Stimulant dependence

Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Historically, total abstinence has been the standard goal of treatment for substance use disorders, however, these findings support the growing recognition that a more nuanced perspective on measuring treatment success may be beneficial. The study, published in Addiction, was led by scientists at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in collaboration with researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. Researchers found that transitioning from high use (five or more days a month) to lower use (one to four days a month) was associated with lower levels of drug craving, depression, and other drug-related challenges compared to no change in use. These results suggest that reduction in use of methamphetamine or cocaine, in addition to abstinence, is a meaningful surrogate or intermediate clinical outcome in medication development for stimulant addiction. Unlike other substance use disorders, such as opioid use disorder or alcohol use disorder, there are currently no U.S. Food and Drug Administration-approved pharmacological treatments for stimulant use disorders. "These findings align with an evolving understanding in the field of addiction, affirming that abstinence should be neither the sole aim nor only valid outcome of treatment," said NIDA Director Nora Volkow, M.D. "Embracing measures of success in addiction treatment beyond abstinence supports more individualized approaches to recovery, and may lead to the approval of a wider range of medications that can improve the lives of people with substance use disorders." Temporary returns to use after periods of abstinence are part of many recovery journeys, and relying exclusively on abstinence as an outcome in previous clinical trials may have masked beneficial effects of treatment. To help address this research gap, investigators analyzed data from previous clinical trials to study the effects of transitioning to reduced drug use or abstinence on a broad range of health measures. Researchers analyzed data from 13 randomized clinical trials evaluating the impact of potential pharmacological medications for stimulant use disorders, which included more than 2,000 individuals seeking treatment for cocaine or methamphetamine use disorders at facilities across the United States. The trials were of varying duration and were undertaken from 2001 to 2017. Researchers compared "no reduced use," "reduced use," and "abstinence" in association with multiple health outcomes, such as severity of drug-related symptoms, craving, and depression. The study found that more participants reduced the frequency of primary drug use (18%) than achieved abstinence (14%). While abstinence was associated with the greatest clinical improvement, reduced use was significantly associated with multiple measures of improvements in psychosocial functioning at the end of the trials, such as a 60% decrease in craving for the primary drug, 41% decrease in drug-seeking behaviors, and a 40% decrease in depression severity, compared to the beginning of the trial. These findings suggest that improvements in health and functioning can occur with reduced use and should be considered in the development and approval of treatments for substance use disorders. Research on alcohol use disorder has shown similar results, with studies finding that transitioning from high-risk to low-risk drinking is associated with functional improvement and fewer mental and general health consequences caused by alcohol. As a result, a reduced number of heavy drinking days is already recognized as a meaningful clinical outcome in medication development for alcohol use disorder. "With addiction, the field has historically acknowledged only the benefits of abstinence, missing opportunities to celebrate and measure the positive impacts of reduced substance use," said Mehdi Farokhina, M.D., M.P.H., a staff scientist in the NIDA Intramural Research Program, and author on the paper. "This study provides evidence that reducing the overall use of drugs is important and clinically meaningful. This shift may open opportunities for medication development that can help individuals achieve these improved outcomes, even if complete abstinence is not immediately achievable or wanted." The authors note that the study did not include behavioral treatment trials, which were too varied to harmonize their data. In addition, the study featured only people who enrolled in clinical trials, which could limit generalizability. Additional research is needed to understand the potential clinical benefits of reduced drug use, along with other harm reduction-based indicators of clinical improvement in real-world populations. The authors highlight that the findings of this study should encourage researchers to re-evaluate treatment outcome measures in their studies and consider non-abstinence treatment outcomes in the development of new medications for the treatment of stimulant use disorders. The authors also write that these new findings need to be replicated in other contexts with additional substance use disorders such as opioid use disorder. "By promoting an understanding of addiction as a treatable disorder with multifaceted causes, society can work towards providing better support, resources, and care for individuals on their way to recovery," said Masoumeh Aminesmaeili, M.D., lead author of the paper. "This approach is not only compassionate, but also clinically valid in addressing the complex nature of addiction." For more information on substance and mental health treatment programs in your area, call the free and confidential National Helpline 1-800-662-HELP (4357) or visit:

