Addressing Problematic Opioid Use in OECD Countries

2. Opioid use in context

2.1. What are opioids and how have they been used?

Opioids can be natural, semi-synthetic or synthetic chemicals. Opiates are the naturally occurring alkaloids of the opium poppy (Papaver somniferum L.), which is a plant that grows in many countries around the world with moderate climates. Opioids, in terminological rigor, are synthetic or semi-synthetic compounds derived from opiates but are not opiates themselves. In this report, the term ‘opioids’ will be used to refer both to natural and synthetic substances.

Opioids, according to their legal status, can be divided in two groups.

• Prescription opioids are analgesic medications that include natural opiates (e.g. morphine, codeine), semi-synthetic opioids (e.g. oxycodone, hydrocodone, hydromorphone, oxymorphone) and synthetic opioids (e.g. methadone, fentanyl, tramadol). These are given by doctors as painkillers, during anaesthesia, or as treatment of heroin and other opioid dependence. (United Nations Office on Drugs and Crime, 2016[1]). Codeine is also available in low doses without a prescription in some countries.

• Illicit opioids constitute a significant product of international illicit trade. Heroin is a semi-synthetic opiate synthesised from morphine and is the most prevalent illicit opioid worldwide. Approximately twice as potent as morphine, heroin has a high potential for problematic use (United Nations Office on Drugs and Crime, 2016[1]). In recent years, fentanyl and fentanyl analogues have become much more prominent in the illicit drugs scene in many countries (see Box 2.1).

Box 2.1. Fentanyl and new fentanyl analogues

Fentanyls are a family of short-acting and highly potent opioids that have gained relevance in the past years by significantly worsen the crisis. Four fentanyl compounds are approved for medical use in anaesthesia and pain management, but a range of fentanyl analogues are produced clandestinely in chemistry labs, which makes its production and distribution much easier.

Fentanyl is often sold mixed with heroin, cocaine or other drugs (in many cases users are not aware of the content), and can have severe repercussions for users as a result of their high potency or toxicity, which can be as high as 10 000 times stronger than morphine in the case of the analogue called carfentanil. A miniscule amount of pure fentanyl (e.g. about the size of a pinch of salt) can be fatal. In the US, Canada and some European countries fentanyl analogues account for a large component of the opioid crisis (ECDD-WHO, 2017[2]; United Nations Office on Drugs and Crime, 2016[1]). In recent years, fentanyl overdose deaths have been also reported in Australia, Finland, Germany, Greece, and the United Kingdom (UNODC, 2017[3]).

2.2. The thin line between appropriate and inappropriate opioid use

Opioid drugs work by binding to specialised receptors on the surfaces of opiate-sensitive cells, reducing pain messages and feelings of pain. These interactions trigger the same biochemical brain processes associated with feelings of pleasure in life activities (e.g. eating and sex). These reward processes can motivate repeated use and can lead to the development of opioid use disorders (OUD) (Kosten and George, 2002[4]).

Prescription of higher doses of opioids, as it has been used for treating chronic pain, is correlated with 32% to 188% higher risk of unintended overdoses and with opioid related morbidity and mortality (Chou et al., 2015[5]). A systematic review found that the incidence of iatrogenic opioid dependence or problematic use in the United States was 4.7% of those patients prescribed opioids for pain (Higgins, Smith and Matthews, 2018[6]). Another study found that one out of 16 surgery patients who use opioids becomes a chronic opioid user (Brummett et al., 2017[7]).

Inappropriate use of prescribed opioids (e.g. to induce feelings of pleasure, to tackle withdrawal symptoms or to alter the effects of other consumed drugs) is also a relevant component of the crisis. In North America, hydrocodone, oxycodone, codeine and tramadol are the main prescription opioids used for non-medical purposes, while methadone, buprenorphine and fentanyl are the most misused reported in Europe (World Drug Report, 2018[8]). In the United States, four out of five heroin users report that their opioid use began with nonmedical use of prescribed opioids. However, only about 4% of people who inappropriately use prescription opioids initiate heroin within five years after the first prescription (Muhuri, Gfroerer and Davies, 2013[9]). Similarly, a simulation study found that policies aimed at reducing opioid prescription supply and related deaths might have led some dependent prescription users to switch to heroin use, which may increase heroin-related deaths (Pitt, Humphreys and Brandeau, 2018[10]).

Higher opioid doses can result in respiratory depression that can lead to overdose death. An increased risk of inadvertent prescription opioid overdose has been found with 20‑50 morphine milligram equivalents a day (comparable to three to seven 5mg oxycodone tablets a day) with fatality more likely with opioid doses above 50 morphine milligram equivalents a day (seven or more 5mg oxycodone tablets a day) (Adewumi et al., 2018[11]).

Polysubstance use is common in people who inappropriately use opioids, consuming them jointly with alcohol and other drugs. This is corroborated by the fact that in many opioid-related overdose deaths there are other drugs involved simultaneously (Frisher et al., 2012[12]). In addition, there is a link between problematic opioid use and mental health illness (Davis et al., 2017[13]).

Patients with OUD who manage to reduce their opioid use, frequently relapse. Over the long term, mortality rate of people with OUD is about six to 20 times greater than that of the general population. Among those who remain alive, the prevalence of stable abstinence from opioid use is quite low (less than 30% after 10–30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids (Hser et al., 2015[14]).

Injection as a route of administration increases the risk of acquiring infectious diseases. The sharing of needles or other injection tools increases the risk of invasive infections from skin bacteria and fungi (e.g. Staphylococcus aureus, Candida sp.) and viral infections (e.g. HIV, hepatitis). A review found that heroin injectors had 2.8 times the risk of HIV seroconversion compared with those not injecting in the past 6 months (Tavitian-Exley et al., 2015[15]).