“The Controlled Substances Act (CSA) places all substances that were in some manner regulated under existing federal law into one of five schedules. This placement is based on the substance’s medical use, potential for abuse, and safety or dependence liability.” The FDA has proposed changing the classification of marijuana from a Schedule I to a Schedule III drug. Let’s break down its thinking.
Marijuana is currently a Schedule I drug – with "high abuse potential with no accepted medical use,” like heroin or LSD. The FDA recommends that it be a Schedule III drug – one with a recognized medical use and “intermediate abuse potential,” less than an opioid, more than diazepam (Valium). These recommendations and those of other agencies are provided to the Drug Enforcement Agency, which makes the final decision. The entire 250-page report of the findings of the FDA and the Department of Health and Human Services can be found here. 
Alcohol is not controlled under the CSA, which typically precludes its use as a “comparator drug” in scheduling placement. The FDA considered it due to its extensive availability, use, and misuse.
What are marijuana’s pharmacologic effects?
Marijuana's primary psychoactive compound, ∆9-THC, acts as an agonist at the CB1 cannabinoid receptor, producing rewarding effects like euphoria and relaxation. Animal studies indicate its reinforcing properties through self-administration and place preference. It can also cause sedation, reduce anxiety, and temporarily impair cognitive functions. Physiological changes include increased heart rate, dry mouth, red eyes, and increased appetite. Chronic use can lead to physical and psychological dependence, resulting in withdrawal symptoms upon cessation.
Does THC have a valid approved medical role?
THC, the main psychoactive component of marijuana, is the active component of two FDA-approved medications. Marinol is approved for treating nausea and vomiting caused by chemotherapy, and Syndros is approved for treating muscle spasms caused by multiple sclerosis.
Does the medical literature support other uses of marijuana?
Despite the need for more rigorous research to fully understand marijuana’s risks and benefits, there is some credible scientific support for the medical use of marijuana in treating specific medical conditions. The FDA commissioned the University of Florida to conduct a systematic review of the use of marijuana in treating medical illnesses. There were mixed results:
- Low to moderate-quality evidence supporting the effectiveness of marijuana as a medical treatment for anorexia, nausea and vomiting, and PTSD.
- Moderate-quality evidence that cannabis helps treat chronic pain, more specifically neuropathic pain. The effect size was characterized as “small” or, in other instances, as “greater than average.”
Based upon that report and other nationally collected data, the FDA concluded:
“Based on the totality of the available data, we conclude that there exists some credible scientific support for the medical use of marijuana in at least one of the indications for which there is widespread current experience in the United States.”
Is marijuana safe?
Overall, the safety profile of marijuana appears to be relatively favorable, with a low risk of serious adverse events. Marijuana's safety profile, even when used nonmedically, is less concerning than many comparator drugs for important outcomes like overdose deaths or hospitalizations; typically, alcohol, heroin, or cocaine are placed in higher positions than marijuana. Epidemiological data indicate that marijuana has a lower potential for causing adverse health effects and the severity of substance use disorders compared to alcohol.
Alcohol-related disorders are more prevalent than marijuana-related disorders in teenagers and adults. However, in young children, marijuana poisoning-related ED visits and hospitalizations are higher than those for alcohol.
I would like to add a point here, not addressed in the HHS report. In considering the safety of marijuana, we should remember that even in states with recreational use, there remains a significant "grey" market where THC concentrations are unknown, and there can be possible adulterants.
What are the patterns of use and abuse of marijuana, other Scheduled Drugs, and alcohol?
Marijuana is the most frequently abused federally illicit drug in the United States. The use of non-medical marijuana is increasing. The prevalence of past-year non-medical marijuana use is 5-6 times greater than that of other illicit drugs like heroin, cocaine, oxycodone, and hydrocodone, at around 16% in 2021. Medical use alone or combined with non-medical use was less than non-medical use alone. Approximately 30% of individuals who use marijuana nonmedically reported using it for an average of more than 20 days per month. In 2021, an estimated 14 million individuals aged 12 or older who use marijuana or other cannabinoid preparations met the criteria for Cannabis Use Disorder (CUD).
Alcohol is the most commonly used substance in the United States. From 2015 to 2019, the prevalence of past-year alcohol use was 5-6 times greater than non-medical use of marijuana. Alcohol is the most common primary substance of abuse in SUD treatment admissions, accounting for 31.2% of admissions in 2020. Approximately 17% of individuals who use alcohol in a given year meet the criteria for an alcohol use disorder.
