ACS Chemical Neuroscience
May 30, 2018
Bruce K. Cassels, Patricio Sáez-briones
84 citations
Mescaline, a cactus alkaloid, has been used for over 6000 years, primarily in peyote (Lophophora williamsii) and wachuma cacti. Spanish colonizers banned these plants, but use persisted and spread. By the late 1800s, mescaline was isolated and shown to cause psychedelic effects; its structure was synthesized in 1929. Its effects mainly involve 5-HT2A serotonin receptor agonism, though it also binds to 5-HT1A and α2A receptors. Most mescaline is excreted unchanged in urine, and its metabolites do not contribute to psychedelic effects. Low potency led to less recreational use compared to more potent analogues. Renewed therapeutic interest may clarify differences among classic hallucinogens.
Natural Product Communications
April 20, 2026
Bruce K. Cassels
11 citations
Cactus alkaloids have been studied for 120 years. Early work identified classic compounds; later research isolated many similar analogs. Synthesis is straightforward, but biosynthesis, especially of isoquinoline alkaloids, remains poorly understood. Mescaline's pharmacology has been studied extensively due to its striking effects, while hordenine and tetrahydroisoquinoline alkaloids have received less attention and are often considered inactive. However, some recorded activities of tetrahydroisoquinolines suggest a need for further study, particularly regarding their co-administration with mescaline in dried cacti and cactus beverages.
Front Pharmacol
February 28, 2019
Patricio Sáez-briones, Vicente Castro-Castillo, Gabriela Díaz-véliz et al.
4 citations
The psychomotor stimulation and pro-social effects of MDMA (ecstasy) in rats are eliminated by aromatic bromination, a chemical modification that replaces a hydrogen atom on the aromatic ring with bromine. The brominated compound retains affinity for the serotonin transporter (SERT), indicating that binding to SERT alone is insufficient to produce these behavioral effects. The findings suggest that other mechanisms beyond SERT binding are necessary for MDMA's characteristic psychomotor and pro-social actions.
ACS Omega
May 13, 2026
Darío Martínez-afani, Breno A. Soares, Jaime Mella-Raipán et al.
1 citation
A set of 22 tryptamine and 22 5-methoxytryptamine derivatives with various N-benzyl substituents were synthesized and tested for affinity and potency at serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. The data enabled QSAR analysis, which showed that meta-substitution on the benzyl ring improves activity, while para-substitution reduces it. These effects are attributed to favorable van der Waals interactions at the meta position and steric hindrance at the para position. The findings suggest that N-benzyltryptamines, previously overlooked as psychedelic ligands, could be leads for treating cognitive disorders, substance abuse, or depression.
Journal of the Chilean Chemical Society
September 1, 2014
Cristián Tirapegui, Miguel A Toro-Sazo, Bruce K. Cassels
1 citation
A group of extremely potent designer drugs called the NBOMe series, which are N-benzylated phenylethylamines, has emerged. While their high affinity for 5-HT2 serotonin receptors is well documented, the molecular basis of their potency and selectivity is not well understood. In a project evaluating halogen bonds in monoaminergic ligand binding, researchers synthesized new phenylethylamine and tryptamine derivatives with bromine atoms in their N-benzyl moiety. This work reports the synthesis of these compounds for further pharmacological study.