How Regulation Stymies Medical Research of Controlled Substances

What Is a Controlled Substance?

A controlled substance is a government-controlled substance or drug deemed to provide little or no medical benefit or has the potential for abuse or dependence. These regulated substances include opioids, hallucinogens, stimulants, depressants, and anabolic steroids. Substances that have been found to provide medical benefits are accessible with a prescription by a licensed medical professional (i.e., Valium). Some controlled substances have no known medical use in the US and therefore are illegal.

Who Is Responsible for Regulation?

To protect public health and safety, all processes of developing a controlled substance are regulated from manufacturing to distribution. In 1973, the US DEA was created to monitor the use of all controlled substances, including prescription medication. The DEA regulates controlled substance prescriptions through prescription drug monitoring programs (PDMPs), databases utilized for tracking controlled substance prescriptions in each state.

What Is the Controlled Substances Act (CSA)?

Organizations responsible for the unlawful manufacturing, dispensing, and distributing of controlled substances are penalized based on the CSA established in 1970. This US drug policy classifies all federally regulated substances, drugs, and precursor chemicals and places them into one of five schedules based on the potential for abuse/dependence, medical use, or safety liability. Today, many hurdles to legitimize illicit drug research stem heavily from the CSA.

Schedule I

Schedule I substances are described as drugs with a high potential for abuse or have no currently accepted medical use. Schedule I drugs include marijuana, psilocybin, heroin, peyote, methylenedioxymethamphetamine (MDMA, ecstasy), lysergic acid diethylamide (LSD), and methaqualone.

Schedule II

Schedule II substances are described as dangerous drugs with a high potential for abuse and could lead to severe physical or psychological dependence. Schedule II drugs include Vicodin, cocaine, fentanyl, methadone, methamphetamine, hydromorphone, meperidine, oxycodone, Dexedrine, Adderall, and Ritalin.

Schedule III

Schedule III substances are described as drugs with a moderate-to-low potential of psychological and physical dependency. These drugs have an abuse potential that is lower than Schedule I and II drugs but is more than Schedule IV. Schedule III drugs include products with less than 90 mg of codeine per dose, anabolic steroids, testosterone, and ketamine.

Schedule IV

Schedule IV substances are described as drugs with a low potential for abuse and dependency. Schedule IV drugs include Soma, Xanax, Tramadol, Darvon, Darvocet, Ativan, Valium, Ambien, and Talwin.

Schedule V

Schedule V substances are described as drugs with a lower potential for abuse than Schedule IV substances and include limited quantities of narcotics. Schedule V drugs include Lomotil, Parapectolin, Lyrica, Motofen, and cough suppressants containing less than 200 mg of codeine per 100 mL like Robitussin AC. These drugs are commonly taken for antidiarrheal, analgesic, or antitussive effects.

Barriers to Conducting Research on Schedule I Substances

Even though certain controversial controlled substances have been shown to hold potential therapeutic benefits, it’s incredibly more cumbersome for scientists to apply to study Schedule I substances.

To conduct medical research on a scheduled substance, researchers are required by the CSA to register for permission with the DEA. Researchers also must gain study approval from an Institutional Review Board (IRB), a standard requirement for the US FDA approval process. While receiving full research approval has been known to take years, obtaining the necessary grant funding can take even longer.

Because a lack of grant funding is often closely associated with the stigmatization of controlled substances, most public universities and laboratories avoid this type of medical research.

In addition, most research laboratories lack the DEA-required security protocols and equipment. Scientists are often required to make expensive and time-consuming modifications to their security procedures which inflate the cost of research.

Once the DEA approves the security of the laboratory, researchers must request all Schedule I substances from the National Institute of Drug Abuse (NIDA) or any manufacturer who holds a Schedule I license. Per CSA guidelines, the DEA can inspect any research laboratory at any time.

“Even experienced researchers have reported that obtaining a new Schedule I registration, adding new substances to an existing registration, or getting approval for research protocol changes is time-consuming,” the NIDA Director, Nora Volkow, said.

Public Interest in Removing Barriers

A shift in public interest has fueled the science behind studying psychoactive substances for therapeutic benefits like psilocybin, MDMA, and marijuana.

A small number of scientists have cleared numerous bureaucratic hurdles to discover illicit drugs’ potential healing properties. In 2016, a group of researchers concluded in the American Journal of Bioethics that “it is likely that several drugs currently classified under Schedule I have significant therapeutic potential for relieving symptoms and managing the underlying chronic conditions. Without research, that potential cannot be detected or verified and the potential benefits cannot be dispersed. The Catch 22 of the status quo is that the classification of drugs as Schedule I amounts to an unsurmountable barrier to research.”

The FDA has found safe and practical uses for several Schedule I drugs, such as marijuana, and because of this, tetrahydrocannabinol (THC) has been legalized for medical use in over 30 US states. According to the Centers for Disease Control and Prevention (CDC), marijuana is the most used federally illegal drug, with roughly 18% of Americans claiming to have used it at least once in 2019.

In 2018, the FDA approved Epidiolex, the first plant-derived cannabinoid prescription medication used to treat seizures connected to Lennox–Gastaut or Dravet syndrome in patients two years of age and older.

Faced with an overwhelming opioid crisis, the NIDA and DEA have signaled support for streamlining the research process of Schedule I drugs. The Biden–Harris Administration has recommended several policy changes to facilitate Schedule I research more efficiently.

Fentanyl — a synthetic, Schedule II opioid incredibly more potent than morphine — is fueling the US overdose crisis. In 2019, over 70% of drug overdose deaths were opioid-related. While strict regulations can limit access to potentially hazardous drugs in a community, a solution to fentanyl dependence could be hidden behind overly stringent rules.

Despite the rapidly growing enthusiasm surrounding the medical benefits of psychedelics and other controlled substances, the difficulty of scheduled drug research deters or prevents most researchers, limiting the development of critical therapeutics and reclassification or declassification of scheduled substances.