Ketamine as a Treatment for Anhedonia?

[DragonOfTheSea]

As ketamine therapy for depression gains renewed attention, and with many individuals dealing with anhedonia—including those affected by GLP-1’s, among other causes—could K potentially serve as a workable option?

Any opinions?

 

[RJ760]

DragonOfTheSea said:

As ketamine therapy for depression gains renewed attention, and with many individuals dealing with anhedonia—including those affected by GLP-1’s, among other causes—could K potentially serve as a workable option?

Any opinions?

That's a thought-provoking perspective. The reasoning makes sense to me, though I'd likely try to work through easier alternatives before considering that path. It feels like quite a bit to introduce on top of everything else.

 

[FlowerFairy]

Ketamine was prescribed to me prior to beginning Tirz. I didn’t see a meaningful change. I discontinued it, and my therapist brought up the nasal version, but the approval process was never initiated.

 

[Calm Logic]

PT-141 lol

Beyond short-term, low-dose use of MT-2, PT-141, and similar compounds aimed at the hypothalamus—the more primitive region of the brain—there exist peptides with more specific targets for mood and cognition, such as Selank, Semax, and PT-22-28. At least, that is what the theory suggests.

When it comes to increasing energy, options include peptides such as SS-31, along with stimulants like caffeine.

Among conventional medications, Wellbutrin\buproprion suits certain people because it may offer modest assistance with weight loss or at minimum energy, functioning as a stimulating antidepressant (its rate of sexual side effects is low, roughly comparable to placebo). As for hormones, TRT/HRT can provide a boost.

 

[lessthanhalf]

When it comes to severe, treatment-resistant depression, ketamine has a reputation for working reasonably well. Using it for anhedonia, though? That seems unlikely to become a standard option, unless the anhedonia is simply a symptom of the depression itself. It's comparable to bringing a brick down on a fly. Typically, it's reserved for cases where several antidepressants and add-on strategies have already been tried without success.

There are some trials looking at lower doses of oral ketamine, but from what I know, clinical practice is still a long way from adopting that approach. Ketamine treatment also calls for professional monitoring in a clinic or hospital setting, with resuscitation equipment on hand. That generally drives up the cost and limits availability in most regions.

Going the DIY route isn't particularly safe either. Beyond the substantial addiction risk, there are some disagreeable side effects, plus the dangers of using anaesthetic drugs without supervision.

As noted earlier, buproprion would be the more sensible pick.

 

[DragonOfTheSea]

Thanks for the feedback and the concrete alternatives mentioned so far.

I get it—and I’m on board—that full-on Ketamine treatment is akin to “using a brick to swat a fly.” I should have been clearer: I was mainly considering micro-dosing and/or oral methods that are gaining popularity right now.

 

[DragonOfTheSea]

FlowerFairy said:

Ketamine was prescribed to me prior to beginning Tirz. I didn’t see a meaningful change. I discontinued it, and my therapist brought up the nasal version, but the approval process was never initiated.

Did a professional oversee the treatment you had before, or did you follow a lower-dose protocol on your own?

 

[Calm Logic]

One idea behind the intense ketamine infusions is that they function through a beneficial kind of depersonalization, similar to what happens with anesthesia, and the strength of those infusions may be what makes that possible. As for my relative, I would not describe them as dramatically improved because of the ketamine injections, though there does appear to be some benefit, particularly during the initial months, when someone is usually beginning from a low point regardless. Also, these injections are serious business, given that you cannot drive yourself home afterward.

Taking into account that depersonalization theory along with my own observations, I suspect a diluted version of ketamine, such as sublingual, would not deliver much, probably no more useful than marijuana gummies.

 

[randompersonrandom]

Calm Logic said:

One idea behind the intense ketamine infusions is that they function through a beneficial kind of depersonalization, similar to what happens with anesthesia, and the strength of those infusions may be what makes that possible. As for my relative, I would not describe them as dramatically improved because of the ketamine injections, though there does appear to be some benefit, particularly during the initial months, when someone is usually beginning from a low point regardless. Also, these injections are serious business, given that you cannot drive yourself home afterward.

Taking into account that depersonalization theory along with my own observations, I suspect a diluted version of ketamine, such as sublingual, would not deliver much, probably no more useful than marijuana gummies.

When it comes to ketamine possibly bringing about major improvement, I count myself among those who believe in it. A very close female friend of mine deals with terrifying depression that could lead her to harm herself. She has pursued every treatment completely and exactly as prescribed: she is incredibly physically fit thanks to working out, she drives herself to participate in many social events, she performs excellently at her job, she is married to the finest man I have ever met, and she has undergone every form of therapy and taken every medication—yet she was STILL experiencing crises of the kind where "he rushed her to the emergency room because there was a serious chance she would board a bus headed for whatever comes next." On ketamine, she has improved a LOT.

