A shea butter-based ketamine ointment: The antidepressant effects of transdermal ketamine in rats.
Merve Akan, Ivan Skorodumov, M. Meinhardt, R. Canbeyli, Gunes Unal
Behavioural Brain Research July 22, 2023 DOI: 10.1016/j.bbr.2023.114594 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical proof-of-concept study Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Intervention | Ketamine |
| Dose | 5% (w/w) ketamine ointment, applied twice a day for 2 days |
| Duration | 2 days of treatment, twice daily |
| Measures | Forced swim test (FST), open field test (OFT), elevated plus maze (EPM), high-performance liquid chromatography |
| Topics | Esketamine Ketamine |
| Key points | Transdermal ketamine delivered in a 5% shea butter-based ointment reduced behavioral despair in the forced swim test without altering locomotor activity or anxiety-like behavior, suggesting that skin-friendly carriers like shea butter may be promising alternatives to current ketamine delivery routes. The authors propose this method could support more sustainable long-term treatment schedules, while noting that long-term use, side effects, and abuse liability remain to be studied. |
Abstract
The delayed onset of monoaminergic antidepressants and disadvantages of traditional administration routes created the need for alternative non-invasive delivery methods with rapid onset therapeutic effect. Ketamine attracted attention as a fast-acting glutamatergic antidepressant with ideal physiochemical properties for alternative routes of administration. However, there is no sufficient data for its transdermal use in depression. In this proof-of-concept study, we investigated the antidepressant effects of transdermal ketamine delivered via a novel ointment with skin protective, emulsifying and permeation enhancing properties. A shea butter-based 5% (w/w) ketamine ointment or a drug-free vehicle ointment were applied to the shaved dorsal skin of male Wistar rats for 2 days, twice a day. Behavioral despair, locomotor activity and anxiety-like behavior were respectively assessed in the forced swim test (FST), open field test (OFT), and elevated plus maze (EPM). The pharmacokinetic profile of the ointment was analyzed with high-performance liquid chromatography. Transdermal ketamine ameliorated behavioral despair without altering general locomotor activity and anxiety-like behavior, showing that skin-friendly drug carriers like shea butter may constitute promising alternatives to current routes of delivery for ketamine. Tested transdermal method aims to provide more sustainable drug delivery for long-term treatment schedules. Future studies can investigate its long-term use, side effects and abuse liability.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
Cites 4
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
- Chronic oral ketamine prevents anhedonia and alters neuronal activation in the lateral habenula and nucleus accumbens in rats under chronic unpredictable mild stress. Neuropharmacology February 20, 2023
- Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial. Journal of Psychopharmacology April 2018