how it came about and how to manage it

how it came about and how to manage it

There is continuing public concern over the North American Opioid Crisis (Anon et al., 2021). The subject has provoked numerous books, documentaries and, recently, a major Disney+ drama series “Dopesick”. Proposals to deal with the Opioid Crisis featured in both the 2016 and 2020 US presidential election campaigns.

There is a core narrative that runs through mainstream commentary about opioid use in the USA. This suggests that opioid addiction was a stable problem, mainly involving heroin use by marginalised people, until the mid-1990s. In 1995, Purdue Pharma, controlled by the Sackler family, marketed OxyContin, which combined a slow-release technology with an existing synthetic opioid, oxycodone. This powerful opioid medication was misleadingly promoted as a safer and more effective alternative to older opioid analgesics. Facilitated by a deeply flawed medications regulation system, this led to explosive growth in the use of opioid medications.

Other synthetic opioid drugs came onto the market for use in chronic non-cancer pain. Prominent amongst them was fentanyl, which is 80 to 100 times more potent than morphine. Fentanyl has been used in anaesthesia since the late 1960s, but in the 1990s a transdermal patch preparation was marketed for use in chronic pain. Many chronic pain patients who would not have been prescribed powerful opioids in the past took these medications in good faith and became addicted.

Mexican drug cartels spotted a market opportunity and increased the availability of street heroin in North America. Patients addicted to prescription opioids graduated to street heroin use. The outcome has been a devastating epidemic of addiction. Deaths from opioid overdose have soared and many small towns in America, which had been untouched by previous waves of drug misuse, are experiencing serious social problems, the origins of which lie with greedy and dishonest conduct within the pharmaceutical industry.

General speaking, this core narrative draws upon hard evidence, but some of the chains of causation may not be so unambiguous and straightforward.

In October 2017, President Trump declared the Opioid Crisis a public health emergency. However, his administration’s policies were not entirely coherent. On the one hand, in 2018 Trump signed legislation to increase federal funding for drug treatment, but, on the other hand, his administration attempted to defund the Office of National Drug Control Policy and consistently undermined Obama’s Affordable Care Act. Deaths by opioid overdose have continued to rise during the Covid-19 pandemic (CDC, 2021).

In the US, deaths by opioid misuse continue to rise during the pandemic. How did the North American Opioid Crisis start and what can we do to manage it?

In the US, deaths by opioid misuse continue to rise during the pandemic. How did the North American Opioid Crisis start and what can we do to manage it?

The Stanford-Lancet Commission on the North American Opioid Crisis

The Commission is a partnership between The Lancet and Stanford University’s addiction research group. The Commission started its work in late 2019 under the Trump presidency. It comprised a group of North American experts on various aspects of the Opioid Crisis, who came together to make “a coherent, empirically grounded analysis of the causes of, and solutions to, the opioid crisis”.

The Commission’s 50-page report is the primary output of its work. It comprises two main elements:

  • an historical overview of the origins of the current situation; and
  • a series of policy recommendations to address the Opioid Crisis.

The Report is mainly concerned with the situation in the USA and Canada. The Commission explicitly avoided a comprehensive literature review on the grounds that the Opioid Crisis has been “well characterised”  in previous authoritative reviews. Instead, it presents a detailed narrative review of the development of the current situation. The Commission formed a number of sub-groups to address particular themes, following a procedure resembling a Delphi technique (Niederberger & Spranger, 2020) to derive consensus expert recommendations on public policy. Within the iterative process they used, major conclusions and recommendations were discussed and modified until they achieved 90% support amongst the Commissioners. If 90% support could not be achieved, the conclusion or recommendation was dropped. The work of the Commission was supported by epidemiological modelling that has been reported in a separate paper (Rao et al., 2021). The Commission Report was published alongside a Lancet editorial (Anon et al., 2022).

The causes of the North American Opioid Crisis

The Report closely adheres to the core narrative concerning the Opioid Crisis set out above. The approval of OxyContin for use in the USA in 1995 is firmly identified as the start of the Opioid Crisis. The Report states that the Opioid Crisis emerged “when insufficient regulation of the pharmaceutical and health-care industries enabled a profit-driven quadrupling of opioid prescribing”. The Report sets out a catalogue of failings that have contributed to a massive increase in opioid use, namely: pharmaceutic company misconduct; regulatory failures; inappropriate relationships between opioid manufacturers and a range of other groups, including regulators, universities, professional societies, patients advocacy groups and politicians; and aggressive and misleading promotion of opioids to prescribers and the general public.

The Report identifies three waves of the Opioid Crisis, and describes some of the public health consequences, particularly focusing on deaths by opioid overdose:

  1. According to the Report, the first wave started in the 1990s and involved prescription opioids;
  2. the second began around 2010 when illicit heroin traffickers identified people addicted to prescription opioids as a new market;
  3. the third wave is said to have started in 2014, when drug traffickers introduced illicitly manufactured synthetic opioids into the American street drug market, particular fentanyl, which is sometimes used in counterfeit prescription drugs, such as fake OxyContin.

