Abstract: Provided are methods of administering an entactogen in conjunction with psychotherapy to treat a condition and/or to treat one or more comorbidities in a subject. In other aspects, provided are compositions, such as pharmaceutical compositions, comprising an entactogen for use in an entactogen-assisted psychotherapy (EAP) regimen. In some embodiments, the entactogen is MDMA, for use in MDMA-assisted therapy. In some aspects, the provided EAP methods are used to treat a substance use disorder (SUD) or a behavioral addiction. In some embodiments, the SUD is alcohol use disorder (AUD), including physically dependent (“dependent use”) AUD or non-physically dependent (“harmful use”) AUD. In a further aspect, the provided EAP methods are used to treat one or more of a comorbid SUD, behavioral addiction, or mental health disorder.