Stimulants Venlafaxine and Amphetamines

[Pinkerton125]

Hello people, i've just joined and would like a bit of advice. I've been on Venlafaxine XR for nearly 2 years and i'm on 37.5mg. Mentally i'm stable and to be honest i'm more on the drug now because its so longwinded and awful attempting to get completely clean from the drug. I have a chaotic home life which makes complete withdrawal practically impossible for the moment.

Anyway I've got a few grams of amphetamine i'm in the UK so its not meth or anywhere close to that kind of potency. Can i take a bit of this and expect half decent effects? or would the Venlafaxine even at such a low dose block the effects and spoil it? I've been reading although Venlafaxine is classed as an SNRI at lower doses it works as an SSRI which could work in my favor right?

Of course i don't plan going overboard i just want to have a few bombs/lines get a nice buzz going and feel productive. I got benzos at hand if shit did hit the fan.

even if i got 60-80% of effects would be worth it for me.

 

[Jabberwocky]

You might wanna read through http://www.bluelight.org/vb/threads/535037-SNRI-and-amphetamine-interaction

It doesn't look like a very good mix. Maybe save the amph for when you're off the the Venlafaxine or if you're going to take the amph then start very small.

 

[Jekyl Anhydride]

I was stupid enough to take 70 mg of weak amphetamine along with my usual 150 mg of Venaflaxine and no more than two hours later I was seizing in the middle of a hallway. This stuff is not a joke! If you want to take any stimulants then you must wait for the venafalxine to leave your system first and even if you do this it is likely that a few months down the road you are going to feel the effects of withdraw from the Venaflaxine which are supposedly some of the worst, and thats if you dont feel them right away.

...

 

[Scrofula]

SO. This would be easy if it was regular, ol' boner-destroying fluoxetine/Prozac. Or most other SSRIs, like sertraline/Zoloft. You can read about combining the latter with methamphetamine in my 26-volume treatment of the subject as relates to jerking off (spoiler: meth makes it more good).

Problem is, venlafaxine/Effexor is a lot like Prozac or Zoloft, but somehow a bit shittier, if that's possible. I don't mean to knock a drug that's working for you, what I mean is that venlafaxine isn't an SNRI at normal doses (NET inhibition begins above 150mg/day), and it isn't an SSRI, either (not selective by any stretch, and some 100-fold less potent than sertraline). It's more like the straight-edge, but still sloppy, cousin to tramadol. Tramadol without the vague "did I take an old Vicodin by mistake before I seized?"

Venlafaxine and Tramadol are structurally nearly identical. Seriously, see if you can spot the difference:



Tramadol is known for its unusual side effect of "don't ever take more than 450mg in a day to avoid nosy paramedics interrupting your daily seahorse walk." [post-ictal humor, you wouldn't understand] But because both it and its active metabolite have broad binding profiles, it isn't really clear what's causing the few high-dose seizures; it's probably not norepinephrine reuptake inhibition, though. Meaning it's some uncharacterized, probably NMDAr-related shenanigans. Which is probably shared by venlafaxine.

"But, you don't hear about people seizing on Effexor," you astutely point out. I astutelier-ly point out that venlafaxine is even worse at u-opioid receptor agonism, so huge numbers of folks haven't tried eating their whole bottle (yet). Without knowing the source of the more dangerous aspects of tramadol, there's no way to know if it's shared with venlafaxine, but every reason to think it totally is.

So, the next question you're about to ask, is, "Is it okay to take a few grams of whatever this amphetamine "paste" stuff is they sell in my weird country, with my tramadol?"

OK, good point, if no one knows the cause, other than "taking too much of it," what's the risk when combined with stimulants? It's known that using stimulants, any kind, can lower your seizure threshold (meaning it takes less to trigger one). And that's pretty much it--why take chances?

But really, the last hundreds of words could be solved by knowing a little data: the half-life of venlafaxine is ~5 hours, which is extended in extended-release forms. The active metabolite desvenlafaxine (being developed for menopause. Not kidding, look it up) lasts for 11 hours. Neither accumulate. Compare that to the 23 hours for sertraline (which accumulates), or the 4-6 days for Prozac long-term users (ditto).

One way to avoid much risk of interaction is to just skip that morning's dose.

ETA: noticed your jibe at our super-strength meth, remembered another reason for you in particular to be cautious, is the high-rate of adulterants in UK speed. I'm not making a joke about that. You are much more likely to encounter a more potent stimulant with more potential seizure risk. Even if it's just a cutting agent in the form of crushed-up bupropion. Especially if you haven't been a regular user for years. So, be careful.

 

[Pinkerton125]

Thanks for all the replies especially scrofula for the very informative post. I think i will definitely give it a miss now and wait until i'm clean from the venlafaxine. It's not worth the risk of seizures, i had one years ago when i was withdrawing from a daily etizolam habit and i stupidly smashed 100mg codeine which left me fitting in front of my mother in the kitchen. Ended up waking up in the hospital half undressed wondering how i got there.

I think it was a case of me trying to talk myself into it even though i knew it was 90% chance of being a bad move.

Theres no doubt this amphet will be cut with lord knows what.... caffeine at best or BZP or some random RC at worst! if only we could get Adderall or Dexedrine over here.

I also have MDMA crystal i can't take.. will have to stick with modafinil and opiates for now i guess!

I will be sure to check out your 26 volume meth masturbation madness scrofula!

