Cocaine Wonder Why Cocaine is Relaxing?

[G_Chem]

For those that know cocaine, it has a relaxing quality to it that isn’t found with many other stimulants.. Here’s probably the reason why.

The role of beta-endorphin in the acute motor stimulatory and rewarding actions of cocaine in mice - Psychopharmacology

Rationale Opioid receptor antagonists have been shown to attenuate the rewarding and addictive effects of cocaine. Furthermore, cocaine has been shown to cause the release of beta-endorphin, an endogenous opioid peptide. Objective We assessed whether this neuropeptide would play a functional...

link.springer.com

It seems cocaine releases beta-endorphin, and this also mediates it’s effects. That seems to make sense to me, may also explain why the most positive effects fade quickly once we’ve depleted our own endorphin.

-GC

 

[negrogesic]

Yeah crack and cocaine freebase feel particularly relaxing and narcotic-like.

I bet the serotonergic properties of cocaine (which makes it quite unique among common reuptake inhibitor stimulants) plays a role in some of it as well.

 

[LucidSDreamr]

Now days cocaine is more relaxing because of the added fentanyl

 

[plumbus-nine]

Yeah I too assumed serotonin to be the primary mediator of relaxation from good cocaine - both are pure serotonin releasers sedating (5-AI if I remember correctly, for example) and cocaine analogues with less SERT affinity like troparil are said to lack this quality.

Wonder if this effect on beta-endorphin happens on e.g. MDMA as well?

 

[G_Chem]

Europe PMC

Europe PMC is an archive of life sciences journal literature.

europepmc.org

Another one showing b-endorphin lacking mice didn’t get the good-good but mu knockout mice did?..

Yeah I too assumed serotonin to be the primary mediator of relaxation from good cocaine - both are pure serotonin releasers sedating (5-AI if I remember correctly, for example) and cocaine analogues with less SERT affinity like troparil are said to lack this quality.

Wonder if this effect on beta-endorphin happens on e.g. MDMA as well?

I was also wondering this… Here’s one to show enkephalins might mediate MDMA.

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1369-1600.2009.00156.x

-GC

 

[Pickledlemons]

The first hit of any stimulant is kind of relaxing... in the way that your problems melt away from the euphoria. I mean I've even got that effect from meth. It obviously doesn't last long... but thats what I always assumed this paradoxical effect was about. The dopamine rush is so euphoric that it takes your mind off other things that have been bothering you, and that is... relaxing in a way.

 

[plumbus-nine]

The first hit of any stimulant is kind of relaxing... in the way that your problems melt away from the euphoria. I mean I've even got that effect from meth. It obviously doesn't last long... but thats what I always assumed this paradoxical effect was about. The dopamine rush is so euphoric that it takes your mind off other things that have been bothering you, and that is... relaxing in a way.

Meth is serotonergic too, not strongly so but enough to be different than plain amphetamine. But yeah, even an alpha-PVP overdose was calming first before the stimulation hit me like a bomb, was outside struggling through the whole night.. but I also took it in a pretty desperate moment. Phenidates on the other side don't have this effect for me,

Interesting stuff about beta-endorphin. Would intranasal or injected b-e cross the BBB? Why has nobody made a b-e prodrug/releaser yet?

Reinforces my curiosity about oxytocin as well, I have the hunch that this chem is greatly under-rated when seen purely as a tool to induce birth. Doesn't MDMA release loads of it, and some arylcyclohexylamine dissociatives like ketamine are oxytocinergic too.

 

[Higherfocus420]

Yeah crack and cocaine freebase feel particularly relaxing and narcotic-like.

I bet the serotonergic properties of cocaine (which makes it quite unique among common reuptake inhibitor stimulants) plays a role in some of it as well.

Really I feel super excited super high really quick head high ringing ears and it fades really quick and instantly want more and am left jittery unless I have brown which I usually do

 

[G_Chem]

Meth is serotonergic too, not strongly so but enough to be different than plain amphetamine. But yeah, even an alpha-PVP overdose was calming first before the stimulation hit me like a bomb, was outside struggling through the whole night.. but I also took it in a pretty desperate moment. Phenidates on the other side don't have this effect for me,

Interesting stuff about beta-endorphin. Would intranasal or injected b-e cross the BBB? Why has nobody made a b-e prodrug/releaser yet?

