Opiate Cocktail Reduces Tolerance ?

[lukilu]

Could somebody who can understand Clinical Trials read This Article Maybe Vaxn8 or Whoever and see if you can make sense of it or if you have heard anything about it, give me their insight on it ?


Current Biology
An Opiate Cocktail That Reduces Morphine Tolerance and Dependance
By Li He and Jennifer Whistler
WWW.Sciencedirect.com/science (http://www.Sciencedirect.com/science)
..................Lukilu

[Powdered Love]

I think that link you posted is bad??

[lukilu]

Sorry but I am not great with Links . You will need to type in the Article or the authors to bring it up at that site I beleive or if somebody could help me out and find the article somehow and type in direct link I would appreciate it ! I know , Lame but Ya Know Its me :( . Thanks ........Lukilu

[vaxn8]

Luk- I can pull it up from the info you gave if the link doesn't work for me.

V

[lukilu]

www.medicalnewstoday.com/medicalnews.php?newsid=25760 (http://www.medicalnewstoday.com/medicalnews.php?newsid=25760) this may work

[vaxn8]

The short version (from the abstract) is saying that you can prevent morphine dependence by giving methadone along with morphine. They are saying this works because when methoadone binds to opiate receptors, it causes them to be carried into a cell and eaten up. When this happens, NMDA receptors can't be upregulated (just means more of them aren't made) which is normally a response that causes morphine dependence.

Looks really interesting, i'll tell you more after i finish reading it. I thought it was funny that they are at the Ernest Gallo clinic, isnt that the wine guy?

[lukilu]

I have the full version, if you found that great, if not I can email it to you but the address is humongous ! Did you find the full report ? Thanks yea Ernestly:D

[vaxn8]

I was able to pull up the full version, just had to log in to work.

OK, they already knew before starting that with chronic morphine administration, there is no endocytosis of the mu recetptors but there is endocytosis with methadone. That was the reasoning for using the mixture of morph/methadone. Many people believe that receptor endocytosis is involved in tolerance and dependence.

They did their work both in vitro (in individual cells) and in vivo (in actual rats). The problem with their work was they really didn't run the experiment very long, 5 days is not a long time. You are just starting to see low-level tolerance and dependence at that point. They gave the drug combo (and gave them alone) for 5 days and found that with the combo, they didn't see tolerance developing or dependance. I think it's really too soon to tell from this work. If they would have carried it out longer, they may have found that this is something that was temporary or is reversed.

They also looked at the subunits (parts) of the NMDA receptor. They already knew that with endocytosis of the mu receptor, upregulation of the NMDA receptor isn't seen. They also know that NMDA receptors are upregulated after chronic morphine is given. They wanted to see if there was upregulation using their cocktail.

To look for the number of NMDA receptors, they were counting the subunits of it that they had. Again, they didn't carry the experiment out very far and most of their findings were not significant. They only found that one part of the NMDA receptor was increased in one part of the brain (and they looked at several). This may or may not mean anything. They may have seen better results looking for the whole receptor instead of subunits.

The other thing they briefly looked at was cyclic AMP superactivation. This happens with chronic morphine use and is easy to measure. In the first part of the experiment (looking at receptor endocytosis) they looked for expression of proteins that would tell them this was happening.

They really had a good idea here, but they didn't follow through with it. In dependence and tolerance research, you normally dose an animal at least 7 days before you consider it dependent. While it was a good idea to see what was going on at day 5, it should have been carried out to see what happens at day 10 or 15 and further. If you have any quesitons, or if any part of it isn't clear, let me know!

[dorje]

So if I follow you Van in dependence research the yardstick is dependence in 7 days ? Hell I was dependent in one day. Which is a thread idea but probably done to death How you lose your dope virginity I'll UTFSE to see. Really the first shot or maybe it WAS the 7th was best.

[vaxn8]

Dor- in that example and in models used for dependence research, that's the minimum time before the animal is physically dependent and would w/draw if not given it's drug. We used to use morphine pellets in the lab I was in, and implant them subcutaneously. We also gave the mice (in our case) a couple shots a day to get them hooked.

Mentallly, i would agree with you, it's usually the first shot that does it! Another thing I meant to say but left out of my explanation, they were dealing with rats in this study, so it's nto a clinical trial and hasn't been done on humans. Who knows though, they may be on to something. You would first have to find out if human opiate receptors go through the same endocytotic process (get eaten up) in response to methadone. I think there is some evidence that it happens. A maint methadone person can stay on the same dose for quite a while. If they were on morphine, it would have to be increasing with time. This tells you the body deals with the done a little differently! If the done stimulates the eating of the receptors, that means the cell must make more. If this is constantly happening, it is possible that there is never a significant upregulation (creation of extra ones), which may be involved in causing tolerance/dependence.

For example... If I'm a cell and i have 10 opiate receptors to start with. Someone gives me morphine and 10 or the morphine molecules can stick to my receptors and make good things happen. If someone keeps giving me morphine, I'm going to try to make more receptors to deal with the extra morphine floating around. Soon, i may have 20 receptors on my cell surface.

On the other hand, if someone gave me done, I can still have 10 of them stick to me, but after that happens, maybe 6 get eaten and are gone. Now, I have to make more so I do but making more only gets me back to the original 10. I must be loosing it, now I'm thinking like I'm a cell!



edit... Good idea for a topic Dor, not sure if it's been done, it would be cool to see though!

