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Combining stimulants and depresants - what is the real risk?

theWorldWithin

theWorldWithin

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Joined
Oct 22, 2005
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I know this has been discussed before on bluelight in OD but there has not yet been a conclusive answer. Obviously cocaine is a dangerous drug to combine with other psychoactive because it is highly cardiotoxic on its own, so let us set cocaine aside from this discussion.

What is the real long term or specific cardiovascular dangers in combining downers such as opiates with non-toxic DARI's (methyphenidate) and amphetamines? Clearly there is no major complications from benzos and amphetamines so I am weary to buy into the old 'sending two different messages to your heart' theory. Now everyone should be aware of the potential overdose danger if a stimulant wears off early but I am interested more in the cardiovascular risks or other long term health consequences of this activity. Is it really as bad as conventional wisdom leads us to believe? There are many chronic pain patients who are on strong opiods and amphetamines, and these are not exclusively terminal patients to my knowledge. Do these combinations only become dangerous once you pass a certain dosage threshold? If so can someone cite examples of a safe range in a non-tolerant individual for comparisons sake?

Can anyone please clear this up for me in scientific or medical terms because it is a question that has been eating away at me for quite some time?
 
I would also love to hear a technical explanation of this.

The only explanation I've ever been given was something like "you shouldn't eat speed and downers at the same time because you'll be pulling your mind in two different directions, up and down, and thats not good it can be too stressful on your body"

which of course should strike you as hogwash...what does that explanation even really mean I wonder?

However, I believe Jamshyd pointed out to me that eating benzos while on speed (meth) may actually reduce the toxicity of the meth! So I dunno anymore if there is a general "downers on uppers is bad" rule you can follow here!

I've always saved my downers til the end when the peak effects wear off...it just feels the best way to take them. better yet, nowadays I don't even take downers or uppers and just remain more even-keeled (and have more money in my pocket!).
 
theWorldWithin said:
What is the real long term or specific cardiovascular dangers in combining downers such as opiates with non-toxic DARI's (methyphenidate) and amphetamines? Clearly there is no major complications from benzos and amphetamines so I am weary to buy into the old 'sending two different messages to your heart' theory. Now everyone should be aware of the potential overdose danger if a stimulant wears off early but I am interested more in the cardiovascular risks or other long term health consequences of this activity. Is it really as bad as conventional wisdom leads us to believe?
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I've heard that the opiate/amphetamine combinations are dangerous simply because the opiate causes respiratory depression, while the stimulant causes you to not notice that you have almost ODd and are nodding out. More or less, the two drugs cancel out the warning signs of any harm that is being done. Of course, this explanation is purely based off of the things I've read from posters in OD (not the most reliable source).

I have my own theory though, it could make sense that as the opiate causes RD, your body is getting slightly less oxygen and has poorer circulation. Lower blood oxygen levels along with vasoconstriction and increased heart rate from the stimulant seem to most likely cause some sort of negative effect, though I dont know what exactly. Again, this is all just guessing on my part, if anyone could correct me I would be grateful.

Overall I'm pretty sure it has do to with cardiac risk due to something along the lines of what I described, and its not a neural signaling issue (dopamine reuptake vs endorphin release?) that causes the damage.
 
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It seems to me that the most reasonable explanation for why this bit of folk wisdom exists within the firmament of recreational drug use is that a correlation was noted by certain drug-cocktailing fiends between the mixing of such substances and a diminution of the effects of both; when relayed to less sophisticated drug-abusing guttersnipes, something was lost in translation and the conclusion was reached that there lay danger in combining uppers with downers rather than mere futility and waste of precious resources rarefied by limited funds and ridiculous anti-drug laws.

It's like that game that kids play where they all stand in a row and a child on either end whispers in the ear of the nearest other child and so on until some version of the message has been relayed to all of the other children and the child who's last heard it must speak it aloud in order to illustrate for all present the general faultiness of the human intellect, our auditory ability, will to work together and not sabotage one another, and so forth...

