Psychopharmacology of synesthesia; the role of serotonin S2a receptor activation

Synesthesia is a hereditary condition seen in 4% of the general population – different tones evoke different colors or every grapheme (visually presented number or alphabet) is tinged with a specific color [1–3]. The synesthetically [4] induced color vanishes at low contrast and can lead to perceptual texture segregation and apparent motion [5]; evidence that it is an early sensory process. We proposed that grapheme – color synesthesia is caused by ‘‘anatomical cross wiring’’ between the color area V4 and ‘‘number area’’ which lie next to each other in the fusiform gyrus. Recent DT imaging has confirmed this [6]. These effects are seen only in a subset of synesthetes we call ‘‘lower synesthetes’’ (about 15% of all synesthetes). We also suggested that in another group (‘‘higher synesthetes’’) the cross wiring is at a higher more cognitive level in the vicinity of the angular gyrus; this too is consistent with DT imaging results. In addition to cross wiring (caused by ‘‘defective pruning’’ genes) there may also be a pharmacological basis for some types of synesthesia. We report four observations (including three new ones) which support this and present a specific pharmacological model.