Executive summary

Publication Details


These guidelines were developed in response to a resolution from the United Nations Economic and Social Council (ECOSOC), which invited the World Health Organization (WHO), in collaboration with the United Nations Office on Drugs and Crime (UNODC), “to develop and publish minimum requirements and international guidelines on psychosocially assisted pharmacological treatment of persons dependent on opioids” [1]. In accordance with WHO policy, the recommendations in these guidelines are based on systematic reviews of the available literature and consultation with a range of experts from different regions of the world. The GRADE evidence tables summarizing these reviews are contained in Annex 1 of this document.


These guidelines are intended to be read by those involved in providing psychosocially assisted pharmacological treatments at any level. The readership falls into three broad groups:

  • policy makers and administrators who make decisions on the availability of medicines and the structure and funding of services in countries or in subnational health administrative regions
  • managers and clinical leaders responsible for the organization of specific health-care services, and for the clinical care those services provide
  • health-care workers treating patients within the health-care system.


UNODC estimates that there are 25 million problem drug users in world, of whom 15.6 are problem opioid users and 11.1 problem heroin users (approximately 0.3% of the global population) [2].1

The global epidemic of HIV and acquired immune deficiency syndrome (AIDS) is often fuelled and maintained by unsafe injection practices, with an estimated 30% of new cases of HIV outside sub-Saharan Africa due to unsafe injecting, [5] particularly unsafe opioid injecting. The cost of this epidemic is counted in the millions of lives lost each year and the billions of dollars spent [6]. A comprehensive package of interventions to prevent the transmission of HIV must include measures to reduce unsafe injecting of opioids, including the treatment of opioid dependence [7,11].

As with other chronic conditions, opioid dependence tends mostly to follow a relapsing and remitting course.


Psychosocially assisted pharmacological treatment refers to the combination of specific pharmacological and psychosocial measures used to reduce both illicit opioid use and harms related to opioid use and improve quality of life. While the psychosocial measures are varied, only a few specific medications are used for the treatment of opioid dependence.

Opioid agonist maintenance treatment is defined as the administration of thoroughly evaluated opioid agonists, by accredited professionals, in the framework of recognized medical practice, to people with opioid dependence, for achieving defined treatment aims [8,9,10. Both methadone and buprenorphine are sufficiently long acting to be taken once daily under supervision, if necessary. When taken on a daily basis they do not produce the cycles of intoxication and withdrawal seen with shorter acting opioids, such as heroin. Both methadone and buprenorphine can also be used in reducing doses to assist in withdrawal from opioids, a process also referred to as opioid detoxification. Methadone and buprenorphine have a strong evidence base for their use, and have been placed on the WHO model list of essential medicines [8].

A different approach is that of assisting people dependent on opioids to withdraw from opioids completely, a process also referred to as opioid detoxification. Both methadone and buprenorphine can also be used in reducing doses to assist in withdrawal from opioids. Alpha-2 adrenergic agonists – such as clonidine – can also be used for opioid detoxification, to reduce the severity of opioid withdrawal symptoms.

Following detoxification, the long-acting opioid antagonist naltrexone can be used to prevent relapse to opioids. Naltrexone produces no opioid effects itself, and blocks the effects of opioids for 24–48 hours.

The short-acting opioid antagonist naloxone can be used to reverse the effects of opioid intoxication and overdose.


Opioid agonist maintenance treatment

Of the treatment options examined, opioid agonist maintenance treatment, combined with psychosocial assistance, was found to be the most effective.

Oral methadone liquid and sublingual buprenorphine tablets are the medications most widely used for opioid agonist maintenance treatment. In the context of high-quality, supervised and well-organized treatment services, these medications interrupt the cycle of intoxication and withdrawal, greatly reducing heroin and other illicit opioid use, crime and the risk of death through overdose.

Compared to detoxification or no treatment, methadone maintenance treatment (using mostly supervised administration of the liquid methadone formulation) significantly reduces opioid and other drug use, criminal activity, HIV risk behaviours and transmission, opioid overdose and all-cause mortality; it also helps to retain people in treatment.

Compared to detoxification or no treatment, buprenorphine also significantly reduces drug use and improves treatment retention.

Methadone compared to buprenorphine for opioid agonist maintenance treatment

Comparing the evidence from clinical trials on the effectiveness of methadone and buprenorphine for opioid agonist maintenance treatment, both medications provide good outcomes in most cases. In general, methadone is recommended over buprenorphine, because it is more effective and costs less. However, buprenorphine has a slightly different pharmacological action; thus, making both medications available may attract greater numbers of people to treatment and may improve treatment matching.

