Ketamine

I don’t want to discuss the vaccines every single day. People who are vaccinated can’t unvaccinate themselves. The number of unvaccinated people planning on getting vaccinated has dropped to almost zero. There is nobody left whose mind I could change and we’ll find out what happens, regardless of whether I write about it.

So today we’re going to discuss… ketamine! Specifically, the benefits it can offer for your brain. There’s a difference between classical psychedelics (mushrooms,DMT,LSD and mescaline) and dissociatives (ketamine,DXM,nitrous oxide). Whereas classical psychedelics make you view the external world from a different perspective, dissociatives disconnect your consciousness from your external environment. On a lucid dissociative like ketamine, your brain gets to focus on itself.

You may have read that psychedelics and ketamine are showing really good effects for treatment resistant depression. This is true, but they work in different manners. With psychedelics, particularly LSD, you’re mainly rewiring the brain. You’re taking the neurons that are already there and you’re stimulating new connection between them. If the new connections are better, you’re left with an improved perspective on your life that lasts for a pretty long time.

On the other hand, with dissociatives like ketamine, something different happens. With ketamine, you’re more busy encouraging your brain to repair itself. People sometimes use the analogy that psychedelics update your software, whereas ketamine updates your hardware. Ketamine is sometimes compared to fertilizer for your brain.

Dissociatives have a bad reputation because of studies that found Olney’s lesions in rats. No evidence of such lesions has been found in humans. There are risks involved in taking ketamine, but those mainly depend on the dose you take and the route of administration. Ketamine starts causing very nasty problems if you take it too regularly. There are no reports of kidney and bladder problems in people who take less than 600 milligram a day against pain. However, there are plenty of reports of people who take ketamine daily for months and end up suffering bladder problems.

What about your brain? Well, the evidence generally suggests that taking ketamine improves cognitive function in people who suffer depression. A review study reported:

One study reported cognitive impairment after ketamine treatment for processing speed and verbal memory. Five studies reported improvements in processing speed, verbal memory, visual memory, working memory, or cognitive flexibility. The esketamine study suggested no changes to performance. Lower attention, slower processing speed, and higher working memory are reported as predictors of antidepressant response. Brain areas for emotional and reward processing, including the amygdala, insula, and orbitofrontal cortex, show a normalizing tendency after ketamine.

In other words, the balance of evidence suggests that ketamine actually improves your cognitive function (provided you suffer treatment resistant depression), at least in moderate doses. Problems always tend to emerge when people do things in excess. If you always take cannabis, it will cause problems. If you always take alcohol, it will cause problems. If you can’t handle sobriety, the best alternative to sobriety is polysubstance use.

The brain can be compared to a battery, that stores stressful life events. With ketamine, the stress from these life events is released. If you suffer from depression, the best treatment option is really going to depend on the nature of the depression. As an example, existential depression and fear of death are the sort of problems that can be effectively solved by Psilocybe mushrooms. The same is true for having toxic belief systems.

Psychedelics however are subject to diminishing returns. They’re going to rewire your hardware to the best of their ability, but if the hardware itself is damaged (as it tends to be in people who have had stressful life experiences), then they can’t really solve that. Oftentimes, these toxic belief systems are an attempt by the brain at coping with trauma. As an example, if everyone mistreated you in your childhood, then the idea that everyone who doesn’t share your religious beliefs is going to suffer forever in hell after death becomes appealing.

On the other hand, ketamine is a very effective solution for the sort of depression that is caused by traumatic events in childhood and repetitive exposure to social stress. In this sort of depression you see that mice start to suffer anhedonia, activities they normally find pleasing are no longer pleasing to them. They avoid social interaction and they change their time schedule, they become mainly active at night.

As with many molecules, ketamine has two mirror images, there is esketamine and arketamine. The most psychoactive version is esketamine, the most effective antidepressant version is arketamine. There is a nasal spray that contains esketamine used in the US in clinics, but almost all ketamine on the black market is racemic ketamine, which contains one part arketamine for every part esketamine. Pure arketamine would be an interesting experience, but it’s practically impossible for regular individuals who don’t work in labs to get. If you think you found arketamine on the black market, it’s probably a scam. Separating the two yourself isn’t practical either.