Reinforces my curiosity about oxytocin as well, I have the hunch that this chem is greatly under-rated when seen purely as a tool to induce birth. Doesn't MDMA release loads of it, and some arylcyclohexylamine dissociatives like ketamine are oxytocinergic too.

I just discovered a pretty decent one, 8-methoxy-kaempferol in the form of Rosemary Honey pretty reliably releases b-endorphin for both myself and people I’ve tried it on. Even my brother who hardly feels anything said he felt good after 2 tablespoons. I feel it on 1-3 teaspoons.

I haven’t experimented enough yet to find out how heavily opiate dependent people react, only 2 subjects so far with tolerances that said they didn’t feel it but they don’t feel anything that isn’t in pill form with a bunch of letters and numbers printed on the front. Still gotta see if it actually works for people using other opiates, based on the research it’s likely to work for people in withdrawal.

-GC

 

[DeathIndustrial88]

Would this indicate that buprenorphine might block some of the subjective relaxing effects of cocaine then as well?

I ask only because I assume beta-endorphin probably attaches to opioid receptors?? Or am I wrong?

I have not used cocaine on bupe before, but that could be an experiment for people who have access to both.
The cocaine should feel noticeable different with enough of a bupe-blockade dose.

Or can beta-endorphins out compete buprenorphine?

Hell, now I'm wondering if bupe can block any endorphin rushes from anything at all, which would lead to some one being depressed after awhile.

 

[plumbus-nine]

Hell, now I'm wondering if bupe can block any endorphin rushes from anything at all, which would lead to some one being depressed after awhile.

Dissociatives work on bupe as always and I guess they will release a lot of endorphins from the subjective feeling but it was in the beginning when I was freshly put on bupe and just 4mg, maybe not enough to occupy all receptors (I wasn't opioid dependent so no tolerance, I was in need of a legal replacement for dissos). Would say there was some antidepressant activity but very different from other agents, more of an absence of negative thoughts than a mood lift. Only realized this in retrospection but given the situation I was in at that time I had surprisingly few negative thought loops.

But interesting question!

I just discovered a pretty decent one, 8-methoxy-kaempferol in the form of Rosemary Honey pretty reliably releases b-endorphin for both myself and people I’ve tried it on. Even my brother who hardly feels anything said he felt good after 2 tablespoons. I feel it on 1-3 teaspoons.

Gonna buy this. Really, just honey? Nice! Just that I as well tend not to feel anything from the more soft natural things like valerian, chamomile etc...

 

[DeathIndustrial88]

Dissociatives work on bupe as always and I guess they will release a lot of endorphins from the subjective feeling but it was in the beginning when I was freshly put on bupe and just 4mg, maybe not enough to occupy all receptors (I wasn't opioid dependent so no tolerance, I was in need of a legal replacement for dissos). Would say there was some antidepressant activity but very different from other agents, more of an absence of negative thoughts than a mood lift. Only realized this in retrospection but given the situation I was in at that time I had surprisingly few negative thought loops.

But interesting question!


Gonna buy this. Really, just honey? Nice! Just that I as well tend not to feel anything from the more soft natural things like valerian, chamomile etc...

I had a pretty decent antidepressant effect when I first started bupe.

Your description is a good way to put it. I use to be very suicidal & self harm & even though bupe didn't necessarily 'cure' my depression, it did at least stop some of my self destructive behavior.
I've always attributed it to it's kappa antagonism blocking dynorphin. And on the days that bupe really makes me feel better, it's most likely the slight partial mu-agonism.

Im curious if buprenorphine can block endorphin rushes from mere things such as exercise/running, etc..

 

[G_Chem]

Dissociatives work on bupe as always and I guess they will release a lot of endorphins from the subjective feeling but it was in the beginning when I was freshly put on bupe and just 4mg, maybe not enough to occupy all receptors (I wasn't opioid dependent so no tolerance, I was in need of a legal replacement for dissos). Would say there was some antidepressant activity but very different from other agents, more of an absence of negative thoughts than a mood lift. Only realized this in retrospection but given the situation I was in at that time I had surprisingly few negative thought loops.

But interesting question!


