Some signs that substance use is negatively affecting mental well-being include increased irritability, mood swings, and heightened anxiety or depression. You might notice a decline in performance at work or school, as well as strained relationships due to erratic behavior. Individuals might isolate themselves from social activities or lose interest in hobbies they previously enjoyed. Physical signs like changes in sleep patterns, weight fluctuations, or neglecting personal hygiene might also indicate the negative impact of substance use on mental well-being.