Analysis of HHS Cannabis Rescheduling Rationale

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On August 30th, 2023, the Department of Health and Human Services (HHS) announced it recommended the reclassification of marijuana to Schedule III to the Drug Enforcement Administration (DEA). Four months later, HHS released an unredacted version of its recommendation to reclassify the drug. The 252-page review had been hidden from the public and was only released after legal action was threatened against HHS.  

This HHS recommendation is based on cherry-picked data and represents a weak and intellectually dishonest argument to reschedule marijuana. This summary describes just a few of the many flaws in the HHS methodology and conclusions. SAM’s full report provides an in-depth analysis of what the HHS got wrong and how the process could have been strengthened.  

1. In years past, the FDA, an agency of the HHS in charge of approving medicinal drugs, used an established five-factor analysis in determining whether Schedule I drugs have “currently accepted medical use.” In the current report supporting the recommendation to reschedule marijuana, the FDA changed these criteria to get its desired answer.  

 If marijuana had been held to the same standards as other drugs, it would not be deemed to have “currently accepted medical use,” due to the infeasibility of measuring all strains and the insufficient amount of existing research into its safety and efficacy. In fact, the FDA’s new two-factor test explicitly states that studies used to support marijuana’s accepted medical use do not need to be controlled, a standard that was required in the five-factor test (save an evaluation done by a consensus of experts). 

2. It is not clear why the FDA moved away from the five-factor test, unless the agency approached the rescheduling review with a pre-determined conclusion.  

The five-factor test has been used for decades by Republican and Democratic Administrations. Additionally, the United States Court of Appeals for the District of Columbia Circuit examined and validated the test in Alliance for Cannabis Therapeutics v. Drug Enforcement Administration. The marijuana industry petitioners in that case even conceded that the five-factor test had no flaws, as explained in the opinion for the court. 

3. The FDA now considers the existence of state medical marijuana programs as evidence that marijuana has currently accepted medical use.  

A drug’s popularity among the public has never been used as a standard to determine medicine. Supreme Court Justice Steven Breyer in Gonzalez v Raich (545 U.S. 1 (2005), a case involving a medical necessity for the use of marijuana, opined during oral arguments that “medicine by regulation is better than medicine by referendum.” The Court’s 6-3 decision, which Justice Breyer joined, upheld the prohibition of marijuana for medical use under the Controlled Substances Act (CSA). The FDA’s novel standard in recommending marijuana’s rescheduling is rooted in a logical fallacy: some people say that marijuana is medicine, so marijuana must be medicine. The FDA is delegating its authority to determine that medications are safe and effective to popular opinion, a practice that not only exceeds the statutory authority of the agency but makes a mockery of the congressional intent of the Food, Drug, and Cosmetic Act to protect the public health. Following the FDA’s logic, psychedelic drugs, which are seeing a popular push for medical legalization, could also be considered medicine and be rescheduled due to shifting public opinion. 

4. The FDA compares marijuana to a limited, hand-picked list of other controlled and noncontrolled substances (e.g., heroin, alcohol, cocaine), not all Schedule I drugs. 

In the recommendation, the FDA measured marijuana’s potential for abuse by comparing it to a hand-picked selection of Schedule I, II, and III drugs. For example, the FDA compared marijuana to heroin, another Schedule I drug. The recommendation claims that because marijuana has a lower abuse potential than heroin, it shouldn’t be in the same category. Yet the FDA failed to compare marijuana to other Schedule I drugs, such as LSD. Comparing marijuana’s abuse potential against all Schedule I drugs would have allowed for a more rigorous analysis, but it would not have allowed the FDA to conclude that marijuana belongs in Schedule III. To qualify for Schedule III, a drug or other substance must have “potential for abuse less than the drugs or other substances in Schedules I and II” (21 USC 812(b)). Fifty years of data published by HHS show that marijuana does not meet this standard. 

5. None of the studies used by the FDA to justify its claim that marijuana is medicine support that conclusion. 

The FDA determined that marijuana is acceptable for medical use for pain, nausea and vomiting, and anorexia. Only three studies were used to justify this claim. The first (University of Florida), concluded that results were “inconclusive or mixed.” The second (National Academies of Sciences & Medicine) relied primarily on a study for which the results were not statistically significant. For the third (Agency for Healthcare Research and Quality), the FDA concluded that the positive effects of marijuana in the study were small and that “the increased risk of dizziness, nausea, and sedation [from marijuana use] may limit the benefit” (page 27 of 252). Furthermore, some of these studies were with inhalable marijuana; prior FDA evaluations have excluded inhalable marijuana studies because of their unreliability and questionable practices. 

Why marijuana fans should not see approval for epilepsy drug as a win for weed→

A Food and Drug Administration panel recommended approval of a drug made of cannabidiol on April 19 to treat two types of epilepsy. The FDA is expected to decide in June whether to accept the panel’s 13-0 recommendation to approve Epidiolex, which would would become the first drug made of cannabidiol, a compound in the cannabis plant, to gain approval from the FDA.

