior medical advisor to GW Pharmaceuticals (email, March 27, 2014). “Most side effects of cannabis usage are attributable to THC, the primary psychoactive ingredient, which can certainly cause anxiety, panic and even temporary toxic psychosis when too much is taken, or an individual is naïve to its effects, or is simply sensitive to them.”

“However, THC works in these instances because it binds to the CB1 cannabinoid receptor in the brain,” explained Dr. Russo. “This receptor is not present in the breathing regulatory centers in the medulla (lower brainstem), and thus THC cannot produce apnea (breathing cessation). Similarly, cannabinoids have little or no end-organ toxicity; that is, they do not damage the liver, kidneys or bone marrow.”

Weed 2’s medicinal cannabis patient testimonies and the fact of cannabis’ relative safety may cause one to long for some investigation by the filmmakers into the parties — if any — responsible for perpetuating the US federal government’s rejection of the medicinal value of cannabis, which makes research approval especially difficult to obtain. However, such an investigation may veer too far from Dr. Gupta’s scientific stomping ground. (He does mention in his editorial that a number of legislators — whom he does not name — contacted him following the release of Weed to voice their support or to learn more.⁶)

Weed 2 is strongly in favor of increased medicinal cannabis research, but it glosses over the process through which proposed medicinal cannabis studies must obtain approval in the United States, a process which certainly has the potential to seem convoluted, but in fact could be explained adequately with a visual aid — a chart would do the trick. Instead, the logos and buildings of various federal agencies involved in the process are shown in Weed 2, with no guiding information regarding the necessary approval order or submission guidelines.

Since 1968, the National Center for Natural Products Research (NCNPR) at the University of Mississippi has been the sole supplier of cannabis for scientific research in the United States through its contract with the National Institute on Drug Abuse (NIDA).⁸ Human clinical trials for investigational new drugs (IND) that involve controlled substances must be cleared by both the DEA and the US Food and Drug Administration (FDA). Unlike with other controlled substances, trials using cannabis must receive approval from one additional government agency, the Public Health Service (PHS).⁸ In order to attain FDA’s permission, NIDA must first confirm that it has adequate cannabis for the research.⁸ Proposals can be rejected by PHS even if both the DEA and FDA have approved.⁸ The current process is lengthy and limiting.

Geoffrey Guy, MD, chairman of the United Kingdom’s GW Pharmaceuticals (maker of the patented, cannabis-derived oral spray Sativex^®), described in Weed 2 the US government’s medicinal cannabis research approval process as having a “greater level of rigor at all levels of regulatory inquiry” than that of the UK — where cannabis is also illegal. Sativex has been approved and is on the market in 25 countries, but is still being investigated in the United States. Dr. Guy sees “generations” of cannabis-derived drugs in GW’s future.

“The reasons for FDA authority in drug development in proving drug safety and efficacy before approval for general use would have been very instructive,” said Dr. Russo. “Much more detail on how Sativex has undergone and surpassed such hurdles might have been very helpful in emphasizing how doctors may be quite willing to prescribe a product for their patients that has gone through the regulatory process,” he added, “whereas they would never consider recommending a black market preparation of unknown provenance, quality or consistency over time.”

Contamination

“The major issue that physicians have is in the consistency of the product. How do you know what the person is getting? And the answer is: We don’t,” Dr. Maa told Dr. Gupta in Weed 2.

Without federal regulations to adhere to, uniformity and contamination are serious concerns. According to a 2013 study featured the Journal of Toxicology, “there are no approved pesticides or application limits established for use on cannabis crops by the US [Environmental Protection Agency]; therefore, all pesticide use on this crop is currently illegal.”⁹ However, the authors write that pesticide use has been determined to be quite common in cannabis cultivation.⁹ The results of their study — conducted using specially configured pipes — show that those pesticide residues transfer to both the cannabis smoke and the cannabis smoker.⁹

“Additionally, unregulated cannabis supplies may harbor molds, or bacteria such as that causing meningococcal meningitis, and these have occasionally caused serious disease in people smoking them,” said Dr. Russo. “Another trend in the cannabis market,” he said, “is the totally unregulated use of cannabis concentrates such as cannabis oils, hemp oil, ‘wax’ or ‘dabs.’ These are frequently manufactured by inexperienced and unqualified kitchen chemists employing potentially toxic solvents such as butane, naptha or isopropyl alcohol.”

Conclusion

“My concerns,” said Dr. Abrams, “continue to be that high-CBD cannabis preparations are available from other places beyond the [Stanley Brothers] in Colorado who seem to be attracting a lot of attention with their product. We have CBD products in dispensaries in California that benefit many patients with conditions above and beyond these unusual seizure disorders.”

“[T]here is a bit of a downside to focusing only on CBD, the non-psychoactive medicinal component of cannabis in that most of the work has actually been done on THC,” noted Dr. Abrams, “and this is providing an opportunity for prohibitionists to demand that the only cannabis products that be made available should be CBD without THC, which I think is unfortunate.”

While it may have been taboo to bolster the therapeutic benefits of THC in a documentary that focused primarily on medicinal cannabis treatment for a two-year-old girl, in fact, CBD and THC, as well as other compounds in the plant, are more effective together (even when some are present only in small amounts) according to the isolator of THC, Raphael Mechoulam, PhD, due to what he has deemed the “entourage effect.”³ Whole-plant extracts can be designed to include a range of the various cannabis compounds necessary to benefit a variety of health conditions.

“It is very difficult to approach the subject of cannabis, especially its medicinal usage, in just one hour,” said Dr. Russo. “It is a very complex subject in every respect, and requires consideration of botany, agriculture, biochemistry, genetics, politics and law, among others. Certainly, this effort complements the first program, but even taken ensemble, it would be a mistake to declare it definitive.”

—Ash Lindstrom

References

1. Weed 2: Cannabis Madness. CNN. Originally released March 11, 2014.
   
   
2. Weed: A Dr. Sanjay Gupta Special. CNN. Originally released August 11, 2013.
   
   
3. Stafford Mader L. Dr. Sanjay Gupta’s WEED documentary: a critique. HerbalGram. 2013;100:25-29. Available here. Accessed March 20, 2014.
   
   
4. Majority Now Supports Legalizing Marijuana. Pew Research Center. April 4, 2013. Available here. Accessed August 28, 2013
   
   
5. Healy J. Familes see Colorado as new frontier on medical marijuana. New York Times. Available here. Accessed March 21, 2014.
   
   
6. Gupta S. Gupta: I am ‘doubling down’ on marijuana. Available here. Accessed March 19, 2014.
   
   
7. Patent No. 6630507. Available here. Accessed March 24, 2014.
   
   
8. Stafford Mader L. The state of clinical cannabis research in the United States. HerbalGram. 2010;85:64-68. Available here. Accessed March 20, 2014.
   
   
9. Sullivan N, Elzinga S, JC Raber. Determination of pesticide residues in cannabis smoke. J Toxicol. 2013. doi:10.1155/2013/378168.