Evidence-Based Cocaine Addiction Treatment: What New Research on Craving and Use Reveals

By Luciana D'Agnone BA, MSc | Clinical Operations Leader & Editorial Expert

Cocaine use disorder remains one of the most challenging conditions in addiction medicine to treat, in part because there is still no medication licensed specifically for it, and because recovery rarely follows a single, predictable path.¹ For clinicians, this raises a genuinely difficult question at the heart of cocaine addiction treatment: when full abstinence is not immediately achievable, how should we measure whether treatment is actually working?

A new paper published in Drug and Alcohol Dependence (2025), led by Professor Ramin Mojtabai and an international team of addiction researchers offers a fresh, evidence-based perspective. By tracking cocaine craving and cocaine use together, the study shows that reductions in craving and use are meaningful parameters in their own right, and that recovery is more varied between individuals than trial averages usually reveal. We spoke with Professor Mojtabai, who leads addiction research at Tulane University School of Medicine, and is featured as an expert contributor here at The OAD Clinic, to explore what these findings mean for everyday practice and how they shape the evidence-based cocaine addiction treatment approach The OAD Clinic delivers.

Why Craving Matters in Cocaine Addiction Treatment

Craving – the intense, sometimes overwhelming urge to use a substance – is a core clinical feature of cocaine use disorder and other substance use disorders. It was added as a formal diagnostic criterion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), partly on the view that craving “may become a biological treatment target”. In practice, many pharmacotherapy trials for stimulant use disorders specifically select candidate medications for their potential to reduce cocaine craving.

Yet, as Professor Mojtabai's paper notes, there has been surprisingly limited research into how craving actually behaves over the course of treatment, and how closely it tracks with real changes in drug use and wider recovery. Individual responses to experimental medications are known to be highly variable, and this variability may partly explain why so many stimulant pharmacotherapy trials have produced negative or inconclusive results. If the average result hides several very different patterns of response, then the average tells us less than we assume – a crucial insight for any clinician designing effective cocaine addiction treatment.

What the Research Found: Three Recovery Trajectories in Cocaine Use Disorder

Rather than looking at craving or use in isolation, Professor's Mojtabai's paper examined how weekly cocaine craving and cocaine use moved together over time and found that:

• 36.8% of participants experienced a reduction in cravings but high use, and this group was associated with baseline alcohol use and was more likely to use multiple drugs. This suggests that the co-use of alcohol and other substances may weaken the link between reduced craving and reduced cocaine use. Lower craving, in short, does not automatically translate into lower use for everyone.

  
  

• More severe drug use and a longer history of cocaine use were less likely to achieve best outcomes. However, for a success story of a patient presenting with long-term cocaine use, read Elizabeth’s testimonial.

  
  

• Reductions in craving and use provided meaningful improvements in a person's wider health and social functioning, including the Addiction Severity Index (ASI) domains of drug use, alcohol use, psychiatric status, and relationships, giving these outcomes real clinical validity.

  
  

• Most of the change occurred within the first one to two weeks of treatment. This indicates that early change in craving could act as an indicator of recovery.

The OAD Practice

At The OAD Clinic, recovery is tracked throughout treatment by assessing many of the parameters used in this research, including craving, use, polysubstance use, wellbeing, the environment and relationships, so that progress or stalling is recognised across multiple facets wherever it is genuinely happening.

Modafinil for Cocaine Addiction Treatment

The researchers validated that Modafinil at a dose of 200mg per day made a reduction in craving significantly more likely. None of the other medications produced this effect, and notably neither did the higher 400mg dose of modafinil, which was associated with more adverse events and more frequent discontinuation. Then, there are the variables in-between patients who experience low cravings and high cocaine use while medicated. 

