Reduced drug use as an alternative valid outcome in individuals with stimulant use disorders: Findings from 13 multisite randomized clinical trials
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Background and aims: Total abstinence has historically been the goal of treatment for substance use disorders; however, there is a growing recognition of the health benefits associated with reduced use as a harm reduction measure in stimulant use disorders treatment. We aimed to assess the validity of reduced stimulant use as an outcome measure in randomized controlled trials (RCTs) of pharmacological interventions for stimulant use disorder. Design: We conducted a secondary analysis of a pooled dataset of 13 RCTs. Setting and participants: Participants were individuals seeking treatment for cocaine or methamphetamine use disorders ( N = 2062) in a wide range of treatment facilities in the United States. Measurements: We validated reduced stimulant use against a set of clinical indicators drawn from harmonized measurements, including severity of problems caused by drug use, comorbid depression, global severity of substance use and improvement, severity of drug‐seeking behavior, craving and high‐risk behaviors, all assessed at the end of the trial, as well as follow‐up urine toxicology. A series of mixed effect regression models was conducted to validate reduction in frequency of use against no reduction in use and abstinence. Findings: More participants reduced frequency of primary drug use than achieved abstinence (18.0% vs. 14.2%, respectively). Reduced use was significantly associated with decreases in craving for the primary drug [60.1%, 95% confidence interval (CI) = 54.3%–64.7%], drug seeking behaviors (41.0%, 95% CI = 36.6%–45.7%), depression severity (39.9%, 95% CI = 30.9%–48.3%), as well as multiple measures of global improvement in psychosocial functioning and severity of drug‐related problems, albeit less strongly so than abstinence. Moreover, reduced use was associated with sustained clinical benefit at follow‐up, as confirmed by negative urine tests (adjusted odds ratio compared with those with no reduction in use: 0.50, 95% CI = 0.35–0.71). Conclusion: Reduced frequency of stimulant use appears to be associated with meaningful improvement in various clinical indicators of recovery. Assessment of reduced use, in addition to abstinence, could broaden the scope of outcomes measured in randomized controlled trials of stimulant use disorders and facilitate the development of more diverse treatment approaches.
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Changes in MA use following psilocybin dosing were expressed as reduced use or abstinence because these reductions have been associated with meaningful improvements in clinical indicators of recovery.
“In addition, changes in MA use following psilocybin dosing were also expressed as reduced use (from greater than 5 days use at baseline to less) or abstinence, as these reductions have been associated with meaningful improvements in clinical indicators of recovery [47].”
From Psilocybin‐assisted psychotherapy for methamphetamine use disorder: A pilot open‐label safety and feasibility study. (2025) · cites this paper as [47]
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“35 For example, a qualitative assessment of the re - covery pathways of long-term methamphetamine users found that the majority in recovery for great - er than 1 year used replacement substances in a “non-problematic” manner as a tool for recovery maintenance.”
López‐Castro, T., Gette, J. A., Back, S. E., Blakey, S. M., Killeen, T. K., Morgan‐López, A. A., Norman, S. B., Ruglass, L. M., Saavedra, L. M., McGovern, M. P., et al. (2025) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2025.112837
Nonmedical Stimulant Use and Stimulant Use Disorders in Palliative Care #522
Langmann, G. A., & Low, C. (2025) · Journal of Palliative Medicine · doi:10.1177/10966218251383705
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Self-citationEfficacy signals in a 12-week trial of clavulanic acid to decrease cocaine use
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Impact of Comorbid Psychological Distress on Stimulant Use Disorder Treatment Outcomes
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“Consistent with prior studies, 36-38 the frequency of use was categorized into 3 levels: no use (0 days), low-frequency of use (1-4 days), and high-frequency of use ( ≥ 5 days).”
Self-citationNon-invasive vagus nerve stimulation for substance use disorder: A narrative review
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“There is growing evidence supporting the clinical efficacy of medication for StUD; however, no medications are currently approved by the US Food and Drug Administration (FDA) or any other regulatory authority worldwide, which limits access to evidence-based care [6].”
A multi-reward framework to improve translation in alcohol use disorder
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- Authors
- Amin‐Esmaeili, M., Farokhnia, M., Susukida, R., Leggio, L., Johnson, R. M., Crum, R. M., & Mojtabai, R.
- Affiliations
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
- Corresponding author
- Amin‐Esmaeili, Masoumeh
- Venue
- Addiction
- Publisher
- Wiley
- Published
- 2024-01-10
- Volume
- 119
- Issue
- 5
- Pages
- 833-843
- ISSN
- 0965-2140 (ISSN-L)
- 1360-0443
- PMC
- PMC11009085
- OpenAlex
- W4390704561
- Cited by
- 43
- References
- 56
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 13
- FWCI
- 13.04
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-06-26)
- Open access
- bronze
- doi.org
- Locations
- Addiction (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01DA054700(PI, RM))
- Intramural Research Program (ZIA‐DA000635(PI, LL))
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
- Keywords
- stimulant use disorder, cocaine dependence, methamphetamine dependence, harm reduction, abstinence, outcome validity, craving, drug-seeking behavior, depression, urine toxicology, pharmacotherapy
- MeSH terms
- Central Nervous System Stimulants, Cocaine, Humans, Methamphetamine, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Substance-Related Disorders
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