The international picture
5-MeO-DMT is not listed in the 1971 UN Convention on Psychotropic Substances, which is why national approaches differ so widely. Many countries have scheduled it under their own drug laws. Others control it through analogue provisions that capture substances structurally similar to listed ones. A small number have not addressed it explicitly at all.
An absence from a schedule is not the same as permission. Analogue laws, medicines legislation, import and export controls, and general public health provisions can all apply to a substance that no statute names.
United States
5-MeO-DMT has been a Schedule I controlled substance federally since 2011. Possession, distribution, and manufacture are federal crimes. State law adds its own layer. There is no approved medical use, and the early-phase clinical research being conducted proceeds under research authorisation, which is a narrow and specific permission held by the sponsors of those trials.
Separately, the Sonoran Desert toad is protected under New Mexico state law, where it is listed as endangered. Wildlife protections exist independently of drug scheduling and are enforced by different agencies.
Mexico
Mexico is where a large part of the retreat activity in this field takes place, and the reason usually given is that 5-MeO-DMT is not enumerated by name in the relevant Mexican health legislation. That is broadly the situation as commonly described, and it is a narrower point than it is often made to sound.
Several things remain true regardless. Mexican wildlife and environmental law governs the capture, handling, and transport of native species, and the Sonoran Desert toad is a native species. Health legislation governs anything presented as medical treatment. Commercial operation, immigration status, and tax obligations all apply. And the citizens of other countries do not stop being subject to their own laws on importation when they fly home.
People also frequently assume that an activity taking place lawfully in one jurisdiction is therefore ethically settled. It is not the same question.
Wildlife law is separate
This is a distinction that catches people out. A jurisdiction may say nothing about the molecule while saying a great deal about the animal. Collection, possession, transport across borders, and commercial use of a protected native species can carry serious penalties entirely independent of drug law.
Anyone whose supply chain involves a wild-caught animal has two legal exposures, not one. It is another argument for synthetic material. See Bufo alvarius and the toad question.
Religious exemption claims
In the United States, religious use exemptions under the Religious Freedom Restoration Act have succeeded in specific, narrow, heavily litigated cases involving established traditions with long histories. Those cases required years of litigation and detailed factual records.
Forming an organisation and declaring a religious purpose does not, on its own, create an exemption, and a considerable number of people have discovered this expensively. Anyone considering that route needs a lawyer, not a website.
Why this is not advice
Drug law changes, varies by state and province, and turns on facts specific to a person and a place. This page is a general orientation written for study. If you are making a decision with legal consequences, retain a qualified lawyer in the relevant jurisdiction.