JRT (drug)

Last updated

JRT
JRT.svg
(+)-JRT.png
Above: JRT molecular structure
Below: 3D representation of a (+)-JRT molecule
Clinical data
Other namesIsoindole-LSD; Isotryptamine-LSD
Drug class Serotonin receptor modulator; Serotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen; Psychoplastogen
ATC code
  • None
Identifiers
  • (7S)-N,N-diethyl-6-methyl-6,9-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),2,10,12(16),13-pentaene-4-carboxamide
PubChem CID
Chemical and physical data
Formula C20H25N3O
Molar mass 323.440 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)C1CN([C@@H]2CN3C=CC4=C3C(=CC=C4)C2=C1)C
  • InChI=1S/C20H25N3O/c1-4-22(5-2)20(24)15-11-17-16-8-6-7-14-9-10-23(19(14)16)13-18(17)21(3)12-15/h6-11,15,18H,4-5,12-13H2,1-3H3/t15?,18-/m1/s1
  • Key:ZYTVEPYZRGXVRK-KPMSDPLLSA-N

JRT, also known as isoindole-LSD or isotryptamine-LSD, is a serotonin receptor modulator, psychoplastogen, and serotonergic psychedelic related to lysergic acid diethylamide (LSD). [1] [2] It is the analogue of LSD in which the embedded tryptamine structure within the ergoline ring system of LSD has been replaced with an isotryptamine structure (or indole replaced with isoindole). [1]

Contents

The drug acts as a non-selective serotonin receptor modulator, including as a partial agonist of the serotonin 5-HT2A receptor and as an agonist or antagonist of various other serotonin receptors. [1] [2] The drug has psychedelic-like, psychoplastogenic, antipsychotic-like, antidepressant-like, and pro-cognitive effects in animals and preclinical studies, whilst lacking apparent pro-psychotic-like effects. [1] [2] It has significant but reduced psychedelic-like effects compared to LSD in animals. [1] [2] The drug is a racemic mixture of (+)- and (–)- enantiomers, with (+)-JRT being the active and employed form. [1]

JRT was first described in the scientific literature by 2022 and was described in greater detail in 2025. [1] [2] It was developed by David E. Olson and colleagues in association with Delix Therapeutics. [1] [2] The drug is being investigated as a possible treatment for schizophrenia. [1]

Use and effects

The properties and effects of JRT in humans do not yet appear to be known. [1] [2]

Interactions

Pharmacology

Pharmacodynamics

(+)-JRT is highly selective for a subset of serotonin receptors and does not bind to various dopamine, adrenergic, or histamine receptors, which is in contrast to LSD. [1] It shows high affinity for the serotonin 5-HT2 receptors, with Ki values ranging from 2.0 to 184 nM. [1] The drug is a potent partial agonist of the serotonin 5-HT2A and 5-HT2B receptors (Emax Tooltip maximal efficacy = 33–81% and 48–51%, respectively) and a full agonist of the serotonin 5-HT2C receptor (Emax = 89%). [1] It is also an agonist of the serotonin 5-HT1A and 5-HT7 receptors, an antagonist of the serotonin 5-HT5A and 5-HT7 receptors, and a ligand of the serotonin 5-HT6 receptor. [1] (+)-JRT does not have significant affinity for the serotonin 5-HT1B or 5-HT3 receptors, whereas its affinities for the other serotonin 5-HT1 receptors and the serotonin 5-HT4 receptor were not reported. [1]

The drug is 4.4- to 180-fold less potent than LSD as a serotonin 5-HT2A receptor agonist in vitro (EC50 Tooltip half-maximal effective concentration = 0.4–90 nM vs. 0.09–0.5 nM, respectively) and is less efficacious than LSD in activating the receptor (Emax = 33% vs. 44–63%, respectively). [1] It has been found to dissociate from the serotonin 5-HT2A receptor approximately 10-fold more quickly than LSD. [1]

(+)-JRT produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents, and hence would be expected to be hallucinogenic in humans. [1] However, the drug shows a reduced HTR compared to LSD, producing less than half the maximal number of head twitches. [1] It can also antagonize or diminish the HTR induced by LSD. [1] Hence, (+)-JRT may be less psychedelic than LSD in humans. [1] LSD and (+)-JRT are of similar potency in producing the HTR, with a maximal HTR being achieved at a dose of 0.2 mg/kg for both drugs. [1]

(+)-JRT does not affect locomotor activity and does not produce any serotonin behavioral syndrome-type effects. [1] It has been found to inhibit dextroamphetamine-induced hyperlocomotion in female but not male mice, to not exacerbate phencyclidine (PCP)-induced hyperlocomotion, to not worsen dizocilpine (MK-801)-induced prepulse inhibition (PPI), and to not induce PPI deficits itself. [1] Some of these findings are in contrast to reuslts with LSD, and are suggestive that (+)-JRT lacks psychotic-like effects and may have antipsychotic potential. [1]

In addition to its other effects, (+)-JRT has been reported to increase neuroplasticity and hence to act as a psychoplastogen, to produce antidepressant-like effects, and to promote cognitive flexibility. [1] It was equivalent with LSD in terms of producing psychoplastogenic effects. [1]

Chemistry

JRT is the analogue of the lysergamide lysergic acid diethylamide (LSD) in which the embedded tryptamine structure within the ergoline ring system of LSD has been replaced with an isotryptamine structure (or indole ring within the ergoline ring system replaced with isoindole ring). [1] Hence, JRT is not an ergoline, lysergamide, or tryptamine itself, but could be considered a cyclized isotryptamine. [1] [2] JRT exists as four enantiomers, including (+)-JRT and (–)-JRT, with (+)-JRT being the active enantiomer and the form used in scientific research. [1]

History

JRT was developed by Jeremy R. Tuck (J.R.T.), Lee E. Dunlap, David E. Olson, and other colleagues at Delix Therapeutics and the University of California, Davis. [1] [2] It was first described in the scientific literature by 2022 [2] and was subsequently described in greater detail in 2025. [1]

Research

JRT is being investigated as a possible treatment for schizophrenia. [1] [2]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Tuck JR, Dunlap LE, Khatib YA, Hatzipantelis CJ, Weiser Novak S, Rahn RM, et al. (April 2025). "Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential". Proceedings of the National Academy of Sciences of the United States of America. 122 (16) e2416106122. Bibcode:2025PNAS..12216106T. doi: 10.1073/pnas.2416106122 . PMC   12037037 . PMID   40228113.
  2. 1 2 3 4 5 6 7 8 9 10 11 Dunlap L (2022). "Chapter 5. An Analog of LSD With Antipsychotic Potential". Development of Non-Hallucinogenic Psychoplastogens (PDF) (Ph.D. thesis). University of California, Davis. pp. 105–114.
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