Linking Ketamine Use and Dissociation
- Abigail Simpson
- Oct 3
- 4 min read
Ketamine is a drug first used as a dissociative human and animal anaesthetic, where patients are still conscious but may experience memory loss and loss of awareness of surroundings. More recently, it has been studied in the potential of treating depression, where it was found ketamine can cause rapid anti-depressive responses, which would've taken weeks or months for standard antidepressants to achieve. It is also a popular recreational drug, taken due to it's euphoric, dissociative, relaxing effects. But while this feeling is enjoyed by some, others take ketamine and have a completely different, and often negative experience (Zanos et al., 2018).
Why does recreational ketamine cause an enjoyable feeling?
Ketamine can reshape reality for many users, and cause a very euphoric and out-of-body experience. This is due to the drug blocking NMDA glutamate receptors in the brain, which causes a burst of glutamate to be released, activating other AMPA receptors, which causes reality to morph into more of a dreamlike state, as well as mood enhancement alongside it. This causes the dissociative out-of-body experience, with altered sensory feelings, causing time perception to be changed, and sensory information like visual images and music to be perceived differently. It also increases dopamine to further produce euphoria (Zanos et al., 2018). It is understandable why some people highly enjoy the feeling of this drug, causing boosted mood, emotional detachment, and dreamlike experiences and novel perceptions of reality.
Is there long-term dissociate effects of ketamine?
The ketamine experience is partly based on the way the brain is interpreting the experience of the drug, and no two people are going to have the same experience, as the brains of all users will work slightly differently in response to the drug. Theoretically, long-term dissociation could occur in someone with trauma/extreme anxiety, but has not been documented.
Ketamine's main action in blocking NMDA receptors is the same in an anxious user, however the brain may be reacting differently. In this case, the brain may have heightened arousal in the amygdala area of the brain, and as dissociation can occur in people as a protective mechanism, anxious brains that are going through the experience of ketamine may theoretically rewire certain circuits in the brain that can cause persistent experiences of dissociation, especially since ketamine allows for easier rewiring of neurons. Anxious people are often hyper-vigilant, and have a need for control, and so the experience of ketamine may not be euphoric and relaxing, and instead may be frightening or threatening, and anxiety may be heightened even further, since the person may feel they are not in control of their body and are loosing touch with their surroundings. However long-term dissociation has not been recorded with ketamine use, however, theoretically, it is possible for anxiety to drive dissociative episodes.
It has been suggested that lower hippocampal activity is linked to heavy recreational ketamine use, which is then linked to dissociative and schizophrenic symptoms. Lower hippocampal activity in the brain with dysregulated glutamate signalling can underlie dissociative symptoms, and this activity of the hippocampus is decreased with heavy recreational ketamine use to cause possible persistent dissociation (Morgan et al., 2014). This is very unlikely in clinical treatment as doses would not be this high.
Transience of dissociation in ketamine use
Thankfully, ketamine's effects are mostly transient in single and low doses, and any long-lasting psychological effects would be attributed to extreme anxiety/trauma in heavy doses, but there is a lack of research into ketamine's long term dissociative effects due to the rarity of this. Many clinical trials into using ketamine to treat depression record dissociation as a major side effect, causing extreme discomfort in patients, who are told to listen to their favourite song, a way of providing positive stimuli, to encourage a more positive experience instead of a frightening one. This helped alleviate a patient's symptoms from a study and decreased her feelings of confusion and unpleasantness (Pereira et al., 2021). This may be useful in a real-world situation of dissociation in recreational use, where the user needs to be reassured that they are safe, and given positive stimuli in order to reduce the severity of longevity of their symptoms.
Nevertheless, it is a clear and well-documented side effect of recreational and clinical ketamine use, which can induce extreme panic and fright, and more research should be done into the long term effects of this on a patient's mental health, not just their physical brain chemistry. It is well known how long-term ketamine use reduces grey and white matter volume in the brain in heavy users, as well as causing dysfunctional connections between different parts of the brain, causing long-term memory impairment (Strous et al., 2022), but more studies should be done into long-term dissociation and the resulting anxiety and depression that accompanies that.
Research into long-term dissociation, whether from anxiety or physiological brain changes, is critical for the mental health of many users of ketamine, and will unravel new insights into the way that this drug affects the brain, to possibly allow us to alleviate these symptoms and treat dissociate and schizophrenia spectrum symptoms, or to understand if, and how, dissociation may fit into the therapy of treatment-resistant depression.
References:
Morgan, C. J., Dodds, C. M., Furby, H., Pepper, F., Fam, J., Freeman, T. P., Hughes, E., Doeller, C., King, J., Howes, O., & Stone, J. M. (2014). Long-Term Heavy Ketamine Use is Associated with Spatial Memory Impairment and Altered Hippocampal Activation. Frontiers in psychiatry, 5, 149. https://doi.org/10.3389/fpsyt.2014.00149
Embrace Autism (2025) Embrace Autism. Available at: https://embrace-autism.com (Accessed: 13 August 2025).
Pereira, S., Brennan, E., Patel, A., Moran, M., Wallier, J., & Liebowitz, M. R. (2021). Managing dissociative symptoms following the use of esketamine nasal spray: a case report. International clinical psychopharmacology, 36(1), 54–57. https://doi.org/10.1097/YIC.0000000000000327
Strous, J. F. M., Weeland, C. J., van der Draai, F. A., Daams, J. G., Denys, D., Lok, A., Schoevers, R. A., & Figee, M. (2022). Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review. Frontiers in neuroanatomy, 16, 795231. https://doi.org/10.3389/fnana.2022.795231
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., Jr, & Gould, T. D. (2018). Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacological reviews, 70(3), 621–660. https://doi.org/10.1124/pr.117.015198
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