Reviewing the current situation, the report notes that 2020 was the worst year on record for fatal opioid overdoses in both the USA and Canada, both in terms of absolute numbers and percentage increase over the previous year. Some of the results of the Commission’s modelling exercise are reported here. The associated Lancet editorial reports the projection that an additional 1.2 million opioid overdose deaths are likely to occur between 2020 and 2029 if there is no change in public policy.

The Report goes into some detail about temporal, demographic and geographical variations in opioid death rates. It touches on a range of other issues, including poly-drug abuse. There is a passing discussion of the management of chronic pain but a detailed discussion of treatment is outside of the scope of the report. Although the Report attributes much blame to weak or corrupt regulatory systems in the USA, it rejects the idea that the Opioid Crisis is solely a consequence of a unique, highly-marketised health care system. It claims that Canada has an Opioid Crisis of a similar magnitude to the US, despite having a system of universal healthcare. It warns that other countries may encounter similar problems to those in North America in due course.

An additional 1.2 million opioid overdose deaths are likely to occur in the USA and Canada between 2020 and 2029 if there is no change in public policy.

The Lancet editorial reports that an additional 1.2 million opioid overdose deaths are likely to occur in the USA and Canada between 2020 and 2029 if there is no change in public policy.

Policy recommendations

The larger part of the Report sets out the rationale for its main recommendations, falling under seven domains:

  • “The US and Canadian opioid crisis as a case study in multi-system regulatory failure
  • Opioids’ dual nature as both a benefit and a risk to health
  • Build integrated, well-supported and enduring systems for the care of substance misuse disorders
  • Maximise the benefit and minimise the adverse effects of the criminal justice system’s involvement with people addicted to opioids
  • Create healthy environments that yield long-term declines in the incidence of addiction
  • Stimulate innovation in the response to addiction
  • Prevent opioid crises beyond the USA and Canada”

There are 32 main recommendations, many of which subsume further, more detailed, recommendations. The recommendations are wide ranging, including regulatory reforms for the pharmaceutical industry and social policy to improve environments that foster substance misuse. Many of the recommendations are uncontroversial to anyone familiar with the scientific literature on substance misuse, such as reframing addiction as a chronic health condition rather than a crime, alongside the provision of methadone and buprenorphine treatments through networks of publicly funded treatment centres. Others recommendations reflect optimistic aspirations, for example, “Prioritise redesign of opioid molecules and development of non-opioid medications for pain and addiction”. Some recommendations are concerned with reversing past policy failures associated with ‘the War on Drugs’, such as US penal policy.

The authors have taken care to frame their recommendations in such a way as to avoid replacing current problems with different problems. For example, they emphasise that they do not advocate flooding the opioid market with buprenorphine and methadone and that they do not advocate the prohibition of opioid prescribing for chronic pain.

The US and Canadian opioid crisis as a case study of weak policy and regulatory failure,  and an expensive health care system.

The US and Canadian opioid crisis as a case study of weak policy and regulatory failure, and an expensive and inaccessible health care system.

Strengths and limitations

This Report is an important and authoritative summary of the development of the Opioid Crisis in North America as it is usually understood, together with a series of evidence-based policy recommendations. It is an invaluable resource for anyone interested in the problems associated with opioids, whether prescribed or purchased illegally. The 387 references provide access to much of the best quality evidence supporting the core narrative. The way that the Commission was established meant that it was unlikely to challenge orthodoxies, and it does not.

As a UK clinician with experience in the treatment of both chronic pain and substance misuse, I feel that the Report has a number of weaknesses. There is no statement of the intended readership, but it appears to address policymakers in the USA and Canada. Joe Biden’s victory in the 2020 Presidential election has undoubtedly created a more receptive environment for the Commission’s conclusions. Indeed, Tom Coderre withdrew from the Commission when he took a post as a policy-maker in the Biden Administration.

The Commission had a very wide remit and it has generated a long report. Nonetheless, it skims over some important issues, particularly those concerning the management of chronic pain. Tolerance and withdrawal symptoms are inevitable consequences of sustained opioid use, but this does not mean that people with chronic pain inevitably display addiction behaviours. On the contrary, the majority do not. However, high-dose long-term use does lead to significant cognitive impairments and hyperalgesia.

The phenomenon of hyperalgesia is not mentioned in the Report, although it occurs with both opioid and non-opioid analgesics, and probably has a major role in sustaining high-dose opioid regimens (Bailey et al., 2021). This has an impact on the recommendation that better and non-addictive pain medications can and should be developed, which appears to invite exactly the same errors as were made around OxyContin. In my opinion, at the heart of the international opioid problem is a false belief that pain can be eliminated pharmaceutically. If we are to move forward, the health care professions and the general public need to embrace a rehabilitation approach to chronic pain where opioids play a small and specific role, rather than continuing a discredited search for the analgesic magic bullet. The pain-elimination myth is not solely the creation of the pharmaceutical industry; it has deep-seated roots in medical socio-cultural beliefs (Illich, 1976).

