Prescription of Controlled Substances: Benefits and Risks

Link to article at PubMed

2021 Feb 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.


One of the single most difficult challenges for any prescriber is to distinguish between the legitimate prescription of controlled substances versus the prescription potentially used for illegitimate purposes. To discern the difference, prescribers need to understand the signs, symptoms, and treatment of acute and chronic pain as well as the signs and symptoms of patients misusing controlled substances.

A common reason people seek the care of medical professionals is pain relief. While many categories of pain medications are available, opioid analgesics are FDA-approved for moderate to severe pain. As such, they are a common choice for patients with acute, cancer-related, neurologic, and end-of-life pain. The prescribing of opioid analgesics for chronic pain is controversial and fraught with inconclusive standards.

In the 1990s, due to the chronic failure of health professionals to undertreat severe pain, opioid analgesic prescribing was expanded. Unfortunately, this led to increased overuse, diversion of drugs, opioid use disorder, and overdose. The "Catch-22" seems to be either health professionals undertreat, and there is needless suffering, or they overtreat, with a potential to cause adverse effects like increased opioid analgesic use disorder and potential overdose.

The prescription of opioid analgesics peaked in 2011. Since then, both prescribing and overdose have been declining, yet as a society, in both the lay and scientific literature, there are grave concerns that we are still in the middle of an opioid crisis.

Perhaps the biggest challenge of caring for patients with pain is that individuals have different levels of tolerance and require variable opioid doses to obtain adequate pain relief. Patients may have a range of behavioral, cultural, emotional, and psychologic responses to pain versus a substance use disorder; often, it is challenging to tell the difference. All health professionals engaged in pain management need an understanding of the treatment recommendations and safety concerns in prescribing opioid analgesics. Appropriate opioid prescribing requires a thorough patient assessment, short and long-term treatment planning, close follow-up, and continued monitoring. All providers need to be aware of not only appropriate patient assessment and treatment planning but also the possibility of use disorder, diversion, and potentially dangerous behavioral responses to controlled substances, e.g., opioid analgesics differ from pseudo-addiction and physical dependence.

It is unfortunately clear that many clinicians know little about opioid use disorder. They do not understand it is a disease, and many believe opioid dependence is the same as opioid use disorder. Lack of a clear understanding results in clinicians confusing a patient with chronic non-use disorder from the one who is misusing their prescribed opioid. Lack of training and educational deficits often interfere with the appropriate prescription of opioid analgesic agents. To prevent the misuse of controlled substances, providers that prescribe controlled substances should learn prescribing practices that minimize or prevent adverse consequences.


  1. Addiction - according to the American Society of Addiction Medicine (ASAM): "Addiction is a primary, chronic disease of brain reward, motivation, memory, and related circuitry. Dysfunction in these circuits leads to characteristic biologic, psychologic, social, and spiritual manifestations. This is reflected in an individual pathologically pursuing reward or relief by substance use and other behaviors." Addiction is now termed "use disorder," and is characterized by an inability to consistently abstain, craving the drug, impairment in behavioral control, diminished ability to recognize significant problems with one's behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, use disorder often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, use disorder is progressive and can result in disability or premature death."

  1. Appropriate opioid prescribing: providing pain control while minimizing toxicity, use disorder, or the risk of use disorder and implementing safeguards to reduce drug diversion.

  1. Inappropriate opioid analgesic prescribing: non-prescribing, inadequate prescribing, excessive prescribing, or continued prescribing despite evidence of the lack of effective opioid treatment.

  1. Controlled substances: drugs or medications that possess the potential for being misused and are considered to be substances that have a substantially high risk of resulting in substance use disorder.

  1. Opioid analgesics: these comprise drugs that dull the senses and relieve pain, e.g., morphine. Also, these medications may induce sleep. Please note that the Drug Enforcement Administration (DEA, USA) uses the term "narcotic" to refer to drugs that are opioid analgesics.

Five Characteristics of Addiction/Use Disorder (ASAM)

  1. Craving for drug or reward

  2. Diminished recognition of significant problems in one's behavior

  3. Dysfunctional emotional response

  4. Impairment in behavioral control

  5. Inability to consistently abstain

Drug Schedules of Controlled Substances

All providers should be familiar with the guidelines and laws for each schedule, which have, as their basis, the purpose of the drug and the risk of use disorder. In the United States, controlled substances are under strict regulation by both federal and state laws that guide their manufacture and distribution. Controlled substances have a high risk of resulting in an addiction and substance use disorder. As the schedules decrease, I-V, the drugs listed within each category have a lower potential to cause a substance use or addiction disorder.

Controlled Substance Act

In the United States, the Comprehensive Drug Abuse Prevention and Control Act was passed in 1970, and it included the Controlled Substance Act. The Controlled Substance Act covers drug:

  1. Classification and regulation, according to their content and purpose.

  2. Manufacturing

  3. Distribution

  4. Exportation and sale

The Controlled Substance Act established five drug schedules and classified them to control their manufacture and distribution. Part of the regulation requires providers that prescribe scheduled drugs and pharmacists that fill them to obtain a license from the Drug Enforcement Administration. Health professionals' licenses include specific license numbers allowing controlled substance prescriptions to be tracked and linked to a particular provider or distributor.

Of the five schedules, each has parameters based on their medical value, the risk of addiction, and the ability to cause harm. The schedules range from Schedule I (most potential for addiction and use disorder) to Schedule V (least potential for addiction/use disorder).

Schedule I

  1. Schedule I drugs possess the highest potential for use disorder and misuse. They have no medical use and are illicit or “street” drugs.

  2. Examples of Schedule I drugs include heroin, lysergic acid diethylamide, mescaline, methylenedioxymethamphetamine (MDMA), and methaqualone.

