Drug Regulations

Until the nineteenth century, there were few standards or guidelines to protect the public from unsafe and ineffective drug, and unscrupulous purveyors. In those days there were many medicinal concoctions that, even if nontoxic, were not effective. Examples of early remedies include heroin for asthma and coughs, and rattlesnake oil for rheumatism. Codeine use started in the late nineteenth century and with that came the advent of addiction-related problems.

The first historical milestone in U.S. Food and Drug Laws was the publication of U.S. Pharmacopoeia (USP) in 1820.21 The USP listed standards for drug purity and strength, and directions for synthesis. In 1975, the USP and the National Formulary (NF), published by the American Pharmaceutical Association (APhA) merged. The new publication, the U.S. Pharmacopoeia-National Formulary (USP-NF), is still published with regular updates.

To protect the public from deceitful and unsafe practices by manufacturers, in the early 1900s the U.S. Congress began to enact and enforce tougher drug laws.21,22 The Biologics Control Act of 1902 was enacted to ensure the purity and safety of serums, vaccines, and other similar products used to prevent or treat diseases in humans. Subsequently, Congress enacted the Food and Drug Act of 1906, prohibiting interstate commerce in misbranded and adulterated drugs.

The Harrison Narcotic Act of 1914 required prescriptions for products exceeding the allowable limit of narcotics and mandated increased record-keeping by physicians and pharmacists who dispensed such drugs. The Federal Food, Drug, and Cosmetic Act of 1938 consolidated the Food and Drug Act of 1906 and its many amendments, extended control over cosmetics and therapeutic devices, and required that the safety of new drugs be established before marketing.

The Durham-Humphrey Amendment of 1951 defined the kinds of drugs that cannot be safely used without medical supervision and prohibited their sale without a prescription by a licensed practitioner. The Kefauver-Harris Drug Amendments of 1962 required manufacturers to prove that a drug was effective, that adverse effects observed after the drug was marketed be reported to the FDA, and that drug ingredients be listed by the generic name in labeling and advertising.

The Drug Abuse Control Amendments of 1965 required accounting for drugs with potential for abuse, i.e., depressants, stimulants, and hallucinogens. The Comprehensive Drug Abuse Prevention and Control Act of 1970, also known as the Controlled Substances Act (CSA) of 1970, collected all legislations related to drugs with abuse potential into a single legislation and created a “closed” system for legitimate manufacturing, distribution, and dispensing of drugs.

Drugs under the Controlled Substances Act of 1970 were divided into five schedules (Table 4). The current list of controlled substances can be found in Section 1308 of the most recent issue of Title 21 Code of Federal Regulations (CFR).23 Drugs are placed in their respective schedules based on whether they have a currently accepted medical use, their relative abuse potential, and the likelihood of causing dependence when abused.

Table 4. Schedules of controlled substances.23
Schedule Comments Examples
Schedule I
  • No currently accepted medical use in the U.S.
  • Lack of accepted safety for use under medical supervision
  • High potential for abuse
  • Schedule I substances
    • heroin
    • lysergic acid diethylamide (LSD)
    • marijuana (cannabis)
    • peyote
    • methaqualone
    • 3,4-methylenedioxymethamphetamine (“Ecstasy”)
Schedule II/IIN
  • High potential for abuse
    • May lead to severe psychological or physical dependence
  • Schedule II narcotics
    • hydromorphone (Dilaudid®)
    • methadone (Dolophine®)
    • meperidine (Demerol®)
    • oxycodone (OxyContin®, Percocet®)
    • fentanyl (Sublimaze®, Duragesic®)
  • Other Schedule II narcotics
    • morphine, opium, codeine, and hydrocodone
  • Schedule IIN stimulants
    • amphetamine (Dexedrine®, Adderall®)
    • methamphetamine (Desoxyn®)
    • methylphenidate (Ritalin®)
  • Other Schedule II substances
    • amobarbital, glutethimide, and pentobarbital
Schedule III/IIIN
  • Potential for abuse less than with Schedules I or II substances
    • Abuse may lead to high psychological dependence
    • Abuse may lead to low- to-moderate physical dependence
  • Schedule II narcotics
    • Products containing not more than 90 milligrams of codeine per dosage unit (Tylenol with Codeine®)
    • buprenorphine (Suboxone®)
  • Schedule IIIN non-narcotics
    • benzphetamine (Didrex®)
    • phendimetrazine
    • ketamine
    • anabolic steroids such as Depo®-Testosterone
Schedule IV
  • Low potential for abuse relative to Schedule III substances
  • Schedule IV substances
    • alprazolam (Xanax®)
    • carisoprodol (Soma®)
    • clonazepam (Klonopin®)
    • clorazepate (Tranxene®)
    • diazepam (Valium®)
    • lorazepam (Ativan®)
    • midazolam (Versed®)
    • temazepam (Restoril®)
    • triazolam (Halcion®)
Schedule V
  • Low potential for abuse relative to Schedule IV substances
    • Consist primarily of preparations containing limited quantities of certain narcotics
  • Schedule V substances
    • Cough preparations containing not more than 200 milligrams of codeine per 100 milliliters or per 100 grams (Robitussin AC®, Phenergan with Codeine®), and ezogabine

Based on existing federal regulations, drugs fall into two major categories: non-prescription and prescription drugs. Prescription drugs are further divided into legend drugs and scheduled drugs. Legend drugs require a prescription because they are considered to be potentially harmful if not used under supervision by a licensed practitioner. Legend drugs are known as such because their labels bear the legend “Caution: Federal Law Prohibits Dispensing without a Prescription.”

While scheduled drugs are also prescription drugs, their distribution and use are more tightly control by Federal and State regulations. A licensed practitioner who administers, prescribes, or dispenses controlled substances must register under Controlled Substances Act of 1970 with the Drug Enforcement Administration (DEA) and obtain a DEA number, which must be included on every prescription for a controlled substance. Many States have additional requirements.

The Diversion Control Amendments of 1984, part of the Comprehensive Crime Control Act of 1984, authorizes the U.S. Attorney General to grant or deny an application for a DEA number based on the (1) recommendation of State licensing boards, (2) applicant’s experience in dispensing or conducting research with controlled substances, and (3) applicant’s conviction record related to the manufacture, distribution, or dispensing of controlled substances.24