The EADD 3-FPM Megathread

[Ceres]

10mg vaped has definately had an effect on me, i feel pretty wired. I have zero tolerance for stims.

 

[SquidInSunglasses]

I would not expect to feel anything off 10mg either. Is that the dose you usually take? My rule of thumb is bang a pile down and keep tooting till you feel something. Depending upon type, that can take a few minutes to several hours.

@Sprout: If DRAs are inherently neurotoxic, why isn't amphetamine? Or is it?

It is. The neurotoxicity comes from the oxidative breakdown of dopamine in the brain, which causes the buildup of reactive oxygen and nitrogen species, that then proceed to fuck up the nearby cells. It's worth noting that, apart from the obvious HR measures of not pulling ridiculous benders and massive doses, you can prevent DRA neurotoxicity to some degree by loading up on fat soluble antioxidants, to soak up the ROS produced by the excess of dopamine and by taking NMDA antagonists, which inhibit the activation of microglia, which are responsible for the breakdown of dopamine that causes problems (it's sort of an autoimmune type thing). Here's a paper looking at NMDA antagonists for protecting against meth neurotoxicity, but since the mechanism is the same as any DRA, the results should be generally applicable.

 

[Ceres]

^ fascinating, thankyou. I had dosed some 3-meo-pcp earlier today before I vaped 10mg of 3-fpm. I don't know how anyone could do doses larger than 20 - 30mg without being strung out as fuck.

 

[F.U.B.A.R.]

It is. The neurotoxicity comes from the oxidative breakdown of dopamine in the brain, which causes the buildup of reactive oxygen and nitrogen species, that then proceed to fuck up the nearby cells. It's worth noting that, apart from the obvious HR measures of not pulling ridiculous benders and massive doses, you can prevent DRA neurotoxicity to some degree by loading up on fat soluble antioxidants, to soak up the ROS produced by the excess of dopamine and by taking NMDA antagonists, which inhibit the activation of microglia, which are responsible for the breakdown of dopamine that causes problems (it's sort of an autoimmune type thing). Here's a paper looking at NMDA antagonists for protecting against meth neurotoxicity, but since the mechanism is the same as any DRA, the results should be generally applicable.

I see thank you. What is it that makes methamp more neurotoxic than amphetamine? Is it simply that meth releases more dopamine? Or does the significant serotonin release exacerbate the toxic effects?

 

[Sprout]

It is. The neurotoxicity comes from the oxidative breakdown of dopamine in the brain, which causes the buildup of reactive oxygen and nitrogen species, that then proceed to fuck up the nearby cells. It's worth noting that, apart from the obvious HR measures of not pulling ridiculous benders and massive doses, you can prevent DRA neurotoxicity to some degree by loading up on fat soluble antioxidants, to soak up the ROS produced by the excess of dopamine and by taking NMDA antagonists, which inhibit the activation of microglia, which are responsible for the breakdown of dopamine that causes problems (it's sort of an autoimmune type thing). Here's a paper looking at NMDA antagonists for protecting against meth neurotoxicity, but since the mechanism is the same as any DRA, the results should be generally applicable.

Just finished editing my post, looked up and saw this.
EADD needs you, Squid, stick around and spread some science with me?

 

[SquidInSunglasses]

I see thank you. What is it that makes methamp more neurotoxic than amphetamine? Is it simply that meth releases more dopamine? Or does the significant serotonin release exacerbate the toxic effects?

I don't know exactly, but I think it's a combination of increased dopamine release, and that after serotonin release, the dopamine degradation products can be uptaken into the serotonin vesicles, which are not well suited to handle them and so can be severely damaged. (I will try and find a reference for that second part, because I definitely read it somewhere and I can't remember details off-hand).

 

[Sprout]

I see thank you. What is it that makes methamp more neurotoxic than amphetamine? Is it simply that meth releases more dopamine? Or does the significant serotonin release exacerbate the toxic effects?

More DA release and enhanced BBB penetration leads to greater formation of ROS which is directly toxic.
Interestingly, Amp produces a moderate inhibition of MAO-a and MAO-b, not enough to cause major issues a la Selegiline and MDMA, but enough to slow the radical production that DA's metabolism by MAO-b can produce. Meth however is much less able to inhibit the enzymatic process, which rapidly leads to an overwhelming concentration of toxic metabolic products.

The SE release only adds to the mess, inducing even greater hyperthermia which simply compounds the impact of forcing one's neural system to act in a way it hasn't evolved to handle sufficiently.

 

[SquidInSunglasses]

Just finished editing my post, looked up and saw this.
EADD needs you, Squid, stick around and spread some science with me?

I'll be around as long as I'm taking anything fun, I might hide when drama kicks off but I'll come back.

 

[F.U.B.A.R.]

Okay, thank you Squid & Sprout (wouldn't they make a lovely couple? )

Last question honest (first one to answer satisfactorily has my next dose dedicated to them publicly)...

I believe that MDPV, an NDRI can actually have a protecting effect on methamp toxicity. If this is correct, how the fuck does this work then? Surely DRAs and DRIs both result in the same net effect - I.e. an excess of dopamine in the synapses. Why does one protect and the other maim? Am I totally missing the point? I'm living proof that a little knowledge is a dangerous thing... :D

 

[SquidInSunglasses]

Okay, thank you Squid & Sprout (wouldn't they make a lovely couple? )

Last question honest (first one to answer satisfactorily has my next dose dedicated to them publicly)...

