This is related to what I used to study. I’d say the difficulty with the question lays with how we interpret “biggest high”. Stimulation of those systems produces a qualitatively different user experience, and even more so depending on the dose, mechanism, and selectivity of the agonist. So serotonergic activation can produce experiences that range from relaxation to full blown psychedelic experiences. Activation of the opioid system can produce warm comfort to catatonia.