DMT (N, N-dimethyltryptamine) and ketamine are both being explored for their rapid-acting antidepressant and anti-anxiety properties. [1], [2] Though their mechanisms differ – with DMT acting as a serotonin agonist and ketamine blocking NMDA receptors [3] – they may have synergistic effects.
Only a few studies have examined DMT-ketamine interactions. One study in rats found that a low dose of DMT enhanced and extended the antidepressant-like effects of ketamine. [4] This may be because both drugs increase brain-derived neurotrophic factor (BDNF). [5] Another study showed DMT boosted ketamine’s effects on neuronal plasticity. [6]
Potential advantages of combined treatment include faster and longer-lasting relief of depression and anxiety. The drawbacks are that high doses of each drug can induce psychosis, hypertension, and out-of-body sensations. Ketamine also carries risks of abuse and bladder toxicity. [1], [3]
Overall, preliminary research indicates DMT may amplify ketamine’s therapeutic benefits. However, human studies are needed to establish safety and efficacy. Given the powerful psychological effects of both drugs, careful dosage control is essential. More research is required before clinical recommendations can be made.
- Carhart-Harris, R.L., & Goodwin, G.M. (2017). The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacology, 42(11), 2105-2113.
- Schenberg, E.E. (2018). Psychedelic-assisted psychotherapy: a paradigm shift in psychiatric research and development. Frontiers in pharmacology, 9, 733.
- Stahl, S.M. (2013). Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge university press.
- Fortunato, J.J., Réus, G.Z., Kirsch, T.R., Stringari, R.B., Fries, G.R., Kapczinski, F. & Hallak, J.E. (2010). Effects of β-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: further evidence of antidepressant properties. Brain research bulletin, 81(4-5), 491-496.
- Pham, T.H., Gardier, A.M., David, D.J., & Guiard, B.P. (2018). Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & therapeutics, 189, 1-10.
- Abdallah, C.G., Sanacora, G., Duman, R.S. & Krystal, J.H. (2015). Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annual review of medicine, 66, 509-523.