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  #1  
Old 13-06-2007, 10:53
Paracelsus Paracelsus is offline
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An overview of the dangers of tramadol abuse

An overview on the dangers of tramadol abuse

0. Introduction

Tramadol is a synthetic opioid analgesic. It is commonly prescribed for moderate to severe pain, usual doses being up to 200 mg/day. The maximum allowed daily dose is 400 mg.

Tramadol provides analgesia through 3 mechanisms: mu-opioid binding (through its metabolite O-desmethyltramadol), serotonin reuptake inhibition (through (+)-tramadol) and norepinephrine reuptake inhibition (through (-)-tramadol). O-desmethyltramadol (which is formed from tramadol through O-demethylation catalyzed by CYP2D6) is responsible for the opiate-type effects of tramadol.

Tramadol abuse is becoming more and more popular, mainly because in most countries (including USA), tramadol is the only available non-scheduled opiate (with the exceptions of things like loperamide or some possible opiate research chemicals). If tramadol abuse will get public attention (through many hospitalizations and fatalities), this will change soon.

Being a seizure threshold-reducing drug, a serotonin reuptake inhibitor and an opioid, tramadol can be dangerous, especially when combined with the wrong substances. I will try to provide information about most known health risks of tramadol, without insisting on side effects such as dizziness, somnolence and constipation.

1. ‘Classic’ opiate health risks

Being an opioid, tramadol carries all possible risks known from other opiates. Tramadol causes respiratory depression, although usually weaker than that seen with other opiates and opioids. Tramadol can cause psychological and physical addiction similar to that of other opiates. Nausea, the possibility of choking on one’s own vomit, etc. Those experienced with opiates can probably are familiar with these and will usually be able to handle them.

2. Seizures


Seizures from tramadol occur at least once in about 0.87% of persons prescribed to tramadol. Risk factors included a history of drug abuse (which might involve high-dose use) and combining tramadol with other drugs.
Seizures are likely to be caused by tramadol itself. The risk of seizure increases with dosage (that is why the daily limit is 400 mg). Most reported seizures have been caused by exceeding this limit.
It can be concluded that seizures from tramadol are a real possibility, especially if it is used by the wrong persons, combined with wrong substances or used in high amounts.

3. Dangerous combinations with tramadol


3.1. ‘Classic’ opiate interactions

Being an opioid, tramadol shouldn’t be mixed with other depressants, because of increasing respiratory depression.

Also because it causes respiratory depression, tramadol should not be used recreationally by those suffering from asthma or other conditions which impair respiration.

3.2. Other serotoninergic drugs

Because it is a serotonin reuptake inhibitor, tramadol can cause serotonin syndrome when combined with other serotoninergics (drugs which raise serotonin levels). This has been reported with paroxetine, sertraline and dextromethorphan (all in therapeutic doses), and some others. Although serotonin syndrome is rarely fatal, some deaths have been attributed to combinations of tramadol and other serotoninergics (a handful, I didn’t count them – do a Pubmed search if you want more details).

Serotoninergic drugs include but are not limited to: most antidepressants (SSRIs, SNRIs, tricyclics, trazodone, nefazodone, etc.), MDMA and analogs (MDA, MDE, methylone, etc.), many phenethylamines and tryptamines (especially AMT, 5-MEO-AMT and AET), most amphetamines, cocaine, piperazines, DXM, some opioids (pethidine, fentanyl, propoxyphene, methadone), l-tryptophan and 5-HTP, lithium, 5HT agonists (triptans), etc. MAO inhibitors also keep serotonin levels raised, contributing to the possibility of serotonin syndrome.
Needless to say, if one has used one of these in the past two weeks, tramadol isn’t a good idea.

3.3. Other seizure threshold-reducing drugs (STRDs)

These can increase the chance of seizure if tramadol is used. Risk of seizure is dose-dependent.

STRDs include: anaesthetics (enflurane, isoflurane, propofol), antibiotics (penicillin, cephalosporins, amphotericins, imipenem), antidepressants (SSRIs, MAOIs, doxepin, nefazodone), antihistamines (azatadine, cyproheptadine, pheniramine, methdilazine, promethazine), triptans, antipsychotics, aminophylline and theophylline, DXM, bupropion, amphetamines, cocaine, all other stimulants (including caffeine), etc.

Other factors such as epilepsy, CRT monitors, withdrawal from sedatives (alcohol, barbiturates, benzodiazepines, GHB and analogs, etc.), use of brainwave generators, etc. also reduce the seizure threshold.

