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Home/Research/Ketamine/Medicinal Chemistry & Drug Development

Ketamine for Medicinal Chemistry & Drug Development

16 papers and 3 clinical trials exploring ketamine as a treatment for medicinal chemistry & drug development.

CompoundArylcyclohexylamine

Ketamine

A dissociative anesthetic with rapid-acting antidepressant properties, widely used in clinical settings for mood and pain disorders.

Full Ketamine profile
IndicationOver 300 million people worldwide experience depression, with many also suffering from related anxiety disorders.

Medicinal Chemistry & Drug Development

Medicinal chemistry plays a crucial role in the development of novel psychedelic compounds, focusing on their molecular structures and interactions. Researchers utilise innovative methods to enhance safety and efficacy in psychedelic substances.

Full Medicinal Chemistry & Drug Development profile

Academic Research

16 papers
Paywallindividual

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.

Published
October 13, 2025
Journal
ACS Chemical Neuroscience
Authors
Agrawal, R., Gillie, D., Mungenast, A., Chytil, M., Engel, S., Wu, M. C., Rasmussen, K., Salinas, E., Olson, D. E.
Open Accessindividual

A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers

In a Phase 1 single- and multiple-ascending IV dosing study in healthy volunteers, (2R,6R)-hydroxynorketamine was well tolerated with minimal adverse events, showed no anesthetic or dissociative effects and demonstrated dose-proportional pharmacokinetics with confirmed CNS exposure in CSF. Quantitative EEG showed increases in gamma power in some participants, supporting progression of RR‑HNK into Phase 2 development.

Published
July 25, 2024
Journal
Clinical Pharmacology and Therapeutics
Authors
Raja, S. M., Guptill, J. T., Mack, M., Peterson, M., Byard, S., Twieg, R., Jordan, L., Rich, N., Castledine, R., Bourne, S., Wilmshurst, M., Oxendine, S., Avula, S. G. C., Zuleta, H., Quigley, P., Lawson, S., Mcquaker, S. J., Ahmadkhaniha, R., Appelba, L. G., Kowalski, K., Barksdale, C. T., Gufford, B. T., Awan, A., Sancho, A. R., Moo, M. C., Berrada, K., Cogan, G. B., Delarosa, J., Radcliffe, J., Pao, M., Kenne, M., Lawrence, Q., Goldfeder, L., Amanfo, L., Zanos, P., Gilbert, J. R., Morr, P. J., Moaddel, R., Gould, T. D., Zarate, C. A., Thomas, C. J.
Open Accessindividual

Randomized Placebo-Controlled Phase 2 Study of Extended-Release Ketamine Tablets (R-107) for Treatment-Resistant Depression - the BEDROC Study

In this phase 2 randomised, placebo‑controlled enrichment study, extended‑release oral ketamine tablets (R‑107) given twice weekly maintained antidepressant response in treatment‑resistant depression, with the 180 mg dose producing a significant 13‑week MADRS improvement versus placebo (least‑square mean difference −6.1, P = 0.019). R‑107 was generally well tolerated with minimal blood‑pressure, sedation or dissociation effects, showed a dose–response reduction in relapse rates, and most dosing was performed at home.

Published
June 24, 2024
Journal
Nature Medicine
Authors
Glue, P., Loo, C., Fam, J., Lane, H. Y., Young, A., Surnam, P.
Open Accessindividual

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Plus a Newly Initiated Oral Antidepressant in Adult Patients with Treatment-Resistant Depression: A Randomized, Double-Blind, Multicenter, Active-Controlled Study Conducted in China and USA

This double-blind, randomised Phase III trial (n=227) finds no significant difference between esketamine plus a new antidepressant versus only the antidepressant (and a placebo) at day 28 on depression scores (MADRS). The study reports one death in the esketamine group. It also states esketamine to be effective and safe though only the first claim could be credibly made if one only looks at the immediate (24-hour) effects.

Published
March 31, 2023
Journal
American Journal of Psychiatry
Authors
Chen, X., Hou, X., Bai, D., Lane, R., Zhang, C., Canuso, C., Wang, G., Fu, D. J.
Paywallmeta

Acute effects of ketamine and esketamine on cognition in healthy subjects: A meta-analysis

This meta-analysis assessed the effects of ketamine administration in healthy participants (n=1,041) on several cognitive domains. Deficits in verbal learning/memory were most prominent, whereas response inhibition was the least affected. Negative effects were dependent on infusion dose and plasma level but unaffected by enantiomer type, route of administration, sex or age.

Published
August 1, 2022
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Authors
Zhornitsky, S., Pelletier, R., Assaf, R., Potvin, S., Li, C-S., Tourjaman, V.
Paywallmeta

Pharmacogenomics of ketamine: A systematic review

This review (2021) explores the pharmacogenomic predictors of ketamine's clinical benefits and adverse effects. The review identified three predictors; 1) brain derived neurotrophic growth factor (BDNF) was associated with reduced antidepressant and anti-suicidal effects, 2) CYB2B6 was associated with more severe dissociative effects and 3) NET was associated with greater cardiovascular complications. Limitations include small sample sizes and heterogeneity of study design.

Published
January 1, 2022
Journal
Journal of Psychiatric Research
Authors
Meshkat, S., Rodrigues, N. B., Vincenzo, J. D. D., Ceban, F., Jaberi, S., Mcintyre, R. S., Lui, L. M. W., Rosenblat, J. D.

Clinical Trials

3 trials
Not yet recruitingPhase I

A study comparing two formulations of R-107 under fasting conditions

Phase I randomised, blinded crossover PK/bioavailability study (n=34) comparing R-107-H (3×60 mg) versus R-107-P (3×60 mg) in healthy volunteers under fasting conditions.

Started
October 9, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
ACTRN12624001308583
CompletedPhase I

A Phase I Randomized, Placebo Controlled, Double-Blind, Single-Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PCN-101 (Arketamine) and a Relative Safety Comparison of PCN-101 and Esketamine in Healthy Volunteers

Phase I, randomized, double-blind, placebo-controlled study in healthy volunteers assessing single ascending IV doses of PCN-101 (arketamine) and a crossover relative safety comparison with esketamine (15 mg IV).

Started
February 25, 2020
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
ACTRN12620000226909
CompletedPhase III

The Role of mTOR (Mammalian Target of Rapamycin) Signaling Pathway in the Antidepressive Effect of Ketamine in Patients with Depressive Disorder

This single-blind, placebo-controlled crossover trial (n=30), sponsored by Prague Psychiatric Centre, investigated whether mTOR activation differentiates ketamine responders from non-responders in patients with major depression.

Started
April 25, 2013
Type
interventional
Blinding
single
Randomized
No
Registry ID
2013-000952-17

Explore further

Search all Ketamine papers Search all Medicinal Chemistry & Drug Development trials Full Ketamine profile Full Medicinal Chemistry & Drug Development profile