Heroin addiction was a major public health problem long before 1995. Much is understood about the impact of social factors and the availability of cheap heroin on prevalence. Whilst a majority of US heroin addicts report prior use of prescribed opioids, this does not necessarily imply a strict causal chain; it is an epidemiological truism that association does not imply causation. The strong emphasis on prescribed opioid use as a prelude to heroin addiction reiterates the contested “gateway drug” argument that has been a justification for discredited cannabis criminalisation policies (Degenhardt et al., 2010; Nkansah-Amankra &, Minelli, 2016).

The Report is particularly weak on the international implications of the North American Opioid Crisis. The UK does have a significant problem with prescribed opioids, but it appears to be quite different to the situation in the USA. Although there is always some bleeding of prescription drugs into the street drug market, there is no evidence that opioid prescribing has driven a significant increase in heroin addiction here. Although drug related deaths have increased in the UK (ONS, 2021), this appears to be due to the reduced availability of substance misuse treatments and a huge increase in deaths due to cocaine toxicity. The argument that a US-style Opioid Crisis is coming is unconvincing, as new opioid medications have been available here just as long as they have been in the USA.

In the UK, gabapentinoids are frequently used alongside heroin, and the combination is a potent cause of respiratory depression and death. Gabapentinoids have a limited role in pain management, but they are widely prescribed. They are dependency forming in much the same way as benzodiazepines (Goins et al., 2021). Gabapentinoids are not mentioned in the Report.

The Stanford-Lancet Commission report overlooked the management of chronic pain, tolerance and withdrawal symptoms inevitably displayed in people with addictive behaviours.

The report overlooked the management of chronic pain, tolerance and withdrawal symptoms inevitably displayed in people with addictive behaviours.


The Report is a welcome addition to the literature on the North American Opioid Crisis, but it appears to have limited relevance to the UK, where we need to develop an effective response to what appears to be a rather different set of problems related to opioid prescribing. Nonetheless, there are two important messages for the UK:

  1. Firstly, the Report stands as a dire warning of the consequences of deregulation of medicines at a time when the post-Brexit UK Government is contemplating the adoption of US-inspired models of health care and regulation.
  2. Secondly, the Report emphasises the importance of harm reduction approaches to drug addiction that were developed in the UK and have a strong evidence-base. Since 2010, British health policy has reduced the availability of these treatments. The steady increase in deaths amongst UK drug users is in part attributable to this policy, which is driven by ideology, not science.
The Stanford-Lancet Commission report touches on the importance of harm reduction approaches and policies to drug addiction, but has limited relevance to the UK.

The Stanford-Lancet Commission report touches on the importance of harm reduction approaches and policies to drug addiction, but has limited relevance to the UK.

Statement of interests

Rob Poole leads a research group working on harms related to prescribed opioids. He has no other competing interests.


Primary papers

Humphreys K, Shover CL, Andrews CM, Bohnert ASB, Brandeau ML, Caulkins JP, Chen JH, Cuéllar MF, Hurd YL, Juurlink DN, Koh HK, Krebs EE, Lembke A, Mackey SC, Larrimore Ouellette L, Suffoletto B, Timko C. Responding to the opioid crisis in North America and beyond: recommendations of the Stanford-Lancet Commission. Lancet. 2022 Feb 5;399(10324):555-604. doi: 10.1016/S0140-6736(21)02252-2.
The Lancet Editorial. Managing the opioid crisis in North America and beyond. Lancet. 2022 Feb 5;399(10324):495. doi: 10.1016/S0140-6736(22)00200-8. Epub 2022 Feb 2. Erratum in: Lancet. 2022 Feb 16.

Other references

A time of crisis for the opioid epidemic in the USA. Lancet 398:10297, 277.

Bailey J, Nafees S, Jones L, Poole R (2021) Rationalisation of long-term high-dose opioids for chronic pain: Development of an intervention and conceptual framework British Journal of Pain 15(3) 326–334

Degenhardt L, Dierker L, Tat Chiu W, Medina-Mora ME, Neumark Y, Sampson S, Alonso J, Angermeyer M, Anthony JC, Bruffaerts R,  de Girolamo G, de Graaf R, Gureje O, Karam AN, Kostyuchenko S, Lee S, Lépine J-P, Levinson D, Nakamura Y, Posada-Villa J, Stein D, Wells JE, Kessler RC (2010). Evaluating the drug use “gateway” theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO World Mental Health Surveys. Drug and Alcohol Dependence108: 1–2. 84-97

Goins A, Patel K, Alles S, (2021) The gabapentinoid drugs and their abuse potential. Pharmacology & Therapeutics 227: 107926

Illich I (1976). Limits to medicine. Medical nemesis: the expropriation of health. London: Maryon Boyars.

Niederberger M, Spranger J (2020) Delphi Technique in Health Sciences: A Map. Front. Public Health 8:457. doi: 10.3389/fpubh.2020.00457

Rao IJ, Humphreys K, Brandeau ML (2021). Effectiveness of Policies for Addressing the US Opioid Epidemic: A Model-Based Analysis from the Stanford-Lancet Commission on the North American Opioid Crisis. Lancet Reg Health Am. 3:100031.

Nkansah-Amankra S, Minelli M (2016) “Gateway hypothesis” and early drug use: Additional findings from tracking a population-based sample of adolescents to adulthood, Preventive Medicine Reports, 4, 134-141,

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