Instead of using unsafe Rust to optimize the interpreter loop, I would prefer to write a transpiler that compiles the source UXN binaries to local CPU binaries, which would not require making code unsafe/less readable and would permit further speed enhancements by getting rid of an interpreter loop altogether.
There are Uxn instructions which write to RAM; normally, this is used for storing data, but nothing prevents programs from editing their own code as they're running.
On some platforms writing to memory mapped in with PROT_EXEC will trigger a page fault and the process will be killed. In other words, self modifying executables are effectively forbidden by design (the workaround is to unmap the memory, map it as PROT_WRITE, modify, unmap, map it in as PROT_EXEC, and resume execution - which is what JITs do on MacOS, for example).