It’s worth asking yourself: Why do people take large doses of alcohol? Why do people who went through trauma often become alcoholics? This is self-medication. Alcohol is an NMDA antagonist in sufficiently high doses. It dissociates your conscious mind from your body. Ketamine is also an NMDA antagonist, but it is more selective, causes less oxidative stress and is overall just better at doing what people are doing when they’re drinking large amounts of alcohol.

In the future we’re going to see ketamine used for far more conditions. However, as with anything, it’s not without risk. Specifically the risk with ketamine is with overdoing it. Think back of the metaphor of ketamine as fertilizer for the brain. Too much fertilizer will kill plants. Paint patients safely take up to 600mg daily without problems, but I wouldn’t recommend this much to anyone. Rather, it’s best to do it perhaps once or twice a month.

12 Comments

  1. Why do you think are the effects of these drugs (given appropriate dosing) so universally positive? Or why doesnt the body produce them?

    • Why doesn’t your body produce vitamin C? Why doesn’t your body produce N-Acetyl Cysteine? Your body does the bare minimum that it has to do, for your ancestors to be able to raise children into adulthood.

      It’s also largely down to selection bias. We discover drugs on a daily basis that are not fun to take and that don’t have beneficial health effects. You generally don’t hear much about those.

  2. I wonder if dextromethorphan would have a similar effect. I wonder if it could be used as an adjunct to psychotherapy. I wonder if it would be safe in the doses required.

    • >I wonder if dextromethorphan would have a similar effect.

      Not sure. They’re both NMDA antagonists, but it’s increasingly doubtful that Ketamine works through NMDA antagonism, the AMPA receptor seems more important for its effect.

      Scopolamine is worth looking into too.

  3. The ultimate brain chemical is knowledge.The software,aka design of the human mind ,has evolved over millenium to form complex data routing
    Structures.We then compound those routings with verifiable non-contradictory knowledge else create other routings etcetc. Within this complex process,a trauma is a contradiction that occurs. Anything after is the mind attempting to resolve the contradiction with the data it has.Perhaps association of already held data could reduce the trauma people might have . Psychedelics do definitely help as they alter perceptions, associate data .

    I might try LSD in Goa soon. Kinda scared since well I’m worried about my heart rate. Any cool points about LSD trips you wanna share?

  4. I like this comment. It’s not far off from my way of looking at things. My view is that trauma is when an experience doesn’t allow for the organism to reduce its arousal level. Or to put it in more everyday language, when a person experiences something painful but there is no appropriate outlet to express the pain and thereby receive comfort and resolve the situation, and so the person has to rely on inhibitory mechanisms to cope. The implicit conclusion is that there is something wrong with themselves or they would have received the comfort and reconciliation that they needed. But the mechanism of inhibition prevents permanent resolution because it prevents the details of the event from getting and staying in conscious awareness where the resolution can take place. Consciousness is where sense is made of things. It is where inputs from different parts of the brain can be compared with one another and put into context. If the inhibition prevents full conscious awareness, then it prevents resolution. So, if a drug somehow circumvents the inhibition, and allows these memories to enter conscious awareness, then it will allow the resolution of events that were, until then, not resolvable (because they weren’t becoming conscious).

    • >If the inhibition prevents full conscious awareness, then it prevents resolution. So, if a drug somehow circumvents the inhibition, and allows these memories to enter conscious awareness, then it will allow the resolution of events that were, until then, not resolvable (because they weren’t becoming conscious).

      Interesting. This makes a lot of sense to me. However, it also seems to be the opposite of what you often hear, that depression is associated with endless ruminating on events from the past.

  5. I’ve tried LSD many many times as well as Mushrooms and most of my experiences have been positive with a 1-3 week afterglow. Ketamine, however, blew my mind apart way more than acid. It was so terrifying that I vowed never to try it again. Perhaps it wasn’t Ketamine as I didn’t test it. I am curious to try it again though since reading that it can treat depression.

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