2-Minute Neuroscience: Ketamine

Ketamine is an anesthetic, analgesic, antidepressant, and recreationally used drug. In this video, I discuss hypotheses about how ketamine produces its effects.

TRANSCRIPT:

Ketamine was initially developed as an anesthetic, but today it is also used as an analgesic and an antidepressant. It has been used as a recreational drug since the 1970s.

After administration, ketamine is rapidly and extensively metabolized into an active metabolite called norketamine, which is thought to play an important role in ketamine’s anesthetic and analgesic effects. Ketamine and norketamine both act at a receptor for the neurotransmitter glutamate called the NMDA receptor. Glutamate is the primary excitatory neurotransmitter in the brain, and ketamine and norketamine act as antagonists at the NMDA receptor, which means that they block the receptor and inhibit activity there. Inhibition of NMDA receptors can substantially affect neurotransmission, and is thought to be critical to the anesthetic and analgesic effects of ketamine.

While most other antidepressants take several weeks to achieve a therapeutic effect, ketamine can begin to improve depressive symptoms within hours and last for up to 2 weeks after a single administration. The mechanisms underlying ketamine’s antidepressant action are not fully understood, but it’s thought that it cannot be explained by NMDA antagonism alone. One hypothesis is that another glutamate receptor known as an AMPA receptor may play a key role. AMPA receptors may be stimulated indirectly by ketamine or directly by other ketamine metabolites such as hydroxynorketamine. Stimulation of AMPA receptors may lead to the activation of multiple signaling pathways.

and downstream effects such as new synapse formation in areas of the brain like the prefrontal cortex and hippocampus. These synaptic connections may bolster neural circuits involved with regulating stress and mood. Ketamine also acts on a number of other receptors, however, and there is still much more to learn about ketamine’s antidepressant mechanism of action. Additionally, more evidence about the safety and effectiveness of ketamine needs to be collected for more physicians to support the use of ketamine as an antidepressant.

REFERENCES:


Tyler MW, Yourish HB, Ionescu DF, Haggarty SJ. Classics in Chemical Neuroscience: Ketamine. ACS Chem Neurosci. 2017 Jun 21;8(6):1122-1134. doi: 10.1021/acschemneuro.7b00074. Epub 2017 Apr 21. PMID: 28418641.

Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13. PMID: 29532791; PMCID: PMC5999402.

[lasher]

I work at the Seattle Neuropsychiatric Treatment Center as a ketamine and transcranial magnetic stimulation clinician. I’ve fairly new, but already I’ve seen the light brought back into my depressed and suicidal patients- within one month. It is so hopeful what is to come down the road (fairly soon) with neuroscience and psychiatry. I hope that we can gravitate away from the “one size fits all” depression med dx approach. Thank you for this video! ☺️

[imaginestudios]

Two of my adult children have had ketamine treatment and it has changed their lives. This new anti-depression therapy is nothing short of miraculous.

[Just_JennAy]

I have Major depressive disorder.... I was prescribed ketamine nasal spray 2 years ago and it really has changed my life. I was even able to get off of my Effexor XR. My insurance doesn't cover it since it's not approved for treating depression yet. But it only costs me $43 a month. I'm in Little Rock, Arkansas.
Total game changer!!!! Thank you for sharing this! ♥️💯

[TheDeatz]

Ketamine therapy is like being your own therapist. Ketamine allows your brain to literally put your thoughts on hold and look at your life/trauma/experiences from a different perspective, often a positive one. Neurochemistry aside, the experience of ketamine therapy and afterglow and profound realizations you can have while in it’s altered state cannot be discounted or not brought up. SHIFTING PERSPECTIVES…people generally take years to do that and in 1 hour it can happen with this therapy

[Jennifer-dinl]

Had a treatment yesterday and I haven't felt this normal since I was a child (I'm 45). My chronic headache is gone, PTSD gone but most of all I see myself so differently. I'm scared my old brain is going to come back I didn't even realize how horrible my mind was on a daily basis.

[TheManWhoCan]

I get 1 110mg IM injection a month and 2-3 60mg SC injections with psychotherapy. I started with 2 100mg injections a week for 3 weeks during the induction series. It’s worked wonders for the depression and bp1. And the trips are so jarring and fascinating. But my ptsd still hasn’t improved much

[miloelite]

Not here for ketamine’s affect on depression (interesting to know), but rather for it’s anesthetic properties. Thanks for the vid.

[hdhshdhs]

I’ve taken pretty much any and everything someone could take to alter themselves, among many different combinations/dosages. Nothing…NOTHING comes close to ketamine.

[gabebagatell]

I love your videos and your book! Awesome work!

[Filzzy]

I first tried ketamine at 13 years of age I'm now 28 and I don't have any problems with my bladder or gallbladder and I'd say I'm a pretty heavy user as I've used it most weekends since I was 13

The only time I've ever become dependent on a drug was when I was addicted to heroin but I used ketamine then to ween off it

[BoredT-Rex]

it didnt work for me. neither did ect. but i am glad that many others have found it effective

[sergiolazaromartinez]

How is it possible that ketamine inhibits neurotransmission (by blocking NMDAR activity), but also enhances synaptic plasticity? I read something about ketamine mainly acting on inhibitory interneurons, thereby lifting the inhibition and increasing neurotransmission... But is it possible that ketamine has such specificity?

[brando]

I’m going to be trying it in a week. Can’t wait!

[andyrendon]

I'm doing this drug as a project for my class, and it is interesting on how it has been used with patients. It seems like it really does work with depression.

[jaiitherip]

wow! thanks for informative video, but may I ask a question?
if we can block AMPARs and NMDAs, what would happen to mGluR-dependent long-term depression ?

[angrylarsulrich]

I was given ketamine as a very young child, i remember the experience like it was yesterday, I think I changed forever lying on that bed, idk if it was for the better. I think obviously not.

[syriek]

Awesome!!
Does agmatine work in a similar way as antidepressant?

[Tiznado]

So a single ketamine dose lasts up to 2 weeks, so with continual use, does the body require higher doses each session ?

[jonathanjollimore]

Ketamines a type of tranquilizer and I know first hand how those effect drugs effect memory. My second year of privet school a complete blur if I was going a lot of ketamine how wound my recollection of that time be effected?

[Thatsbannanas-dc]

Why use Ketamine for depression and anxiety, when it’s neuro excitatory and it would give a person massive anxiety?