Chapter 47:
Even if Orochimaru were to collect enough Sharingan genes and successfully fuse the Mangekyō Sharingan with his body, he wouldn't necessarily lose his mind. However, there would certainly be mental side effects. The intense spiritual power required to wield the Mangekyō would undoubtedly affect his psyche.
When using the advanced abilities of the Mangekyō Sharingan, the body is put under incredible strain. Over time, side effects such as myopia, eye bleeding, and severe physical pain are almost guaranteed. The sheer power of the ocular jutsu overloads the body's capacity to manage the strain, leading to these complications.
Some might wonder: If a body is strong enough, does that mean using the Mangekyō Sharingan would have no side effects?
The answer is yes with a strong enough body, the side effects can be minimized or even eliminated.
Take Uchiha Obito, for example. After transplanting the cells of the First Hokage, and later integrating White Zetsu's body, he was able to use his Mangekyō Sharingan freely, without suffering from common side effects. He didn't experience bleeding eyes, myopia, or body pain, despite constantly using powerful techniques like Kamui.
Orochimaru hypothesized that after using an advanced genetic enhancement serum, he, too, would be able to use the **Mangekyō Sharingan without those physical side effects. Moreover, if he managed to fuse the cells of the First Hokage into his body, it would even be possible for him to use the Rinnegan without difficulty.
To Orochimaru, the Rinnegan was far more advanced than the Mangekyō Sharingan at least a full level above it in terms of power and capability.
Obito, despite having the First Hokage's cells, struggled when it came to the Rinnegan. It was clear that simply integrating Hashirama's cells wasn't enough to fully master it. Even with the strength of those cells, the Rinnegan was too much for his body to handle comfortably.
Using a pair of Rinnegan? That was an entirely different challenge. To control both eyes of the Rinnegan, a ninja would need the physique of someone from the Uzumaki or Senju clans those with an exceptionally strong life force and chakra reserves. Just transplanting Hashirama's cells wasn't enough.