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Wellcome Leap: Unconventional Projects. Funded at Scale.


Untangling Addiction

Worldwide, someone dies from drug or alcohol addiction every 4 minutes.

Globally, 108 million people are estimated to be addicted to alcohol, and nearly 40 million are addicted to illicit drugs. In 2019, alcohol use disorder (AUD) killed 168,000 people worldwide and was a risk factor in an additional 2.44 million deaths. In the same year, substance use disorder (SUD)—partly defined by continued use of substances despite negative consequences—killed over 128,000 people worldwidei. And the numbers are getting worse.

The number of people with SUDs between 2009 and 2019 increased by 45%–from 27.3 million to 39.5 million globally. In the United States alone, an estimated 29.5 million people 12 years old or older met the criteria for having an AUD in 2021; 24 million for an SUD. Globally, AUD and SUD cause an estimated 131 million years lived with disability (YLDs), resulting in an annual cost of over $740 billion in healthcare, lost work productivity, and crime. No country or region is immune. The prevalence of AUDs is highest in Europe (14.8% of the population), followed by the Americas (10.6%) and Africa (5.1%), and the prevalence of illicit SUDs is highest in North America (2.7% of the population), followed by Oceania (2.3%) and Europe (1.5%)ii.

Addiction continues to rise despite increased expenditures.

Reliable values of global expenditures on drug abuse prevention and treatment are difficult to obtain. However, the US spent $24 billion to prevent and treat alcohol and drug abuse in 2009iii and $32.6 billion in 2019iv. These expenditures represent an increase of 35% over ten years. In that same period, the proportion of US adults who met the AUD and SUD criteria rose from 8.5% in 2013 to 12.5% in 2021. Efforts and resources devoted to addressing addiction have risen, but it’s not working.

“Most people with addictions try to quit. Most can’t quit.”

In 2021, in the US, fewer than 4 million of the more than 46 million people with an AUD or SUD received treatmentv. In total, that’s less than 9% of the US population with AUD or SUD having received treatment. Percentages in the UK are a bit better for SUD treatment, with 20% of people meeting the criteria of SUD receiving treatment. However, the numbers for AUD are comparable to those seen in the US, with only 5% of those meeting the criteria of AUD receiving treatmentvi.

“Drug Addiction is a chronic, relapsing brain disorder characterized by 
compulsive drug seeking and use despite harmful consequences.”

— National Institute on Drug Abuse (NIDA)

Among those treated, the statistics for relapse are equally alarming. For alcohol addiction, studies have shown relapse rates of approximately 50% within the first three months after completion of intensive inpatient programs. One study showed a 91% relapse rate for opiates, with 59% relapsing within the first week and 80% within a month.

This calls for a radical rethinking of our current approaches. A new approach that measures and characterizes the underlying neural and physiological factors that are affected and altered by addiction and incorporates that understanding into the treatment and tracking of recovery.

Why are we stuck?

Worldwide efforts at reducing and treating addiction have been ineffective primarily because (1) only a fraction of people with addictions get treatment; (2) treatment approaches are one-size-fits-all with minimal, if any, matching of treatment to the underlying physiology of the person with addiction; and (3) there are no standard relapse prevention programs with the result that more than half of those treated to achieve abstinence reverting to their addiction within 90 days. To make matters worse, potentially addictive substances are increasing in number and potency.

Prescription opiates: A new source of addiction.

‘Super meth’ and other mixed use of illicit drugs are on the rise, but perhaps most troubling has been the emergence of prescription opioids. Historically, most substance abuse stems from the recreational use of illicit drugs and alcohol. Nevertheless, in the past 20 years, the rise in the legitimate prescription of potent opioid pain relievers has spurred an alarming new wave of misuse and addiction. Naturally occurring opiates, like opium and morphine, have been used for medicinal purposes for millennia to relieve pain and induce sleep. More recently, synthetic opioids, like fentanyl and sufentanil, have become available that are 100x and 500x more potent, respectively, than morphine.

Opioids are the most effective pain relievers available and have become indispensable to the practice of medicine, particularly for relieving severe pain, such as that caused by cancer, surgery, or trauma. However, opioids can also evoke feelings of intense euphoria and are highly addictive, such that about 10% of patients prescribed opioids for chronic pain begin to abuse themvii. In 2019, nearly 10 million Americans misused prescription opioids, and the number of overdose deaths directly resulting from prescription opioids was four times higher than a decade earliervi. In 2021, 9.2 million people in the US over the age of 12 misused opioidsv, and 8.7 million misused prescription opioid pain relieversv. Opioids currently contribute to over 70% of overdose deaths in both the USi and the EUii. Alarmingly, a 2014 study found that 75% of recent heroin users first abused prescription opioidsviii. Thus, opioids are not only a growing source of addiction but increasingly the dominant cause of death in addiction.

What needs to change?

