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Opioid Addiction (Archived)

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Last Update: July 21, 2023.


Opioid use disorder and opioid addiction remain at epidemic levels in the US and worldwide. Three million US citizens and 16 million individuals worldwide have had or currently suffer from opioid use disorder (OUD). More than 500,000 in the United States are dependent on heroin. The diagnosis of OUD is made by meeting two or more of the eleven criteria in a year time period. 

The key elements are as follows:

  • Increasing dose/tolerance
  • Wish to cut down on use
  • Excessive time spent to obtain or use the medication
  • Strong desire to use
  • Use interferes with obligations
  • Continued use despite life disruption
  • Use of opioids in physically hazardous situations
  • Reduction or elimination of important activities due to use
  • Continued use despite physical or psychological problems
  • Need for increased doses of the drug
  • Withdrawal when the dose is decreased

The increase in OUD can be partially attributed to overprescribing of opioid medications. Healthcare providers in the 1990s increased opioid prescribing in response to the "pain as fifth vital sign" campaign, downplay of the abuse potential of opioids, and aggressive marketing of drugs such as Oxycontin and Opana. Risk factors for misuse of these medications are initiation at a young age, previous history of illicit drug or alcohol abuse, family history of illicit drug or alcohol abuse, sexual abuse in females, adverse childhood experiences, and psychological comorbidities (depression, bipolar disorder, and attention deficit hyperactivity disorder)[1]


Opioid addiction results from many practices and behaviors. The United States possesses an insatiable appetite for the prescription of opioid medications. In 2015, 91.8 million individuals in the United States used prescription opioids. Due to their inarguable abuse potential, these drugs are frequently misused, with high numbers of patients developing dependence. Opioid medications prescribed for mild to moderate acute pain were continued indefinitely, with no intention of tapering or ceasing use. Due to pharmacologic effects, opioids are highly addictive. Tolerance is achieved within days, and the withdrawal syndrome is severe. [2][3][4]


Opioid addiction afflicts individuals from all socioeconomic and educational backgrounds. Four million people admit to the nonmedical use of prescription opioids. Perhaps more concerning, 400,000 people had used heroin in the past month based on data from 2015 through 2016. Roughly 80% of new heroin users in the United States report pills as their initiation to opioid use and subsequent OUD.

From 2002 through 2011, approximately 25 million people in the United States began nonmedical use of pain relievers. More than 11 million misused the medications.

Emergency department visits due to complications and overdose have increased annually since 2010. Rates of ED visits involving opioids more than tripled from 1999 through 2013. 

In 2017, opioid overdose was declared a national emergency in the United States. [5][6]


Opioids bind to receptors in the central and peripheral nervous systems (primarily delta, kappa, and mu), with treatment effects for pain, cough, and diarrhea. Action on these same receptors induces intense euphoria. This causes many individuals to continue using with the intention of recreating that first high. Most people who misuse opioids do so for pain relief or to prevent withdrawal symptoms. Increasing evidence is dispelling the myth that opioids are effective long-term analgesic medications.

Below are receptors matched to physiologic effects in the central nervous system (nociceptin and zeta receptors are increasingly researched):

  • Delta: analgesia, antidepressant, convulsant, physical dependence, modulate mu-related respiratory depression
  • Kappa: analgesia, anticonvulsant, depression, hallucination, diuresis, dysphoria, miosis, neuroprotection, sedation
  • Mu: analgesia, physical dependence, respiratory depression, miosis, euphoria, reduced GI motility, vasodilation. Peripheral mu receptors are tissue-specific with higher concentrations in bronchial smooth muscle and the digestive tract. This is the reason for opioids suppressing the cough reflex and causing constipation.[7]

Withdrawal symptoms manifest when opioids are discontinued abruptly, though can occur with tapered cessation of medications. Withdrawal symptoms present in acute, subacute, and chronic phases. Most healthcare providers are aware of the acute withdrawal symptoms: hot/cold flashes, nausea, vomiting, diarrhea, sweating, lacrimation, insomnia, anxiety, generalized muscle pain, tachycardia, piloerection, and dehydration. However many providers do not have experience with the prolonged subacute chronic phases.