The agency is asking for comments on the draft guidelines within the next 60 days. The FDA has never had the chance to approve a stimulant use disorder treatment and so the agency has laid out its current thinking on clinical trial design, population selection and clinical endpoint selection, all in an effort to spur new interest in the space.  An unpublished draft guidance, “Stimulant Use Disorders: Developing Drugs for Treatment,” will include recommendations for clinical trials designed specifically to assess treatments for stimulant use disorders, excluding symptoms associated with caffeine or nicotine use. The guidance tackles challenges unique to the space, such as determining the appropriate populations for trials and choosing proper clinical endpoints. The FDA document expands beyond basic considerations of the drug development process, delving into approaches that have proved unsuccessful before and ways to make clinical trial design more patient-centric.  “Currently there is no FDA-approved medication for stimulant use disorder,” Marta Sokolowska, Ph.D., deputy center director for substance use and behavioral health in FDA’s Center for Drug Evaluation and Research, said in an Oct. 4 release. “When finalized, we hope that the guidance will support the development of novel therapies that are critically needed to address treatment gaps.” The FDA provides recommendations on data collection, methods to assess treatment response, subject safety and new drug application requirements.  The final version will be the agency’s first guidance about program development and trial design for drugs to treat cocaine use disorder, methamphetamine use disorder and prescription stimulant use disorder. The agency is asking for comments on the draft guidelines within the next 60 days. Some players in the stimulant use disorder treatment space include Sparian Biosciences, which has an early-stage dual sigma receptor antagonist/dopamine transporter inhibitor in development, as well as Myosin Therapeutics, which touts a preclinical small molecule modulator candidate. Both companies have received NIH funding for their work. Beyond the guidance, the FDA has also recently held workshops and public meetings to encourage the development of treatments for stimulant use disorder. 

SILVER SPRING, Md., Oct. 4, 2023 /PRNewswire/ -- Today, the U.S. Food and Drug Administration published a new draft guidance to assist sponsors in developing treatments for stimulant use disorders. The guidance, Stimulant Use Disorders: Developing Drugs for Treatment, when finalized, will be the first to provide the FDA's current thinking on the overall development program and clinical trial design to develop drugs and biologics to support treatment of moderate to severe cocaine use disorder, methamphetamine use disorder and prescription stimulant use disorder. "Currently there is no FDA-approved medication for stimulant use disorder. When finalized, we hope that the guidance will support the development of novel therapies that are critically needed to address treatment gaps," said Marta Sokolowska, Ph.D., deputy center director for Substance Use and Behavioral Health in FDA's Center for Drug Evaluation and Research. "The guidance is one of the actions within the agency's Overdose Prevention Framework, which includes appropriate prescribing of prescription stimulants as well as development of evidence-based treatments for stimulant use disorder." Among other things, the draft guidance contains recommendations regarding clinical trial design related to evaluating stimulant use disorder treatments. Designing clinical studies to evaluate the safety and effectiveness of stimulant use disorder treatments presents a number of unique challenges—from selecting appropriate populations for studies to determining the most appropriate clinical endpoints—that require careful review. However, there are opportunities to improve clinical trial design and develop trials that are more person-centered, which may result in increased sensitivity to detect a treatment effect, with the potential for treatment effects to be linked to meaningful long-term outcomes. The draft guidance also describes basic considerations throughout the drug development process including trial conduct, data collection, methods to assess treatment response, subject safety and new drug application requirements. For example, the guidance incorporates lessons learned about approaches that are unlikely to be successful and reflects current recommendations about approaches for treating stimulant use disorders and evaluating response to treatment. Stimulant use disorder describes a range of symptoms associated with the use of stimulant drugs, including methamphetamine, cocaine, and amphetamines, but not including caffeine or nicotine. A diagnosis of stimulant use disorder is made when a clinician identifies a pattern of use of an amphetamine-type substance, cocaine, or other stimulant that leads to clinically significant impairment or distress, including an inability to reduce or control consumption, cravings to use a stimulant, continued use of a stimulant despite it causing negative consequences, and the need to use increased amounts of a stimulant to achieve the desired effect. The agency has taken action to promote safe use and appropriate prescribing of prescription stimulants by requiring sponsors to update and standardize prescribing information for medications used to treat attention deficit/hyperactivity disorder (ADHD) and other disorders where stimulants are prescribed. Additionally, the FDA awarded the National Academies of Sciences, Engineering, and Medicine a grant to convene a workshop on the diagnosis and treatment of ADHD in adults. It has also funded several research projects to inform prevention of prescription stimulant misuse, addiction and overdose. The FDA continues to encourage the development of treatments for stimulant use disorder and novel trial designs. Over the last several years, the agency has held workshops and public meetings with patients and patient advocates, researchers, industry and other stakeholder groups to better understand the stimulant use disorder landscape and inform the FDA's understanding of the clinical context for drug review and regulatory decision making. Comments on the draft guidance are requested within 60 days to ensure the agency considers them. Additional Resources: FDA Guidances Prescription Stimulant Medications Media Contact: Lauren-Jei McCarthy 240-702-3940 Consumer Inquiries: Email or 888-INFO-FDA The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration