Silk Road forums
Discussion => Drug safety => Topic started by: yokes101 on February 13, 2013, 11:56 am
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I was started on SSRI medication not to long ago, I know it's not safe to mix with X and I have really been missing it!
I just wanted to i know is any thing safe to take with SSRIs? 2CB or Moxy maybe?
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Generally, MDMA is safe to user with SSRI's. It's just that nothing will happen. The SSRI will dull the roll and you won't feel it much.
This is true of most serotonergics, since an SSRI will also lead to downregulation. Your best bet are drugs that don't act on serotonin - cannabis, GHB, amphetamine.
I would highly suggest you think of trying to get off the SSRI. They have a huge amount of negative side effects (some permanent) and do not make you happy. They just make you not realize you aren't happy. Most people see this when they get off. Get off them before you are hooked - it can be difficult to stop if you've been on a long time.
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Generally, MDMA is safe to user with SSRI's. It's just that nothing will happen. The SSRI will dull the roll and you won't feel it much.
Really I thought there was a risk of serotonin syndrome? Anyway MD does sound worth it if I wouldn't feel much.
This is true of most serotonergics, since an SSRI will also lead to downregulation. Your best bet are drugs that don't act on serotonin - cannabis, GHB, amphetamine.
Can you give me a longer list of drugs that don't act on serotonin, What i'm really looking for some thing that acts like MDMA. So GHB might do the trick.
What about 2CB, Very interested to know if that will be safe?
I would highly suggest you think of trying to get off the SSRI. They have a huge amount of negative side effects (some permanent) and do not make you happy. They just make you not realize you aren't happy. Most people see this when they get off. Get off them before you are hooked - it can be difficult to stop if you've been on a long time.
Well I haven't been on them long so I want to give them a chance. Anyway I using them more for anxiety then depression.
I'm unfamiliar with there negative side effects, guess I have some googleing to do.
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as far as i know only benzos and opiates can be used with ssri-s.
but ghb should be fine too. (but i know nothing about this combo)
Dont take MDMA . Thats an unsafe combo.
also no 2c-b . i would not risk it.
And no amphetamine. I have found info about bad interactions on the web.
google is your friend. every drug that is used as a medication has documented history with every other drug out there.
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as far as i know only benzos and opiates can be used with ssri-s.
but ghb should be fine too. (but i know nothing about this combo)
Dont take MDMA . Thats an unsafe combo.
also no 2c-b . i would not risk it.
And no amphetamine. I have found info about bad interactions on the web.
google is your friend. every drug that is used as a medication has documented history with every other drug out there.
Dammit I was really hoping 2BC would be safe to use!
I'm a assuming that acid is fine to take. What about 25I/25C-NBOMe can anyone tell me is that serotonergic?
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... google is your friend ...
Google is NOT your friend!
Google by proxy is a safer choice - try Startpage.com, it won't store your IP address or track your movements over the internet.
Regarding SSRI's, I was prescribed 50mg Sertraline a day for 3 months to try to combat depression. It did absolutely fuck-all. If anything, I felt worse. So i ditched the quick-fix doctor, weaned myself of that shit and actually feel better now than when i was on it.
... They just make you not realize you aren't happy ...
^^^ This.
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Well I haven't been on them long so I want to give them a chance. Anyway I using them more for anxiety then depression.
I'm unfamiliar with there negative side effects, guess I have some googleing to do.
Once sexual dysfunction sets in you'll be convinced that there are side effects.
This could be worth in in case of severe depression, but taking srri's for anxiety will probably turn out to be a fairly fruitless ordeal.
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as far as i know only benzos and opiates can be used with ssri-s.
but ghb should be fine too. (but i know nothing about this combo)
Dont take MDMA . Thats an unsafe combo.
also no 2c-b . i would not risk it.
And no amphetamine. I have found info about bad interactions on the web.
google is your friend. every drug that is used as a medication has documented history with every other drug out there.
Dammit I was really hoping 2BC would be safe to use!
I'm a assuming that acid is fine to take. What about 25I/25C-NBOMe can anyone tell me is that serotonergic?
I have taken some pretty massive doses of NBOMe (b, c, d, and i) while on an SSRI. Only two minor side effects I've experienced.
Body temperature does rise, especially with larger doses, but I think that is normal for anyone.
I also noticed when taking large doses (like 20mg in 24 hours) that I would get minor pains in my inner thighs, making it slightly painful to walk. Anyone else experienced this?
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Anyone saying MDMA and SSRIs are unsafe together is either not educated about the subject or is over-the-top paranoid about anything that could go wrong. To the point they shouldn't be crossing the street. Sorry.
MDMA and SSRIs are definitely safe, as the mechanism by which they work is competitive. In fact, you could say it's even safer, as it's harder to OD on MDMA...but I digress
Nothing will mimic the effects of MDMA while you are on an SSRI. The SSRI inhibits the mechanism by which it works, and no other mechanism mimics it. None. GHB isn't even close (it's about as similar to MDMA as LSD is). If you want to feel like you are rolling, get off the SSRIs and wait a few weeks before rolling.
Psychedelics are safe to take with SSRIs as well, but again, you will get diminished results. It can be difficult / impossible to trip for you, depending on your SSRI dose. Psychedelics include LSD, 25i, 2cb, DMT, MDA, etc. You can find out if a drug is serotonergic with a quick google search, but here are a few that come to mind: alcohol, weed, GHB, opiates, benzos, ketamine, amphetamine.
As Ben mentioned, SSRIs can have the side effect of sexual dysfunction. Which is usually when people go "oh shit, I should get off this", and then they do. And guess what? For some people, it's permanent. Yep, they just screwed themselves over for years / the rest of their life, for something that is pretty common and their doctors didn't even warn them about. Sorry, I hate SSRIs more than meth, so I can get a bit carried away...
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I hate SSRI's the psychiatry field needs to stop pushing them so hard.
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Wow clearly I need to do a lot more research into SSRIs!
In fact I noticed some sexual issues lately, That in it's self is making me reconsider taking the medication.
Ok well if SSRIs are not the way to go can anyone recommend treatment for anxiety and depression that works?
I was doing some reading about kratom, Sounds like it could be beneficial but reviews seem to be mixed. Does anyone have first had experience with this stuff?
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Seriously man the best advice I can give you is too get of the SSRI's.. they do way more harm than good. My ex-gf was on them for a while and it made her a lot worse, when she came off them she eventually released she was a lot better without them (even though she craved them for a few weeks after she come off). Basically SSRI's aren't your friend.
To help combat the depression/anxiety the best thing I can recommend is working out. Lift some weights for a hour or so 5 days a week and go on a mile run every few days and you'll feel overall a lot better within a few weeks if you keep it up. I know it sounds silly but it seriously does work in giving you a better overall sense of well doing. Much better than any pills! Also have lots of sex, it helps.
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Anyone saying MDMA and SSRIs are unsafe together is either not educated about the subject or is over-the-top paranoid about anything that could go wrong. To the point they shouldn't be crossing the street. Sorry.
MDMA and SSRIs are definitely safe, as the mechanism by which they work is competitive. In fact, you could say it's even safer, as it's harder to OD on MDMA...but I digress
Psychedelics are safe to take with SSRIs as well, but again, you will get diminished results. It can be difficult / impossible to trip for you, depending on your SSRI dose. Psychedelics include LSD, 25i, 2cb, DMT, MDA, etc. You can find out if a drug is serotonergic with a quick google search, but here are a few that come to mind: alcohol, weed, GHB, opiates, benzos, ketamine, amphetamine.
Look . You can have a positive experience with ssri and mdma combo but its not worth the risk. Both drugs work by inhibiting serotonin reuptake. That means you will have a shit load serotonin between your neurons because it cant be reabsorbed. This can lead to serotonin poisoning called serotonin syndrome.
according to wikipedia these are the documented chemicals that can cause you serotonin syndrome :
Antidepressants : Monoamine oxidase inhibitors (MAOIs), TCAs, SSRIs, SNRIs, bupropion, nefazodone, trazodone, mirtazapine
Opioids : tramadol, pethidine, fentanyl, pentazocine, buprenorphine, oxycodone, hydrocodone
CNS stimulants : MDMA, MDA, phentermine, diethylpropion, amphetamine, sibutramine, methylphenidate, methamphetamine, cocaine, dextromethorphan
5-HT1 agonists : triptans
Psychedelics : 5-Methoxy-diisopropyltryptamine, LSD
Herbs :St John's Wort, Syrian rue, Panax ginseng, Nutmeg, Yohimbe
Others : tryptophan, L-Dopa, valproate, buspirone, lithium, linezolid, dextromethorphan, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir
most of the Tryptamines and Phenethylamines are not on the list but that does not mean they are safe.
they are not up here because there were no medical reasons to test these chemicals.
also keep in mind that dosage increase increases risks and it is possible that on low doses you can have good experiences even with very dangerous combinations.
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Look . You can have a positive experience with ssri and mdma combo but its not worth the risk. Both drugs work by inhibiting serotonin reuptake. That means you will have a shit load serotonin between your neurons because it cant be reabsorbed. This can lead to serotonin poisoning called serotonin syndrome.
I understand you are trying to help, but it helps to have a real understanding of how the brain works in this scenario. MDMA doesn't make you roll by simply inhibiting serotonin reuptake. Otherwise, SSRI's would make you roll. MDMA actually takes the reuptake inhibitors and reverses them, spitting out 5ht from the pre-synaptic neuron into the synapse. It also causes the release of 5ht from vesicles into the cytoplasm, so there is 5ht to spit out into the synapse.
Adding an SSRI into the mix doesn't make it more intense. Why? Because all the reuptake pumps are already bound to MDMA (well, depending on your dose, of course...). What does this mean? The SSRI will haev to compete with MDMA to bind to the pumps. And when the SSRI is successful (I believe some SSRIs actually have a higher affinity for it than does MDMA), the MDMA ceases to function is a reuptake reverser. Which is why people on SSRI's can't roll; the SSRI inhibits MDMAs mechanism of action.
TL;DR: SSRIs + MDMA do not make you "poisoned" by serotonin syndrome, they actually do the opposite. Some people use it as an "antidote".
according to wikipedia these are the documented chemicals that can cause you serotonin syndrome :
Yea, and so can cheese and turkey. Should we all stop eating cheese and turkey together because it could cause serotonin syndrome? ::)
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Seriously man the best advice I can give you is too get of the SSRI's.. they do way more harm than good. My ex-gf was on them for a while and it made her a lot worse, when she came off them she eventually released she was a lot better without them (even though she craved them for a few weeks after she come off). Basically SSRI's aren't your friend.
To help combat the depression/anxiety the best thing I can recommend is working out. Lift some weights for a hour or so 5 days a week and go on a mile run every few days and you'll feel overall a lot better within a few weeks if you keep it up. I know it sounds silly but it seriously does work in giving you a better overall sense of well doing. Much better than any pills! Also have lots of sex, it helps.
Please stop generalizing your own experiences; what worked best for you is not what will work best for everyone.
That said, the exercise advice is spot on. There are tons of studies that suggest frequent (3-4 times a week) exercise for at least 20 minutes per session is either as good an anti-depressant as the standard meds, or better. Nothing is stopping you from taking advantage of both. Life is short, and you won't get the time you lose back -- try to enjoy every second :)
MDMA and SSRIs can, in some cases, lead to Serotonin Syndrome. That is to the best of my knowledge. I am not a doctor, but I'm not uneducated in these matters either. It's very rare, but if you're on SSRIs, what I've read says you DO Have an increased chance of this happening if you combine your meds with MDMA. I've done it and been fine. I also take insane amounts of methamphetamine and amphetamine and I've also always been fine. I tend to push things further than I should though: if you want to be 100% safe, you cannot roll while on SSRIs. But if you want to be 100% safe, you can't really do more than one drug every 2 weeks either, soooo... dunno. I personally would totally ignore the miniscule risk and do it anyway (infact I did and do), but again, I tend to push too far when it comes to my health.
BTW, I rolled just fine off a 2C-B + MDMA roll from BruceCampbell. Infact I was so fucked up I wasn't even sure how long I had been fucked up throughout the experience. Kept thinking "didn't I just take that...? Wait, what time was it again? ... and what time is it now exactly?" I mean I was totally unable to function. Fucking gone. But I hadn't rolled for about 8 years, so... shrug. That probably helped.
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Look . You can have a positive experience with ssri and mdma combo but its not worth the risk. Both drugs work by inhibiting serotonin reuptake. That means you will have a shit load serotonin between your neurons because it cant be reabsorbed. This can lead to serotonin poisoning called serotonin syndrome.
I understand you are trying to help, but it helps to have a real understanding of how the brain works in this scenario. MDMA doesn't make you roll by simply inhibiting serotonin reuptake. Otherwise, SSRI's would make you roll. MDMA actually takes the reuptake inhibitors and reverses them, spitting out 5ht from the pre-synaptic neuron into the synapse. It also causes the release of 5ht from vesicles into the cytoplasm, so there is 5ht to spit out into the synapse.
Adding an SSRI into the mix doesn't make it more intense. Why? Because all the reuptake pumps are already bound to MDMA (well, depending on your dose, of course...). What does this mean? The SSRI will haev to compete with MDMA to bind to the pumps. And when the SSRI is successful (I believe some SSRIs actually have a higher affinity for it than does MDMA), the MDMA ceases to function is a reuptake reverser. Which is why people on SSRI's can't roll; the SSRI inhibits MDMAs mechanism of action.
You're leaving out the part about there being a dozen different kinds of serotonin each with its own affinity for dozens of different areas of the brain, not to mention the hundreds or thousands of neurotransmitter cascades that only PhD researchers know about -- and even then, you're leaving out the ones we still haven't discovered yet. We don't understand the brain. We have a child's inkling of how we work, but little more.
To boil it down *that* far is as misleading as it is informative. Granted, you do have the facts more or less correct... just... inaccurate.
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MDMA and SSRIs are definitely safe, as the mechanism by which they work is competitive. In fact, you could say it's even safer, as it's harder to OD on MDMA...but I digress
Nothing will mimic the effects of MDMA while you are on an SSRI. The SSRI inhibits the mechanism by which it works, and no other mechanism mimics it. None. GHB isn't even close (it's about as similar to MDMA as LSD is). If you want to feel like you are rolling, get off the SSRIs and wait a few weeks before rolling.
FWIW, I heard from what I consider to be a reliable source that doubling the MDMA dose will allow someone on SSRIs to roll. I'm not suggesting anyone try this, and I'm sure there would be increased side effects. I won't name the source, but I will say he's heavily involved in MDMA research and many, but not most, people would recognize his name. I didn't speak with him personally -- I saw it in a video, which I can't seem to find at the moment.
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^OK, edited briefly after a nap.
Without getting into nitty-gritty, doubling/+upping the dose of MDMA
- may "override" the SSRI effects in some cases (I am not so sure about that - not consistent with my personal experience, but have not seen objective data - I'd be interested in the video if you find it, gambino, or the name) but
- DOES NOT reduce the toxicity from that doubled+ dose (not arguable. You know what's helpful in MDMA poisoning? Coreg. Awesome shit, that Coreg is. Coreg, lorazepam, and fluids. Put it in your wallet if you decide to use. You can leave a note -- "Some Random Internet Person Who Might Read About Or Might Know Or Have Dated a Person In or Be in Toxicology or I Don't Know What, It's Complicated, Anyway, That Chick Said Coreg Kicks Ass For MDMA Poisoning / Hyperthermia. I'd Give You Her Number But I Don't Know It. So, Uh, First You Download TBB…" Probably too much to write on a card in your wallet, never mind.)
Also, since MDMA clears through CYP2D6/inhibits 2D6 (one of those autoinhibiting drugs that play push-pull with themselves as the dose escalates, because that makes this all easier!) ....one would want to be careful with other major inhibitors of 2D6 - which include bupropion (Wellbutrin), fluoxetine (Prozac), and paroxetine (Paxil.) Major inhibitor here will be defined as >80% DEcrease in clearance. Moderate inhibitors include duloxetine and sertraline.
I will tell you that *bupropion* (a DNRI) plus MDMA can be a very bad idea. Been there, done that, had the seizure from ++++MDMA level and hyponatremia (and Spicy V8/ice is my drink of choice on MDMA, being overcautious - I am not overconsuming hypotonic fluids. Still had a serum sodium value of "oh shit.")
Anyway - upping the MDMA to override the SSRI sets up some bad interaction scenarios and unless we're talking about a very low dose of a non-2D6 SSRI, it's not on my list of things I'd say, "Sure, try it, why not?" Hold the SSRI and let it washout. 5 half-lives is the rough wash-out time if nothing else is involved to slow clearance. (This is burdensome with fluoxetine, obviously.)
AARRRGGHH serotonin syndrome.
Yes indeedy, it does come up with MDMA.
From my anecdata banks, I can tell you that combining Wellbutrin and MDMA is indeed a Bad Idea (™) (not just for me, but for other people) and that MDMA and tramadol is also not a great mix…
Please read up on the topic; you may end up knowing more than a typical hospitalist.
hxxp://www.psychotropical.com/index.php/serotonin-toxicity <<clearnet link. too much to c/p here.
Gillman's a little snarly but he is good at his job.
This article is also long, but discusses some of the MDMA/rx issues.
hxxp://jat.oxfordjournals.org/content/35/4/219.full.pdf
If you go to the *hint* bookmarkworthy Flockhart page on CYP450 interactions
hxxp://medicine.iupui.edu/clinpharm/ddis/table.aspx <<clearnet
it lists the substrates, inhibitors.
for more in depth information that includes UGT and transporters,
hxxp://www.pharmacologyweekly.com/content/pages/online-drug-therapy-tables <<clearnet
is a useful quick reference
and for a good basic overview of the ideas, the article on Opioid Metabolism below is outstanding.
hxxp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/ <<clearnet
Here's a very abbreviated psych version, not limited to SSRIs. I apologize, I bet someone on Bluelight has already done this and far better. I just used Flockhart and a quick-n-dirty search or three to whip this up, I did not exhaust the topic. Look through this and then consider the implications of various inhibiting/clearing factors - there are a lot more than just CYP450 clearance. Maybe it's a question of "which SSRI is the least risky if its levels are dramatically increased," or "which SSRI washes out fast enough that I can hold it for a few days before the festival, but doesn't make me feel awful while it clears" (I'm looking at you, Paxil), or maybe even "which SSRI works best with my usual drugs of choice," I don't know.
It would be really simplistic to go with "this INCREASES the level and this DECREASES the level" as the only decision point, but it is maybe a good place to start.
(But it's complicated. Increasing clearance may result in increased levels of active metabolite and then more complications.)
From Flockhart --
Strong inhibitor is one that causes a > 5-fold increase in the plasma AUC values or more than 80% decrease in clearance.
Moderate inhibitor is one that causes a > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance.
Weak inhibitor is one that causes a > 1.25-fold but < 2-fold increase in the plasma AUC values or 20-50% decrease in clearance.
All other inhibitors.
AUC = area under the curve - if you are not familiar, TheBody has a nice explanation - hxxp://www.thebody.com/content/art875.html <clearsite
1A2 Substrates
antidepressants/anxiolytics: amitriptyline, clomipramine, fluvoxamine, imipramine NDeME
antipsychotics: haloperidol, olanzapine
skeletal muscle relaxants: cyclobenzaprine, tizanidine
relevant other drugs that might come up: caffeine, zolpidem, estradiol (hey, it's a psych drug. same as testosterone. trust me. also, oral contraceptives are of interest to many of us.), propranolol, tacrine, chlordiazepoxide, MDPV (in vitro), MDMA
1A2 Inhibitors
Strong (>80% reduction in clearance)
fluvoxamine, ciprofloxacin
Moderate (50 - 80% reduction in clearance)
cimetidine (OTC - Tagamet)
Other: citalopram, interferon (if you're on interferon, someone should be willing/able to talk with you about interactions), cannabis
1A2 Inducers
environmental stuff: broccoli, charred meats, smoke (of any kind, tobacco, cannabis, wood; 10 cigarettes or about 6 handrolls/d seems to be threshold, or heavy environmental smoke exposure - BBQ operator on up to smokejumper; as a clue, olanzapine dose has to be doubled with 1 pack per day cigarettes)
stimulants/eugeroics: modafinil
relevant other drugs that might come up: insulin, omeprazole, tobacco (apparently broken out from smoke itself by Flockhart) - in other words, nicotine replacement therapy such as Nicotrol/Nicorette will not induce 1A2, but chewing tobacco might
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2B6 Substrates
antidepressants: bupropion, sertraline
opioids: methadone
relevant other drugs that might come up: ketamine, MDMA
2B6 Inhibitors
no psychotropics or common intoxicants per flockhart; some literature suggests cannabis is an inhibitor at least in vitro
2B6 Inducers
antiepileptics: phenobarb, phenytoin
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2C8 Substrates / Inhibitors / Inducers
no psychotropics per flockhart
Substrate - zopiclone
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2C9 Substrates
antidepressants/anxiolytics: amitriptyline, fluoxetine, sertraline (also an inhibitor)
NSAIDs: diclofenac, ibuprofen, celecoxib, see flockhart for other NSAID
relevant other drugs that might come up: ketamine, s-warfarin, dronabinol / THC, sildenafil, phenytoin
2C9 Inhibitors
Major (as above): fluconazole
Moderate (as above): amiodarone (if you are on amiodarone, you have a pharmacist involved in your life now. Ask him or her about all these interactions, including anything ingested/unprescribed.)
Weak:
antidepressants/anxiolytics: fluvoxamine, sertraline
antitubercular and stealth MAOI: isoniazid
stimulants/eugeroics: modafinil
other drugs that may come up: CBD (partial; maybe more so with oral ingestion)
2C9 Inducers:
secobarbital
THC
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2C19 substrates
antidepressants/anxiolytics: amitriptyline, clomipramine, citalopram (also weak inhibitor), escitalopram, sertraline
benzodiazepines: diazepam→Nor
antiepileptics: phenytoin(O)
PPIs: lansoprazole, omeprazole, pantoprazole, rabeprazole(these are all also weak inhibitor)
muscle relaxant/sedative: carisoprodol
relevant other drugs that might come up: propranolol, r-warfarin, progesterone, MDPV (in vitro), THC, cannabidiol (in vitro)
2C19 Inhibitors:
No strong/mod inhibitors - but citalopram should be dosed low if these are added due to cardiac risks, and amitrip/clomip levels must be checked.
antidepressants/anxiolytics: fluoxetine, fluvoxamine, citalopram
stimulants/eugeroics: modafinil
antiepileptics: oxcarbazepine, topiramate (dose dependent)
2C19 Inducers
antiepileptics: carbamazepine, NOT pentobarbital
relevant other drugs that might come up: norethindrone, prednisone
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2D6 Substrates
antidepressants/anxiolytics: amitriptyline, nortriptyline, clomipramine (also an inhibitor), desipramine, imipramine, fluoxetine (also a strong inhibitor), paroxetine (also a strong inhibitor), fluvoxamine, venlafaxine, duloxetine (also a moderate inhibitor), mirtazapine, trazodone
antipsychotics: haloperidol (reduced, it becomes an inhibitor), perphenazine (also an inhibitor), risperidone→9-OH, thioridazine, aripiprazole, chlorpromazine
stimulants/eugeroics and attention: amphetamine, atomoxetine, methoxyamphetamine, methamphetamine, MDMA
opioids: morphine, codeine (→O-desMe), oxycodone, tramadol, dextromethorphan (could go under a lot of categories, let's put with the opioids), hydrocodone, fentanyl, meperidine, methadone (also inhibitor during startup)
relevant other drugs that might come up: clonidine, donepezil, metoclopramide, propranolol, fenfluramine, mCPP, TFMPP, MDPV (in vitro), DOx and TMA
2D6 Inhibitors
Strong: bupropion, fluoxetine, paroxetine
Moderate: duloxetine, sertraline
Mild: cimetidine
Others
antidepressants/anxiolytics: citalopram, clomipramine, doxepin, escitalopram
antipsychotics: chlorpromazine, perphenazine, reduced-haloperidol
opioids: methadone (during startup)
relevant other drugs that might come up: cocaine, chlorpheniramine (often in combo products with dxm), diphenhydramine (often in combo products with dxm), MDMA, DOx and TMA, cannabidiol
2D6 Inducers
dexamethasone
ethanol
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2E1 substrates
ethanol
2E1 inhibitors
disulfiram
2E1 inducers
ethanol
isoniazid
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3A457 Substrates
antidepressants/anxiolytics: trazodone, buspirone, citalopram, sertraline (also inhibitor), mirtazapine
benzodiazepines: alprazolam, midazolam, triazolam, diazepam, clonazepam, temazepam
nonbenzo sedhyps: zaleplon, zolpidem, eszopiclone
opioids: codeine-N-demethylation, dextromethorphan, alfentanil, fentanyl, methadone (3A4 is the primary enzyme), hydrocodone, buprenorphine, oxycodone, tramadol, morphine-N-demethylation (UGT is main path though)
antipsychotics: aripiprazole, haloperidol, pimozide, quetiapine, risperidone, ziprasidone
relevant other drugs that might come up: ketamine, cocaine, MDMA estradiol, testosterone, cafergot, caffeine→TMU, propranolol, sildenafil, tadalafil, "cannabinoids" (this is too big a topic for this post, includes THC and dronabinol, cannabidiol in vitro), ergotamine, modafinil (also an inducer), sibutramine, warfarin (r)
3A457 inhibitors
Strong:
clarithromycin (NOT azithromycin); nefazodone
Moderate:
antibiotic/antifungal: erythromycin, fluconazole
grapefruit juice*
antihypertensives: verapamil, diltiazem
Mild:
cimetidine
Other:
antidepressants/anxiolytics: fluvoxamine, norfluoxetine (active metabolite of fluoxetine), sertraline
environmental: starfruit
relevant other drugs that might come up: cannabidiol, estradiol, ciprofloxacin
CYP 3A457 Inducers:
anitepileptics: phenobarbital and barbiturates, carbamazepine, oxcarbazepine, phenytoin
stimulants/eugeroics: modafinil
relevant other drugs that might come up: glucocorticoids, St. John's wort, methadone (induces during startup)
environmental: cafestol (found in unfiltered coffee)
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ok. that gets most of the basics. :)
*grapefruit juice - important point. "Grapefruit juice is unique among CYP3A inhibitors because, when consumed in usual dietary volumes, only enteric CYP3A is affected. Therefore, **GFJ has no impact on the pharmacokinetics of CYP3A substrate drugs administered intravenously, and does not prolong the plasma half-life of orally administered agents.** Ingestion of GFJ causes an irreversible loss of enteric CYP3A protein, without a decrease in CYP3A mRNA. Clinically, implies that prior exposure to GFJ is sufficient to cause an interaction – i.e., **GFJ does not have to be physically present in the gastrointestinal tract for an interaction to occur. Recovery of CYP3A activity requires de novo enzyme synthesis, and the half-life for this process is approximately 23 hours.**" emphases mine. (see PMID 3071161)
I've undoubtedly missed many relevant things. Let me know, I'll put 'em in. I have another source of info on other drugs that I'll add in today.
I kind of over think these things and I guess I didn't really answer the OP's question, so -
- would avoid Prozac due to the length to clear and the build-up if you further inhibit clearance
- would avoid Celexa over 20 mg/d because there are too many things that inhibit it, and it is now blackboxed at 60 mg due to cardiac/electrophys risk at higher doses - the articles above cite it as lower risk but pre-date that blackbox
- would keep SSRI/SNRI dosing conservative; perhaps a lower dose level-based cyclic antidepressant (like nortrip) would get you what you want clinically and then you could - monitor serum levels. CAs are not for everyone, though. Also, high levels of CAs can fuck you up or, you know, kill you, so knowing the interactions is important. Personally, I've had fairly good luck with lower dose lamotrigine. But that's a little bit esoteric and weird and won't do much for anxiety.
- would look up half-lives and consider the idea of short-term washouts. If that leaves you suicidal or nonfunctional, then, uh, don't do that.
- personally, I would not recommend MDMA + SSRI/SNRI and just bumping up the MDMA - I'm open to other information
- I think I would avoid all of the substituted cathinones with S/NRIs, due to interactions being fairly unknown, kinetics being defined only to a limited extent, and a pretty high serotonin toxicity risk with some of them. But I'm a chicken.
- I am of a strong personal belief that tramadol plus an SSRI is not a good idea (also tramadol plus bupropion, for the record, is not a good idea.) Make your own decisions, but I wouldn't combine them.
- there's a credible case report of serotonin toxicity with 5-MeO-DMT + MAOI, another case report of rhabdo and possible serotonin toxicity with 5-MeO-DIPT. Would probably be careful with these. (Not judging... OK, judging... but taking novel drugs with MAOIs seems particularly ill-advised.)
- without getting into psychic effects of the drugs, ketamine, GHB, cannabis should all be tolerated and not bad interactors on first glance. LSD is fine as far as interactions, but you won't get far; SSRIs are great at blocking its effect. Opioids are usually tolerated but check interactions, levels can end up much, much higher than one expects (not always for the reason you'd expect - can block conversion to the active form, leading to higher dosing, etc). Note the amphetamines and the inhibitors in 2D6, I've seen some people be unpleasantly surprised when they added a potent 2D6 inhibitor to their methamphetamine/amphetamine, if there was no counseling to reduce the stim dose first. The issue of dampening euphoric effect from stimulant... that's another discussion.
much love,
thyme
edited again for another article.
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LOL... you're awfully cute, Thyme.
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great posts. i learned a lot !
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my advice? - get off SSRIs and pick up MAOIs, selegiline + moclobemide is the strongest/most effective anti-despressent combo with no noticeable downsides other then dietary restrictions.
