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PatientPlus articles are written for doctors and so the language can be technical. However, some people find that they add depth to the articles found in the other sections of this website which are written for non-medical people.

Opioid Dependence

Opioids have been around for centuries, dating before the Egyptians. There are estimated to be almost 300,000 drug misusers in the UK.1 Opioids can be used intravenously, subcutaneously, smoked or even intranasally. Despite the long presence of opioids the underlying cellular causes of dependence and tolerance still remain elusive.2

Some distinctions

  • Opiate - analgesics derived from naturally occurring opium e.g. morphine, diamorphine (heroin) and codeine.
  • Opioid - includes opiates and synthetic analgesics (e.g. partially synthetic diamorphine, oxycodone and completely synthetic, fentanyl and methadone).

Method of action of opiates

  • Opiates stimulate opioid receptors.
  • Opioid receptors are found in the periaqueductal grey, spinal cord, peripheral nerves, gastrointestinal tract and the adrenal medulla.
  • There are five types: mu, kappa, sigma, delta, and epsilon.
  • Binding to the mu and sigma receptors account largely for the euphoric effect.2,3

Opiates have two major effects

  • Analgesic effect
  • Euphoria - this is the main reason they are abused

Opioid addiction

Characteristic features include drug craving and maladaptive behaviour focussed on obtaining opioids at any cost. Opioid misuse can be defined as a continuous compulsion to use opioids despite physical, psychological or social harm to the user.1

Dependence and tolerance

Definition of Dependence (DSM IV)4(Presence of three or more features, for one year or more)

  • Tolerance: a need for markedly increased amounts of the substance to achieve intoxication or desired effect or markedly diminished effect with continued use of the same amount of the substance.
  • Withdrawal: the characteristic withdrawal syndrome for the substance or the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.
  • The substance is often taken in larger amounts or over a longer period than was intended.
  • There is a persistent desire or unsuccessful efforts to cut down or control substance abuse.
  • A great deal of time is spent in activities necessary to obtain the substance, use the substance or recovering from its effects.
  • Important social, occupational or recreational activities are given up or reduced because of substance use.
  • The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

Opiate dependence occurs with in 2-10 days of continuous use and can be physical and psychological (onset and duration varies for each drug).3

  • Physical: mostly autonomic e.g. sweating, tachycardia, hypertension and other symptoms e.g. diarrhoea, rhinorrhoea, abdominal cramps, nausea and vomiting.
  • Psychological: such as anxiety and sleeplessness.
  • Dependence results in the need to continue to take the drug.
  • Tolerance also occurs and results in the need for a higher dose of opioids to maintain the initial effect. (Also get tolerance to the analgesic and adverse effects e.g. respiratory depression and sedation).

Health problems relating to opioid dependence include

  • Simultaneous abuse of other substances e.g. crack cocaine
  • IV use associated with spread of blood borne viruses
  • Intoxication
  • Skin infection
  • Accidental overdose
  • Higher death rates
Treatment of opioid dependence and intoxication

If patient acutely intoxicated - refer urgently to hospital

  • Therapy is mostly supportive e.g. maintain airway, ventilation if necessary and IV fluids.
  • Naloxone - a pure opioid antagonist used for reversing opioid intoxication - has a rapid onset of action and can be given IM or IV.

Approach to a patient with a known history of opioid dependence

  • Do they want to undergo detoxification?
  • Are there any co-morbid medical or psychiatric conditions (these reduce the chances of success)?
  • Assess mental health of the patient - are there any other underlying psychiatric disorders which need treating?
  • Are there any adverse health affects from drug misuse, thus check FBC, U and E, LFT, HIV, hepatitis and syphilis serology.

Approach to the management of a patient with opioid dependence

  • Discuss with the local community drug team or specialist.
  • Patient and family education: include coping strategies, avoidance of high risk situations and local support groups.5,6
  • Psychological therapies: cognitive behavioural therapy, supportive therapy, group therapy etc.
  • Pharmacological strategies for substitution: e.g. Naloxone in acute setting and methadone for maintenance therapy.5 Start with low doses and gradually titrate upwards.
  • Review regularly - weekly at first and then at 3 month intervals once the patient has stabilised. Supervised consumption is usually undertaken until the patient is stabilised, this may take up to 6 months.