Seems to me that because amphetamines are generally highly noradrenergic and minimally serotonergic, they largely negate or diminish the effects of opioids. Opioids, in turn, possibly reduce some of the stimulatory effects of amphetamines because they have an antagonistic effect on adrenergia. Adrenergia also seems to attenuate serotonergia (and vice versa) and opiates depend upon good serotonergic tone to produce strong effects.

Edit: To state that in a more succinct and clear fashion: Serotonergia and mu-opioidergia are synergistic, whereas adrenergia and serotonergia+opioidergia are inversely correlated and antagonistic to one another.

Edit2: Anyone ever notice how commonly alpha 2 adrenergic agonists are prescribed to diminish the severity of opioid withdrawals?
 
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I've combined many opioids like H, opium poppy, oxycodone, hydrocodone, codeine, and kratom with many stimulant drugs and plants including various amphetamines, methylphenidate, ephedrine, caffeine, cocoa, yohimbe, yerbe mate, tobacco, and potent sativa weed with no problems whatsoever during and after the experience. Theirs also tramadol which in itself is a stimulant and depressant - NE and DA + 5-HT, mu-opioid, and NMDA antagonist.

I think that in some cases their might be some complications. Obviously if you combine an agonist of an inhibitory receptor, with a drug that antagonizes that receptor somehow, for example combining opioids which block GABA receptors (causing dopamine release), and a benzo or barb which potentiate GABA receptors, they will cancel each other out.
 
Interesting explanation shibireru, it makes alot of sense from a pharmacological standpoint. But even though neither drug is able to express its full spectrum of effects, in practice most users would argue that the upper/downer combo is much more euphoric than either alone, so there is clearly some positive synergy.

Also look at how greatly amphetamine potentates the analgesic properties of morphine (an old school favorite for the terminally ill). Now this can in part be due to amphetamine having its own analgesia and could be dismissed as additive, but it would seem that the vast majority of subjective reports suggest it is more along the lines of synergistic potentiation. Along these lines of thinking maybe the opiate amphetamine combo increases dopamine in the synapse so greatly that that alone is the source of cariotoxicity as it is well known that large excess' of DA can have negative effects on the heart.
 
Some opioids exert an action on catecholamine and serotonin receptors as well, Demerol being the best known example. Agonism of certain 5-ht receptors may cause damage to the heart, although in the long term. I wouldn't be surprised if some opioids' serotonergic action combined with that of many stimulants can prove harmful, though, again, only after long term abuse.
 
^ meperidine is also a potent anti-cholinergic.
 
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I am scripted opiates, benzo's and Ritalin by my pain doctor.

She told me, the main risk in combining stimulants with downers, is that the stimulant may keep you awake and taking more downers, but it does NOT lower the risk of respiratory depression by much. People are less likely to fall asleep before they take enough downers to stop their heart, if they take stimulants also. I believe that is where the heart risk primarily lies with stimulant / downer combo's.

I THINK she said that with some "downer" overdoses they give stimulants to counteract it.

Will
 
^ One of my friends got 2mgs IV ativan after a caffeine overdose at the hospital. Also walked out with a small xanax script.
 
I'm taking oipioids (first oxycodone 2x20mg, now buprenorhphine 35ug/h) + antidepressants (clomipramine 2x150-300mg) and stimulants (first a lot of methylphenidate, now amphetamine usually 2x20mg) at the same time for years now. The only real dangarous side effect i have noticed is the lower seizures threshold. Wich is mainly based on clomipramine. That's why i now sometimes even take phenobarbital together with all these other substances...

Belief it or not - I'm feeling fine...
 
System speeds up, or system slows down. No gettin pulled in half. One of the biggest mistakes people make in visualizing biology or science in general is applying morphological concepts like pulling, pushing, squeezing, holes-in-whatever, when those concepts don't apply. If the heart is too fast from cns stimulants, downers can slow the heart down to a safe level. Picture this tho, what if your downer gets broken down via the same metabolic pathway as your stimulant? You can easily compound the initial problem and end up worse than before. The old wisdom of not mixing uppers and downers probably has more to do with not mixing drugs period than specifically those two classes.