3.4. CYP2D6 inhibitors

Besides significantly weakening the opiate-like effects of tramadol, CYP2D6 inhibitors also increase the risk of serotonin syndrome and seizure, because these are caused by tramadol itself (and CYP2D6 inhibitors make the metabolization of tramadol slower).

CYP2D6 inhibitors include: fluoxetine, paroxetine, sertraline, chlorpheniramine, other first-generation antihistamines (in high doses), bupropion, amiodarone, haloperidol, ritonavir, indinavir, methadone, quinidine, celecoxib, cimetidine (Tagamet), DXM and codeine (the latter two are probably only relevant in recreational doses).

As a side note, codeine and tramadol has been reported to cause a seizure, while codeine after the tramadol peak (when levels of O-desmethyltramadol are highest) is reported to be quite enojyable (for both reports, search for "codeine tramadol synergy").

4. Who should not use tramadol


Epileptics should definitely stay away from tramadol because of very high risk of seizure. Because of this, physicians won’t prescribe it to epileptics anyway (otherwise go shoot your doc NOW). Persons with a history of seizures or a higher risk of seizures should also abstain from tramadol, even if they aren’t epileptics. This includes persons prescribed to any seizure threshold-reducing drugs (see 3.3.).

Persons who know to be CYP2D6 poor metabolizers shouldn’t even bother with tramadol – they won’t get any opiate-like effects from it, because much less O-desmethyltramadol is formed. If one doesn’t get any opiate-like effects from normally active doses of tramadol, that person COULD be CYP2D6 deficient.

Persons with a high tolerance to opiates should not use tramadol, because they won’t feel any opiate-like effects unless very high doses are consumed, which is dangerous because of the high risk of seizure. If one doesn’t get satisfactory effects from 300-400 mg, the dose should not be increased.

Persons who are physically addicted to any sedative (alcohol, barbiturates, benzodiazepines, GHB and analogs, etc.) should not use tramadol. If these are currently under the influence of the particular sedative, respiratory depression may become dangerous when tramadol is also consumed. If these are currently withdrawing from the particular sedative, the risk of seizures becomes extremely high.

Persons who have had an anaphylactoid reaction to any other opiate should be very cautious with tramadol.

Persons with severe renal or hepatic insufficiency should not use tramadol.

6. Tramadol deaths


25 deaths of adults involving tramadol have been reported. 20 of these are considered not to be caused by tramadol intoxication but by concomitant consumption of other drugs (mainly benzodiazepines and serotoninergics). 2 have been caused by tramadol alone, in concentrations 5- respectively 6-fold higher than the toxic level of tramadol (2 mg/L). So the main risk factor is combining tramadol with other substances, particularly sedatives and serotoninergics. Just say no.

-----
Please add anything you know so this post can be expanded.

Post Quality Evaluations:
Great Post. We needed this.
great info. solid post
such informative posts!
Sadly my doc didn't inform me on any of this, I could've certainly used the seizure and SSRI activity 2 years ago...
Very informative
Very good warning!
Very informative post, this is info that swimmers can use!
Much needed specific information.Guess the dose does make the poison ;)
Highly informative
I wish I had known this sooner! Great post!
Wish there was research to back some of this up- especially the "1 in .87%", as that is not a valid ratio.
Very Useful info, Lacks Refs

Last edited by Paracelsus; 14-06-2007 at 07:26. Reason: added cimetidine to CYP2D6 inhibitors
  #2  
Old 13-06-2007, 21:26
snapper Gold member snapper is offline
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Re: An overview on the dangers of tramadol abuse

Great summary

BTW, cimetidine (tagamet) is also a cytochrome inhibitor and grapefruit juice would also qualify. Many people use the latter to potentiate opiates, and SWIM recalls reading that it does not work for Tramadol (which makes sense according to the above summary).
  #3  
Old 13-06-2007, 22:23
Bajeda Bajeda is offline
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Re: An overview on the dangers of tramadol abuse

Nice overview. Looking at your post and then looking at the thread below makes me wonder a bit though.

Tramadol + GHB + MDMA + Ketamine + Cannabis



Quote:
Originally Posted by snapper View Post
BTW, cimetidine (tagamet) is also a cytochrome inhibitor and grapefruit juice would also qualify. Many people use the latter to potentiate opiates, and SWIM recalls reading that it does not work for Tramadol (which makes sense according to the above summary).
It is still debatable, but some people (including swim) believe that grapefruit juice does indeed potentiate Tramadol.

