Let’s talk about ketamine. 

Ketamine has been used for acute pain and sedation for years. More recently, though, we’re realizing ketamine can be incredibly effective in treating a range of pathologies, including depression and neuropathic pain. 

Ketamine has been shown to be helpful with anxiety, Post Traumatic Stress Disorder (PTSD), suicidal ideation and Obsessive Compulsive Disorder (OCD). 

It has also been shown to reduce pain and inflammation. Neuropathic pain is pain caused from damage to nerves. The damage can be from inflammation, infection, compression on the nerves and so on. If pain persists for six months or more, that’s usually a good indication that nerves are involved. 

How does ketamine work?  

Let’s get into a little neuroscience. 

The central glutamatergic system, which is the main excitatory neurotransmitter in the nervous system, and NMDA receptors play a big role in pain and mood. There are three types of glutamate receptors: NMDA, AMPA and kainate receptors. When glutamate binds to these receptors it causes an influx of mainly sodium. This influx depolarizes the neuron and propagates an electrical action potential.

When NMDA receptors are upregulated, pain signals are sent to the brain. Ketamine is a potent NMDA antagonist which decreases the pain signals.

Ketamine blocks the NMDA receptor as you can see in the GIF but does not block the AMPA receptor. The AMPA receptor upregulation causes remodeling of synaptic connections and may explain why ketamine has effects beyond the actual infusion period. It also enhances anti-inflammatory effects in the central nervous system. Ketamine also has local anesthetic action and opioid receptor agonism. 

How long has ketamine been around?

Named for the ketone and amine group in its chemical structure, Ketamine is a dissociative anesthetic that was first given to humans in 1964. It is used by veterinarians to sedate animals and has an expanding use in humans. In the early days, ketamine was found to be unsuitable for humans because it caused an emergent delirium when patients woke up and produced a sensory deprivation syndrome. Ketamine was approved by the FDA in 1970 and was used on injured soldiers during the Vietnam War. In 2000, the first randomized, double-blinded study was published in Biological Physchiatry.

Ketamine is a clear fluid that is commonly administered in a 40 minute IV drip for chronic pain or depression. Studies show that repeated ketamine drips may have a greater anti-depressive effect than a single ketamine drip. Ketamine can also be administered as an intramuscular injection, intranasally, subcutaneously, transdermally, transmucosally and orally. The reason we prefer injections is the oral bioavailability is only 17-29% so most of it is not absorbed.