Purpose of Review This review summarizes recent clinical trial research on pharmacological treatments for substance use disorders, with a specific focus on agents with potential abuse liability. Recent Findings Pharmacological treatments for substance use disorders may include gabapentinoids, baclofen, modafinil, ketamine, cannabinoids, gamma-hydroxybutyrate, and psychedelics. Gabapentinoids may decrease negative subjective effects of withdrawal in alcohol and cannabis use disorders. Cannabinoids similarly appear to decrease use and withdrawal symptoms in cannabis use disorder, while research shows stimulant medications may reduce cravings and increase abstinence in cocaine use disorder. Ketamine and psychedelics may help treat multiple substance use disorders. Ketamine may reduce withdrawal symptoms, promote abstinence, and diminish cravings in alcohol and cocaine use disorders and psychedelics may promote remission, decrease use, and reduce cravings in alcohol and opioid use disorders. Summary Regardless of current regulatory approval statuses and potentials for abuse, multiple agents should not be dismissed prematurely as possible treatments for substance use disorders. However, further clinical research is needed before effective implementation can begin in practice. Supplementary Information The online version contains supplementary material available at 10.1007/s40429-022-00432-9.