How does ketamine work in the body? The short answer is that we don’t know, which is very common in medicine – we don’t know exactly how a lot of drugs work.
We do know that ketamine produces important and useful effects.
What Ketamine Does:
There are lots of things we do know: We know that ketamine can rapidly reduce symptoms of depression, anxiety and post-traumatic stress disorder (PTSD), and for pain conditions such as CRPS. We know that it can have the most noticeable effect on acute symptoms such as acute suicidal thoughts, and acute anxiety. We know that it can help around 70% of people with mood disorders like depression, PTSD, anxiety, even when they have treatment-resistant symptoms and have not have responded to other treatments such as ECT, TMS, SSRIs, or other medications. We know this from an increasingly large body of research and from clinical results – including the results from our patients here at Lone Star Infusion.
But, exactly HOW ketamine results in rapid reduction of symptoms – the mechanism(s) of its action – is much less well understood and is part of the focus of ongoing research and discussion.
NMDA, AMPA, mTOR … Oh My:
Ketamine affects multiple receptors and multiple pathways in both the brain and the body.
One of the key pathways thought to be at play is the glutamate pathway. Ketamine is an NMDA receptor antagonist. It binds to the NMDA receptor protein on cell membranes and blocks glutamate from binding there. Other NMDA receptor antagonists however have not been found to have such strong anti-depressant effects or any anti-depressant effects at all!
Ketamine also acts on the mTOR pathway and the AMPA receptor and even the opioid receptors in the brain – how much each pathway interacts with the others or if one path is most important is still not understood. The mTOR pathway is thought to be how ketamine drives the growth of new neural connections – but, again although we know that ketamine increases neural connectivity and neuroplasticity we don’t know exactly how this happens.
Recently, studies have examined whether metabolites of ketamine (the products that result when our bodies break down the medication) may be responsible for the action of ketamine. This has led to additional research and at least one new medication that is now in human trials. As this thread of research and development has moved forward conflicting data appears to show that metabolites aren’t as effective in humans as the first papers originally showed.
Here’s How We Think Ketamine Works:
This is our working model at Lone Star Infusion, summing up the best of what we know:
- Ketamine permits or encourages robust neural activity
- This increased neural activity likely helps the brain, and other affected neurons, to function more normally
- The increased neural activity likely also creates neuroplasticity – allowing a patient’s neural activity to overcome unhealthy recursive patterns:
- Allowing a depressed patient to reduce or get away from recursive negative thoughts
- Allowing a patient with OCD to take advantage of aversion therapy
- Allowing a substance abuse patient to more readily establish healthy thoughts and routines outside of their addictive behaviors
- Allowing a pain patient to get out of a pain feedback loop
Ketamine Is an Exceptional Tool in Medicine:
A lot of the detail of how a medication works breaks down when you look too closely– how does Propofol work exactly? Or Prozac? Or Crestor? In many cases we don’t fully know and in some cases we don’t really know at all! The body is vastly complex, and our understanding of its functions and interactions with chemicals and environments is still very minimal in many cases.
Decades of research and clinical results support effects, side-effects, and safety information for ketamine. It has a safe profile when administered by appropriately trained professionals. It is a versatile anesthetic for the operating room. It is an exceptional tool and for the treatment of depression, anxiety, PTSD and other mood disorders and neuropathic pain conditions including neuralgias and CRPS / RSD.
About Me, Dr Allison Wells: I started Lone Star Infusion, here in Houston, to provide ketamine infusions for depression, anxiety, PTSD, CRPS and other mood disorders and pain conditions. I am a licensed, board-certified anesthesiologist. I am super passionate about being a partner in helping people feel their best with evidence-based medicine.
An Important Disclaimer: The information in this and other blog posts represents my informed opinion or the opinion of others, and does not constitute medical advice and should not be relied upon to make decisions regarding medical care. To address the specific details of your medical conditions and treatments please speak with your doctors.