While the panel’s unanimous decision is not binding, the action will no doubt heighten public debate about the use of cannabidiol, medical marijuana, medical cannabis and hemp oil. Should cannabidiol, or CBD, or marijuana be legalized for medical purposes? What is the evidence that these products are beneficial? Are these products safe to use?

Those who support the use of marijuana for recreational or medicinal purposes might have found the timing of the panel’s ruling interesting. National Weed Day is April 20.

But weed is not cannabidiol, even though both come from cannabis.

No high, but healing?

A cannabis leaf. The plant produces several compounds, one of which is CBD

As a professor of pharmacy with a special interest in epilepsy, I find it important that CBD may be a new option for the treatment of epilepsy. This new use has led me to carefully study published literature on CBD and discuss it as an option with patients who have epilepsy. Additionally, I have been involved with the American Epilepsy Society’s ongoing review of CBD as a possible treatment for epilepsy. From this perspective, I believe that CBD may offer benefits for patients with some types of epilepsy and possibly other disorders.

The cannabis plant produces hundreds of different compounds, many of which have differing effects in the body. Tetrahydrocannabinol, or THC, is the substance that is most known for its psychoactive effects, or the “high” associated with marijuana.

However, there are many other substances from the cannabis plant that also produce effects in the body. Many of these differ from THC in that they are not psychoactive – and they do not produce a “high.” Cannabidiol, or CBD, is one of those substances.

Cannabidiol is a complex molecule that is produced by the cannabis plant. Cannabis has been proposed for centuries as a medicinal plant. Only recently has CBD been studied scientifically for various disorders.

Compared to THC, CBD works at different receptors in the brain and other parts of the body. In this way, CBD is very different from THC and may offer new mechanisms of treatment. For this reason, CBD has received a great amount of attention as a possible treatment for many different disorders.

CBD has been proposed as a cure or treatment for many disorders and diseases, including epilepsy, chronic pain, anxiety, multiple sclerosis, amyotropic lateral sclerosis (ALS or Lou Gehrig’s disease) and insomnia. Some of these uses are based on science, but others are proposed by advocates of CBD and medical marijuana. Several anecdotal reports, case reports, case series and small studies have reported on CBD for many of these disorders. Information from these reports is conflicting. Case reports, case series and small studies are considered insufficient evidence to prove or disprove the safety and efficacy of a drug or treatment. This is because these studies are usually unable to distinguish between the effect of a drug and a placebo effect, or the patient thinking the drug is working when it really is not providing benefit.

However, there are two well-designed, large studies that indicate CBD is effective in two different epilepsy syndromes. In these studies, about 40 percent of patients taking CBD had a significant reduction in specific types of seizures.

Epilepsy is the only disorder where there is solid scientific evidence demonstrating that CBD is safe and effective. This does not mean that CBD will not work for other disorders, but epilepsy is the only one where we have clear, well-documented evidence that CBD helps.

Results from these studies show that CBD does have side effects. The most common ones are drowsiness, nausea, intestinal cramping, bloating and diarrhea. More serious side effects can occur. In one of the studies in epilepsy, about 10 percent of patients taking CBD had an increase in laboratory tests of liver function. These tests commonly indicate damage to the liver. About 2-3 percent of patients taking CBD had to discontinue it due to large increases in certain liver enzymes in laboratory tests, showing possible liver damage.

We are also learning about drug interactions that occur with CBD. In these studies, CBD slowed the metabolism of several drugs that are commonly given to individuals with epilepsy. The interactions between CBD and other drugs patients were taking caused side effects. It is unclear if these side effects were due to CBD, the other drugs, or a combination. Doses of the other drugs were reduced, due to the interactions.

The mechanism for these interactions indicate that there are likely several other interactions between CBD and other common medications. Cannabidiol needs to be used cautiously in combination with other medications.

Issues beyond effectiveness

There are several other factors to consider in regards to CBD. Cannabidiol does not dissolve well in water. For this reason, oral products of CBD are made with an oil, often some type of vegetable oil. It is important that the right oil is used.

Also, less than 20 percent of an oral dose of CBD is absorbed. This makes it difficult to produce a CBD product where CBD is reliably and consistently absorbed.

An FDA study of unregulated CBD products available on the market shows these products are frequently contaminated with things like pesticides, herbicides, fungus or bacteria. Additionally, the FDA found that over 50 percent of CBD products may not contain the amount of CBD on the label. This is especially true in states where CBD products are not regulated by the state. In 17 states where there is regulation, there is much better control on product quality and purity.

Finally, there are two pharmaceutical-grade CBD products that have been studied for production by a pharmaceutical company. One is Epidiolex, approved by the FDAD panel on April 19, and the other is still being studied. Epidiolex would be approved only for use in two types of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome.

So far, the evidence is that CBD is safe and effective for specific epilepsy syndromes. There is insufficient scientific evidence to indicate that it is effective or ineffective for other disorders. Information from well-designed studies do indicate that CBD causes important side effects and drug interactions that must be considered. Individuals who wish to use CBD should be managed and monitored by health care professionals familiar with its use.