See ----> Possible Grapefruit Juice Potential for Greater Tramadol Experience

And this post in particular by Paracelsus.
  #4  
Old 13-06-2007, 22:29
Nicaine Nicaine is offline
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Re: An overview on the dangers of tramadol abuse

The seizure risk is actually fairly low, compared to quite a few psychotropic substances... well under 1/1000 people (0.1%). Must be dramatically less than say, cocaine, as well as less than most SSRI antidepressants.

Higher than most opiates, but SWIM doesn't think more than typical substances that mess with serotonin and norepinephrine... quite probably less.
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Old 13-06-2007, 22:53
old hippie 56 old hippie 56 is offline
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Re: An overview on the dangers of tramadol abuse

Swim wife had a bad seizure while taking tramadol, but also she has secondary progressive multiple sclerosis. Plus she is one of the 1% with spms with a seizure disorder. Swim will always wonder if the tramadol is responsible.
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Old 13-06-2007, 23:10
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Re: An overview on the dangers of tramadol abuse

WOW Paracelsus your the man this was one of the most insightful posts in forever thanx swim has a script for ultram 200mg er great info
  #7  
Old 14-06-2007, 02:00
Nicaine Nicaine is offline
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Re: An overview on the dangers of tramadol abuse

Quote:
Originally Posted by old hippie 56 View Post
Swim wife had a bad seizure while taking tramadol, but also she has secondary progressive multiple sclerosis. Plus she is one of the 1% with spms with a seizure disorder. Swim will always wonder if the tramadol is responsible.
Well, the issue with tramadol is probably the unexpectedness of a pain-killer lowering the seizure threshold... SWIM guesses that if SWIY's wife had considered it a stimulant of some sort, she might have been on the lookout for that sort of thing, or perhaps thought twice before taking it.
That may be why tramadol seems to get a lot of blame for this, although the total number of deaths appears very low for a substance this widespread.

Add - SWIM notes also the fairly narrow therapeutic index, i.e. limit of 400mg/day before seizures apparently become more of a problem (note that 'how much of a problem' seems to be something that isn't widely advertised).
  #8  
Old 14-06-2007, 07:25
Paracelsus Paracelsus is offline
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Re: An overview on the dangers of tramadol abuse

A study has estimated that the risk of seizures is 0.87%. It is most likely much higher if used recreationally, used by persons who are susceptible to seizures or mixed with other substances lowering the seizure threshold. Tramadol is one of the few opioids known to cause seizures (the other ones are pethidine and fentanyl).

Snapper: You are right about cimetidine. It inhibits both CYP2D6 and CYP3A. I added it to the list. Grapefruit juice only inhibits CYP3A, which is desirable (it potentiates tramadol), so it doesn't belong to CYP2D6 inhibitors.
  #9  
Old 25-07-2007, 06:06
CHEMDUDE CHEMDUDE is offline
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Re: An overview on the dangers of tramadol abuse

swim was put on tramadol and experimented on how much was too much..BE WARE..swim took a large quantity once (don't remember how many exactly.swim was more worried for his life after the dose he took)it started in swims cheast,breathing became more laboured and then all of asudden,swim got this life changing experiance (from the point of taking tramadol anyway,swim is still stupid enough to push quantaties of a chem to the max for one never knows) his heart felt like it was coming to a stop and he was going to DIE.this happened during one winter.swim resorted to taking all his clothes off and walkingaround his 7 1/2 acre property.walking faster and faster as the symptoms became worse.swims chest felt numb and like his heart was stopping (scared shitless) swim ran from one end to the house to call for an ambulance to takehim to hospital,but as god,budda,halle salassi I,or whom ever was looking after swim in this state of panic,the symptoms stopped and swims cheast,heart and mind were again as one...DON'T FUCK WITH THIS STUFF IN SWIMS OPINION.IT SCARED THE FUCKING CRAP OUT A HIM..PLEASE LET THIS BE A WARNING TO OTHERS CONCIDERING PUSHING THE LIMITS OF HOW MANY IS TOO MANY....LIFE IS MORE IMPORTANT THEN AN EXPERIMENT WITH TRAMADOL.This could have just been a reaction to the drug that others may or may not get.BUT BELIEVE ME WHEN SWIM SAYS "DON'T DO/TRY IT.swim never wants to experiance anything like that ever again...scary shit..peace`n` be safe..c_d
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Old 01-08-2007, 10:10
Paracelsus Paracelsus is offline
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Re: An overview on the dangers of tramadol abuse

