Drug Scheduling Under the Controlled Substances Act

March 27, 2025

Implemented in 1970, the Controlled Substances Act consolidated previous American and international drug policies to regulate the production, distribution, and use of drugs with the potential for addiction or dependency in response to growing concerns about drug abuse around the world (1). The Controlled Substances Act instituted a framework for categorizing drugs into five different schedules to allow different levels of regulation and enforcement by the Drug Enforcement Administration (DEA) and the Food and Drug Administration (FDA) (1, 2).

The five different schedules, numbered I through V, consider three criteria: the presence of accepted medical uses, the possibility of abuse or dependency, and the potential for harm (1, 2). In general, drug scheduling under the Controlled Substances Act is first determined by whether or not the drug maintains at least one accepted medical use – if not, the drug is considered illegal and classified in Schedule I, but if so, the drug is considered legal and categorized into one of Schedules II through V according to its addictiveness and harmfulness, which determines the level of surveillance and restriction (3).

Many commonly used drugs in anesthesia remain in highly controlled schedules, due to their high potential for addiction, diversion, and harm alongside their multiple accepted medical uses. Additionally, ostensively similar medications have varying classifications according to their unique risks and uses – for example, some intravenous anesthetic drugs are found in Schedules II and III, while other intravenous and all inhalational anesthetics are not controlled substances (4). The caveats of drug scheduling demonstrate the necessity of awareness about their potential dangers to patients and implications for providers.

Currently, the Controlled Substances Act has led to the following drug scheduling for anesthesia-related drugs (4-7).

  • Schedule V (minimal risk)
    • Few anesthesia-related drugs, except narcotic-containing anti-diarrheals and cough medicines
    • Least regulatory monitoring and fewest restrictions
  • Schedule VI (low risk)
    • Sedatives, hypnotics, and mild narcotics – including most benzodiazepines, tramadol, propoxyphene, and etomidate – as well as propofol in some states and institutions
    • Closer monitoring and quantity and timing restrictions (e.g., five refill maximum within six months)
  • Schedule III (moderate risk)
    • Ketamine, most barbiturates, buprenorphine
    • Closer monitoring and similar quantity and timing restrictions as Schedule IV drugs
  • Schedule II (high risk)
    • High-potency anesthetics and analgesics, including opioids (e.g., morphine, fentanyl, oxycodone) and pentobarbital
    • Close monitoring and many restrictions (e.g., prohibition of verbal prescriptions except in emergencies, strict timing and quantity regulations, no refills)
  • Schedule I (highest risk, no accepted medical uses)
    • Some formerly used anesthesia-related drugs, such as methaqualone and most forms of gamma-hydroxybutyrate (GHB)
    • Closest monitoring and prohibited use, with strict enforcement and severe penalties

To monitor prescription and prevent diversion, the Controlled Substances Act established multiple rules for providers, which are required by the DEA but managed by states (8). First, any provider who administers, prescribes, or dispenses any controlled drug must register with their state’s DEA office through their workplace to obtain DEA licensure, which grants them legal privileges but requires that they limit their prescriptions to their scope and workplace with few exceptions (8, 9). Second, mandatory use of state prescription drug monitoring program (PDMP) databases ensures that thorough consideration of patients’ prior drug history precedes controlled substance prescription (9). Third, the CSA also requires careful handling of controlled substances through state-specific protocols, which typically include proper identification of the substance, justification for its use, and adequate records of administration (10, 11).

Providers, specifically those in the anesthesia field, must remain vigilant about Controlled Substances Act drug scheduling regulations and changes to adequately control addictive substances, especially given the current prevalence of prescription drug addiction and proposed reform of recreational drug policies (12). Notably, the act allows the DEA to reschedule drugs in response to public health concern, as exemplified by the temporary relocation of fentanyl-containing drugs into Schedule I for several years (13). In the future, providers should continue operating with extensive knowledge of DEA and state policies for the drugs they prescribe, while also anticipating further changes to address rising issues amid the current prescription drug addiction crisis.

References

1: Ortiz, N. and Preuss, C. 2024. Controlled Substance Act. StatPearls, StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK574544/

2: Gabay, M. 2013. The federal Controlled Substances Act: schedules and pharmacy registration. Hospital Pharmacy, 48(6). DOI: 10.1310/hpj4806-473

3: Aro, H., Hussain, A. and Bobrin, B. 2023. Controlled substances. StatPearls, StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK554383/

4: Controlled Substance Analogue Enforcement Act, 21 U.S.C. § 802. 2025.

5: Drug Enforcement Administration. 2023. Benzodiazepines. Diversion Control Division, Drug Enforcement Administration. URL: https://www.deadiversion.usdoj.gov/drug_chem_info/benzo.pdf

6: Preuss, C., Kalava, A. and King, K. 2023. Prescription of controlled substances: benefits and risks. StatPearls, StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK537318/

7: Burnett, G., Taree, A., Martin, L. and Bryson, E. 2022. Propofol misuse in medical professions: a scoping review. Canadian Journal of Anesthesia, 70. DOI: 10.1007/s12630-022-02382-2

8: Lopez, M., Preuss, C. and Tadi, P. 2023. Drug Enforcement Administration. StatPearls, StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK557426/

9: D’Souza, R., Lang, M. and Eldridge, J. 2024. Prescription drug monitoring program. StatPearls, StatPearls Publishing. URL: https://www.ncbi.nlm.nih.gov/books/NBK532299/

10: Breve, F., LeQuang, J. and Batastini, L. 2022. Controlled substance waste: concerns, controversies, solutions. Cureus, 14(2). DOI: 10.7759/cureus.22564

11: Horn, D., Vu, L., Porter, B. and Sarantopoulos, K. 2024. Responsible controlled substance and opioid prescribing. StatPearls, StatPearls Publishing. URL: https://pubmed.ncbi.nlm.nih.gov/34283451/

12: Piomelli, D., Weiss, S., Boyd, G., Pacula, R. and Cooper, Z. 2018. Cannabis and the opioid crisis. Cannabis and Cannabinoid Research, 3(1). DOI: 10.1089/can.2018.29011.rtl

13: Weedn, V., Zaney, M., McCord, B., Lurie, I. and Baker, A. 2021. Fentanyl‐related substance scheduling as an effective drug control strategy. Journal of Forensic Science, 66(4). DOI: 10.1111/1556-4029.14712

Copyright © 2019