O-PCP

[Allylbenzene]

I hope we can agree that the point of an antidepressant is to improve mood over a prolonged period of time. Not to produce euphoria which ends in a crash.
...
But a compound KNOWN to be a DRI stands out as a truly terrible option.

Agreed, although it's (S)-ketamine thats used as an antidepressant aka esketamine, spravato and not the DRI (R) form (according to your posts on R/S differences).

 

[tryptakid]

Because long experience has taught me to doubt the potential of all antidepressants.

But a compound KNOWN to be a DRI stands out as a truly terrible option. May as well go back 130 years to when Freud discovered that cocaine was an 'effective antidepressant'. Or just 90 years when amphetamines were discovered to be 'effective antidepressants' or indeed all of the various amphetamine derivatives from nomifensine to the newer compounds such as McN5652 and JNJ-7925476.

I hope we can agree that the point of an antidepressant is to improve mood over a prolonged period of time. Not to produce euphoria which ends in a crash.

There is a part of me that agrees with you, and a part of me that disagrees with you.

The motivation - the nudge - that can sometimes help build momentum is something that can be quite helpful in depression. Ketamine and dissociatives in general, have a way of making one prone to wander and explore. This can be quite powerful when dealing with the depressed mindset, one that is static and afraid. The nudge to curiosity overrides the complacency to hide in fear. All activating substances (amphetamine, cocaine, heroin, ketamine) have anti-depressive qualities. It's the quality of the depression that requires particular types of nudges.

 

[4DQSAR]

There is a part of me that agrees with you, and a part of me that disagrees with you.

The motivation - the nudge - that can sometimes help build momentum is something that can be quite helpful in depression. Ketamine and dissociatives in general, have a way of making one prone to wander and explore. This can be quite powerful when dealing with the depressed mindset, one that is static and afraid. The nudge to curiosity overrides the complacency to hide in fear. All activating substances (amphetamine, cocaine, heroin, ketamine) have anti-depressive qualities. It's the quality of the depression that requires particular types of nudges.

I can see certain psychoactive compounds where a single large dose can provide that 'nudge' but think about it, it's not a profitable model. I'm sure I don't need to point out that when buprenorphine was first studied as a potential treatment for opiod dependece, their model was the patient taking it for a couple of WEEKS. But what do we see? People being parked on buprnorphine as they are parked on methadone.

I suggest it's that total change of head-space that breaks through the depression. The fact it IS novel to the patient. But once it becomes mundane... I don't see it working too well.

 

[Allylbenzene]

All activating substances (amphetamine, cocaine, heroin, ketamine) have anti-depressive qualities.

You can add allopregnanolone to that list (and it's precursor pregnenolone) as an FDA approved fast-acting antidepressant.
Allopregnanolone is a potent endogenous GABA PAM. The closest drugs are alcohol, Z-drugs & benzos. GABA inhibits the secretion of CRH, a hormone which stimulates the production of stress hormones.

The biosynthesis of allopregnanolone and pregnenolone has been associated with the emergence of depressive disorders and post-traumatic stress disorder (PTSD).
Allopregnanolone and pregnanolone show remarkable anxiolytic and antidepressant effects, both in humans and in preclinical models.

In corticolimbic neurons, neurosteroids regulate affect by modulating neuronal excitability and stress response. Allopregnanolone and pregnenolone positively modulate GABAA receptors and contribute to stress-induced mood disorders. Mounting preclinical and clinical evidence suggests that these endogenous neuromodulators are promising therapeutics for psychiatric disorders, including postpartum depression, major depression, and post-traumatic stress disorder (PTSD)

Endogenous synthesis of allopregnanolone via pregnenolone:

 

[tryptakid]

I can see certain psychoactive compounds where a single large dose can provide that 'nudge' but think about it, it's not a profitable model. I'm sure I don't need to point out that when buprenorphine was first studied as a potential treatment for opiod dependece, their model was the patient taking it for a couple of WEEKS. But what do we see? People being parked on buprnorphine as they are parked on methadone.

I suggest it's that total change of head-space that breaks through the depression. The fact it IS novel to the patient. But once it becomes mundane... I don't see it working too well.

You're quite right.

 

[emkee_reinvented]

Because long experience has taught me to doubt the potential of all antidepressants.

But a compound KNOWN to be a DRI stands out as a truly terrible option. May as well go back 130 years to when Freud discovered that cocaine was an 'effective antidepressant'. Or just 90 years when amphetamines were discovered to be 'effective antidepressants' or indeed all of the various amphetamine derivatives from nomifensine to the newer compounds such as McN5652 and JNJ-7925476.

I hope we can agree that the point of an antidepressant is to improve mood over a prolonged period of time. Not to produce euphoria which ends in a crash.

When one is prescribed 35 mg dextro-Amphetamine/ day.
Takes about 25 daily year s, the anti suppressant/ mood elevation remain.

Just like the effect s on ADHD, now last 2 month s i overdid it ?
So ended 1 week short, i am in my second. I experience sleepiness.
But my prescribed dose is low, maybe taken in one go a little euphoria.

Do very little now but sure gonna ration the next prescription.
I am worth little atm.

 

[abc1986]

This one is best described as icy cool and crystalline which very much is it's own flavor. At low doses it's incredibly clear headed and zen and makes meditation just flow. Thoughts are displaced with cool and icy tranquility. At higher doses it becomes this truly chilly and frosty thing but yet with just a tiny bit of warmth lapping up at the edges that's also just a touch floaty, I found the true potential of this one with ladder IN dosing. Take little baby lines over time and an arc and trip will build and linger. And linger it does and while it lingers it kept me up and up even if I felt tired. As icy as it was I found tea and honey to be incredibly grounding and something I could anchor from the other side and ride the tension and sit on the flow between rather than identified and discrete.

 

[Innerpeace]

You can add allopregnanolone to that list (and it's precursor pregnenolone) as an FDA approved fast-acting antidepressant.
Allopregnanolone is a potent endogenous GABA PAM. The closest drugs are alcohol, Z-drugs & benzos. GABA inhibits the secretion of CRH, a hormone which stimulates the production of stress hormones.



Endogenous synthesis of allopregnanolone via pregnenolone:

Good stuff . I take allopregnanolone from time to time, since 2020, topical transdermal, and it seems to work well

Not to be weird but transdermals if you apply them on the testes, they're supposed to absorb 3-5 xs more. I've only done this a handful of times and used a very small amount and seemed to work well

I take pregnenolone in capsule form 10 mgs very low and absorption rate, and seems to work fine

I haven't used either in months however if I think anxiety is high And or feeling really stressed , I take it pre bed. I've taken it in daytime and at work and glad I experimented but before bed is best for me

I read that hormones can change brain chemistry, neurotransmitters much more longer lasting han non hormonal drugs