Harrisons Manual of Medicine, 18th Ed.

CHAPTER 212. Narcotic Abuse

Narcotics, or opiates, bind to specific opioid receptors in the CNS and elsewhere in the body. These receptors mediate the opiate effects of analgesia, euphoria, respiratory depression, and constipation. Endogenous opiate peptides (enkephalins and endorphins) are natural ligands for the opioid receptors and play a role in analgesia, memory, learning, reward, mood regulation, and stress tolerance.

The prototypic opiates, morphine and codeine, are derived from the juice of the opium poppy. The semisynthetic drugs produced from morphine include hydromorphone (Dilaudid), diacetylmorphine (heroin), and oxyco-done (OxyContin). The purely synthetic opioids and their cousins include meperidine, propoxyphene, diphenoxylate, fentanyl, buprenorphine, tramadol, methadone, and pentazocine. All of these substances produce analgesia and euphoria as well as physical dependence when taken in high enough doses for prolonged periods of time.


The 0.14% annual prevalence of heroin dependence in the United States is only about one-third the rate of prescription opiate abuse and is substantially lower than the 2% rate of morphine dependence in parts of Asia. Since 2007, prescription opiates have surpassed marijuana as the most common illicit drug that adolescents initially abuse.

Acute Effects

All opiates have the following CNS effects: sedation, euphoria, decreased pain perception, decreased respiratory drive, and vomiting. In larger doses, markedly decreased respirations, bradycardia, pupillary miosis, stupor, and coma ensue. Additionally, the adulterants used to “cut” street drugs (quinine, phenacetin, strychnine, antipyrine, caffeine, powdered milk) can produce permanent neurologic damage, including peripheral neuropathy, amblyopia, myelopathy, and leukoencephalopathy; adulterants can also produce an “allergic-like” reaction characterized by decreased alertness, frothy pulmonary edema, and an elevation in blood eosinophil count.

Chronic Effects

Tolerance and withdrawal commonly occur with chronic daily use after 6–8 weeks depending on the dose and frequency; the ever-increasing amounts of drug needed to sustain euphoriant effects and avoid discomfort of withdrawal strongly reinforce dependence once it has started.


Withdrawal produces nausea and diarrhea, coughing, lacrimation, mydriasis, rhinorrhea, diaphoresis, twitching muscles, piloerection, fever, tachypnea, hypertension, diffuse body pain, insomnia, and yawning.

With shorter-acting opiates such as heroin, morphine, or oxycodone, withdrawal signs begin 8–16 h after the last dose, peak at 36–72 h, and subside over 5–8 days. With longer-acting opiates such as methadone, withdrawal begins several days after the last dose, peaks at 7–10 days in some cases, and lasts several weeks.

TREATMENT Narcotic Abuse


• High doses of opiates, whether taken in a suicide attempt or accidentally when potency is misjudged, are potentially lethal. Toxicity occurs immediately after IV administration and with a variable delay after oral ingestion. Symptoms include miosis, shallow respirations, brady-cardia, hypothermia, and stupor or coma.

• Managing overdose requires support of vital functions, including intubation if needed.

• The opiate antagonist naloxone is given at 0.4–2 mg IV or IM with an expected response within 1–2 min; repeated doses may be needed for 24–72 h depending on the opiate used in overdose


• Long-acting opiates such as methadone or buprenorphine can be used to treat withdrawal and achieve detoxification by slowly tapering the dose over weeks to months. Buprenorphine produces fewer withdrawal symptoms compared with methadone but does not appear to result in better outcomes.

• Several α-2-adrenergic agonists have relieved opioid withdrawal and achieved detoxification by suppressing central noradrenergic activity. Clonidine and lofexidine are commonly used orally in three to four doses per day. Completion rates of managed withdrawal are similar to methadone.

• Rapid opiate detoxification can be accomplished with naltrexone combined with an α-2-adrenergic agonist. Completion rates are high, but the approach is highly controversial due to the medical risks and even mortality associated with this approach.


• Methadone maintenance is a widely used treatment strategy in the management of opiate addiction. Methadone is a long-acting opioid optimally dosed at 80–150 mg/d (gradually increased over time).

• The partial agonist buprenorphine can also be used; it has several advantages, including low overdose danger, potentially easier detoxification than with methadone, and a probable ceiling effect in which higher doses do not increase euphoria. In the U.S. primary care physicians can prescribe buprenorphine; this may improve access and quality of treatment.


• Rationale is that blocking the action of self-administered opioids should eventually extinguish the habit; poorly accepted by many pts.

• Naltrexone can be given three times a week (100- to 150-mg dose); a depot form for monthly injection is available and improves adherence, retention, and decreases opioid use.


• Medication-free treatments in inpatient, residential, or outpatient settings have poor 1- to 5-year outcomes compared with pharmacotherapy; exceptions are residential programs lasting 6–18 months, which require full immersion in a regimented system.


Preventing opiate abuse is a critically important challenge for physicians. Sources of opiates for the 9000 adolescents in the United States that become abusers daily are most commonly family members, not drug dealers or the Internet. Except for the terminally ill, physicians should carefully monitor opioid drug use in their pts, keeping doses as low as is practical and administering them over as short a period as the level of pain would warrant in the average person. Pts must dispose of any remaining opiates after treatment. Physicians must be vigilant regarding their own risk for opioid abuse and dependence, never prescribing these drugs for themselves.


For a more detailed discussion, see Kosten TR: Opioid Drug Abuse and Dependence, Chap. 393, p. 3552, in HPIM-18.