Nature
January 1, 2021
Lindsay P Cameron, Robert J Tombari, Ju Lu et al.
468 citations
Ibogaine, a psychedelic alkaloid, shows anti-addictive effects in humans and animals but has safety issues including toxicity and heart arrhythmias. Researchers engineered tabernanthalog, a water-soluble, non-hallucinogenic, non-toxic analogue made in a single step. In rodents, tabernanthalog promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects. This demonstrates that careful chemical design can create safer, non-hallucinogenic variants of psychedelic compounds with therapeutic potential.
Proceedings of the National Academy of Sciences
April 14, 2025
Jeremy R Tuck, Lee E Dunlap, Yara A Khatib et al.
32 citations
A newly designed compound, (+)-JRT, structurally similar to LSD but with reduced hallucinogenic effects, promotes the growth of dendritic spines in the cortex—a process that is diminished in neuropsychiatric diseases such as depression, addiction, and schizophrenia. In behavioral tests, (+)-JRT showed antidepressant-like and cognition-enhancing effects without worsening signs related to psychosis. This suggests that nonhallucinogenic compounds that promote neuroplasticity could be safer alternatives to psychedelics for treating conditions where psychedelics pose risks.
ACS chemical neuroscience
March 1, 2023
Robert J Tombari, Paige C Mundy, Kelly M Morales et al.
15 citations
Thirteen psychoactive compounds from different chemical classes were screened in larval zebrafish for developmental toxicity. Psychedelic tryptamines and ketamine were less neurotoxic than LSD and psychostimulants. The results provide a reference database for comparing neurotoxicity profiles of novel psychedelics being developed as therapeutics.
The Journal of organic chemistry
October 6, 2023
Jeremy R Tuck, Lee E Dunlap, David E Olson
7 citations
A novel seven-step formal synthesis of LSD has been developed, focusing on connecting the A- and D-rings first and then bridging the B- and D-rings last. The synthesis uses cross-coupling, intramolecular α-arylation, borrowing hydrogen alkylation, and rhodium-catalyzed C-H insertion to form the tetracyclic ergoline core. The methods enable the first introduction of substitutions on the C-ring, though each strategy faces unique challenges when elaborating to ergoline natural products. These findings provide insights that will guide future synthetic strategies toward ergolines and related compounds.
ACS chemical neuroscience
May 6, 2026
Maxemiliano V Vargas, Cassandra J Hatzipantelis, Lee E Dunlap et al.
A safer analogue of MDMA, called R-MDDMA, shows promise for treating PTSD and depression without the abuse potential of MDMA. Unlike MDMA, R-MDDMA does not activate 5-HT2B receptors, induce serotonin release, cause head-twitch responses, affect body temperature, or increase locomotion at therapeutic doses. However, it still promotes structural neuroplasticity in cortical neurons, facilitates fear extinction learning, and produces sustained antidepressant-like effects. These results suggest that R-MDDMA might be a safer MDMA analogue with similar therapeutic properties.