Despite the high prevalence of non-medical use of marijuana, an overall evaluation of epidemiological indicators suggests that it does not produce serious outcomes compared to drugs in Schedule I or II or alcohol.
Does marijuana have the potential for abuse:
- Animal studies have shown that the primary psychoactive component of marijuana, -THC, has rewarding effects, suggesting its potential for abuse. Individuals who use marijuana indicate that it produces euphoria, sedation, anxiety, and other psychoactive effects, consistent with its abuse potential.
- Epidemiological data demonstrate that marijuana has the potential to produce both physical and psychological dependence in individuals who use it regularly or in high doses based on its rewarding properties.
- Withdrawal symptoms associated with marijuana discontinuation include sleep difficulties, decreased appetite and weight loss, craving, irritability, anger, anxiety or nervousness, and restlessness; typically peak within 2-6 days and decline over 1-2 weeks.
- Marijuana can produce psychological dependence due to its ability to produce rewarding effects. Individuals who develop psychological dependence on marijuana may experience problems in their personal, social, or occupational functioning as a result of their marijuana use.
The available evidence suggests marijuana meets the criterion for abuse potential based on human evidence of its rewarding effects and the observed patterns of non-medical use. While both marijuana and alcohol can have harmful physical and psychological impacts, alcohol generally poses a higher risk of severe dependence and associated health problems. Alcohol withdrawal can include severe symptoms like seizures, delirium, and even death. Alcohol dependence is often considered more severe, with a higher risk of addiction and related health consequences.
Does marijuana pose a risk to public health?
Epidemiological data indicate that marijuana use has the potential to create hazards to the health of the user and the safety of the community. Some individuals who use marijuana, particularly among high-potency marijuana users, experience adverse outcomes, including:
- impaired cognitive function,
- impaired driving performance, increasing the risk of accidents
- increased in marijuana use disorders
- a heightened risk of the onset of mental health issues
- respiratory issues.
There have been increasing reports of unintentional marijuana “poisoning” among children. The long-term safety profile of marijuana, particularly for heavy users and vulnerable populations, remains unclear due to limited research and the recency of widespread legalization.
However, epidemiological studies suggest that marijuana has a lower risk of abuse compared to substances like heroin, cocaine, and prescription opioids. Marijuana abuse leads to fewer negative outcomes than drugs in Schedule I or II, despite the availability of marijuana products with high levels of THC. These outcomes include emergency department visits, hospitalizations, unintentional exposures, and overdose deaths. Marijuana ranks lowest among comparator drugs in terms of overdose deaths and related emergencies.
While there is evidence that some individuals are taking marijuana in amounts sufficient to create a hazard to their health or the safety of other individuals and the community, the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes for themselves or others.
How does that risk compare to alcohol?
Epidemiological studies suggest that marijuana has a lower abuse potential compared to alcohol, with higher rates of overdose deaths, hospitalizations, and social problems than marijuana. Marijuana intoxication typically produces relaxation, euphoria, and altered sensory perception, while alcohol intoxication can lead to impaired judgment, aggression, and risk-taking behaviors. Driving under the influence of marijuana is associated with an increased risk of accidents, but the risk is generally lower compared to driving under the influence of alcohol. Long-term marijuana use may be associated with respiratory problems and mental health issues, while long-term alcohol abuse can lead to liver damage, heart disease, and various cancers.
Is marijuana a gateway drug, an immediate precursor to other controlled substances?
“Marijuana is not an immediate precursor to another controlled substance.”
Has the FDA and HHS made a case for marijuana’s medical use and a risk-benefit profile similar to those drugs classified as Schedule III? I believe they stand on the firmest ground that our current scientific understanding allows. Will the DEA follow the words of Harry Anslinger, the first Commissioner of the Federal Bureau of Narcotics, the DEA’s regulatory ancestor?
“No one knows, when he places a marijuana cigarette to his lips, whether he will become a joyous reveller in a musical heaven, a mad insensate, a calm philosopher, or a murderer...”
Or will it follow the science we have at hand?
 In another example of the lack of transparency in regulatory decisions, this document was withheld from the public and was only released last week after a Freedom of Information suit, as reported by the NY Times. Why we continue to tolerate this secrecy in our public officials is disheartening. For the Federal government, which rightly believes government-funded research should be freely available to the public, they should begin by taking a hard look in the mirror and ending this behavior on their part.