Recommended readings 4
Ketamine, historically an anesthetic, has been shown to be a promising molecule for bringing about therapeutic changes. Ketamine is part of the WHO Model List of Essential Medicines.1 Ketamine is a dissociative but has been included in most of the broader definitions of psychedelics (as atypical psychedelic). Dissociative drugs are substances causing the perception of detachment from one’s body and environment. Like many other psychoactive substances, ketamine is also used recreationally and its effects are highly dependent on the dose.
The duration and follow-up effects of ketamine are typically shorter than those of ‘classic,’ serotonergic psychedelics (psilocybin, LSD). A sub-anesthetic or therapeutic dose is typically administrated via sublingual lozenges, intramuscularly, or intravenously. All routes of administration lead to perceptional effects, such as dissociation and visual distortion. There is, however, much variation in its bioavailability – a lozenge’s bioavailability will be around 15-25% as efficient as intravenous delivery.2 Intravenous doses in the framework of ketamine-assisted psychotherapy (KAP) usually are set around the standard dose of 0,5 mg/kg body weight.
The ketamine molecule comes in two variations3 (enantiomers, mirror images, just like a left and a right hand), R- and S-ketamine (arketamine and esketamine). If not specified otherwise, studies are usually done with racemic ketamine containing 50% of each. Esketamine was developed by Johnson & Johnson as a nasal spray under the brand name Spravato4 for treatment-resistant depression (TRD). Their choice of enantiomer was based on the evidence that esketamine is a stronger inhibitor of action on the NMDA receptor.5 Further studies have now suggested that this pathway is probably not the key mechanism behind the antidepressant effects and arketamine may still prove to be a more effective therapeutic agent.6
This selection of research on ketamine for mental health will explore its promise in treating not only depression but also the positive effects on suicidal ideation, addiction, and further symptoms of mental health disorders.
2. Wieber, J., Gugler, R., Hengstmann, J. H., & Dengler, H. J. (1975). Pharmacokinetics of ketamine in man. Der Anaesthesist, 24(6):260-263.
3. Hashimoto, K. (2019). Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective. Psychiatry and clinical neurosciences, 73(10):613-627.
5. Temme, L., Schepmann, D., Schreiber, J. A., Frehland, B., & Wünsch, B. (2018). Comparative pharmacological study of common NMDA receptor open channel blockers regarding their affinity and functional activity toward GluN2A and GluN2B NMDA receptors. ChemMedChem, 13(5):446-452.
6. Zhang, J. C., Li, S. X., & Hashimoto, K. (2014). R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacology Biochemistry and Behavior, 116:137-141.