 

[1qaz2wsx]

So, it sounds like you are hypothesizing that Venlafaxine might cause seizures when combined with amphetamine because the structure Venlafaxine is similar to that of Tramadol. Yes it is true they have similar structures, I have noticed that as well. But I really doubt that this implies that Venlafaxine would encourage seizures, even when combined with a powerful stimulant. One reason is that Venlafaxine, like any drug approved by the FDA, has gone through extensive testing, and no such side effect has been documented. Secondly, even minor changes in molecular structure can totally change the receptor binding of a drug. For example morphine can be changed from mu opioid receptor agonist to antagonist by changing the methyl on the nitrogen to an allyl moiety. Or likewise, moving the hydroxyl at the 3 position on morphine to some adjacent position on the benzene ring eliminates its effectiveness. Likewise the hydroxyl on Venlafaxineis para to the cyclohexane decorated group, but for Tramadol is is meta. And of course there are other differences between the two, the placement of the amine and the extra carbon in the connection to the cyclohexane group. These are plenty enough changes that one cannot make any assumptions about the effects of one drug based on the structure of the other. SAR is useful for guessing at effects but must be confirmed by testing.

 

[Jekyl Anhydride]

So if postulating that it causes seizures is a stretch, then would you agree that anecdotes of bad personal experiences with combing the two is enough to discourage their concomitant use?

I was prescribed both effexor and Dexedrine for years with no serious side effects. LOTS of uncomfortable ones though,

 

[Scrofula]

So, it sounds like you are hypothesizing that Venlafaxine might cause seizures when combined with amphetamine because the structure Venlafaxine is similar to that of Tramadol.

No, I didn't hypothesize anything at all. I never said I thought venlafaxine would or could cause seizures, with or without other drugs on board. OP wanted to know if Bluelight thought the combo was a good idea or not, and the wordy answer explains why he wasn't just referred to the many, many SSRI & stims threads here, or the many strict no-go threads, either.

These are plenty enough changes that one cannot make any assumptions about the effects of one drug based on the structure of the other. SAR is useful for guessing at effects but must be confirmed by testing.

But you see, my very point was about not assuming it was safe to combine with stimulants. It's the unknowns that are a reason to avoid the combo, including the unknowns in OP's speed, which has a real possibility of encountering other drugs that look a lot like cathinones.

I haven't predicted anything about venlafaxine's activity, other than it's gonna have other CNS effects we don't know about. Some of these may be indirect in someone who's been using it for two years. Not knowing a full binding profile, or even having one, isn't enough to declare the combo safe for a Friday night of just fucking around with drugs. I kind of have to go with safety as the final word, what with the job title, and all the great power and great responsibility that goes with it.

Spoiler: More pharma and chem stuff for when the jocks have left

Venlafaxine, like any drug approved by the FDA, has gone through extensive testing, and no such side effect has been documented.

I used to work for a corporation much larger than Wyeth, but I'm sure they still manage to outpay and outstaff the FDA. Not that its necessary when they can just point out that after bupropion, the agency's hands are tied on acceptable seizure risk and venlafaxine dosage is below that threshold, so the public has no right to know. You'll have to wait for a class-action suit to even know if those documents exist.

Like I said above, we know tramadol has a risk associated, because it's an opioid agonist, and people like those--intentional overdose is guaranteed. It is with antidepressants, too, but figure the abuse rate for opioids is about 99%. Bupropion had a SEIZURE risk as high as 4% before the fine oversight of the FDA decided that was a bit much. The answer was to lower the max dose below the effective dose, for a drug that never makes it to your brain PO in the first place (it's only a DNRI when IV or intranasal).

Moving the hydroxyl at the 3 position on morphine to some adjacent position on the benzene ring eliminates its effectiveness.

I wouldn't call moving polar hydrogen-bond acceptors minor, but would point out that acetylating both of them gives you heroin. Inhibits receptor binding, but gets the molecule into your brain a bit quicker.

Likewise the hydroxyl on Venlafaxineis para to the cyclohexane decorated group, but for Tramadol is is meta.

Meta- and para- subs don't cause a lot of calamity for catecholamines, though.

And of course there are other differences between the two, the placement of the amine and the extra carbon in the connection to the cyclohexane group.

One thing you'll notice is I lied a bit and, let's say strongly implicated NMDARs in the seizure risk. First glance of the two structures makes me, at least, think of dopamine and norepinephrine, or amphetamines, you can always get an indole out of there for your serotonergic function. Important to think of constraints and freedoms, lipophilicity, groups that resist metabolism.

I been lost for the last ten hours comparing to ketamine and methyl hexedrone. Meanwhile, the cyclohexyl ring should have made me think gabapentin.

What do both the above actually have in common, but a dimethyl propanolamine backone. What does that get you? No idea, but looks a bit like GABA. I do know those tertiary alcohols aren't metabolised, for whatever that's worth.

Now, pretend you aren't seeing various non-seizure prone things when you don't do your own secret SAR again right now.

 

[zephyr]

I gotta be honest here, Ive been on 150mg daily for years and have had drugs of various kinds off and on in that time. Had a few decent little binges a couple grams and im fine.


I wouldnt worry about that combo at all, but everyones different.


I always thought serotonin syndrome was more of a worry with mdma and ssri especially when pinging over a weekend at festivals whatever and redosing with dehydration etc.

I see a lot of hoo haa about it regarding combos that havent had that worry in my and my friends experience.

Im not saying that its a concern but its not shared in my neck of the woods.