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Harm Reduction ⫸DANGEROUS Drug Combos⫷

kleinerkiffer

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It's about time for a megathread where we can discuss dangerous combos to prevent avoidable deaths, like the passing of the Bluelighter Oxydexmorphetamine, who most likely died due to the combination of DXM and Effexor(SSNRI) leading to Serotonin Syndrom. http://bluelight.org/vb/threads/790985-*WARNING-DEADLY-COMBO*Effexor-600mg-of-DXM-ambien-and-lyrica

Dangerous combos by Banquo from the Dangerous Combos FAQ with a few small changes
Central Nervous System [CNS] Depressants
Central nervous system [CNS] depressants are drugs that slow down brain activity. CNS depressants include a wide range of drugs such as alcohol, barbiturates (Amytal, Nembutal, Seconal), benzodiazepines (Ativan, Halcion, Librium, Valium, Xanax), chloral hydrate, GHB, GBL, methaqualone (Quaaludes), buspirone (Buspar), and zolpidem (Ambien). CNS depressants can cause confusion and dizziness, and impair judgment, memory, intellectual performance, and motor coordination, especially when taken in excess and combined with one another. When mixed together, CNS depressants amplify each other's effects, which can cause severely reduced heart rate and even death. Overdoses of depressants produce effects that are the same as alcohol overdoses. The person becomes extremely drowsy and passes out. Their heartbeat slows and respiration will become shallow. Their skin may feel cold and clammy, and death may result from respiratory failure. CNS depressants are also dangerous when combined with opiates and opioids (like codeine, hydrocodone, oxycodone, and heroin).
Combining benzos with other CNS depressants or just high doses of benzos can lead to a blackout.

Opiates and Opioids
This is a class of drugs that includes opium, heroin, morphine (MS Contin), codeine (Tylenol 2, Tylenol 3, Tylenol 4), hydromorphone (Dilaudid), oxycodone (Percodan, Percocet, and Oxycontin), meperidine (Demerol), hydrocodone (Vicodin, Norco, Lortab), propxyphene (Darvocet and Darvon), fentanyl (Duragesic and Actiq), and others. Like alcohol, opiates are dangerous when used in combination with drugs that suppress breathing. These include alcohol, barbiturates, benzodiazepines (Xanax, Valium, Ativan), CNS depressants (see above) and GHB. Combining opiates with other drugs that make you sleepy can basically lead the user into a sleep from which they will never wake up. It should be noted that opiate overdose is easily treatable and can be counteracted with Narcan available at your local emergency room.

Hallucinogens
This is a class of drugs that includes LSD, PCP, ketamine, mushrooms, mescaline, and Ecstasy. The most dangerous combination is the combination of PCP-like drugs with alcohol or other sedatives. This combination can kill you. Taking atropine-like drugs with anything that stimulates the cardiovascular system or raises the body temperature (like Ecstasy) can lead to dangerous disturbances of heart rhythms or increased body temperature. Hallucinogens with amphetamine-like actions (like mescaline) can be dangerous when taken in combination with other stimulants. This goes for Ecstasy (MDMA) also. MDMA, which has stimulant properties, may cause a user's heart rate to rise to dangerous levels when used in combination with other stimulants, like cocaine or methamphetamine (also see Stimulants below). Reactions may vary from person to person. As always, err on the side of caution.

Ketamine
As noted, using ketamine and alcohol is a dangerous combination. At lower levels, nausea and sickness will result. At higher levels serious health problems can occur. Ketamine, by itself, is valuable in a medical setting since it slows breathing at a lower rate than other anaesthetics. But combining ketamine with another CNS depressant, including GHB, can slow down breathing to a dangerously low or even fatal level (see CNS Depressant section). PCP (phencyclidine), like ketamine, is also an NMDA antagonist. As such, combinations with ketamine, alcohol, and other CNS depressants can also lead to negative health consequences.

MAOIs
Monoamine oxidase inhibitors (MAOIs) can cause a dangerous or lethal increase in heart pressure when combined with Ecstasy. Nardil (phenelzine), Parnate (tranylcypromine), pargyline, Marplan (isocarboxazid), Eldepryl (l-deprenyl), and Aurorix / Manerix (moclobemide), Ayahuasca also contains MAOIs (harmine and harmaline). Combining MDMA and MAOIs has been pushed by some, usually the uninformed, as means for increasing Ecstasy's effects. However, this is an extremely dangerous and potentially lethal combination.