BUT as ppl have mentioned they do tend to mask one another's signs that youve had enough, just because xanax keeps you feeling straight by promoting muscle relaxation and slowing heartrate when youre spun doesn't mean you're safe from nerve toxicity in the brain and your liver is going to hate you all the more.
 
I combined 4mg of Clonazepam and 30mg of D-amphetamine on a daily basis for 2 years. I withdrawed from the clonazepam cold turkey, and d-amphetamine is now not the same for obvious crippling benzodiazepine withdrawal reasons. I'm fine, I'm healthy. All my organs are functioning, I just lack a fuckload of GABA.
 
HeyDude12345 said:
I combined 4mg of Clonazepam and 30mg of D-amphetamine on a daily basis for 2 years. I withdrawed from the clonazepam cold turkey, and d-amphetamine is now not the same for obvious crippling benzodiazepine withdrawal reasons. I'm fine, I'm healthy. All my organs are functioning, I just lack a fuckload of GABA.
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If you don't mind me asking, why would you stop taking a depressant "cold turkey" instead of tapering down over an extended period safely?
 
Tsukasa said:
I've combined many opioids like H, opium poppy, oxycodone, hydrocodone, codeine, and kratom with many stimulant drugs and plants including various amphetamines, methylphenidate, ephedrine, caffeine, cocoa, yohimbe, yerbe mate, tobacco, and potent sativa weed with no problems whatsoever during and after the experience. Theirs also tramadol which in itself is a stimulant and depressant - NE and DA + 5-HT, mu-opioid, and NMDA antagonist.

I think that in some cases their might be some complications. Obviously if you combine an agonist of an inhibitory receptor, with a drug that antagonizes that receptor somehow, for example combining opioids which block GABA receptors (causing dopamine release), and a benzo or barb which potentiate GABA receptors, they will cancel each other out.
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im pretty sure its the oppisite, stimulants are related to the release of dopamine, and opiates release GABA and endorphins, and enkaphalins, which also causes some dopamine relase, only moderate though, simalar to the amount caused by alcohol i think... gives u this "rush" stimulants and opiates give u a rush. for some more than others, and for some reason, opiates can make u nod off and sleepy too, not sure how this works im not an expert on opiates, someone fill me in, cuz as far as im concerned, endorphins give u a "rush" just like when u cut and burn urself. tell me if my info is slanted
 
No, opioids have an inhibitory effect on GABA which causes the disinhibition of DA, leading to moderate increases.

The sedation from opioids is unrelated to GABA. There is more than one way to become sleepy in your body. Adenosine agonists, antihistamines, opioids. All through different mechanisms.

Opioids do not release endorphins.

Stimulation of opioid receptors is enough to produce a rush, other receptor systems aren't needed. Even those on antipsychotics (dopamine receptor antagonists) will experience a rush with IV opioids.

Tramadol's effect on NMDA receptors is rather minimal, I think something like 15% inhibition @ 10um vs. the 80% for ketamine at the same concentration- and ketamine isn't potent at all.
 
Hammilton said:
No, opioids have an inhibitory effect on GABA which causes the disinhibition of DA, leading to moderate increases.

The sedation from opioids is unrelated to GABA. There is more than one way to become sleepy in your body. Adenosine agonists, antihistamines, opioids. All through different mechanisms.

Opioids do not release endorphins.

Stimulation of opioid receptors is enough to produce a rush, other receptor systems aren't needed. Even those on antipsychotics (dopamine receptor antagonists) will experience a rush with IV opioids.

Tramadol's effect on NMDA receptors is rather minimal, I think something like 15% inhibition @ 10um vs. the 80% for ketamine at the same concentration- and ketamine isn't potent at all.
Click to expand...

Quoted for truth.
 
I should have said GABA-B agonists like baclofen instead of benzo's or barbs. Opioids release dopamine by blocking gaba-b.
 
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