Professor's Mojtabai's view is clear:

"It is quite plausible that a combination of medications or a combination of medications with behavioral treatments would prove more effective than a single medication in treatment of stimulant use disorders (i.e., cocaine and methamphetamine use disorders). For example, in a 2021 randomized controlled trial, combined treatment with injectable naltrexone and oral bupropion proved efficacious in treatment of methamphetamine use disorder"

At The OAD Clinic, it is recognised that medication effects are often partial, dose-specific, and best understood as one component of a broader, evidence-based treatment plan when cravings become less intense but use is not decreased. Following research findings, clinicians at The OAD Clinic distinguish between reducing craving and unchanged use habits as separate, potential parameters as potential guides to the recovery journey. Further, pharmacotherapy is almost always integrated with other therapies, reflecting a multi-faceted approach to cocaine addiction treatment.

Beyond Abstinence: Measuring Progress in Cocaine Use Disorder Treatment

Traditionally, the success of addiction treatment has been judged against a single benchmark: complete abstinence. But abstinence is not always attainable, particularly in the short term, and holding it up as the only valid outcome risks writing off progress that is genuinely clinically significant.

Further, the sheer heterogeneity of responses reinforces a principle at the heart of good addiction care: treatment should be matched to the individual, not delivered as a one-size-fits-all protocol. Clinicians at The OAD Clinic recognise individual variability by adapting treatment when cravings are not reduced, using a number of  evidence-based parameters to try to find the cause for any potential low treatment response and adapt treatment accordingly.

The case for multi-faceted models in treatment plans

Dr Mojtabai’s position on this is unambiguous:

"Full recovery from these pervasive disorders would often require a comprehensive treatment program including changes in environment, incentives, and cognitions. Medications are a potentially important component of such a comprehensive treatment program."

The OAD Practice

The OAD Clinic's approach is based on recognising individual differences in cocaine addiction treatment and assessing environmental and other factors known to potentially affect treatment progress and outcome. We integrate these assessment findings into all care plans.

How The OAD Clinic Delivers Evidence-Based Cocaine Addiction Treatment

The value of research lies in what it changes in day-to-day practice. The OAD Clinic's approach to cocaine addiction treatment is built directly on the latest clinical evidence base, and this study reinforces five principles that guide how we work with every patient.

Comprehensive, combined treatment. In the trials analysed, every participant received cognitive behavioural therapy alongside their medication – a reflection, as Professor Mojtabai notes, of the widely accepted role of combined treatment in stimulant use disorders. The OAD Clinic mirrors this in practice: pharmacological options, where appropriate, are always delivered as part of a comprehensive programme that includes psychological therapy, changes to environment and routine, and structured psychosocial support.

Measuring progress across multiple dimensions. Because the research shows that genuine recovery moves in step across craving, drug and alcohol use, mental health, relationships and the environment, The OAD Clinic's protocol is to assess and re-assess all of these domains. Progress is defined broadly and realistically, not reduced to a single abstinence test.

Individualised, evidence-matched care. The three distinct trajectories identified in the study are a powerful reminder that no two people with cocaine use disorder respond identically. The OAD Clinic's treatment planning is individualised from assessment onwards, and the plan is adjusted as a patient's own pattern of craving and use becomes clearer.

Monitoring craving as an early signal. With most of the meaningful change in the best-outcome group occurring in the first one to two weeks as Professor Mojtabai’s study suggests, early craving trends can offer an important clue to how treatment is progressing. At The OAD Clinic, clinicians monitor craving deliberately and use it alongside other measures and parameters to inform timely adjustments rather than waiting for problems to compound.

Thorough assessment of alcohol and polysubstance use. The study found that higher baseline alcohol use and the use of multiple drugs were linked to a weaker connection between reduced craving and reduced cocaine use. The OAD Clinic's assessments tests for alcohol and other substance use in detail from the outset, so co-use is identified and treated as part of the whole clinical picture.

Underpinning all of this is a commitment to person-centred, non-abstinence-inclusive outcomes. Where complete abstinence is not immediately achievable, meaningful reductions in cocaine craving and use – and the improvements in health and relationships that accompany them – are treated as real, valid progress. Evidence-based cocaine addiction treatment at The OAD Clinic is guided by the research and tailored to the person.

The OAD Practice

The research validates the person-centered, multi-faceted, evidence-led model The OAD Clinic already follows, and sharpens where we focus our attention: on combined treatment, on individual variation, and on the early signals that a patient is beginning to recover.