Alcohol
It is dangerous to combine anything with alcohol that makes you sleepy (see CNS section). This includes opiates/opiods (heroin, morphine, Demerol, Percocet, Oxycontin), barbiturates, benzodiazepines (Xanax, Valium, Ativan) and GHB. It should also be noted that a large percentage of deaths and hospitalizations associated with Ecstasy have usually involved a combination with alcohol.

Marijuana
Possible dangerous combinations include a mix of marijuana with heart or blood pressure medication or with drugs that supress the function of the immune system. One recent study shows that the combination of marijuana with cocaine can lead to very dangerous effects on the heart.

Stimulants
This is a class of drugs that includes cocaine, methamphetamine (Desoxsyn), amphetamine (Adderall), MDMA (ecstasy -- which has hallucinogen and stimulant characteristics), dextroamphetamine (Dexedrine), methylphenidate (Ritalin), and dexmethylphenidate (Focalin). Stimulants can be dangerous when taken in combination with over-the-counter cold remedies that contain decogestants because the combined effect of the two can raise blood pressure to a dangerous level. Stimulants can also be dangerous when taken in combination with MAOIs. Cocaine is dangerous in combination with anything that makes people more sensitive to seizures, such as the prescription medication buspirone or extremly high levels of xanithines, like caffeine or theophylline. Stimulants are also dangerous when taken in combination with one another. Negative effects include heart attack, stroke, and death. People with a history of hypertension or other heart problems are especially susceptible problems associated stimulant and stimulant combinations.
Combining different stimulants can lead exacerbate the effects of both, leading to hypertension, Serotonin Syndrom etc.

Benzodiazepines
This is a class of drugs that is intended for the relief of short-term anxiety. Alprazolam (Xanax), bromazepam (Lexotan), clobazam (Frisium), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), prazeman (Centrex), oxazepam (Serenid), flunitrazepam (Rophynol), temazepam (Euhypnos), and Triazolam (Halcion) are all benzodiazepines. While these drugs are not particularly toxic by themselves, at certain doses, amnesia-like side effects result in reduced inhibition, impaired judgment, poor coordination, and slower reaction time. All of these things can lead to unsafe behavior. When combined with other CNS depressants (see above), like alcohol, and/or opiates, benzodiazepines can lead to a blackout, shallow breathing, respiratory failure, and even death.

Methadone
Methadone magnifies the effects of alcohol and other central nervous system [CNS] depressants, such as antihistamines, cold medicines, sedatives, tranquilizers, other prescription and over-the-counter (OTC) pain medications, barbiturates, seizure medications, muscle relaxants, other opiates, and certain anesthetics including some dental anesthetics. Some dentists use a drug called Stadol (butorphanol artrate) which is a narcotic agonist/antagonist that reportedly will send a methadone user into acute withdrawl. Opioid partial agonist and agonist/antagonist drugs such as Buprenex, Talwin, Stadol, and Nubaine should never be used in the methadone-tolerant individual. Severe opiate withdrawal syndrome can be precipitated by drugs of this type. Alcohol and other central nervous system depressants should not be taken or consumed while methadone is being taken. Combinations taken in excess can lead to shallow breathing, respiratory failure, and, ultimately, death.

Tramadol
Reports have indicated that tramadol (Ultram and Ultracet) is more likely to induce seizure activity when given together with a selective serotonin reuptake inhibitor (SSRI). Use of tramadol with MAO inhibitors or SSRIs increases the risk of adverse events, including seizure, serotonin syndrome, and even death. Use of tramadol with CNS depressants increases the rate of respiratory depression. Tramadol on it's own lowers the seizure treshhold and anything over 300mg can be dangerous. Seizures occured with even less than 300mg



***REMEMBER***
Please note that while some may use one of the dangerous drug combinations listed above at low doses without negative consequences, even a small step up in dose can multiply the health risk by a greater factor where drug combinations are concerned. A person in an altered state of consciousness does not always use the best judgment – so please be careful and ALWAYS error on the side of caution.

Information gathered and quoted from:
Cynthia Kuhn, Scott Swartwelder, and Wilkie Wilson from the Duke University Medical Center and their book "Buzzed" W.W. Norton and Co., 1999; web sources; and Bluelight members.
 
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Znegative

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Nice idea my man! This can be a place where GL's and BL's can make inquiries as to the safety of certain combinations as well. While we have a potentiation megathread already, maybe we can add a section on that too, in case someone accidentally and unknowingly drinks a cup of WGF juice before their usual deadly cocktail of CNS depressants and dies. In all seriousness though, that might be beneficial.

