Ketamine Thoughts/experiences/antidepressant Qualities

franc0

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I know this probably isn't the most 'Peat Friendly' substance in the world, and this thread may even be one for the shroomery. Nonetheless, I've experimented two times this week with Ketamine and I have to say it has had a positive impact on my mood.
I found myself to be much more open minded and positive the day after its use, almost like I've had a mini holiday from it all.
Obviously you're all probably more well read than I am, as to why i'm interested what your thoughts are on Ketamine?

Ketamine for depression
Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. - PubMed - NCBI
"ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients "

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. - PubMed - NCBI
"Her mood stabilized, and she showed a nearly 50% reduction in the severity of her depressive symptom."

The rapid-onset antidepressant effect of ketamine: More surprises? - PubMed - NCBI
"inhibition of the NMDA subtype of glutamate receptor"
Peaty am I right?

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine. - PubMed - NCBI
"ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model."
Helping with learned helplessness?

Personal Experience:
The second time I did Ketamine, was the most profound, I did it intranasally, I don't know how much but wasn't enough to K-hole, nonetheless quite a substantial amount. My vision became very blurred, like being kind of drunk, I spent my time high listening to music on my bed closing my eyes, I had closed eye visuals of rotating glass bottles, people dancing in neon lights, reminiscent scenes of childhood memories which were very vivid, so much so that I picked out details that I hadn't realised since these events had happened.
I felt quite relaxed and floaty on the Ketamine. Certainly an interesting and mind opening experience.
 
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LUH 3417

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From what I’ve read the research on ketamine and even PCP was both exciting and promising in the 1970s.

The downside is that it can cause kidney damage with long term use. I would imagine it’s very yin and perhaps hard on the body in ways I don’t understand.
 

Frankdee20

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From what I’ve read the research on ketamine and even PCP was both exciting and promising in the 1970s.

The downside is that it can cause kidney damage with long term use. I would imagine it’s very yin and perhaps hard on the body in ways I don’t understand.

I recall people needing bladder surgeries from abusing the substance. It’s basically an NMDA receptor antagonist. Similar to PCP.
 

LUH 3417

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I recall people needing bladder surgeries from abusing the substance. It’s basically an NMDA receptor antagonist. Similar to PCP.
Interesting. Maybe if one used it and added beef kidney to their diet it wouldn’t be too damaging.
 

Frankdee20

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I wonder what the biochemical reasons are for this.

Ketamine has affinity for NMDA receptors, I believe it’s an antagonist. PCP (related disassociative anesthetic compound) has its own binding site on the receptor.
 

managing

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I wonder what the biochemical reasons are for this.
I haven't had any of the extreme psychological symptoms he has had (the article I linked before), but the overheating is something I still deal with constantly.

But where would one get ketamine?

I do think the therapeutic doses are orders of magnitude smaller than the recreational doses.
 

Waynish

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I'm sure you can find Ketamine if you know how to look... However, I would recommend larger doses - and just rarely have it. Maybe a few times is enough. If you have to go back to a substance so often, then that's evidence you're not using it right (or you're not using everything else right yet :P).
 

Frankdee20

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Doesn’t Ketamine usage cause some thing where the bladder fails ? People had to get surgery to correct it. Not joking

I believe the actual ketamine in the urine eats away at the epithelial lining.
 

managing

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Doesn’t Ketamine usage cause some thing where the bladder fails ? People had to get surgery to correct it. Not joking

I believe the actual ketamine in the urine eats away at the epithelial lining.
Yes. I am not looking at numbers at the moment. But I believe the bladder issues were long term chronic use at like 10x the "normal" recreational dosage. The therapeutic dosage being used is something like .10 the rec dosage. And also delivered intranasally. I am not advocating anybody experimenting on their own though.
 

LeeLemonoil

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It activates murine Olfactory receptors too, which are GPCRs. Humans have many analouges to mouse-ORs, so maybe that is another facet of Ketamines action:

Molecular recognition of ketamine by a subset of olfactory G protein-coupled receptors. - PubMed - NCBI

Molecular recognition of ketamine by a subset of olfactory G protein-coupled receptors.

Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered nonresponding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug.
 

LeeLemonoil

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Wow, from 2016. I missed that one.

Curiously, there is also a sex-difference involved in the effects of the metabolite.
 

LeeLemonoil

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Still, the Wiki-article about the metabolite in question writes about a study a year later tat confirmed NMDA-involvement. Estrogen REcetor alpha is said to be also involved.
 

LeeLemonoil

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Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression.
Ho MF, et al. Biochem Pharmacol. 2018.
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Abstract
Major depressive disorder (MDD) is the most common psychiatric illness worldwide, and it displays a striking sex-dependent difference in incidence, with two thirds of MDD patients being women. Ketamine treatment can produce rapid antidepressant effects in MDD patients, effects that are mediated-at least partially-through glutamatergic neurotransmission. Two active metabolites of ketamine, (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-HNK, also appear to play a key role in ketamine's rapid antidepressant effects through the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. In the present study, we demonstrated that estrogen plus ketamine or estrogen plus active ketamine metabolites displayed additive effects on the induction of the expression of AMPA receptor subunits. In parallel, the expression of estrogen receptor alpha (ERα) was also significantly upregulated. Even more striking, radioligand binding assays demonstrated that [3H]-ketamine can directly bind to ERα (KD: 344.5 ± 13 nM). Furthermore, ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites displayed similar affinity for ERα (IC50: 2.31 ± 0.1, 3.40 ± 0.2, and 3.53 ± 0.2 µM, respectively) as determined by [3H]-ketamine displacement assays. Finally, induction of AMPA receptors by either estrogens or ketamine and its metabolites was lost when ERα was knocked down or silenced pharmacologically. These results suggest a positive feedback loop by which estrogens can augment the effects of ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites on the ERα-induced transcription of CYP2A6 and CYP2B6, estrogen inducible enzymes that catalyze ketamine's biotransformation to form the two active metabolites. These observations provide novel insight into ketamine's molecular mechanism(s) of action and have potential implications for the treatment of MDD.
 

LeeLemonoil

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So some ER-Alpha mediated Action is crucially involved in Ketamines action.
I wonder if some androgens could have similar properties.
 

Waynish

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This is one I'd use for the experience, not the biological effects. Have a considerable dose - but not too much if you're scared of K-holes - and be somewhere worth being. Taking it often will just wear you down; I certainly notice long term users having problems.
 
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My doctor just prescribed this for chronic fatigue syndrome, pain, insomnia. Some aspects of it seem peaty, but maybe the estrogen aspects aren’t good. I guess I could take dhea to offset
 

Frankdee20

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My doctor just prescribed this for chronic fatigue syndrome, pain, insomnia. Some aspects of it seem peaty, but maybe the estrogen aspects aren’t good. I guess I could take dhea to offset

How did he prescribe it ? As the nasal spray variant ? It fetches thousands does it not ? Or did he prescribe standard Ketamine ?
 

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