Gonna buy this. Really, just honey? Nice! Just that I as well tend not to feel anything from the more soft natural things like valerian, chamomile etc...

As I tell people worse case scenario you get a honey with at least good medicinal effects. Yup really just honey, and I’ve only tried one brand so far I’m willing to bet there’s even better ones out there.

I do also have a purified kaempferol extract I need to try but based on my reading it seems the bioavailability of the 8-methoxy-KMF in honey is much higher than that of Kaempferol extracts which often come in the form of glycosides.

The great part about releasing your own endorphin, I’ve found very little if any rebound effect/withdrawal in comparison to morphine. There’s also no tolerance build either.

-GC

 

[Drag2019]

I just discovered a pretty decent one, 8-methoxy-kaempferol in the form of Rosemary Honey pretty reliably releases b-endorphin for both myself and people I’ve tried it on. Even my brother who hardly feels anything said he felt good after 2 tablespoons. I feel it on 1-3 teaspoons.

I haven’t experimented enough yet to find out how heavily opiate dependent people react, only 2 subjects so far with tolerances that said they didn’t feel it but they don’t feel anything that isn’t in pill form with a bunch of letters and numbers printed on the front. Still gotta see if it actually works for people using other opiates, based on the research it’s likely to work for people in withdrawal.

-GC

Rosemary also does some regarding GABA that has caused set backs in benzo withdrawal I've read.

 

[Snafu in the Void]

Yeah crack and cocaine freebase feel particularly relaxing and narcotic-like.

agreed, more so than snorted

it's a very serene euphoria, before the paranoia kicks in at least

 

[G_Chem]

Rosemary also does some regarding GABA that has caused set backs in benzo withdrawal I've read.

Yup many of the bioavailable flavonoids found in honey and elsewhere seem to have GABA effects, and while Kaempferol and related methoxylated compounds do too it seems the bulk effects are mediated by b-endorphin with GABA antagonists only partially blocking effects.

Speaking of though, just tried Sidr honey which the couple times I used it gave a feel more akin to GABA then Mu. Last time I actually got a little dizzy like one would get from too much booze.. Sidr feels dirty and less euphoric than Rosemary Honey though.

-GC

 

[Drag2019]

I'm trying to lower my dose of benzos. Do you think this would help during difficult times after a cut in my dose or I'd be better of not using at all?

I recently started using NAC (N-Acetyl-L-Cysteine) as an attempt to help regulate glutamate & it seems to be working well at reducing the severity of benzo withdrawal. I use other things like L-Theanine, Magnesium, Zinc daily use long-term alongside other stuff like Valerian.

 

[Snafu in the Void]

I'm trying to lower my dose of benzos. Do you think this would help during difficult times after a cut in my dose or I'd be better of not using at all?

I recently started using NAC (N-Acetyl-L-Cysteine) as an attempt to help regulate glutamate & it seems to be working well at reducing the severity of benzo withdrawal. I use other things like L-Theanine, Magnesium, Zinc daily use long-term alongside other stuff like Valerian.

my #1 tip for benzo taper or reduction is eating healthy non-processed food (veggies, lean proten - AVOID carbs and sugar which are counterproductive) and aerobic exercise

I guarantee it will help more than things like rosemary and NAC (but those will help, too)

it will actually repair your receptors, not just take the edge off

 

[negrogesic]

I'm trying to lower my dose of benzos. Do you think this would help during difficult times after a cut in my dose or I'd be better of not using at all?

I recently started using NAC (N-Acetyl-L-Cysteine) as an attempt to help regulate glutamate & it seems to be working well at reducing the severity of benzo withdrawal. I use other things like L-Theanine, Magnesium, Zinc daily use long-term alongside other stuff like Valerian.

Frankly I found nothing to work well for benzo withdrawal, at least not for any significant amount of time. Certain things help but the things that help the most (like giant doses of taurine) often make the matter worse in the end via direct GABAergic. And things like NAC seemed to work at first but quickly stopped (but with increasing side-effects).

One strange thing I found is that kratom worked surprisingly well in reducing the misery of benzo withdrawal symptoms (namely anxiety), though has the risk of increasing dissociative symptoms when it wears off. And of course, kratom is highly addictive so I wouldn't recommend this unless you are experienced with opioids and consider the side-effect of kratom addiction to be worth it.