Use of methadone in maintenance treatment

The initial methadone dose should be 20mg or less, depending on the level of opioid tolerance, allowing a high margin of safety to reduce inadvertent overdose. The dosage should be then quickly adjusted upwards if there are ongoing opioid withdrawal symptoms and downwards if there is any sedation. From there, the dose should be gradually increased to the point where illicit opioid use ceases; this is likely to be in the range of 60–120 mg methadone per day. Methadone use should be supervised initially. The degree of supervision should be individually tailored, and in accordance with local regulations; it should balance the benefits of reduced dosing frequency in stable patients with the risks of injection and diversion of methadone to the illicit drug market. Patients should be monitored with clinical assessment and drug testing. Psychosocial assistance should be offered to all patients.

Use of buprenorphine in maintenance treatment

Buprenorphine maintenance treatment should commence with a dose that is tailored to the pattern of opioid use, including the level of tolerance, the duration of action of opioids used and the timing of most recent opioid use (usually 4mg). From there, the dose should be rapidly increased (i.e. over days) to one that produces stable effects for 24 hours; this is generally in the range of 8–24 mg buprenorphine per day. Generally, if there is continuing opioid use, the dose should be increased. Dosing supervision and other aspects of treatment should be determined on an individual basis, using the same criteria as for methadone maintenance treatment.

Treatment for withdrawal and prevention of relapse

Opioid withdrawal (rather than maintenance treatment) results in poor outcomes in the long term; however, patients should be helped to withdraw from opioids if it is their informed choice to do so. Withdrawal from opioids can be conducted either on an outpatient or an inpatient basis, using reducing doses of methadone or buprenorphine, or alpha-2 agonists. Methadone and buprenorphine are the preferred treatments for opioid withdrawal, because they are effective and can be used in a supervised fashion in both inpatient and outpatient settings. Inpatient treatment is more effective, but it is also more expensive and is recommended only for a minority of patients (e.g. those with polysubstance dependence, or medical or psychiatric comorbidity). Accelerated withdrawal techniques using opioid antagonists in combination with heavy sedation are not recommended because of safety concerns.

Use of naltrexone to prevent relapse

Naltrexone can be useful in preventing relapse in those who have withdrawn from opioids, particularly in those who are already motivated to abstain from opioid use. Following opioid withdrawal, patients who are motivated to abstain from opioid use should be advised to consider naltrexone to prevent relapse.


Psychosocial interventions – including cognitive and behavioural approaches and contingency management techniques – can add to the effectiveness of treatment, if combined with agonist maintenance treatment and medications for assisting opioid withdrawal. Psychosocial services should be made available to all patients, although those who do not take up the offer should not be denied effective pharmacological treatment.


In planning treatment systems, resources should be distributed in a way that delivers effective treatment to as many people as possible. Opioid agonist maintenance treatment appears to be the most cost-effective treatment, and should therefore form the backbone of the treatment system for opioid dependence. Countries with established opioid agonist maintenance programmes usually attract 40–50% of dependent opioid users into such programmes, with higher rates in some urban environments. Because of their cost, inpatient facilities should be reserved for those with specific needs, and most patients wanting to withdraw from opioids should be encouraged to attempt opioid withdrawal as outpatients.


When treating people with opioid dependence, ethical principles should be considered, together with evidence from clinical trials; the human rights of opioid-dependent individuals should always be respected. Treatment decisions should be based on standard principles of medical-care ethics – providing equitable access to treatment and psychosocial support that best meets the needs of the individual patient. Treatment should respect and validate the autonomy of the individual, with patients being fully informed about the risks and benefits of treatment choices. Furthermore, programmes should create supportive environments and relationships to facilitate treatment, provide coordinated treatment of comorbid mental and physical disorders, and address relevant psychosocial factors.


This section lists all the recommendations contained in these guidelines.

Recommendations for action at policy or health-system levels are marked as either marked “minimal” or “best practice”:

  • minimal recommendations are suggested for adoption in all settings as a minimum standard; these should be considered the minimal requirements for the provision of treatment of opioid dependence
  • best practice recommendations represent preferred strategies for achieving the optimal public health benefit in the provision of treatment for opioid dependence.

The document contains recommendations based on evidence from systematic reviews and meta-analyses, taking into consideration evidence from other sources, technical considerations, resource implications and the risks and benefits of different alternatives. As recommended in the GRADE system, recommendations were divided into two strengths, here termed as “strong” or “standard” recommendations.

  • strong recommendations are those for which:

    most individuals should receive the intervention, assuming that they have been informed about and understand its benefits, harms and burdens

    most individuals would want the recommended course of action and only a small proportion would not

    the recommendation could unequivocally be used for policy making

  • standard recommendations are those for which:

    most individuals would want the suggested course of action, but an appreciable proportion would not

    values and preferences vary widely

  • policy making will require extensive debates and involvement of many stakeholders.

Some recommendations do not include an indication of strength – this means that the recommendation was ungraded.

Summary of recommendations

Recommendations for health systems at national and subnational levels.


Recommendations for health systems at national and subnational levels.

Recommendations for treatment programmes.


Recommendations for treatment programmes.

Recommendations for treatment of the individual patient.


Recommendations for treatment of the individual patient.



The category of “problem drug user” is generally defined to include both dependent users and non dependent drug injectors.