Ketamine has a split reputation. To many people it is known only as a recreational drug, but in medicine it has a long history as a dissociative anaesthetic and is now being studied for a surprising range of uses. A review by Jian Xu and Hong Lei, published in CNS Neuroscience & Therapeutics (2014), brings together recent research on both its clinical promise and its dangers.
Much of ketamine's effect comes from the way it blocks NMDA receptors in the brain, a mechanism that underlies most of the benefits described below.
Perhaps the most exciting area is mental health. Conventional antidepressants can take weeks to work, but trials show that a single infusion of ketamine can ease depressive symptoms rapidly, often within hours, with effects lasting several days. Repeated doses have been studied to extend that benefit. Researchers believe ketamine works partly by boosting glutamate signaling and brain-derived neurotrophic factor (BDNF), supporting the brain's ability to form new connections. The review also highlights ketamine's potential for treatment-resistant depression, where standard medications have failed, and for bipolar depression, with several studies reporting rapid improvements in mood.
Closely related is ketamine's effect on suicidal ideation. Studies found that a single low dose could significantly reduce suicidal thoughts within 40 minutes, with benefits lasting hours and, in some cases, weeks. Importantly, this effect appears to work partly through easing depression and anxiety, but also seems to have an independent influence on the wish to live.
Ketamine is not only being studied in psychiatry. The review notes its value in severe asthma attacks, where it can relax the airways and reduce the need for mechanical ventilation. It is also widely used in pain management, particularly as an add-on that reduces the need for opioids after surgery, which is especially useful in children who are sensitive to opioid side effects.
The review is clear that ketamine is also a substance of abuse. While death from acute toxicity is rare, chronic misuse carries serious consequences. Long-term users can develop gastrointestinal problems, including epigastric pain, liver injury, and changes to the biliary system. Even more striking is the damage to the urinary tract. Heavy use is linked to painful bladder symptoms, cystitis, and in some cases hydronephrosis and lasting kidney damage, occasionally severe enough to require dialysis.
Ketamine is a powerful example of how an established drug can be repurposed for new uses. It shows real potential as a fast-acting treatment for depression and other conditions, but its capacity for harm when misused is significant and should not be underestimated. As ever, the difference lies in careful, supervised medical use.
Source: Xu, J. and Lei, H. (2014). Ketamine: An Update on Its Clinical Uses and Abuses. CNS Neuroscience & Therapeutics, 20(12), 1015 to 1020.*