Re: Anhedonic Substance Blockage with PFS/PSSD/PAS

Powers' current theory of anhedonic substance blockage: dopaminergic signaling breaks down because efflux pump/transporter defects let substances accumulate intra- or extracellularly, destroying concentration gradients and effectively silencing signaling — his proposed overlap point between PFS, PSSD, and possibly PAS, via epigenetic reprogramming that isn't readjusted after drug removal. He notes ABCC5 glitches as the most common finding so far but says he's early on PSSD with fewer genomes. He then describes a striking PFS case: a patient with very high LH/FSH continuously producing androgens at high rates but with silenced androgen signaling — a self-fulfilling loop in which metabolites the patient can't break down (due to multiple genetic glitches) compete with functional androgens at the receptor, weakening signaling, prompting more androgen production, and generating more metabolite crowding; no epigenetic break is even needed to sustain it. It began with finasteride in someone already heavily reliant on 5α metabolism because of pre-existing glitches. He hopes temporary chemical castration may fix this patient.