What I'm interested in (just out of curiosity) is whether a drug like Gabapentin or Lyrica would really be classified as CNS depressants, and if they could really cause an overdose if someone say, took a high dose of gabapentin with their usual dosage of Oxycodone.

I found this:
Gabapentin (Neurontin) is an antiepileptic drug commonly prescribed for pain treatment. In the past 15 years, indications for gabapentin have been increasing even though the complete mechanism of action is unknown. Side effects include somnolence, dizziness, ataxia, nystagmus, and fatigue. This study reviewed all cases positive for gabapentin submitted to the Washington State Toxicology Laboratory between January 2003 and December 2007. The concentrations of gabapentin in blood from impaired driving cases (n = 137) ranged from < 2.0 to 24.7 mg/L with a mean of 8.4 +/- 5.4 mg/L and a median of 7.0 mg/L. The driving population was 50% male with a mean age of 43.0 +/- 10.9 years (range 23-73). Of the cases studied, only 7% were positive for gabapentin alone with the remaining 93% indicative of polydrug use. Drug Recognition Expert reports from four cases in which the only drug detected likely to be causing impairment was gabapentin were examined. These reports demonstrated that subjects may exhibit psychophysical indicators of a central nervous system depressant (e.g., horizontal gaze nystagmus, poor performance on standardized field sobriety tests) with clinical indicators (e.g., dilated pupils, low body temperature, and elevated pulse and blood pressure) that are not consistent with a depressant.-Source
Which basically says that it exhibits similarities to both stimulants and depressants. The fact that it raises blood pressure, makes me wonder further whether a gabapentin/opiate combo could result in an overdose. I know Lyrica is stronger and I'm pretty sure that it doesn't suffer from the self limiting qualities that Gabapentin does (the reduced bioavailibility at higher dosages), however I'm still curious about that one too.

One dangerous combination that I just thought of also is using methamphetamine/amphetamine in concurrence with asthma inhalers, I'm thinking specifically albuterol sulfate. I know that an overdose of albuterol is possibly by itself and can result in a heart attack, and I can only imagine what adding speed or cocaine could do.
 

kleinerkiffer

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CYP2D6
Cytochrome P450 2D6 is an enzyme that in humans is encoded by the CYP2D6 gene and a member of the cytochrome P450 mixed-function oxidase system.It's one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, in a process referred to as O-demethylation.

CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism.
There are 4 types:

poor metabolizer – little or no CYP2D6 function (those people won't feel much from codeine, as codeine is a prodrug and needs to be metabolized into morphine)
intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
extensive metabolizer – normal CYP2D6 function
ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function

Warnings:
poor metabolizer -> Don't take Dextromethorphan, as even normal therapeutical doses can make you trip for hours or even days, because you don't metabolize DXM well. This could potentially be lethal
ultrarapid metabolizer -> Don't take codeine, as you will metabolise codeine rapidly into morphine, thus increasing the risk of an overdose


Drugs that are metabilized by CYP2D6:

All tricyclic antidepressants, e.g.
imipramine, amitriptyline
Most SSRIs , e.g.
fluoxetine, paroxetine, fluvoxamine
venlafaxine
duloxetine
mianserin
mirtazapine
opioids
codeine
tramadol
O-desmethyltramadol
N-desmethyltramadol
oxycodone
hydrocodone
tapentadol
antipsychotics, e.g.
haloperidol
risperidone
perphenazine
thioridazine
zuclopenthixol
iloperidone
aripiprazole
chlorpromazine
levomepromazine
remoxipride
minaprine
tamoxifen
beta-blockers
metoprolol
timolol
alprenolol
carvedilol
bufuralol
nebivolol
propranolol
debrisoquine
Class I antiarrhythmics
flecainide
propafenone
encainide
mexiletine
lidocaine
sparteine
ondansetron
donepezil
phenformin
tropisetron
stimulants
amphetamine
methoxyamphetamine
dextromethamphetamine
atomoxetine
chlorphenamine
dexfenfluramine
dextromethorphan
metoclopramide
perhexiline
phenacetin
promethazine


Drugs that inhibit CYP2D6 (this will result in higher and longer blood concentration of the drugs mentioned above, this could lead to increased side effects and could even be lethal or to no effects at all):
White grapefruit juice
Strong
Certain SSRIs
fluoxetine
paroxetine
bupropion
quinidine
cinacalcet
ritonavir