We have a critical gap in our understanding and treatment of substance use disorders. Despite the myriad of factors that can influence treatment outcomes, it remains unclear which or even whether, any of these interventions can be considered universally effective, underscoring the need to consider personalized approaches to substance abuse treatmentixi. By applying knowledge gained from neuroscience, genetics, and pharmacology, we aim to set a new standard for patient outcomes in substance abuse. Indeed, if we are to make impactful change in how substance use disorders are prevented and treated, we need to re-envision two important paradigms.

Why now?

The persistent opioid crisis, coupled with the emergence of new potentially addictive substances and the global resurgence of cocaine abusexvi, underscores the urgent need for innovative approaches to addiction prevention and treatment. Given that lives and communities are at stake, it is critical to adopt and integrate new technologies and methodologies. At this pivotal moment, the field of addiction research and treatment finds itself at a transformative juncture, shaped by recent advances in our understanding of the biological underpinnings of addiction and by novel technological breakthroughs.

Program goals.

The escalating rates of global substance use, addiction, and overdose-related deaths highlight an urgent need for innovative methods to prevent, diagnose, and treat substance use disorders (SUD) and alcohol use disorders (AUD). The myriad of biological factors that determine individual susceptibility to addiction and their responsiveness to intervention is poorly understood. A primary objective of this program is to identify biomarkers that can be detected through non-invasive or minimally invasive methods (e.g., blood tests, somatosensory evoked potentials, etc.) to facilitate quantitative assessment of the fundamental changes and neurobiological underpinnings of drug abuse and, ultimately, to demonstrate increased efficacy of prevention and treatment approaches using these quantitative methods.

To that end, our goals are to:

  1. Develop scalable measures to assess individual addiction susceptibility to a range of addictive and potentially addictive substances. Approaches may include, but are not limited to, analysis of longitudinal samples from existing biobanks, in vitro experiments with patient-derived hiPSCs, or computational methods such as predictive modeling and machine learning algorithms. Measures should demonstrate an accuracy of ≥ 80% in the prediction of progression to addiction.
  2. Quantify addiction risk and progression during prescription drug use. We are particularly focused on prescription opioids with a goal to demonstrate the ability to reduce misuse and subsequent addiction in patient populations by 50%, from an estimated 1 out of 10 patients to 1 out of 20.
  3. Develop innovative treatments and quantifiably assess recovery using new or existing treatments, on a personalized basis, such that the risk of relapse is reduced by a factor of 2 post treatment. Estimated abstinence rates for AUD is ~50% 90 days after treatment, and ~25% 1 year after treatmentxxxiii. The 90-day abstinence rate for SUD varies by drug but is estimated to be between 15-30% for opioids.

Call for abstracts and proposals.

We are soliciting abstracts and proposals for work over three (3) years in one or more of the following thrust areas (see Thrust areas in full program description). Proposers should clearly relate work in these thrust areas to one or more of the program goals.

It is not necessary to form a large consortium or teams to address all facets of the program. The strength of this approach will manifest through program-level integration of efforts from individuals and small agile teams with deep (and sometimes narrow) expertise. Across all projects, Wellcome Leap will facilitate iterative and collaborative integration of findings to refine models and improve and validate predictive measures and adapt approaches as teams make progress towards shared goals.

Program Director.

Kevin Jones, PhD is a practicing professor with expertise in neurophysiology and neuropharmacology of mental health disorders, including schizophrenia, post-traumatic stress disorder and depression. He uses a variety of technical approaches to identify cellular and molecular deficits that can be targeted with novel therapeutics. He earned his PhD in Neuropharmacology from Duke University.

Process and timeline
Program announcement.


15-Day Abstract review round.
/ Day 1
Submission deadline: 21 December 2023
7-page abstracts submitted (from individual organizations or teams) that address one or more thrust areas of the program.
/ Day 15
Abstract feedback sent: 5 January 2024
All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.


30-Day Full proposal review round.
/ Day 46
Submission deadline: 5 February 2024
25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.
/ Day 76
Proposal decision sent: 6 March 2024

All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.

Mechanics of applying

Who is eligible?

Performers from universities and research institutions: small, medium, and large companies (including venture-backed); and government or non-profit research organizations are invited to propose.

Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.

I understand that the information being disclosed will be reviewed and evaluated independently on behalf of Leap. I am submitting information with the intention that it imposes no confidentiality obligations on Leap. Furthermore, my submission does not breach any confidentiality obligations that I owe to others; there is no legal reason why I cannot submit information; and I am not underage or otherwise legally incompetent. By submitting, I am not granting, other than for the purpose of evaluation, any rights in relation to any patent, copyright, or design. I am not relying upon Leap in any way for legal advice, including (but not limited to) whether the contents of my submission can be protected under IP law. I recognize that Leap may already be aware of or funding the same or related efforts as described by my submission. I agree that no contractual obligation or working relationship is being created between myself and Leap by submitting this information. If the submission is deemed of interest, I may be required to sign a further Agreement with Leap so that any confidential information, that is subsequently shared, is protected.

Abstract application steps.