I believe that MDPV, an NDRI can actually have a protecting effect on methamp toxicity. If this is correct, how the fuck does this work then? Surely DRAs and DRIs both result in the same net effect - I.e. an excess of dopamine in the synapses. Why does one protect and the other maim? Am I totally missing the point? I'm living proof that a little knowledge is a dangerous thing... :D

The protective effect is due to reuptake inhibitors preventing all the toxic breakdown products in the extracellular space getting sucked back into the cell where they can cause a lot more damage and will promote cell death. I believe you still get some damage to external structures, but that's less significant than if the ROS get into the cells themselves.

 

[Ceres]

for the record, a couple of hours after vaping that 10mg and i feel fucking horrible, wired, edgy, seriously, this is why I am sworn off stims and that crap is going in the same box as ethylphenidate and other random chems I won't be using again except for analytical purposes.

 

[F.U.B.A.R.]

The protective effect is due to reuptake inhibitors preventing all the toxic breakdown products in the extracellular space getting sucked back into the cell where they can cause a lot more damage and will promote cell death. I believe you still get some damage to external structures, but that's less significant than if the ROS get into the cells themselves.

Thank you Squid. I'm officially dedicating my next dose, plus post dose wank to you.

Sprout, fuck off, yer sacked!

 

[Sprout]

Okay, thank you Squid & Sprout (wouldn't they make a lovely couple? )

Last question honest (first one to answer satisfactorily has my next dose dedicated to them publicly)...

I believe that MDPV, an NDRI can actually have a protecting effect on methamp toxicity. If this is correct, how the fuck does this work then? Surely DRAs and DRIs both result in the same net effect - I.e. an excess of dopamine in the synapses. Why does one protect and the other maim? Am I totally missing the point? I'm living proof that a little knowledge is a dangerous thing... :D

DRI's may produce a net conc. increase but the mechanism by which they act makes a major difference.
As I tried to explain above, DRA's induce a variety of biological changes on top of the direct impact from oxidative reactions.
In particular, the damage to the monoaminergic vesicles has a major impact on the system as a whole - once the capacity to store DA within a stable cell is compromised it leads to an unmediated flow across the synaptic junctions via diffusion. Apoptosis ensues rapidly.

DRI's simply act directly on the transporter proteins (DAT) which provides an acute increase in striatal DA for the duration the inhibitor is present and active, the functionality of DAT returns after a few half-life cycles. They do not affect the vesicle organelles and so lack the induction of the chain reaction mechanism that has massive potential for destruction.

 

[Ceres]

It is also worth pointing out that this class of drug has the potential to lower your seizure threshold and could potentially cause a full on grand mal seizure.

 

[Sprout]

Thank you Squid. I'm officially dedicating my next dose, plus post dose wank to you.

Sprout, fuck off, yer sacked!

I was never hired in the first place. You can't put an end to my shit that easily.
If one combines both posts it provides a more thorough evaluation of the multitude of factors involved.

It is also worth pointing out that this class of drug has the potential to lower your seizure threshold and could potentially cause a full on grand mal seizure.

Very true, especially when combined with alcohol as is commonplace.
An anti-convulsant benzodiazepine is never a bad suggestion, but be careful of developing a hidden dependency.

 

[F.U.B.A.R.]

DRI's may produce a net conc. increase but the mechanism by which they act makes a major difference.
As I tried to explain above, DRA's induce a variety of biological changes on top of the direct impact from oxidative reactions.
In particular, the damage to the monoaminergic vesicles has a major impact on the system as a whole - once the capacity to store DA within a stable cell is compromised it leads to an unmediated flow across the synaptic junctions via diffusion. Apoptosis ensues rapidly.

DRI's simply act directly on the transporter proteins (DAT) which provides an acute increase in striatal DA for the duration the inhibitor is present and active, the functionality of DAT returns after a few half-life cycles. They do not affect the vesicle organelles and so lack the induction of the chain reaction mechanism that has massive potential for destruction.

Alright, you're reinstated.. I'll dedicate my next dose to you (ive already had squid's), but don't think yer getting a wank as well...

 

[SquidInSunglasses]

I was never hired in the first place. You can't put an end to my shit that easily.
If one combines both posts it provides a more thorough evaluation of the multitude of factors involved.



Very true, especially when combined with alcohol as is commonplace.
An anti-convulsant benzodiazepine is never a bad suggestion, but be careful of developing a hidden dependency.

I'll add that to the list of reasons to stick to weed as a mixer instead of booze. Gives a nicer effect anyways.

 

[F.U.B.A.R.]

It is also worth pointing out that this class of drug has the potential to lower your seizure threshold and could potentially cause a full on grand mal seizure.

Are you referring to DRIs, DRAs or just stimulants in general?

 

[koneko]

It is also worth pointing out that this class of drug has the potential to lower your seizure threshold and could potentially cause a full on grand mal seizure.

Is this something people on prescribed SSRI's and SNRI's should be concerned with?

 

[masaz]

I was wondering that myself, actually