Well, the feeling of mental discomfort definitely is a physical phenomenon at the neuron level. However, because we have the ability to reflect on our feelings

Well, the feeling of mental discomfort definitely is a physical phenomenon at the neuron level. However, because we have the ability to reflect on our feelings as we feel them, we have the ability to consider them as one signal out of many. The feeling of happiness or sadness or discomfort or fear is a single signal; others include situational awareness, memories, goals, etc (not describing a strict ontology here). My impression of "transcendence" is the ability to consciously take these signals as input, rather than subconsciously by following feelings. The prerequisite to this is a deep understanding of oneself, the different signals one can perceive, and what real-world phenomena correspond to those signals (vs what the signals themselves say). There's also a lot of anecdotal evidence that various psychedelics aid in this process, with one theory being that because they often delay or otherwise distort the link between your perception and reality, you have to think logically about how to compensate for the difference between your perception and what you consciously know to be reality. Throw the especially pensive nature induced by some variants of marijuana or LSD into the mix, and you've got a recipe for enlightenment. By the way, if that sounds plausible, consider that the euphoria associated with consuming those substances may be an evolutionary adaptation. Seeing really is believing; humans have a hard time properly attributing weight to factors they can't directly perceive (even our own suffering isn't enough to motivate us if it's far enough in the future to be abstract to our current selves). As a result, most people don't acquire the ability to consciously perceive their input signals (and compensate for them) until the difference between perception and reality is made literally visible, e.g. by psychedelics.