Thursday, August 6, 2015

Would Cannabis Stand Up to the Scrutiny of the FDA?

Written by Deena Louise
Last week Speaker of the House, Mike Turzai, told the Pennsylvania Press Club that he still has questions about medical marijuana...questions pertaining to the proposed legislation and about why the FDA isn't involved more. Then he issued statements saying the current bill was "so broadly written" and "far reaching". He said he cares about every kid in high school because "marijuana is an 'entry level drug'" and then concluded by saying we still need a "full vetting" of this issue before we move forward. Once again, I shook my head in absolute astonishment that he would make statements covering the scope of the bill, the criminality of cannabis and the "safety" of high school children without once ever mentioning the patients. This is and has always been about very sick people who have nowhere else to turn, yet he never once mentioned them. 

I thought about his question concerning the FDA as I watched my TV today. I saw a commercial for a newly released pharmaceutical for insomnia. I watched, mouth agape, as I heard the myriad of side effects, some benign, but yet some, quite dangerous and risky. It got me wondering about the comment made by Speaker Turzai about why the FDA wasn't involved more. The first thing I wondered was why is Pennsylvania the only state concerned with this? None of the other 24 medically legal states ever echoed this concern. Then I wondered if cannabis would hold up to the scrutiny that other medications have been put through? Is it unreasonable to assume that cannabis could make it through the rigorous protocol of an organization that approved rat poison to thin your blood, allowed derivatives of chemical warfare as chemotherapeutic agents, approved an injectable toxic poison to erase wrinkles and recently approved a combination pill for weight loss, containing an anticonvulsant that carries a warning of suicidal tendencies? Let's examine this...

All drugs that get approval or disapproval have to go through pre-clinical assessment, then phase 1, 2 and 3 clinical trials. From there it goes to a review process and after the drug is released, it goes through post market analysis to determine if anything else was of concern that was not found during the clinical trials. So, where does cannabis stand in all of this?

Pre-clinical assessment consists of a sponsor developing a "new drug compound". The new compound is then tested on numerous animals to assess safety and efficacy. At this point, that same sponsor submits an IND (investigational new drug) application to the FDA . Although cannabis would not qualify as a "new drug compound" because it is a plant designed by nature, not man, it has been tested extensively on numerous species of animals and found to have no toxicity. Cannabis has already been through a 14 year IND application brought forth by the U.S. government. Therefore, I feel that it is safe to say that it would clearly pass pre-clinical assessment.

Phase 1 trials involve 20-80 people to determine the drug's safety. Side effects and how the drug is excreted and metabolized are also examined during this phase. Technically, cannabis has already passed phase 1 clinical trials if you count the 34 patients who were enrolled under the CIND (Compassionate Investigational New Drug) program that the federal government set up 1978 in response to the Robert Randall lawsuit. Although the CIND program was closed to new patients by President George H.W. Bush in 1992 with no explanation given, 37 years later, it is still active with two remaining patients who were "grandfathered" in. All of the patients enrolled in that program remained safe, got relief from their respective illnesses and suffered no long term side effects.

Phase 2 trials involve hundreds of people and its focus is on effectiveness. Safety continues to be studied in this phase as well. Although cannabis has not been studied federally at this level, the CMCR in California has conducted what would amount to phase 2 double blind placebo controlled clinical trials, and have found inhaled cannabis to be both safe and effective in hundreds of patients.

Phase 3 trials involve thousands of patients and it is at this point that the drug is tested using different dosages and is used in combination with other drugs. Cannabis has strong anecdotal evidence numbering in the thousands, but has not yet made it to this level of examined testing. However, THC (tetrahydrocannabinol), the only part of cannabis that can make one "high", has been through this level of testing and was approved as the drug Marinol in 1985 as a schedule 2 drug. Despite the fact that it is more psychoactive than herbal cannabis, Marinol was considered so safe that is was dropped to Schedule 3 in 1999, an absurdity that has not gone unnoticed by patients who were tested and found herbal cannabis to have less side effects than Marinol. Arguably, THC and its mind altering effects are the only reason that cannabis is illegal in the first place yet, it is the one part that has been tested, found safe and effective thus earning approval. So, why is the milder herbal cannabis still considered to be more dangerous?

As the safety of cannabis has been well established, at least in comparison to other pharmaceuticals, there remains two very big hurdles to getting FDA approval. The first is that cannabis was erroneously placed into schedule 1 of the controlled substances act. Schedule 1 substances are not allowed to seek FDA approval as they are already pre-determined to have no medicinal value. The second is that someone or some entity would have to sponsor it and present it to the FDA for clinical trials. The only drugs that get sponsored are those that can be patented so the sponsor can recoup the exorbitant costs involved with bringing a drug to market. As cannabis is a plant found in nature, it cannot be patented in its whole form. The only way to make money from it would be to extract and isolate a few key components and make a "new drug compound". Is it ok to do this to cannabis? Of course it is. GW Pharmaceuticals is doing this now with Sativex for Multiple Sclerosis and Epidiolex for epilepsy. However, the problem is that by isolating the compounds, it becomes more narrow in its ability to treat, leaving those that don't respond with no more options. One example of the limitation of pharmaceutical cannabis, inhaled herbal cannabis shows efficacy for treating pain, but in phase 3 clinical trials, Sativex failed to produce the same results. Further, Israel has released research that compared single cannabinoid (CBD) medication to full plant extract cannabis concentrates and found that single molecule CBD produced a narrow bell shaped curve dose response that did not occur with the full plant extract.

As Pennsylvania patients are asking for the "compassionate" use of cannabis for medical reasons, the only question that remains is this...does cannabis at least meet the requirements for compassionate use? Yes! With research from Yale concluding that one third of today's pharmaceuticals receive approval based on a single clinical trial, cannabis, having gone through at least a dozen clinical trials that meet phase 1 and 2 requirements, certainly qualifies for at least compassionate use, even by FDA standards.

So, if all I have said above is true, then what is the answer to Speaker Turzai's question about why the FDA hasn't gotten more involved? Is it because of the addictive potential of cannabis? No...the addiction rate falls well below all other substances at a rate of 9%. The FDA has approved many drugs with much greater addiction potential such as benzodiazepines, barbituates, and opiates. Is it because of the alleged harm to the brain? If that were the case then they would have never approved certain anticonvulsants, antidepressants and antipsychotics that have serious side effects including cerebral atrophy, neurotoxicity and suicidal/homicidal thoughts. Clearly the FDA has approved some medications that make cannabis look timid in comparison. So, why hasn't the FDA gotten more involved? The answer to that is simple...they aren't allowed to be based on government restrictions placed upon this plant. The FDA can only prove or disprove what is brought before them. Cannabis can't be brought before them until the laws change. The federal government said it will change when enough states change their own laws first, which means the ball is in your court, Pennsylvania General Assembly. It is time to follow the lead of 24 other states and tell the U.S. government that you are exercising your states' rights out of concern for your sick and suffering citizens! 

1 comment:

  1. This is excellent! Thank you so much for making this intelligent and insightful argument.