Key Takeaways for Drug Addiction Treatment protocols

The interventional aspects examined by the research, namely the potential relationship between cocaine craving and cocaine use, combination of craving reduction medications, cognitive behavioural and other psychotherapeutic interventions and integrated mental health support, reflect the evidence base that The OAD Clinic’s clinical approach is built on. Other factors considered in The OAD Clinic’s protocols include individual responses to treatment at various stages of the recovery journey.

This means in practice:

• Recovery from cocaine use disorder is not uniform.

• Reduced craving and use may be clinically meaningful outcomes.

• Lower craving does not always mean lower use. Co-use of alcohol and other drugs appears to weaken the link between reduced craving and reduced cocaine use.

• Medication effects are partial and dose-specific. Only modafinil at 200mg/day increased the likelihood of craving reduction, and reduced craving did not necessarily mean reduced use. At The OAD Clinic, clinicians have noticed that often, patients experience palpitations on modafinil.

• Evidence-based cocaine addiction treatment should be comprehensive and individualised. Combining pharmacotherapy with psychological therapy, measuring progress across multiple domains, and matching care to the individual have been validated by this research.

Frequently Asked Questions

What is cocaine use disorder?

Cocaine use disorder is a medical condition in which a person continues to use cocaine despite significant harm to their health, relationships, or daily life. It is recognised in diagnostic manuals such as the DSM-5 and can range from mild to severe. Craving, difficulty cutting down, and continued use despite consequences are among its core features.

What is cocaine craving and why does it matter in treatment?

Craving is the intense urge or desire to use a substance, and it is a formal diagnostic criterion for cocaine use disorder. It matters because research shows that reductions in cocaine craving are closely linked to broader improvements in recovery, including better mental health and relationships. This makes craving an important signal of how well treatment is working, though not the only one.

Can cocaine addiction be treated with medication?

No medication is currently licensed specifically for cocaine use disorder, but several have been tested for their potential to reduce craving. In this research, modafinil at 200mg per day increased the likelihood of reduced craving, though not necessarily reduced use. Medication works best as one part of a comprehensive treatment plan that also includes psychological therapy and psychosocial support.

What does evidence-based cocaine addiction treatment involve?

Evidence-based cocaine addiction treatment combines approaches shown to work in clinical research, including cognitive behavioural therapy, pharmacological options where appropriate, and structured psychosocial support. It measures progress across several areas, such as craving, drug and alcohol use, mental health, and relationships, rather than relying on abstinence alone. Care is tailored to the individual, because people respond to treatment in different ways.

Does The OAD Clinic offer treatment for cocaine addiction?

Yes. The OAD Clinic provides individualised, evidence-based treatment for cocaine addiction that combines psychological therapy with pharmacological options where appropriate. The OAD Clinic's assessment process looks at craving, alcohol and other substance use, a patient's environment, mental health, and relationships, so that treatment addresses the whole person rather than a single symptom.

Is abstinence the only measure of successful cocaine addiction treatment?

No. While abstinence is an important goal, it is not always immediately achievable, and meaningful reductions in cocaine craving and use are valuable outcomes in their own right. Research links these reductions to improvements in mental health, relationships, and other substance use, which is why The OAD Clinic recognises progress across multiple areas of a person's life.

About the Research

This article draws on findings from the following peer-reviewed publication:

Mojtabai, R., Susukida, R., Farokhnia, M., Nguyen, T.Q., Leggio, L., Bergeria, C., Dunn, K.E., Amin-Esmaeili, M. (2025): “Cocaine craving and use during pharmacotherapy trials for cocaine use disorder: A multi-trajectory analysis”, Drug and Alcohol Dependence, volume 275:112841. DOI: 10.1016/j.drugalcdep.2025.112841. E-published on: 15 August 2025.