MAOIs will actually increase your trip potential (doubling dose/duration - 4x for type b maois (selegiline) with phenylethamines (2c-b))
as for your question:
GHB, benzos, Cocaine, amphetamines, weed, mdpv, barbiturates should all be unaffected by ssris.
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Ketamine as well. Works fine on them.
Tried smoking 20 mg of DMT and felt nothing! I know it's a small dose, but that bummed me out, and didn't want to waste any more seeing if an increased dose would get me somewhere.
Honestly don't listen to any of these random people saying to just get off the ssris. SSRIs are for your health, drugs are for fun. Maintain priorities, above all else.
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I was started on SSRI medication not to long ago, I know it's not safe to mix with X and I have really been missing it!
I just wanted to i know is any thing safe to take with SSRIs? 2CB or Moxy maybe?
To the person posting staying mdma is safe to use on SSRI's you need an upper cut mate.
Do not take mdma whist on SSRI's I have seen enough people fuck the chemical balance of their brain, if you are taking medication for mood instability you should be leaving anything alone that interacts with your serotonin receptors.
Safe answer would be leave all other drugs alone, fix the issue that got you onto SSRI's in the first place then have a good break (at least 6 months) before even considering taking something else, if at all ever.
You tip the balance too much one way and if you are predisposed you may not come back.
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I have a question for Thyme or anyone else that can shed light,
I have a question about the active metabolite in Sertraline, N-desmethylsertraline. The plasma half life is listed at 62-104 hours depending on metabolism. It's mentioned on the following site in which it is claimed as "barely active as far as being a reuptake inhibitor..." but "may inhibit CYP2D6, which isn’t a big deal if you don’t take any other drug." What impact will this have on MDMA?
Thanks
(clearnet) http://www.crazymeds.us/pmwiki/pmwiki.php/Meds/ZoloftPharmacokinetics#toc8
§1.1 Plasma Half-Life
sertraline hydrochloride has a plasma half-life of:Zoloft itself: 26 hours, give or take an hour. N-desmethylsertraline: 62–104 hours.
§1.2 Estimated Time Zoloft is Cleared/Eliminated from your System
5–6 days.
§2. How Zoloft (sertraline hydrochloride) is Metabolized, and What the Effects and Results of the Metabolism are
This is what pharmacokinetics is all about. How a drug is metabolized in order to be eliminated / cleared from your body. If and how it is transformed into something else and what that is4. How it affects the metabolism of other meds5. To what extent everything is involved. E.g. by the time your liver and kidneys are through with it, 97% of Paxil (paroxetine HCl) has been converted to inactive stuff that gets flushed down the toilet, whereas 70% of the Topamax (topiramate) you take is unchanged in your urine. See the section on CYP450 and UGT enzymes on the Pharmacokinetics page for more details.
§2.1 Elimination Method
Zoloft gives new meaning to the term “extensively metabolized.” While CYP2C19 and, to a lesser extent, CYP3A4 are responsible for metabolizing Zoloft into what you piss away, you only piss away about 60% of it. Zoloft is metabolized into another metabolite for elimination via the UGT system, by primarily by UGT2B7 with some help from 1A3, 1A6, 2B4.
§2.2 Transformation Method
The quasi-active metabolite n-desmethylsertraline may not do much of anything, but your liver is certainly aware of it. In Sertraline Is Metabolized By Multiple Cytochrome P450 Enzymes, Monoamine Oxidases, And Glucuronyl Transferases In Human: An In Vitro Study the authors report CYP2C19, 2D6, 2C9, 2B6, and 3A4 are required to transform sertraline into desmethylsertraline (more-or-less agreeing with the results of this earlier study). After which CYP2C19, 3A4, 1A1, and 2E1 break it down so you can pee it out.
§2.3 Active Metabolites
None really. N-desmethylsertraline is barely active as far as being a reuptake inhibitor or anything like that. It may have an indirect impact on how Zoloft works including Zoloft’s effects on people with coronary problems. The researchers really like using it when testing both Zoloft’s PK data and the PK data of other meds.
N-desmethylsertraline may inhibit CYP2D6, which isn’t a big deal if you don’t take any other drug. Otherwise, that could complicate things.
§2.4 CYP450 or UGT Enzymes (sertraline hydrochloride) Inhibits/Induces/Suppresses
The data are contradictory regarding whether or not Zoloft / desmethylsertraline are inhibitors of 2C9, 2D6, and/or 3A4; and to what extent they may inhibit those enzymes.
We try to list the above CYP/UGT/etc. in descending order of importance/extent of whatever the first one that does the most of the work to the one that does the least. That’s how it is on most PI sheets these days.
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Wow clearly I need to do a lot more research into SSRIs!
In fact I noticed some sexual issues lately, That in it's self is making me reconsider taking the medication.
Ok well if SSRIs are not the way to go can anyone recommend treatment for anxiety and depression that works?
I was doing some reading about kratom, Sounds like it could be beneficial but reviews seem to be mixed. Does anyone have first had experience with this stuff?