  3. Marijuana, which is legal in some states, is still classified as a Schedule I drug at the federal level as of this writing.

Schedule II

  1. Schedule II drugs have a reduced potential for use disorders than Schedule I. They are at high risk for both physical and psychological dependence. They have a high capacity for both use disorder and misuse. They are typically prescribed to treat severe pain, anxiety, insomnia, and ADHD.

  2. Examples of Schedule II substances include fentanyl, hydromorphone, meperidine, methadone, morphine, oxycodone, fentanyl, dextroamphetamine, methylphenidate, methamphetamine, pentobarbital, and secobarbital.

  3. They previously had to be prescribed only via paper prescription, but now are permitted to be electronically transmitted. (Electronic Prescribing of Controlled Substances or EPCS).

  4. No refills are allowed.

  5. Schedule II drugs have the tightest regulations when compared to other prescription drugs.

Schedule III

  1. Schedule III drugs are those with a lower misuse potential than I and II. Drugs in this category may cause physical dependence but more commonly lead to psychological dependence. Medications in this category are often used for pain control, or anesthesia, or appetite suppression.

  2. Examples of Schedule III substances include benzphetamine, ketamine, phendimetrazine, and anabolic steroids.

  3. Opioid analgesics in this schedule include products containing not more than 90 milligrams of codeine per dosage unit and buprenorphine.

  4. Schedule III drugs are prescribable verbally over the phone, with a paper prescription, or via EPCS.

  5. Within a six-month time frame, refill requirements are such that the drug can only have five refills.

Schedule IV

  1. Schedule IV drugs have an even lower misuse potential than I, II, or III. They have a limited risk of physical or psychological dependence.

  2. Examples of Schedule IV substances include: alprazolam, carisoprodol, clonazepam, clorazepate, diazepam, lorazepam, midazolam, temazepam, tramadol, and triazolam.

  3. Drugs in this class may be utilized for pain control as long as the provider deems the drug to be medically necessary and that the patient would benefit.

  4. Schedule IV drugs are prescribable verbally over the phone, with a paper prescription, or via EPCS.

  5. Refills are permitted up to five times in a six-month timeframe from the issuance date.

Schedule V

  1. Schedule V drugs are the least likely of the controlled substances to be misused. They result in very limited physical or psychological dependence.

  2. Examples include cough medicines with codeine, antidiarrheal medications that contain atropine/diphenoxylate, pregabalin, and ezogabine.

  3. Despite their low abuse potential, they still need to be managed appropriately and administered with care.

  4. When they contain codeine, it must have less than 200 mg of codeine per 100 mL.

  5. Partial prescription fills cannot occur more than six months after the date of issue. When a partial fill occurs, it is treated in the same manner and with the same rules as a refill of the drug.

Drug Use Disorder, Abuse, and Misuse

The use disorder of a drug differs from abuse and misuse of a drug.

The drugs taken may be illicit street or stolen drugs or obtained via a legal prescription. Misusing a drug usually involves taking the drug in a harmful or detrimental way that results in personal, professional, or social problems. A patient that is abusing an opioid analgesic may no longer be appropriately interacting with their family, friends or be able to perform their duties at work.

Misuse of a controlled substance refers to the use of a prescribed drug in a way that was not intended. It may be deliberate or accidental. A negative result may or may not occur. Examples of misuse include taking too much of a drug, using an incorrect dose, incorrect route, or using prescription drugs written for another person.

Controlled substances include both prescription drugs and illicit drugs with no recognized medical value. Both have the potential to be abused or misused. While Schedule I drug use is illegal, prescription drugs found in Schedules II-V are also commonly abused and misused, and their misuse is a challenging problem that has increased over the last several years.

The Centers for Disease Control and Prevention has declared prescription drug abuse a problem of epidemic proportions. The CDC believes that absent checks and balances on the prescription and distribution of controlled substances, including those prescribed for medical use, have the potential for abuse and that misuse will continue to increase.

Pill Shopping

Unfortunately, a common practice among those that deliberately misuse controlled substances is to seek out multiple sources of drugs. They do this by seeing different health care providers, and they present with a different list of complaints that are often fictitious and different for each provider. The patient may be able to obtain multiple prescriptions and then fill them at different pharmacies. Many states have enacted systems that allow providers to see all of the prescriptions written for each patient. The use of these systems is gradually curbing "pill shopping."


Some prescription drugs will sell on the street for as much as $50 a tablet. Diversion is when a patient sells their drugs as a method of earning money. Drugs may also be sold to buy food, pay expenses, or purchase more potent street drugs. Worse, in some cases, healthcare providers may divert drugs from patients for the providers' own personal use or sell them to someone else.

Some individuals use controlled substances in ways for which they were not originally intended. Rather than pain control, they may be used to stay awake, induce sleep, or get "high." Before the popularity of prescription drug diversion, the only method to obtain illicit drugs was to import from other countries or manufacture them in private labs. Today, law enforcement agencies have the tremendous challenge of dealing with prescription drugs sold by diversion as well as illicit drugs imported or manufactured. In both instances, these drug sales and usage result in increased criminal activity as well as dangerous overdoses and death.

Methods of Obtaining Prescription Drugs

A review of multiple studies demonstrates a variety of ways individuals obtain prescription drugs. The following summarizes the studies' findings.

  1. 55% free from a friend or relative

  2. 20% from a prescriber

  3. 10% purchased from a friend or relative

  4. 5% stolen from a friend or relative

  5. 5% purchased from a drug dealer

  6. 2% from multiple doctors

  7. 1% from theft from medical practice or pharmacy

  8. Less 1% from internet

Studies also reveal the source of the majority of these drugs was a single legal prescriber.

PMID:30726003 | Bookshelf:NBK537318

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