About Professor Ramin Mojtabai

Professor Ramin Mojtabai is Professor and Vice Chair of Research at Tulane University School of Medicine. He is a psychiatrist and leading researcher in the epidemiology and treatment of substance use disorders and mental illness, based in the Department of Psychiatry and Behavioral Sciences. His work focuses on treatment outcomes, recovery, and the analysis of large-scale clinical trial data in addiction medicine. He is the lead author of “Cocaine craving and use during pharmacotherapy trials for cocaine use disorder: A multi-trajectory analysis”, published in Drug and Alcohol Dependence (2025). 

Professor Mojtabai contributes his clinical and research expertise to The OAD Clinic as an expert voice on addiction psychiatry and the evidence base for multi-faceted and person-centred cocaine addiction treatment. Read Professor Mojtabai's full profile at The OAD Clinic.

Expert Q&A: Professor Mojtabai on craving, combined treatment and individual variation

This Q&A draws on findings from: Mojtabai, R., Susukida, R., et al. (2025): “Cocaine craving and use during pharmacotherapy trials for cocaine use disorder: A multi-trajectory analysis”, Drug and Alcohol Dependence journal; volume 275:112841. DOI: https://doi.org/10.1016/j.drugalcdep.2025.112841. E-publication: 15 August 2025.

Question: Your study suggests that participants administered 200mg of modafinil daily were significantly more likely to experience a reduction in craving but not necessarily reduce cocaine consumption. Would a combination of therapies increase the likelihood of reduced cocaine consumption in such cases?

It is quite plausible that a combination of medications or a combination of medications with behavioral treatments would prove more effective than a single medication in treatment of stimulant use disorders (i.e., cocaine and methamphetamine use disorders). For example, in a 2021 randomized controlled trial, combined treatment with injectable naltrexone and oral bupropion proved efficacious in treatment of methamphetamine use disorder (Trivedi, M.H., Walker, R., Ling, W., Dela Cruz, A., Sharma, G., Carmody, T., Ghitza, U.E., Wahle, A., Kim, M., Shores-Wilson, K. and Sparenborg, S., 2021. Bupropion and naltrexone in methamphetamine use disorder. New England Journal of Medicine, 384(2), pp.140-153). Full recovery from these pervasive disorders would often require a comprehensive treatment program including changes in environment, incentives, and cognitions. Medications are a potentially important component of such a comprehensive treatment program. Of note, all the participants in the trials in our study also provided weekly CBT which is an indication of the general acceptance of the role of combined treatment in management of stimulant use disorders.

Professor Mojtabai

Question: The paper highlights that the Decreasing craving/High use group had a higher baseline ASI alcohol use domain score and was more likely to use multiple drugs. Should preliminary assessment of poly-substance and alcohol consumption be considered a potential indicator of pharmacotherapeutic treatment progress in cocaine addiction treatment?

First, as a general rule, one should be cautious in drawing clinical conclusions from findings of a single study. Replication of findings in future studies is the best test of validity of findings. Also, we did not assess whether baseline characteristics of participants impacted the effect of pharmacotherapies. These characteristics, such as concomitant substance use, may be related to heterogeneity in the population of individuals with cocaine use disorders. The mechanisms of cocaine use disorder, the course of the disorder and the factors that contribute to continued use and recovery likely differ among individuals. We simply need more research to better understand the implications of the interplay of craving and drug use patterns for recovery from stimulant use disorders and for the effect of pharmacotherapies. This research may also shed light on the role of concomitant substance use in recovery from stimulant use disorders.

 Professor Mojtabai

About the Author

This article was written and reviewed by Luciana D'Agnone BA, MSc, Director and Editorial Lead at The OAD Clinic. Luciana oversees all clinical content published on the The OAD Clinic website, ensuring it reflects current evidence, clinical experience, and a commitment to person-centred addiction care.

¹ Mojtabai, R., Susukida, R., Farokhnia, M., Nguyen, T.Q., Leggio, L., Bergeria, C., Dunn, K.E., Amin-Esmaeili, M. (2025): “Cocaine craving and use during pharmacotherapy trials for cocaine use disorder: A multi-trajectory analysis”, Drug and Alcohol Dependence journal, volume 275:112841. DOI: https://doi.org/10.1016/j.drugalcdep.2025.112841. E-publication: 15 August 2025.