The journey to FDA approval is long, pricey, and political, but just how can a Schedule I drug with ‘no accepted medical use’ be for sale on the market now?
In June 2018, America’s FDA approved Epidiolex for the pharmaceutical market. It is a medicine made from cannabis extract, the first of its kind in the U.S. Uninsured patients can expect to fork over $25,000 to $30,000 a year to access this life-saving, anti-seizure drug.
If you’ve dabbled in medical cannabis, then you may ask yourself why anyone would pay the equivalent of the school teacher’s annual salary for something that can be picked up at a cannabis dispensary for a fraction of the cost.
There are plenty of ‘excellent’ reasons why someone may opt for Epidiolex over, say, Charlotte’s Web oil. The biggest reason is legality, as Epidiolex is 100 percent legal (with a prescription), whereas non-FDA-approved CBD oils currently meander into a legal gray area.
The next biggest reason to choose Epidiolex would be perceived reliability. Since Epidiolex is a federally regulated drug, it must undergo stringent lab testing to verify its safety and efficacy. It turns out that there are some concerning side effects, namely increased seizure activity and suicidal thoughts, but the FDA would like you to think it’s safe and effective.
The final reason is that some CBD oils on the market don’t always offer consistency, especially since many CBD companies misreport or outright lie about the CBD content of their products. Epidiolex has to be precisely consistent and can be meted out in exact doses, too.
If it was your kid’s life on the line, would you rely on hooch CBD oil? Or would you go for the guaranteed stuff in Epidiolex? Now ask yourself those same two questions when you factor medical insurance into the mix. Which one will insurance cover, and which ones won’t it cover? It’s not always a straight forward decision.
The Schedule I Drug With “No Accepted Medical use”
There’s nothing particularly special or magical about Epidiolex. According to GW Pharmaceuticals’ CEO, Justin Gover, Epidiolex is simply a CBD tincture. It contains trace amounts of other cannabinoids like THC, but not enough to have any real effects. Yet until recently, the Drug Enforcement Administration (DEA) considered CBD to be a Schedule I drug, right alongside THC.
I won’t get into the long, turbulent history behind drug scheduling. That will require a post of its own. For now, just assume the U.S. government knew that cannabis laws were a great way to target black activists, anti-war protesters, and hippies in one fell swoop. And before you go pointing fingers at Nixon and the Republicans, keep in mind that more House Democrats voted for the Controlled Substances Act than Republicans.
What is Schedule I, exactly? It’s a drug classification reserved only for the most addicting substances that have no accepted medical use. They’re too dangerous to use even with a doctor’s supervision. Supposedly, anyway. Other drugs in Schedule I include heroin, MDMA, and LSD.
Deadly drugs such as oxycontin, amphetamines, cocaine, and opium fall under Schedule II. Schedule II indicates a drug has a high potential for abuse, but it also has accepted medical use. They’re safe to use so long as you’ve got a doctor’s supervision!
As I noted earlier, the DEA considered all CBD products as Schedule I until a couple of weeks ago. After Epidiolex received the FDA’s approval, the DEA reclassified CBD medications with less than 0.1 percent THC as Schedule V. Guess which pharmie contains CBD and less than 0.1 percent THC?
Epidiolex. And as far as the DEA is concerned, only Epidiolex. For now.
Why Cannabis is Still Schedule I
But the DEA would never admit they’re all about the power, right? Exactly. Instead, the DEA argues that because of studies from NIDA and the FDA, cannabis has no accepted medical use. However, if individual components of the cannabis plant can demonstrate medical efficacy, then those components can be manufactured and regulated.
Opium is a great example. Opium, as a plant, is classified as Schedule II. Codeine, a drug derived from opium, is an ingredient in Schedule V cough syrups. The plant is bad; the processed drug is good.
According the government, THC is the dangerous component in cannabis that makes it Schedule I. However, lab-made THC (called dronabinol) is Schedule III. Dronabinol and THC are chemically identical, just one comes from a beaker and the other comes from a plant.
Nowhere in the literature nor in the press nor in government reports have I ever seen the FDA, NIDA, or the DEA claim that the whole plant and its thousands of components make it Schedule I. It’s always THC as the culprit. The DEA has admitted as much: CBD products were classified Schedule I because they contained trace amounts of THC.
How to Reschedule a Drug
Just how could this be? How could a substance classified as Schedule I for half a century suddenly drop down to Schedule V overnight? It boils down to two factors: clinical testing and money. Lots and lots of money. Clinical trials are a series of testing stages (called “phases”) that check to see if the drug (1) is safe for human consumption and (2) actually works.
The first step for getting FDA approval for clinical trials requires a lot of experimental design. The researchers must show how they will test the drug and what results they expect to see. This process can take years.
Expensive Clinical Trials
Once the FDA gives the greenlight for clinical trials, the researchers must raise funds. Clinical trials are expensive and can easily cost hundreds of millions of dollars. Unfortunately, the fundraising process may take years, too.
The key part here is that funding can come from anywhere. For example, with cancer drugs, the U.S. government issues research grants for the most promising treatments. Pharmaceutical companies will often foot the full bill for their own clinical trials. Even non-profits, such as the Multidisciplinary Association for Psychedelic Studies (MAPS), can fund clinical trials.
After the money and the experimental designs are in order, researchers can begin clinical trials. Like the previous two steps, this one can – and almost always does – take several years as well.
All Important Human Trials
The most crucial step is the Phase III clinical trial. Phase III is when the drug is tested on human subjects in a double-blind study. In double-blind studies, neither the researchers administering the drug nor the subjects know if they’ve been given a placebo or the actual drug. Studies of this sort minimize any biases from the subjects or the doctors.
If the researchers conclude that the drug is relatively safe and effective after Phase III, then the FDA can approve it. Once the FDA approves, the DEA will reschedule the drug at the FDA’s recommendation. Last year, Epidiolex cleared Phase III clinical trials, with results published in the prestigious New England Journal of Medicine. This is why Epidiolex is legally hitting the shelves while OG Kush remains outlawed at the federal level.
The last step, Phase IV, doesn’t occur until after the drug goes on the market. Consider Phase IV the “guinea pig” stage, when scientists observe the drug’s consequences after its release into the wild, as it were.
Potential rescheduling of Schedule I drugs isn’t unique to cannabis. Right now, the Schedule I drugs MDMA (a.k.a. “ecstasy”), LSD (a.k.a. “acid”), and psilocybin (a.k.a. “magic mushrooms”) are undergoing successful clinical trials for PTSD, anxiety, and depression. At the rate those three drugs are gliding through the FDA-approval pipeline, we may see them rescheduled sometime in the next several years as well.
Where to Begin?
If you’d like to see clinical trials for the entire cannabis plant, and not just a pharmaceutical that employs just one or two components of the plant, you’re in luck. For two decades, MAPS has worked on getting clinical trials for smokable cannabis. Not an oromucosal weed spray. Not a lab-synthesized weed pill. Only the dankest buds for clinical trials. Last year, they received FDA approval for testing buds as a treatment for PTSD in U.S. combat vets.
It’s likely just a matter of time before the federal government must confront the medical efficacy of cannabis as a whole plant and not simply its chemical components. As to how modern allopathic medicine would integrate a smoked, non-dosable medication into its pharmacopeia remains to be seen.