Even if your SWIM doesn't remember the amount exactly, can he give a rough estimate?
  #11  
Old 01-08-2007, 20:37
CHEMDUDE CHEMDUDE is offline
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Re: An overview on the dangers of tramadol abuse

about 10 capsules if swim remembers corectly.
obviously body weight,life style) should be taken into consideration.swim drinks at least 4 cans of SPECIAL BREW a night,which is 9% ally.can't remember if swim was drinking the first night it happened,but swim dosen't think so.
the second time it happened swim was drinking,see the first time swim thaught it was a type of trip.swim has done acid b4 and it felt a little like a bad trip coming on.thats the only way swim can describe it.....but it could just be me,a certain allergic reaxion with that many pills.swim normaly can take uppes,downers and all arounders all at the same time (swim had a death wish when younger).but swim still continues his quest 4 the best chem combination.at the moment it's codeine/prozac/diazypam/herb and potassium GHB to come down with....hope this helps...peace`n`be safe.DON'T COPY OTHERS TILL YOU KNOEW YOUR OWN TOLLERANCE TO SUBSTANCES
JUST REMEMBER...IT'S better to live and get high another day,then take to many combinations`n`die
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Old 21-08-2007, 00:38
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Re: An overview on the dangers of tramadol abuse

swim uses tramadol regularly jesus maybe the continual pains swim has in their legs and back is bloody withdrawl after all! Gp told me these were non addictive as had a bad prob with DF's before and nearly ended up on methadone script
  #13  
Old 05-12-2007, 03:10
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Re: An overview on the dangers of tramadol abuse

tramadol is the most dangerous opioid swim has ever encountered, and swim has tried them all: from fentanyl to dilaudid. it is the only painkiller that knocked swim unconscious and arrested his respiration for a few minutes. this was after taking a very large dose (about 1000 mg per day for three days in a row.) needless to say, swim's family called 911 and he went to the emergency room that christmas eve. one can only imagine how akward the next morning was unwrapping presents with the family. be warned: just because it's not scheduled does not make it safe.
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Old 07-12-2007, 03:00
delphinen delphinen is offline
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Re: An overview on the dangers of tramadol abuse

Tramadol is fine if you know how to use it (dosage) and your body and brain get used to it (tolerance). Dont take too much, and you can use it constantly for its SSRI/light opiate feeling. If youre gonna trip or take another drug, reduce your dosage at minimum.

I had 2 seizures from Tramadol, the only seizures I had in my life. Both ocurred when mixing Codeine with Tramadol.
On the other hand, I had taken (NOT SAFE) up to a gram of Tramadol in a period of 6 hours and nothing happened, except the bliss after o-desmethylation opiate feeling.

Since a year of use/abuse of this drug, withdrawals are hard, yes, but they can be *really* managed very well with not too much Loperamide, some SSRI stuff to keep you fine (50mg Diphenhydramine every 6 hours worked for me), and keeping you busy so you forget youre detoxing.

Its really a good drug, but you have to use it wisely. And it seems that if you dont have a good CYP2D6 metabolization, the O-Desmethyl Tramadol wont get you high enough to feel the somewhat strong opiate feeling this drug has.

Last edited by delphinen; 07-12-2007 at 03:28.
  #15  
Old 07-12-2007, 06:17
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Re: An overview on the dangers of tramadol abuse

A detail to add: Poor CYP2D6 account for about 10% of caucasian population, a number from erowid if I remember correctly. Another source estimated 7-10%
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Old 07-12-2007, 08:08
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Re: An overview on the dangers of tramadol abuse

Very interesting thread. Swim has only tried a large dose of tramadol once (100 - 200mg?) and it was an ok experience. Swim was offered more, but he was worried about causing major liver damage or stomach damage. Swim finds this post very helpful for future reference.
  #17  
Old 26-12-2007, 20:46
iFeaRNLoathiNg iFeaRNLoathiNg is offline
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Re: An overview on the dangers of tramadol abuse

swim likes the 300-400mg area its great, sweating bullets, eyes closed and a big smile on swim face.
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Old 06-01-2008, 09:20
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Re: An overview on the dangers of tramadol abuse

tramadol put swim in the hospital before with a seizure.... swim had i think 1700mg, maybe more, in a 24 hour period.... last thing he remembers is playing a game and waking up in the back of an ambulance
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Old 08-01-2008, 03:58
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Re: An overview on the dangers of tramadol abuse

