Frontiers in Psychiatry
October 4, 2021
Maxemiliano V. Vargas, Retsina Meyer, Arabo A. Avanes et al.
162 citations
Psychedelics, part of a broader class called psychoplastogens, promote structural and functional neural plasticity in brain circuits relevant to mental health. They produce lasting therapeutic effects after a single dose and show promise for depression, PTSD, anxiety, and substance use disorders. A theoretical framework explains their broad efficacy. Challenges like scalability and hallucinogenic effects may be addressed by non-hallucinogenic psychoplastogens. This shift in neuropsychiatry aims to cure mental illness by repairing underlying pathophysiology, not just treating symptoms.
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.
Nature chemistry
March 1, 2025
Rishab N Iyer, David Favela, Andras Domokos et al.
22 citations
A new chemical method produces ibogaine in seven steps from pyridine, enabling gram-scale synthesis. This approach also creates three additional iboga alkaloids, the unnatural enantiomer (+)-ibogaine, and four analogues. Biological tests show that (+)-ibogaine does not affect cortical neuron growth like natural ibogaine, while (-)-10-fluoroibogamine strongly promotes neuron growth and potently modulates the serotonin transporter. The work provides a platform for making iboga alkaloids and related compounds for further study, supporting research into their therapeutic potential for addiction and other neuropsychiatric conditions.
JACS Au
October 5, 2023
Winston L. Chow, Monica A. Gonzalez, Arabo A. Avanes et al.
7 citations
A general chemical synthesis method for tropane alkaloids—compounds with a characteristic 8-azabicyclo[3.2.1]octane core—enables late-stage structural diversification at positions N8, C3, C6, and C7, which are important for biological activity. The approach constructs the core via aziridination of a cycloheptadiene intermediate followed by vinyl aziridine rearrangement, yielding six tropane alkaloids and several analogues in 5-7 steps. Testing five tropane-containing compounds in cultured cortical neurons for dendritic spine growth—a marker of structural neuroplasticity—suggests that the orientation of the C3 substituent may influence psychoplastogenic effects. This platform supports future structure-activity relationship studies.
August 1, 2015
Stephen J. Chapman, Arabo A. Avanes
3 citations
Proton nuclear magnetic resonance (1H NMR) spectra were collected for 28 purported psychedelic phenylethanamines purchased from 15 unregulated internet vendors in North America and Europe. The samples included members of the 2C and 2C-T series, mescaline analogues, β-substituted phenylethanamines, and N-substituted compounds with NBOMe, NBOH, or NBMD moieties. Several of these spectra had not been previously reported. The study provides a reference database of NMR spectra for these substances, enabling comparison and identification of compounds sold on the grey market.
August 1, 2015
Stephen J. Chapman, Arabo A. Avanes
3 citations
Proton nuclear magnetic resonance (1H NMR) spectra were collected for 28 phenylethanamine compounds sold as psychedelics by 15 online vendors in North America and Europe. The samples included 2C and 2C-T series compounds, mescaline analogues, beta-substituted phenylethanamines, and N-substituted variants with NBOMe, NBOH, or NBMD moieties. Spectra for several of these substances had not been previously documented. The work provides a spectroscopic reference to aid identification of these substances.
ACS Chemical Neuroscience
September 3, 2025
Arabo A. Avanes, Hunter T Warren, Abinaya Senthil et al.
2 citations
Tropane alkaloids and their derivatives are a diverse group of small molecules with many therapeutic uses. Many tropanes affect dopamine and serotonin transporters in the brain. While blocking the dopamine transporter contributes to the addictive potential of tropanes like cocaine, modulating the serotonin transporter may counteract those effects. Serotonin transporter modulators such as MDMA, ibogaine, and SSRIs show promise for treating depression, addiction, and PTSD. This work profiled various tropane subclasses and identified compounds, notably UCD0168 and UCD0820, that potently modulate the serotonin transporter similarly to fluoxetine, MDMA, or noribogaine. UCD0168 acts as a full serotonin releasing agent, and UCD0820 as a partial one. The tropane scaffold can serve as a starting point for developing new serotonin transporter modulators.
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.