Opioid abuse and dependence

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Synonyms and Keywords: Opioid use disorder


With chronic use for treatment of pain, dependence may lead to substance abuse and "aberrant medication-taking behaviors" may occur.[1] From 2000-2005, the abuse of prescribed opiods, especially oxycodone extended release (OxyContin) and hydrocodone, has increased.[2]



Tolerance is the process whereby neuroadaptation occurs (through receptor desensitization) resulting in reduced drug effects. Tolerance is more pronounced for some effects than for others - tolerance occurs quickly to the effects on mood, itching, urinary retention, and respiratory depression, but occurs more slowly to the analgesia and other physical side effects.

Tolerance to opioids is attenuated by a number of substances, including calcium channel blockers[3][4], intrathecal magnesium[5] and zinc[6], and NMDA antagonists such as ketamine.[7]

Magnesium and zinc deficiency speed up the development of tolerance to opioids and relative deficiency of these minerals is quite common[8] due to low magnesium/zinc content in food and use of substances which deplete them including diuretics (such as alcohol, caffeine/theophylline) and smoking. Reducing intake of these substances and taking zinc/magnesium supplements may slow the development of tolerance to opiates.


Dependence is characterised by extremely unpleasant withdrawal symptoms that occur if opioid use is abruptly discontinued after tolerance has developed. The withdrawal symptoms include severe dysphoria, sweating, nausea, rhinorrea, depression, severe fatigue, vomiting and pain. Slowly reducing the intake of opioids over days and weeks will reduce or eliminate the withdrawal symptoms.[9] The speed and severity of withdrawal depends on the half-life of the opioid — heroin and morphine withdrawal occur more quickly and are more severe than methadone withdrawal, but methadone withdrawal takes longer. The acute withdrawal phase is often followed by a protracted phase of depression and insomnia that can last for months. The symptoms of opioid withdrawal can also be treated with other medications, but with a low efficacy.[10]


Addiction is the process whereby physical and/or psychological addiction develops to a drug - including opioids. The withdrawal symptoms can reinforce the addiction, driving the user to continue taking the drug. Psychological addiction is more common in people taking opioids recreationally, it is rare in patients taking opioids for pain relief.[11]


Drug abuse is the misuse of drugs producing negative consequences.

Differential Diagnosis

Epidemiology and Demographics


The 12 month prevalence of opioid use disorder is 370 per 100,000 (0.37%) in ages 18 years and older in the community population.[12]

Risk factors

Variability in opioid prescribing in emergency departments is a risk factor.[13][14] The Centers for Disease Control and Prevention has studied risk factors[15].

Diagnostic Criteria

DSM-V Diagnostic Criteria for Opioid Use Disorder[12]

  • A. A problematic pattern of opioid use leading to clinically significant impairment or distress,as manifested by at least two of the following, occurring within a 12-month period:
  • 1. Opioids are often taken in larger amounts or over a longer period than was intended.
  • 2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
  • 3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
  • 4. Craving, or a strong desire or urge to use opioids.
  • 5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
  • 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
  • 7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
  • 8. Recurrent opioid use in situations in which it is physically hazardous.
  • 9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
  • 10. Tolerance, as defined by either of the following:
  • a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect.
  • b. A markedly diminished effect with continued use of the same amount of an opioid.

Note: This criterion is not considered to be met for those taking opioids solely under appropriate medical supervision.

  • 11. Withdrawal, as manifested by either of the following:
  • a. The characteristic opioid withdrawal syndrome.
  • b. Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.

Note: This criterion is not considered to be met for those individuals taking opioids solely under appropriate medical supervision .

Specify if:

  • In early remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use opioids,” may be met).
  • In sustained remission: After full criteria for opioid use disorder were previously met,none of the criteria for opioid use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong desire or urge to use opioids,” may be met).

Specify if:

  • On maintenance therapy: This additional specifier is used if the individual is taking a prescribed agonist medication such as methadone or buprenorphine and none of the criteria for opioid use disorder have been met for that class of medication (except tolerance to, or withdrawal from, the agonist). This category also applies to those Individuals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist such as oral naltrexone or depot naltrexone.
  • In a controlled environment: This additional specifier is used if the individual is in an environment where access to opioids is restricted.


  1. Martell BA, O'Connor PG, Kerns RD; et al. (2007). "Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction". Ann. Intern. Med. 146 (2): 116–27. PMID 17227935.
  2. Cicero TJ, Inciardi JA, Muñoz A (2005). "Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004". J Pain. 6 (10): 662–72. doi:10.1016/j.jpain.2005.05.004. PMID 16202959.
  3. Santillán R, Maestre JM, Hurlé MA, Flórez J. "Enhancement of opiate analgesia by nimodipine in cancer patients chronically treated with morphine: a preliminary report." Pain. 1994 Jul;58(1):129-32. PMID 7970835
  4. Smith FL, Dombrowski DS, Dewey WL. "Involvement of intracellular calcium in morphine tolerance in mice." Pharmacology, Biochemistry, and Behavior. 1999 Feb;62(2):381-8. PMID 9972707
  5. McCarthy RJ, Kroin JS, Tuman KJ, Penn RD, Ivankovich AD. "Antinociceptive potentiation and attenuation of tolerance by intrathecal co-infusion of magnesium sulfate and morphine in rats." Anesthesia and Analgesia. 1998 Apr;86(4):830-6. PMID 9539610
  6. Larson AA, Kovács KJ, Spartz AK. "Intrathecal Zn2+ attenuates morphine antinociception and the development of acute tolerance." European Journal of Pharmacology. 2000 Nov 3;407(3):267-72. PMID 11068022
  7. Wong CS, Cherng CH, Luk HN, Ho ST, Tung CS. "Effects of NMDA receptor antagonists on inhibition of morphine tolerance in rats: binding at mu-opioid receptors." Eur J Pharmacol. 1996 Feb 15;297(1-2):27-33. PMID 8851162
  8. http://www.worldwidehealthcenter.net/articles-360.html
  9. Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
  10. Hermann D, Klages E, Welzel H, Mann K, Croissant B. Low efficacy of non-opioid drugs in opioid withdrawal symptoms. Addict Biol. 2005 Jun;10(2):165-9. PMID: 16191669
  11. Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
  12. 12.0 12.1 12.2 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
  13. Young N, Silverman D, Bradford H, Finkelstein J (2017). "Multicenter prevalence of opioid medication use as abortive therapy in the emergency department treatment of migraine headaches". Am J Emerg Med. doi:10.1016/j.ajem.2017.06.015. PMID 28645559.
  14. Barnett ML, Olenski AR, Jena AB (2017). "Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use". N Engl J Med. 376 (7): 663–673. doi:10.1056/NEJMsa1610524. PMC 5428548. PMID 28199807.
  15. Shah A, Hayes CJ, Martin BC (2017). "Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015". MMWR Morb Mortal Wkly Rep. 66 (10): 265–269. doi:10.15585/mmwr.mm6610a1. PMID 28301454.

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