"Extremely addictive" is a bit of a misnomer I believe, in terms of both the scientific literature and also much consensus around treatment-focused communities. Please stop spreading this.
What I can say is a similar thing, that it can cause _dependence_ very rapidly. It can be extraordinarily useful for healing certain mental health conditions, but tolerance builds rapidly, and people on the street are often trying to K-hole repeatedly, a basically pointless exercise. Sustained low-dosage usage seems to have fewer bladder effects, the tolerance combined with people using it as an escape (and preferring K-holes), as well as people who are already mentally broken having a nice lever to pull, is what can cause it to get out of hand.
This is not everybody, however. I think it depends upon the circles, and I think it is hard to see people do that regardless of the world. But your circles around you are also not the world at large. Please stay factually rooted in what you're sharing online. To me, substances that would be dangerous would be directly opioidergic or dopaminergic substances (opioids, nicotine, opioidergic hallucinogens) as opposed to one that is opioid _sensitizing_, like Ketamine (which lets it be a kind of opioid replacement for pain relief clinics, for example. Even infusions are helpful.)
It really is important that we all don't take our personal experiences to say "don't listen to what you hear online" too strongly, I guess even myself included here. Hope that helps shine an alternative perspective on the matter.
Ketamine, is foremost a NDMA antagonist (Ki=0.25uM ), sure it act on some type of opioid receptor also as an antagonist (a blocker) (Ki=12uM at KOR2), but this effect is 50x less important. Other NMDA antagonist like PCP that don't act on the opiate receptors are as strong if not stronger at pain suppression.
Ketamine is also a direct dopamine agonist (Ki=0.5uM at D2).
It is indeed a D2 agonist and NMDA antagonist (I forget which site). I think D2 gets much maligned due to the potential induction of psychotomimetic effects at this receptor but remember too that if one subscribes to the D2-activation autoregulation hypothesis of why amphetamines work in ADHD then having a direct agonist available could be a very good thing.
One potential theory hanging about is that if appears to indirectly agonize AMPA through blocking NMDA, and this is what leads to mTOR and then eventually BDNF modulation. However, if activating AMPA is the main goal to getting Ketamine's antidepressant effects, one could just simply take a racetam and be done with it. Racetams seem to be helpful but not drastic like Ketamine here is, which likely I think is because of some concert of fortuitous effects unique to Ketamine itself.
There are other offshoots, like how some metabolites of Ketamine affect how Ketamine is processed, leading to potentially incredibly complex cascades of metabolite interactions in the brain. But this is even more in the weeds and I've rambled enough.
In any case, something special is going on with Ketamine. Otherwise people could just take massive amounts of Agmatine (and L-Lysine along with it for the wise, mouth sores are not desirable) and be done with it. Interestingly, this seems to work for some, but it seems like more than the NMDA is what is necessary (for a side thread: see sarcosine, some of the related methylation supply issues, and how it's an NMDA _agonist_ at the glycine site but still has rapid antidepressant effects. Very strange, this whole business).
I love this topic so I get verbal on it, hope it was an enjoyable ride. :) :thumbsup:
Thanks for that link, I didn't knew about the opiate receptors resensitization.
I suspected, from personal experience with various NMDA antagonist that it's blockade has a similar effect on the dopamine¹ and nicotine/acetylcholine² families of receptors (but not on GABA³ nor CB⁴).
1- A few days after a dose of whatever the NMDA antagonist I currently had my ADD drug felt magical like the first month I took them.
2- As a teen I use to smoke... But I never smoked a cigarette again after trying to smoke during a DXM ( like ketamine, it's a substance with a really funky pharmacological profile ) trip. Every puff felt like it was my first puff but worse.
3- I take 1.5mg of clonazepam a night since I was 18 (I am over 40 now) and they had no effect whatsoever on my sensitivity nor my dependance. Clonazepam dependance is insidiously strong... it was prescribed for anxiety and insomnia, I never abused it, yet I cannot stop, each time I tried my attempt ended a few days later as I started to see scary bugs on the wall.
4- I used to be a pothead and while the combo is quite enjoyable they did nothing on my tolerance to cannabis.
p.s. Nowadays I read about drugs and I have as much fun as I did when I did use them... so I understand your enthusiasm, neuropsychopharmacology is fascinating.
What I can say is a similar thing, that it can cause _dependence_ very rapidly. It can be extraordinarily useful for healing certain mental health conditions, but tolerance builds rapidly, and people on the street are often trying to K-hole repeatedly, a basically pointless exercise. Sustained low-dosage usage seems to have fewer bladder effects, the tolerance combined with people using it as an escape (and preferring K-holes), as well as people who are already mentally broken having a nice lever to pull, is what can cause it to get out of hand.
This is not everybody, however. I think it depends upon the circles, and I think it is hard to see people do that regardless of the world. But your circles around you are also not the world at large. Please stay factually rooted in what you're sharing online. To me, substances that would be dangerous would be directly opioidergic or dopaminergic substances (opioids, nicotine, opioidergic hallucinogens) as opposed to one that is opioid _sensitizing_, like Ketamine (which lets it be a kind of opioid replacement for pain relief clinics, for example. Even infusions are helpful.)
It really is important that we all don't take our personal experiences to say "don't listen to what you hear online" too strongly, I guess even myself included here. Hope that helps shine an alternative perspective on the matter.