Saturday, 7 June 2014

Fighting fire with fire - Part 3 (Ketamine and depression)

The third and final part of my “Fighting fire with fire” series will focus on the potential use of ketamine as treatment for severe depression. Ketamine is a drug licensed for use as an anaesthetic (for humans and animals). However, it is better known as an illegal recreational drug, categorised into Class B. The definition of ketamine as an anaesthetic explains its effects, which are mainly analgesic (pain relieving). These include a loss of feeling in the body and paralysis of muscles. Ketamine use can also lead to a distortion of reality, hallucinations and confusion. 

Ketamine in its liquid form,
most commonly used as an anaesthetic
Ketamine works in the body by antagonising an NMDA receptor, which is a receptor for the substance glutamate. Glutamate is the main stimulatory neurotransmitter in your brain. By antagonising the receptor, ketamine inhibits the action of the NMDA receptor. This therefore inhibits the action of glutamate and its receptor, and so it follows that less glutamate will be released. The effect of this is lowered breathing and circulation. Glutamate is also extremely important in a process called plasticity. This involves the ability of your brain to learn, memorise and adapt. A lack of plasticity would mean a person has a lower capacity to learn and retain new information. The effects of ketamine, therefore, inhibit (or compete with) those of glutamate, and so result in a more sedentary response. 

When doses are administered in smaller amounts than anaesthetic standards, ketamine can result in a dissociative state. This means a person may experience depersonalisation and derealisation – in other words a sense of detachment from the person’s physical body and the external world. 

Ketamine also acts within the brain to reduce levels of activity in an area called the anterior cingulate. This area of the brain is associated with feelings of guilt and worthlessness. 

Depression is a mental condition that usually manifests as a persistent low mood and aversion to any form of activity. People with depression often feel anxious, helpless, guilty, sad and/or worried, and may experience a loss in appetite or overeating, have problems with making decisions and may even contemplate or commit suicide. Unfortunately, like so many other mental disorders depression is hard to pinpoint an exact cause or area where the symptoms originate, and therefore it is extremely difficult to help a person with the condition. Depression also can differ greatly in severity, with some cases requiring no professional treatment. Those that do need medical help, however, currently can be offered psychotherapy, antidepressants or lifestyle strategies (including a healthy diet, meditation, exercise etc). 

So how does ketamine fit in with depression? 

As stated above, ketamine reduces activity in the anterior cingulate area of the brain. In the brains of those suffering from depression, the anterior cingulate has been shown to be over-active. Ketamine, however, restricts blood flow to this area, and so can dampen the effect – thereby reducing the feelings of guilt and worthlessness a person with depression may suffer from. 

PET scans of a brain of a person with depression (L) and without depression (R)

A recent study on 28 people tested the effects of ketamine on depression. The results were encouraging, with experts involved saying “the findings opened up a whole new avenue of research”. The patients were given doses of ketamine over a period of 40 minutes up to 6 times. 8 of the patients showed an improvement in their levels of depression, and 4 even classing themselves as no longer depressed. 

The results of this study are good, even though only 12 of the 28 patients actually reported differences. 12 of 28 is definitely higher than a result by chance, and actually shows the potential for refining this treatment in order to improve effectiveness. It is also important to remember, as Professor David Taylor says, “In these kinds of patients, spontaneous remission almost never happens”. However, the study showed that the results were short lived. The effects of ketamine are not permanent. Some patients were able to enjoy the benefits of the study for around three months, with others relapsing within a few days. Evidently there is room for improvement in technique here. 

Clearly there are beneficial effects in the use of ketamine for depression, but this treatment does not come without detrimental side effects. Ketamine reportedly can cause arrthymias (a change in the rhythm of your heart beat), nausea, increased intraocular (inside-eye) and intracranial (inside-head) pressure. Perhaps the most famous of ketamine’s harmful effects are it’s urinary tract interactions. Ketamine can cause irreversible bladder damage, and in extreme cases can result in some having to wear a catheter for the rest of their life. 

This instance of fighting fire with fire is similar to my first instalment regarding the use of MDMA to treat PTSD – another illegal substance used to treat a mental condition. Again, should the therapeutic benefits of the ketamine be prioritised over its detrimental health effects, and classification as an illegal drug? 

What do you think?


  1. I think it is scary that ketamine could be used for depression. I know everyone is different and it is a decision that comes down to you and your doctor, but I suffered from very bad depression a few years ago and was offered drugs for it, but I battled it in my own way, by completely changing my lifestyle, food and exercise. Worked for me. But I know that doesn't work for everyone.

  2. thanks very much for your honest comment! i agree, everyone is different especially so regarding the mind, and so different forms of treatment will work for others. i'm glad to hear you are in a better place now too!