Quote:
Originally Posted by someone111 View Post
tramadol put swim in the hospital before with a seizure.... swim had i think 1700mg, maybe more, in a 24 hour period.... last thing he remembers is playing a game and waking up in the back of an ambulance
Playing video games while abusing seizure-prone drugs is a pretty bad idea. Not just Tramadol, but DXM and plenty of others.
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Old 08-01-2008, 04:49
Bajeda Bajeda is offline
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Re: An overview on the dangers of tramadol abuse

Quote:
Originally Posted by silentghost View Post
Playing video games while abusing seizure-prone drugs is a pretty bad idea. Not just Tramadol, but DXM and plenty of others.
Quote:
Originally Posted by someone111 View Post
tramadol put swim in the hospital before with a seizure.... swim had i think 1700mg, maybe more, in a 24 hour period.... last thing he remembers is playing a game and waking up in the back of an ambulance
Damn. When taking 1700mg of Tramadol playing video games is the least of your problems! What possessed swiy to take so much?
  #21  
Old 08-01-2008, 04:56
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Re: An overview on the dangers of tramadol abuse

IMO not enough people know about the negatives of ultram ab(use)...can we sticky this considering there has been no mod for 6 months?
  #22  
Old 08-01-2008, 05:35
sarbanes sarbanes is offline
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sarbanes is a decent psychonaut.
Re: An overview on the dangers of tramadol abuse

Actually, people also need to know tramadol is widely used, and is generally considered one of the more benign opioids. VERY few deaths have been attributed to it alone. The typical lethal dose for the typical male is 3-5 grams within 8-16 hour period. this translates to 60-100, 50mg tablets. So if you swallow a whole bottle, you could die. There are dangers of tramadol, but you all need to know it is one of the (overall) safer opioids out there.































As I have to say on every post now (lest a mod pick on it), I can back this up. But I better not post the link!
  #23  
Old 08-01-2008, 06:04
trptamene trptamene is offline
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Re: An overview on the dangers of tramadol abuse

What about daily use of higher doses (greater than the 400mg maximum dose indicated?) With other opiates dosage goes up w/ tolerance with few new side effects, but after gaining a tramadol tolerance and dosing above this dose (even as little as 450mg), the possibility of "seizure like episodes" certainly became noticable for the lab rat.

Quote:
Originally Posted by sarbanes View Post
As I have to say on every post now (lest a mod pick on it), I can back this up. But I better not post the link!
I'd like to see this info, I wonder if it'd be ok to PM it to me? Does it have a .gov ending, or could you give more info as to why dont think can post? Is it on another forum, if so is this just a reproduction from another source or is it proprietary info of said forum?
  #24  
Old 08-01-2008, 11:35
Paracelsus Paracelsus is offline
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Re: An overview on the dangers of tramadol abuse

A main purpose of this thread was to make users aware that tramadol has some quasi-unique (at least among opioids) effects: decreased seizure threshold (which is also very rarely caused by codeine derivatives and by pethidine when certain underlying factors are present) and serotonin reuptake inhibition (which is also caused by pethidine, methadone, propoxyphene, and fentanyl). Because most opiates & opioids do not have these effects, most users would not expect that tramadol does.

It is true that tramadol causes few fatalities in proportion to its widespread use, but I would not consider it more benign than other opioids (apart from having a lower abuse potential in most users).

Post Quality Evaluations:
how does he say it so perfect?

Last edited by Paracelsus; 08-01-2008 at 23:02.
  #25  
Old 09-01-2008, 00:53
delphinen delphinen is offline
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Re: An overview on the dangers of tramadol abuse

Sorry, but youre wrong. As long you control any seizure with some benzo on a high dose of Tramadol, its a safe opioid. Te SSRI effect is unique and makes you happy and talkative like no other opioid does. Try 400mg Tramadol and 4mg Alprazolam.

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Terrible advice.
bad advice.
Highly dangerous advice.
Recommending mixing opiates with benzos to PREVENT harm?! Appallingly bad, very dangerous, incorrect advice.
nore entirely incorrect, as per benga's article 2 posts further
Please do not advocate mixing benzos and opiates!! Very bad advice - what works for swiy may not work for others and could kill them!
EXTREMELY dangerous
Bad advice. This could kill someone!

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analgesic, benzodiazepine, diprivan, drug abuse, grapefruit, grapefruit juice, heroin, intoxication, methadone, opioid, opioids, pain relief, propofol, seizure threshold, tolerance, tramadol, tramadol abuse, tramadol effects, tramadol high, tramal, ultram, withdrawal

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