Can I combine psilocybin with ketamine? Safety profile?

The combination has not been formally studied, but pharmacologically the interaction is unlikely to be dangerous at typical doses. Psilocybin (serotonin 2A agonist) and ketamine (NMDA antagonist) work through entirely different receptors with minimal pharmacodynamic interaction. The main concern is additive dissociation and disorientation — the two together may produce an unexpectedly intense altered state that's harder to navigate than either alone. If you're going to combine, treat it as a new experience, not the sum of your individual experience with each substance.

Practical advice: do not combine on your first use of either substance. Establish your individual responses and dose sensitivities separately before considering combination. If you do combine, use significantly lower doses of each than you would individually. Have a sober sitter present. The combination would likely potentiate both substances' subjective effects. This is not a well-mapped territory.

For therapeutic use specifically: clinical researchers generally do not recommend combining these because the distinct mechanisms and experiences make attribution of therapeutic effect impossible. From a therapeutic standpoint, sequential use (ketamine for rapid acute relief, psilocybin for deeper processing work weeks later) makes more clinical sense than simultaneous combination.