Moderate
sertraline
duloxetine
terbinafine

Weak
amiodarone
buprenorphine
cimetidine
citalopram
escitalopram

Unspecified potency

antipsychotics
haloperidol
perphenazine
thioridazine
zuclopenthixol
risperidone
chlorpromazine
hyperforin (St. Johns Wort)
antihistamines
promethazine
chlorphenamine
diphenhydramine
hydroxyzine
tripelennamine
clemastine
celecoxib
clomipramine
cocaine
doxorubicin
metoclopramide
methadone
moclobemide
doxepin
halofantrine
levomepromazine
mibefradil
midodrine
ticlopidine
cannabidiol


Inducers of CYP2D6:
Strong

glutethimide

Unspecified potency

dexamethasone
rifampicin




From Wikipedia
 
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Znegative

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What makes methadone any different from opioids....

it is an opioid, lol.
I hear you, but at the same time, methadone is probably one of the more dangerous opioids in that it's very easy to overdose due to strength, and it also has a super long half life. in an intolerant user, a dose of 50mg could be fatal, combine that with a xanax bar, and it's not looking too good for you. That being said, the whole time I was on MMT I was taking heaps of benzos, and most of the time was fine, but I did overdose a few times. And now that I think of it, all three of my overdosages included methadone.
 

XANAX XR

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I hear you, but at the same time, methadone is probably one of the more dangerous opioids in that it's very easy to overdose due to strength, and it also has a super long half life. in an intolerant user, a dose of 50mg could be fatal, combine that with a xanax bar, and it's not looking too good for you. That being said, the whole time I was on MMT I was taking heaps of benzos, and most of the time was fine, but I did overdose a few times. And now that I think of it, all three of my overdosages included methadone.

I suppose... Methadone is quite interesting, it's probably my favorite opioid in terms of euphoria -- However, even with a tolerance, I got so high off 10mg, it was crazy, was almost like I never IV'd or took an opiate in my life. Other times, I wouldn't really feel 10mg.
 

kleinerkiffer

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I hear you, but at the same time, methadone is probably one of the more dangerous opioids in that it's very easy to overdose due to strength, and it also has a super long half life. in an intolerant user, a dose of 50mg could be fatal, combine that with a xanax bar, and it's not looking too good for you. That being said, the whole time I was on MMT I was taking heaps of benzos, and most of the time was fine, but I did overdose a few times. And now that I think of it, all three of my overdosages included methadone.
This + methadone inhibits CYP2D6 and a few other cytochromes I think so this can increase the effects of other drugs even more (iirc alprazolam is metabolized by CYP2D6)
 

belfort

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ive never felt closer to death as to when i was on welbutrin/ephedrine and beta blockers..ive taken many drugs in many different cocktails but beta blockers and stimulants and exercise do not play well together
 

Kittycat5

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Got it. Was thinking of QT prolongation summary and maybe PgP and other transporters as potential topics.

Maybe touch on some CYP distribution (GI vs hepatic) too.
 

kleinerkiffer

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Just a raw version for today

What is serotonin syndrome (SS)?
SS or better serotonin toxicity is a consequence of the buildup of serotonin in the synaptic cleft leading to an overstimulation of both peripheral and central postsynaptic serotonin receptors, 5HT-2A receptors being the most important ones. This results in a number of different and possibly life threatening symptoms. So if you think you or a friend suffers from SS call an ambulance now!

What causes SS?
Serotonin syndrome can occur via the therapeutic use of serotonergic drugs alone, an overdose of serotonergic drugs, or classically, as a result of a complex drug interaction between two serotonergic drugs that work by different mechanisms. A multitude of drug combinations can result in serotonin syndrome.

What are the symptoms?
The symptoms of serotonin syndrome usually present within 6 to 8 hours and most likely within 24 of overdosing or combining serotonergic drugs and can be barely noticeable to fatal.

Autonomic effects include:
- Nausea
- Diarrhea (with hyperactive bowel sounds)
- Headache
- Sweating
- Shivering
- Tachycardia
- Rise in blood pressure
- Rapid breathing
- High pulse
- Mydriasis

Somatic effects include:
- Muscle twitching
- Tremor
- Hyperreflexia
- Akathisia
- Ocular clonus (slow continuous lateral eye movement)
- Increased muscle tone (lower limb>upper limb)

Cognitive effects include:
- Confusion
- Hallucination
- Agitation
- Restlessness
- Anxiety
- Delirium
- Coma

Drugs that can cause SS
Mechanisms:

Increased serotonin synthesis
- Tryptophan
- 5-Hydroxytryptophan

Increased serotonin release
- MDMA/MDA
- Amphetamines
- Hallucinogenic amphetamines

Inhibition of serotonin uptake
- SSRIs
- SNRIs
- Tricyclic antidepressants
- Cocaine
- St john’s Wort
- Dextromethorphan (DXM)
- Tramadol

Decreased serotonin metabolism
- Monoamine oxidase-Inhibitors
- Syrian rue

Activation of serotonergic receptors

- Buspirone, Triptans

Increasing the effects of serotonin
- Lithium

Other drugs
- Panax ginseng, Nutmeg, Yohimbe, valproate chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir and linezolid, Fentanyl, methadone, (tapentadol)?