Still, beyond witnessing what appears to have kept her alive, I know very little about it. I feel enormous relief that her situation isn't mine. I've dealt with severe depression at points in my own life, but mine was ALWAYS tied to circumstances, and the fix was simple: "leave that bastard and recover from whatever he put me through."

 

[Calm Logic]

When it comes to mental health, ketamine infusions appear to follow the usual rule that different approaches suit different people, but the area where they stand out is more acute or crisis-type situations, which is what you brought up. They also pair the infusions with talk therapy at the same time, which can help lock in longer-lasting results.

A number of the cognitive mechanisms ketamine might act on are worth going after regardless of the route taken (much like mindfulness, or gummies used to depersonalize/derealize):

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Depersonalization and derealization involve disconnection from one’s body and surroundings. The ketamine-induced sensation of disconnecting from one’s physical body may also be accompanied by detachment from negative affective and pain states, including emotional pain and depressive feelings.

In participants with depression, researchers have observed that a standard therapeutic ketamine infusion (0.5 mg/kg infused over 40 min) brings significant relief from overall depression, anhedonia, and suicidal ideation during the same time frame within which dissociation occurs, which is as early as 5 min into the infusion with resolution typically within 1 h. These observations of acute relief from overall depression and anhedonia can last from days to weeks.

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https://academic.oup.com/brain/article/148/10/3496/8178381

Preclinical studies suggest that ketamine rapidly influences the lateral habenula (involved in punishment processing) and fronto-striatal (reward) systems, reverses negative affective biases in established memories, and promotes long-term stress resilience.

Click to expand...

Click to expand...

In my own case, after years of therapy and meds, exercise plus sunshine does more for me than any conventional therapy. No contest, and exercise and reading are my top two ways to meditate. The handful of drug rehab programs built around exercise strike me as sensible. These days psychiatrists recommend exercise even more strongly too, similar to the "baby steps" approach in behavioral activation. Brain fog from GLPs such as tirz also improves with carbs and getting up and moving.

 

[DragonOfTheSea]

Calm Logic said:

One idea behind the intense ketamine infusions is that they function through a beneficial kind of depersonalization, similar to what happens with anesthesia, and the strength of those infusions may be what makes that possible. As for my relative, I would not describe them as dramatically improved because of the ketamine injections, though there does appear to be some benefit, particularly during the initial months, when someone is usually beginning from a low point regardless. Also, these injections are serious business, given that you cannot drive yourself home afterward.

Taking into account that depersonalization theory along with my own observations, I suspect a diluted version of ketamine, such as sublingual, would not deliver much, probably no more useful than marijuana gummies.

That's a reasonable observation.

 

[FRMN01]

I'd recommend looking into Selank and Bromantane.

 

[RoadRash]

DragonOfTheSea said:

As ketamine therapy for depression gains renewed attention, and with many individuals dealing with anhedonia—including those affected by GLP-1’s, among other causes—could K potentially serve as a workable option?

Any opinions?

Chronic depression was something I dealt with for many years, and during that time I went through ketamine therapy. The results were extremely helpful for me. In my view, it is a very viable option for treating depression. So if GLP1 use is leaving you feeling depressed while you are on GLP1, I would definitely suggest bringing up ketamine sessions with your primary physician.

 

[DragonOfTheSea]

FRMN01 said:

I'd recommend looking into Selank and Bromantane.

Yes, I'm fully engaged with this!

For me, the selank/semax area holds a lot of interest—it appears to be a real breakthrough for my anxiety/adhd-inclined brain! I've been researching this for some time now, and I can see myself putting together some nasal sprays soon.

The Anhedonia aspect is something I worry about more for my wife, so I'm doing my best to educate myself and look into it thoroughly.

 

[Gt3294a]

Calm Logic said:

PT-141 lol

Beyond short-term, low-dose use of MT-2, PT-141, and similar compounds aimed at the hypothalamus—the more primitive region of the brain—there exist peptides with more specific targets for mood and cognition, such as Selank, Semax, and PT-22-28. At least, that is what the theory suggests.

When it comes to increasing energy, options include peptides such as SS-31, along with stimulants like caffeine.

Among conventional medications, Wellbutrin\buproprion suits certain people because it may offer modest assistance with weight loss or at minimum energy, functioning as a stimulating antidepressant (its rate of sexual side effects is low, roughly comparable to placebo). As for hormones, TRT/HRT can provide a boost.

That was a solid post. As for Wellbutrin, I went down that road roughly 20 years back. Ketamine as well…. Calm, you're about to have me trying out the newer options. All joking aside, it'll be worth watching whether the AI Regurgitation Station manages to carve out a role for itself these days.

 

[FlowerFairy]

DragonOfTheSea said:

FlowerFairy said:

Ketamine was prescribed to me prior to beginning Tirz. I didn’t see a meaningful change. I discontinued it, and my therapist brought up the nasal version, but the approval process was never initiated.

Did a professional oversee the treatment you had before, or did you follow a lower-dose protocol on your own?

Clinician-supervised, via Joyous.