  1. Download guidelines
  2. Download abstract template (and cost and schedule template)
  3. We’ll remind you when the application portal opens on 14 December.
  4. Upload your abstract and submit your application before 21 December at 11:59pm ET.

More details will be provided for the proposal round of submissions.

Frequently asked questions.

If you have questions, please review our FAQ section here. – updated 21 November 2023.
Send inquiries to

i Global Burden of Disease (GBD).

ii World Drug Report 2023 – Special Points of Interests. United Nations : Office on Drugs and Crime //

iii White, A. G. et al. Direct Costs of Opioid Abuse in an Insured Population in the United States. J. Manag. Care Spec. Pharm. 26, 1188-1198 (2020).

iv Substance Abuse and Mental health Services Administration.(2019).

v Section 5 PE Tables – Results from the 2021 National Survey on Drug Use and Health: Detailed Tables, SAMHSA, CBHSQ. – tab5.6a

vi Adult substance misuse treatment statistics 2021 to 2022: report. GOV.UK

vii Vowles, K. E. et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156, 569–576 (2015).

viii Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014 Jul 1;71(7):821-6. doi: 10.1001/jamapsychiatry.2014.366. PMID: 24871348.

ix Els, C. et al. High‐dose opioids for chronic non‐cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst. Rev. 2017, CD012299 (2017).

x Kelly, D. E., John. People recover from addiction. They also go on to do good things. STAT (2021).

xi Batchelder, A. W. et al. The shame spiral of addiction: Negative self-conscious emotion and substance use. PloS One 17, e0265480 (2022).

xii National Institute on Drug Abuse. (2012). Principles of Drug Addiction Treatment: A Research-Based Guide: Third Edition.

xiii Percy, A., McAlister, S., Higgins, K., McCrystal, P. & Thornton, M. Response consistency in young adolescents’ drug use self-reports: a recanting rate analysis. Addiction 100, 189–196 (2005).

xiv Broman, M. J., Bista, S. & Broman, C. L. Inconsistency in Self-Reporting the Use of Substances over Time. Subst. Use Misuse 57, 1356–1364 (2022).

xv Seo, S. et al. Predicting the future relapse of alcohol-dependent patients from structural and functional brain images. Addict. Biol. 20, 1042–1055 (2015).

xvi UNODC, Global report on Cocaine 2023 – Local dynamics, global challenges (United Nations publications, 2023).

xvii Samaha, A.-N., Khoo, S. Y.-S., Ferrario, C. R. & Robinson, T. E. Dopamine ‘ups and downs’ in addiction revisited. Trends Neurosci. 44, 516–526 (2021).

xviii Feltenstein, M. W., See, R. E. & Fuchs, R. A. Neural Substrates and Circuits of Drug Addiction. Cold Spring Harb. Perspect. Med. 11, a039628 (2021).

xix Vafaie, N. & Kober, H. Association of Drug Cues and Craving With Drug Use and Relapse A Systematic Review and Meta-analysis. JAMA PSYCHIATRY 79, 641–650 (2022).

xx Tiffany, S. T. & Wray, J. M. The clinical significance of drug craving. Ann. N. Y. Acad. Sci. 1248, 1–17 (2012).

xxi Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4. doi: 10.1126/science.1135926. PMID: 17255515; PMCID: PMC3698854.

xxii Tisdall, L., MacNiven, K. H., Padula, C. B., Leong, J. K. & Knutson, B. Brain tract structure predicts relapse to stimulant drug use. Proc. Natl. Acad. Sci. 119, e2116703119 (2022).

xxiii Bolloni, C. et al. Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study. Front. Psychiatry 7, (2016).

xxiv Dinur-Klein, Limor et al. 2014. “Smoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial.” Biological Psychiatry 76(9): 742–49.

xxv Sanna, A. et al. Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. Front. Neurosci. 13, (2019).

xxvi Garrison, K. A. & Potenza, M. N. Neuroimaging and Biomarkers in Addiction Treatment. Curr. Psychiatry Rep. 16, 513 (2014).

xxvii Shivacharan, R. S. et al. Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating. Nat. Med. 28, 1791–1796 (2022).

xxviii Mak, K. K., Lee, K. & Park, C. Applications of machine learning in addiction studies: A systematic review. Psychiatry Res. 275, 53–60 (2019).

xxix Marsch, L. A. Digital Health and Addiction. Curr. Opin. Syst. Biol. 20, 1–7 (2020).

xxx Mendez, E. F. et al. A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons. Front. Psychiatry 14, (2023).

xxxi Bogenschutz, M. P. et al. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry 79, 953–962 (2022).

xxxii Vargas, M. V., Meyer, R., Avanes, A. A., Rus, M. & Olson, D. E. Psychedelics and Other Psychoplastogens for Treating Mental Illness. Front. Psychiatry 12, (2021).

xxxiii Krupitsky, E. M. & Grinenko, A. Y. Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. J. Psychoactive Drugs 29, 165–183 (1997).

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