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Background: Loneliness is a widespread problem, with demonstrated negative health effects. However, prospective data on the relationship between loneliness and problematic substance use are lacking, and few studies have examined specific commonplace substances, such as alcohol and cannabis. This study used prospective data from a community sample of US adults with problematic alcohol or cannabis use to examine whether loneliness was a predictor of subsequent increased substance use.Methods: Participants (N = 210) were recruited between 05/2016-06/2019 from a New York City medical center. At baseline, 3-month, and 6-month follow-ups, participants completed identical computerized questionnaires. We used generalized estimating equations to assess the average effect of past 2-week loneliness on subsequent number of days of alcohol or cannabis use, controlling for baseline days of use, demographic characteristics, and past 2-week DSM-5 depression.Results: Compared with individuals who were never lonely, participants with moderate or severe loneliness had a significantly higher frequency of alcohol or cannabis use at the subsequent assessment (β = 0.25 95% CI: 0.08-0.42).Conclusion: Individuals experiencing loneliness at least a few times in the past 2 weeks reported more days of subsequent alcohol or cannabis use compared with individuals who were not lonely. This is cause for concern, as national surveys of US adults indicate increasing rates of loneliness, depression and substance use during the COVID-19 pandemic. These results suggest the need for health care providers to screen for feelings of loneliness and potentially harmful coping behaviors such as substance use, and to offer healthier alternative coping strategies. [ABSTRACT FROM AUTHOR]