Chronic opioid use causes alterations in receptor sensitivity, leading to medication tolerance and changes in pain perception. Opioid-induced hyperalgesia (OIH) causes pain perception out of proportion to the stimulus (hyperalgesia) in those who use or misuse opioids long-term.


The toxicokinetics of opioid drugs varies within the class. Half-lives range from minutes (heroin) to many hours (methadone). Potencies of opioids also vary drastically, with more potent synthetic drugs such as fentanyl, carfentanil, and newer compounds causing overdose deaths and necessitating large doses of naloxone for reversal.

Opioids tend to be lipophilic and metabolized in the liver by both phase 1 (modification) and phase 2 (conjugation) reactions.

History and Physical

History and physical examination in patients with OUD vary depending on duration and intensity of use. Patients who sporadically misuse small doses of opioids may have a completely normal physical exam and no clear historical findings. Patients with chronic oral opioid use may have sedation if actively using the drug, along with miosis and hyperactive response to pain. 

Patients who are dependent on intravenous heroin may have the many effects of injection drug abuse: 

  • Bacteremia
  • Endocarditis
  • Track marks and scarring in common sites of injection
  • Skin-popping scars
  • Poor dentition
  • Lack of IV access sites
  • Abscess or cellulitis
  • Stigmata of hepatitis
  • Cirrhosis, and many other findings. 

History may be limited as patients are often not forthcoming when discussing substance abuse patterns. However, it is crucial to obtain detailed history in patients in whom OUD or its sequelae are suspected.


Providers who suspect OUD should begin with a detailed history and physical exam. Patients may initially withhold information. Others may be overtly dishonest and manipulative.

As mentioned above, these patients are at risk for secondary effects of drug abuse. Patients dependent on heroin frequently have infectious complications. Therefore, many patients should have laboratory studies ordered and selected imaging depending on presenting symptoms. [8][9]

Treatment / Management

Practitioners should offer patients who have OUD inpatient or outpatient substance use disorder (SUD) treatment. The short-term use of new opioid prescriptions does not provide long-term benefits. Regulations limiting the prescription of opioids are increasingly incorporated into state laws in the US.

Patients presenting with opioid withdrawal often require antiemetic/antidiarrheal therapy and IV hydration. Medications for OUD (MOUD), such as buprenorphine (a partial mu agonist and kappa antagonist), can be initiated for effective therapy in a medically supervised opioid withdrawal. Buprenorphine should be started in patients with mild-to-moderate withdrawal (Clinical Opioid Withdrawal Scale [COWS] of greater than 10 or 12) symptoms. Methadone, which is a full agonist mu receptor, can also control opioid withdrawal symptoms and complete opioid detoxification. [10]

Opioid overdose should be promptly treated with naloxone to reverse the effects of the drug, particularly respiratory depression. Adequate intravenous access allows IV fluid administration and repeat naloxone dosing when indicated. Begin with an intravenous dose of 0.4 to 0.8 mg to reverse neurologic and cardiorespiratory symptoms[11]. Patients who have taken large doses of very potent opioids may require larger doses. Naloxone can also be administered intranasally and intramuscularly.  

Medications have shown promising results in the treatment of OUD. Nabumetone, buprenorphine, methadone, and naltrexone are used in various combinations to decrease abuse of both oral opioids and heroin. All patients at risk for overdose should have or receive naloxone kits for home use. [12][13][14]

Mainstreaming Addiction Treatment (MAT) Act

The Mainstreaming Addiction Treatment (MAT) Act provision updates federal guidelines to expand the availability of evidence-based treatment to address the opioid epidemic. The MAT Act empowers all health care providers with a standard controlled substance license to prescribe buprenorphine for opioid use disorder (OUD), just as they prescribe other essential medications. The MAT Act is intended to help destigmatize a standard of care for OUD and will integrate substance use disorder treatment across healthcare settings. 

As of December 2022, the MAT Act has eliminated the DATA-Waiver (X-Waiver) program. All DEA-registered practitioners with Schedule III authority may now prescribe buprenorphine for OUD in their practice if permitted by applicable state law, and SAMHSA encourages them to do so. Prescribers who were registered as DATA-Waiver prescribers will receive a new DEA registration certificate reflecting this change; no action is needed on the part of registrants.

There are no longer any limits on the number of patients with OUD that a practitioner may treat with buprenorphine. Separate tracking of patients treated with buprenorphine or prescriptions written is no longer required. 

Pharmacy staff can now fill buprenorphine prescriptions using the prescribing authority's DEA number and does not need a DATA 2000 waiver from the prescriber. However, depending on the pharmacy, the dispensing software may still require the X-Waiver information in order to proceed. Practitioners are still required to comply with any applicable state limits regarding the treatment of patients with OUD.  Contact information for State Opioid Treatment Authorities can be found here: https://www.samhsa.gov/medicationassisted-treatment/sota.

Differential Diagnosis

  • Acute pancreatitis 
  • Bacterial gastroenteritis 
  • Barbiturate toxicity 
  • Benzodiazepine toxicity 
  • Chronic pancreatitis
  • Influenza
  • Peptic ulcer disease
  • Viral gastroenteritis


Patients who abuse heroin have higher rates of motor vehicle accidents than people who are not abusing heroin[15] No data has proven significant driving performance changes in patients on medication-assisted treatment (MAT) [16]

Pearls and Other Issues

OUD has reached epidemic proportions both in the US and worldwide. Forty-nine US states have enacted prescription drug monitoring programs.

Other preventive treatments include good samaritan laws and naloxone distribution for overdose death prevention, harsher penalties for drug dealers, disincentives to the prescription of opioids, needle exchanges to curtail infectious complications, and increased state and federal funding for rehabilitation and recovery. 

Enhancing Healthcare Team Outcomes

Opioids, also called narcotics, are highly addictive pain medications. While they are strong pain relievers, they have high addiction potential. It behooves clinicians to prescribe opioids only for severe pain and discontinue the medication as soon as feasible.

Review Questions


Kaye AD, Jones MR, Kaye AM, Ripoll JG, Galan V, Beakley BD, Calixto F, Bolden JL, Urman RD, Manchikanti L. Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1. Pain Physician. 2017 Feb;20(2S):S93-S109. [PubMed: 28226333]
Abdel Shaheed C, McLachlan AJ, Maher CG. Rethinking "long term" opioid therapy. BMJ. 2019 Nov 29;367:l6691. [PubMed: 31784472]
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Degenhardt L, Grebely J, Stone J, Hickman M, Vickerman P, Marshall BDL, Bruneau J, Altice FL, Henderson G, Rahimi-Movaghar A, Larney S. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. Lancet. 2019 Oct 26;394(10208):1560-1579. [PMC free article: PMC7068135] [PubMed: 31657732]
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Theriot J, Sabir S, Azadfard M. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 21, 2023. Opioid Antagonists. [PubMed: 30725764]
Hayes CJ, Krebs EE, Hudson T, Brown J, Li C, Martin BC. Impact of opioid dose escalation on the development of substance use disorders, accidents, self-inflicted injuries, opioid overdoses and alcohol and non-opioid drug-related overdoses: a retrospective cohort study. Addiction. 2020 Jun;115(6):1098-1112. [PMC free article: PMC7263736] [PubMed: 31944486]
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Disclosure: Mohammadreza Azadfard declares no relevant financial relationships with ineligible companies.

Disclosure: Martin Huecker declares no relevant financial relationships with ineligible companies.

Disclosure: James Leaming declares no relevant financial relationships with ineligible companies.

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Bookshelf ID: NBK448203PMID: 28846246


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