4-Hydroxytryptamine

4-HT is a potent agonist of the serotonin 5-HT_2A receptor similarly to psilocin (EC₅₀Tooltip half-maximal effective concentration = 38 nM and 21 nM, respectively).^[4][10][11] It also shows affinity for the serotonin 5-HT_2C receptor (K_i = 40 nM), the serotonin 5-HT_1A receptor (K_i = 95 nM), and the serotonin 5-HT_1B receptor (K_i = 1,050 nM).^[10][11][12] The drug produces serotonergic peripheral effects in animals,^[1][13] shows similar metabolism and metabolic stability to psilocin,^[4] and appears to cross the blood–brain barrier and hence is centrally penetrant.^[4]

Surprisingly however, the compound, similarly to baeocystin, norbaeocystin, and norpsilocin, does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in animals, and hence is putatively non-hallucinogenic.^[4][7] In older literature, the psychoactive effects of 4-hydroxylated tryptamines have been said to increase in the series of 4-hydroxytryptamine, 4-hydroxy-N-methyltryptamine (norpsilocin], and 4-hydroxy-N,N-dimethyltryptamine (psilocin).^[3]

The reason for the lack of hallucinogenic effects with 4-HT and related compounds is unknown, but may be due to biased agonism of the serotonin 5-HT_2A receptor; or, more specifically, biased agonism for the β-arrestin2 signaling pathway.^[4]

Norbaeocystin is thought to be a prodrug of 4-HT, analogously to how psilocybin is a prodrug of psilocin and how baeocystin is thought to be a prodrug of norpsilocin.^[6][4]

4-HT, also known as 4-hydroxytryptamine, is a substituted tryptamine derivative.^[5] It is a positional isomer of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), an analogue of the serotonergic psychedelic psilocin (4-HO-DMT), and the dephosphorylated form of the tryptamine alkaloid norbaeocystin (4-phosphoryloxytryptamine; 4-PO-T).^[5]

4-HT was first described in the scientific literature by 1959.^[1][21][22] Its pharmacology was first thoroughly characterized in 2024.^[4]

• Substituted tryptamine
• 6-Hydroxytryptamine