Salvinorin A, a naturally occurring hallucinogen as potent as LSD, works by selectively activating the kappa opioid receptor (KOR). It is unique among KOR agonists because it contains no nitrogen. This selectivity suggests the KOR could be a target for developing drugs to treat perception-related disorders such as schizophrenia, Alzheimer's disease, and bipolar disorder.
Psilocybin, a psychedelic compound being tested as a treatment for mental health conditions, strongly activates serotonin receptors found not only in the brain but also in the gastrointestinal tract. Despite evidence that gut-brain signaling is disrupted in conditions where psilocybin is used, no research has examined whether its effects on the gut contribute to mental health improvements. This opinion piece argues that psilocybin's peripheral actions in the gut may play a role in its rapid and lasting therapeutic effects, and that understanding all sites of action could guide more targeted drug development.