Following the passage of the American Indian Religious Freedom Act Amendments of 1994, United States federal law (and many state laws) protects the harvest, possession, consumption and cultivation of peyote as part of "bona fide religious ceremonies" (the federal statute is the American Indian Religious Freedom Act, codified at 42 U.S.C. § 1996a, "Traditional Indian religious use of the peyote sacrament", exempting only use by Native American persons. US v. Boyll expanded permitted use to all persons engaged in traditional Indian use, regardless of race. All US states with the exception of Idaho and Texas allow usage by non-native, non-enrolled persons in the context of ceremonies of the Native American Church. Some states such as Arizona additionally exempt any general bona fide religious activity or spiritual intent. US jurisdictions enacted these specific statutory exemptions partially in reaction to the US Supreme Court's decision in Employment Division v. Smith, 494 U.S. 872 (1990), which held that laws prohibiting the use of peyote that do not specifically exempt religious use nevertheless do not violate the Free Exercise Clause of the First Amendment.

In October 2021, Seattle’s City Council approved a resolution to decriminalize noncommercial activity around non-peyote-derived mescaline.^[22]