I got a script for that stuff, bad bad reaction to one dose, through the box out there and then and ripped up the script.
I'm on mirtazapine its a NaSSA still and antidepressant but it makes you sleepy instead of getting insomnia, Although i was prescribed it for insomnia/anxiety not actual depression. I still don't recommended any antidepressant but this seems to work quite well with anxiety and sleep.
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Wow clearly I need to do a lot more research into SSRIs!
In fact I noticed some sexual issues lately, That in it's self is making me reconsider taking the medication.
Ok well if SSRIs are not the way to go can anyone recommend treatment for anxiety and depression that works?
I was doing some reading about kratom, Sounds like it could be beneficial but reviews seem to be mixed. Does anyone have first had experience with this stuff?
kratom is great! i've used it mostly for my chronic pain and it works wonders. it is definitely effective in treating depression and anxiety as well.
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I have a question about the active metabolite in Sertraline, N-desmethylsertraline. The plasma half life is listed at 62-104 hours depending on metabolism. It's mentioned on the following site in which it is claimed as "barely active as far as being a reuptake inhibitor..." but "may inhibit CYP2D6, which isn’t a big deal if you don’t take any other drug." What impact will this have on MDMA?
"Which isn't a big deal if you don't take any other drug." :D
Crazymeds.us is excellent, I love those guys. I should go look and see if Jared is taking BTC...
The short answer is: "Some impact - you're going to block some (not much at all) effect due to the metabolite, and change the AUC a minimal amount. But sertraline itself will still block MDMA psychological effect."
I'm going to Be That Guy and copypaste something, but Preskorn did this so much better than I could...
Preskorn's helpful (cleartext) site -
h t t p://www.preskorn.com/books/ssri_s6.html
Desmethylsertraline is 1/10th to 1/25th as potent as sertraline at inhibiting the serotonin uptake pump (Table 3.8). Since its concentrations are only 1.5 times higher than the parent drug under clinically relevant dosing conditions,219 it would be predicted to contribute only 6% to 15% (ie, 1.5 times higher levels times 1/10th to 1/25th the potency) to the serotonin uptake inhibitory effects that would occur in patients on sertraline under clinically relevant dosing conditions. The magnitude of this contribution is probably too small to be clinically meaningful in most situations. However, desmethylsertaline like the major metabolites of fluoxetine and paroxetine is virtually equipotent to the parent SSRI as an inhibitor of specific CYP enzymes (Table 8.7). Hence, it would be expected to contribute to the magnitude of such an effect. Since its half-life (62 to 104 hours) is longer than that of the parent drug, it would also be expected to prolong the duration of the effect, but not to the extent that norfluoxetine does.288 The clinical impact of this fact is mitigated by the relatively weak inhibitory effect of sertraline and desmethylsertraline on specific CYP enzymes.
Look through the chapter on clin pharm for the tables, which include information on sertraline and metabolite effect on 2D6 function - it's very, very helpful (I think), for sertraline and a lot of other questions. For anything related to SSRIs, I'd put Preskorn's SSRI material on the self-study list.
h tt p://www.preskorn.com/books/ssri_s8.html (cleartext, again)
To put these results in perspective, fluoxetine and paroxetine appear to produce approximately 85% inhibition of CYP 2D6 activity versus 15% inhibition or less with citalopram, fluvoxamine or sertraline.
There's still a risk for serotonin toxicity with MDMA + sertraline or es/citalopram, but it's mainly an issue of wasting perfectly good MDMA (maybe wasting perfectly good sertraline/es/citalopram, too. Also, MDMA could increase citalopram levels, as I look at this, for a few days post-ingestion, so that could be a potential problem if someone were taking a high dose of citalopram or taking an additional QTc prolonging drug.) Personally, I would not combine MDMA and fluoxetine, would not combine MDMA and paroxetine, would not combine tramadol and MDMA, and would allow for a washout of SSRI (5 half-lives) before MDMA and be aware of impaired clearance for 2-4d afterwards...
But then I don't consider tramadol to be safe with SSRI antidepressants (paroxetine, WTFF, with Wellbutrin, yet), having seen that go awry too many times... and yet they're coprescribed all the time.
So, yes, I'm a huge pussychicken, there's that to consider.
hth. I've no doubt contradicted myself from some earlier post. :-)
And Preskorn, really, is worth a read. Even the older pieces are still relevant.
[edited, connection problems interrupted the process]
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Thank for that info and link Thyme.
Considering N-desmethylsertraline continues to act as an equipotent 2D6 inhibitor, one would also wait 4-6 weeks (5 half-lifes) for the active metabolite of Sertraline to wash-out as there will also be a sharp increase in plasma levels that are dose dependent of any other substance consumed which is metabolized by the CYP2D6 pathway.
So even if one could "roll" off MDMA after approx a week, and the marked depletion of serotonin still allowed you to do so, MDMA levels would be much higher. It is claimed that MDMA itself is not neurotoxic but it's metabolites that cause the neurotoxicty.
People lacking the enzyme who have taken MDMA indicate it is metabolized by additional pathways, but the risk is still unknown whether the higher levels are dangerous.