Another mechanism involves the inhibition of certain cytochrome P450 (CYP450) enzymes (-> see the post above about CYP2D6) like white grapefruit juice, cimetidine, methadone etc.


Management
SS is potentially lethal as hyperthermia, rhabdomyolysis, seizures, kidney failure and aspiration and other symptoms can occur.
Stop taking the drugs/medication and call an ambulance!


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
https://en.wikipedia.org/wiki/Serotonin_syndrome
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464814/
 
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Speed King

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Nice idea my man! This can be a place where GL's and BL's can make inquiries as to the safety of certain combinations as well. While we have a potentiation megathread already, maybe we can add a section on that too, in case someone accidentally and unknowingly drinks a cup of WGF juice before their usual deadly cocktail of CNS depressants and dies. In all seriousness though, that might be beneficial.

What I'm interested in (just out of curiosity) is whether a drug like Gabapentin or Lyrica would really be classified as CNS depressants, and if they could really cause an overdose if someone say, took a high dose of gabapentin with their usual dosage of Oxycodone.

I found this:


Which basically says that it exhibits similarities to both stimulants and depressants. The fact that it raises blood pressure, makes me wonder further whether a gabapentin/opiate combo could result in an overdose. I know Lyrica is stronger and I'm pretty sure that it doesn't suffer from the self limiting qualities that Gabapentin does (the reduced bioavailibility at higher dosages), however I'm still curious about that one too.

One dangerous combination that I just thought of also is using methamphetamine/amphetamine in concurrence with asthma inhalers, I'm thinking specifically albuterol sulfate. I know that an overdose of albuterol is possibly by itself and can result in a heart attack, and I can only imagine what adding speed or cocaine could do.
I used a small dose of albuterol with dextroamphetamine and had a minor panic attack. I recommend that if you need an inhaler, you use it when you are not using amphetamines at all, or discuss with doctor possible alternative medication.

In regards to Gabapentin or pregabalin for that matter, each can be stacked on the hour, to boost the strength of benzodiazepines and therefore be very dangerous in combination with an opiate.
 

Speed King

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Kleinerkiffer, well done thread. It is excellent reference material, that can easily be built on. Thanks. Btw, whoever said 300mg of MS Contin and 10mg Xanax, was recreational, is off by a mile. Even when you "have a tolerance" IMO , is way off. That's a whole lot and no where near harm reduction.
 
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sm0kestack

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I won't forget the time I shot 2 OC 40s and then 2 bags of heroin right behind it. I had forgotten that I had taken XANAX that day.

I woke up with with my face on the table. I looked down and my right was on the floor. Apparently I fell out before I got the whole shot off, because there was still about 15 units of the bloody solution in the syringe left. I got up and looked in the mirror, and the soot from the burnt bottom of the spoon was smeared on the right side of my face. Close call.

Sadly, this did not sober me up, as soon after I mixed up another shot, but I used about a third of the size I had been using. I can say I've learned the lesson to be very careful combining benzos and opiates. It's playing with fire!
 

Elis D

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One dangerous combination that I just thought of also is using methamphetamine/amphetamine in concurrence with asthma inhalers, I'm thinking specifically albuterol sulfate. I know that an overdose of albuterol is possibly by itself and can result in a heart attack, and I can only imagine what adding speed or cocaine could do.[/QUOTE]

Yeah this would definitely be a possibility and i have always thought about it as i suffer from chronic asthma and have to use a nebulizer which i calculated one dose of salbutamol 5mg/2.5ml inhalation ampoules to contain pretty much 5x the amount that is in one salbutamol asthma spray and along with the salbutamole neb solutuon i use ipratropium bromide 500ug/1ml and this combo raises my heart beat to on average 100 b/pm which on longh term scares me enough without the thought of amphetamines ontop of it which I do from time to time. Last time i took methamphetamine and used my nebulizer my heart rate reached 150 b/pm, that's scary shit!!!
 

vblackwood69

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Thanks for this! I didn't know about the Marijuana and Cocaine combination. Both of which I dabble in here and there.

And yeah, tramadol is a shit drug. My sister takes that all the time and she's had like six major seizures in the last two years. Smh
 
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