NICE guidelines describe two strategies for the treatment of opioid dependence

  • Harm reduction - i.e. take the patient off the opioid and supply a substitute for maintenance.3,5 Substitute opioids reduce hunger and result in reduced drug seeking behaviour and better social functioning. However, they are a substitute and have to be continued for as long as the patient gets benefit. In a sense, the patient becomes addicted to the substitute.
  • Detoxification and Abstinence - i.e. come off the opioid altogether. This is considered once the patient has been stabilised on methadone or buprenorphine and made appropriate lifestyle changes and is motivated to detoxify. This is usually initiated under specialist supervision.

The most commonly used medications for substitution are methadone, buprenorphine and lofexidine (all licensed for use in primary care). Naltrexone is used privately but is not licensed. Essentially the dose of the maintenance opioid is gradually reduced - this may take from days to years - it should be tailored to the individuals needs e.g. emergence of withdrawal symptoms.7,8

Ultra rapid detoxification involves heavily sedating patients or administering a general anaesthetic and then giving IV Naloxone such that, acute withdrawal occurs in the unconscious state. Residual symptoms usually persist, such as, vomiting and diarrhoea. However, insomnia can be severe and is a common cause for failure.3,9

Opioid agonists used for maintenance therapy

  • Methadone - most widely used in the UK. Methadone is a synthetic opioid agonist that binds to the opiate receptor and results in a slower onset of action so that the euphoric high is less prominent. It is usually taken orally and has a half-life of 24 hours.7,10 Long term therapy with methadone is associated with tolerance to the analgesic and euphoric effects. Side-effects include constipation and weight gain. Studies have shown that methadone maintenance reduces fatal and non-fatal heroin overdoses.6
  • Buprenorphine - is a synthetic partial opioid agonist and potent antagonist with strong analgesic effects. Taken sublingually as poorly absorbed from the gut.3,11
  • Naltrexone - is a long acting mu opioid antagonist, which is a derivative of Naloxone and licensed for prevention of relapse after abstinence. It accelerates detoxification, but craving may still occur. It is however, difficult to use as it requires abstinence on behalf of the patient and therefore is associated with high drop out rates. Also if the patient uses opiates whilst on naltrexone it can cause immediate withdrawal effects which can be serious.5,1 It should only be initiated under specialist supervision.

Non-opioid medications used in maintenance therapy

  • Clonidine - this is an alpha 2 agonist which reduces central noradrenaline release and works well at suppressing autonomic symptoms, but it needs to be used along with an opioid antagonist e.g. naltrexone.3,5
  • Lofexidine - similar to clonidine and also an alpha adrenergic agonist and is effective in reducing withdrawal symptoms.


Document references
  1. Drug misuse - naltrexone, NICE Technology Appraisal Guidance (2007); Naltrexone for the management of opioid dependence.
  2. Taylor DA, Fleming WW; Unifying perspectives of the mechanisms underlying the development of tolerance and physical dependence to opioids. J Pharmacol Exp Ther. 2001 Apr;297(1):11-8. [abstract]
  3. Drug misuse - methadone and buprenorphine, NICE Technology Appraisal Guidance (2007)
  4. DSM-IV Diagnostic Criteria: Substance Dependence
  5. O'Connor PG, Fiellin DA; Pharmacologic treatment of heroin-dependent patients. Ann Intern Med. 2000 Jul 4;133(1):40-54. [abstract]
  6. Sporer KA; Strategies for preventing heroin overdose. BMJ. 2003 Feb 22;326(7386):442-4.
  7. Krambeer LL, von McKnelly W Jr, Gabrielli WF Jr, et al; Methadone therapy for opioid dependence. Am Fam Physician. 2001 Jun 15;63(12):2404-10. [abstract]
  8. Lingford-Hughes A, Nutt D; Neurobiology of addiction and implications for treatment. Br J Psychiatry. 2003 Feb;182:97-100.
  9. Kaye AD, Gevirtz C, Bosscher HA, et al; Ultrarapid opiate detoxification: a review. Can J Anaesth. 2003 Aug-Sep;50(7):663-71. [abstract]
  10. Stebbings R, Berry N, Stott J, et al; Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfection. Virology. 2004 Dec 5;330(1):249-60. [abstract]
  11. Manlandro JJ Jr; Buprenorphine for office-based treatment of patients with opioid addiction. J Am Osteopath Assoc. 2005 Jun;105(6 Suppl 3):S8-13. [abstract]

Internet and further reading AcknowledgementsEMIS is grateful to Dr Gurvinder Rull for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 377
Document Version: 3
DocRef: bgp1623
Last Updated: 8 Oct 2007
Review Date: 7 Oct 2008

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