[orangejuice]

Vaxn8, as always, well said, its greatly appreciated! i found the topic very interesting, though some of the terms didnt click with me ( i just woke up) i can always depend on you to do research and come through with the best work. Great job, i cant tell you how much its good having a person like you on these message boards. Plus im a sucker for anything methadone, as yall kno :)

[vaxn8]

After you wake up. let me know if there's any terms you want explained better. I try to keep the weird ones out or explain them, but may ahve missed some. Also, I talk to dorky scientists all day, so some words seem common to me and they aren't common outside a lab.

i fgured you'd be reading this with the M word mentioned! now all you have to do is cut your done down to a mg and switch to morphine and no more tolerance (that is if your body works like a rat's):)

[dorje]

Sorry Van I woke up at 3:00 A.m Are you saying endocytosis (the destruction of receptors) is the reason for dependence ? In other words, in the morphine example the cell creates more receptors so I become dependent. And in the methdone example, no or less receptors are destroyed so my dependence doesn;t leapfrog ? I'm not understanding the statistical correlation. Less receptors =more dependence or the reverse. Also, if I understand WD's besine being CNS rebound hyperactivity is a result of a lot mote opiate deprived receptors or is tha a seperae mechanism.

[orangejuice]

Sweet, its definitly something i'll be trying. Main problem is the availibility of morph. Never seen it around. I've only had it once, for a 7 day stent. I was on the pump after my kidney surgury years ago.

I got a question vaxn8, it should be right up your ally. I have a cat, that has this really bad sore. Its really different from a regular sore. I forgot what the vet called it the first time he had it. I got to where it was a hole inside of his cheek, not entirely through, but damn close. Its a round hole, that now is red with raw skin, it did have puss emiting from it. I'll try a picture real quick. I kno what it is, just forgot the name. I think its an infection from a rough cut that turned into this. Its an absess, thats the word i was looking for. The first time the vet sold me this antibiotic, one used on humans too, i just forgot what it was. I went to a mom and pop pet store thursday, to see if they had any anitbiotics. They didnt have any specifically for cats, but they had a couple for fish, but the only ingredient was the antibiotic. I had a choice between amoxicillin, or penicillin. I chose amox, because i thought if it was one of those two i had before, it was the amox. Do you have any ideas on a medicine or a treatment i can do on em. I really care for this cat a lot. He was clearly feeling rough the first few days, but since i started giving him 250 mgs of amox 2 to 3 times daily hes noticably feeling better. Again, i thought you'd be the one that would kno, gimme an idea or something please. Heres a picture. and an extra pic of my birds, i dont kno why it got in there. but there are two pictures of the absess, hopefully they will show up good on your computer, they are big, and do good on my computer, i just had to go run and take it real quick he was trying to run though.

Sorry about breaking this thread, as you were. :)

[orangejuice]

if you want vaxn8, for the sake of this thread, and how i always seem to hijack em, you can pm me about this ^ . that is, if you want to. Either way it doesnt matter, i have no regard for thread etiquitte anyways lol :( sorry again people.

[dorje]

OJ-Damn man that's a BIG abscess. Give the cat some done with the Amox. Cats have a heriditary defect. Wounds close too fast trapping germs inside. Pus builds up and then there's a hole. Lions die from this a lot and no done for them but you could crush some up in the cat food,dig.Or dog food (see other thread)

[orangejuice]

Yeah, good to kno dorje. Your right about that. But yeah, i failed to mention that i have been giving the amox i bought for em. i wrote that i got some up there. I've been giving em 250 mgs 2 or 3 times daily. I bought a shitload of soft can food for em so i can mix it up. He doesn't even notice it. they are capsules so its easy, just bust em open and mix with a half a can.
Yeah, i got ONE soft side, that cat. Hes tha best. Thats a mental son of a bitch lol. Hes a killer. ill have to find the picture of him shooting up the hood.

But yeah, i wish i had a picture of the first absess a few months ago. It was at the corner of his mouth and looked like it was cut further back.Bad absess, that one was really bad lots of puss, i didn't kno what it was because none of my cats ever had one. So i took him to the vet and he said what you said dorje. I forgot what med he gave for him, so this time i guessed and go amoxil.

[LayinLow]

Ah, so you have cokatiels OJ? Not my favorite, but they are nice. One made me bleed the other day at my work. got me good right on the tip of the ol finger. I'm just starting to get into birds... REALLY love the Conure's. But I've always loved cats, have 3 of them... they cause as much havok as possible... defiantly shut the door when I'm busy getting "better"

[orangejuice]

Yeah, cockateils are the only birds ive ever had. Ive been raising them, breeding with them lol i mean breeding them, and selling them right now i have about 13. they are pretty alright, one is my favorite. The one with only white and grey and no orange spot is my main man andy. Cats are the shiznat, that cat up there, ZIPPO, would be getting better with me lol.

[vaxn8]

OJ- while it looks painful, your cat's wound looks clean. Has it gone from pussy** to looking like that since you started him/or her on the ammox? If so, and if it appears to be feeling better, I would stay with it for 7-10 days. How much are you giving him though? It may start to have stomach probs if the dose is too high. I'm on my way to work, and I'll check on proper cat dosing when I get in there. Do you have any idea what it weighs?
Another thing that may be helpful is neosporin (or the generics Walsporin, Kmart-sporin, any of those). I'll check on that and cats also. We use neosporin on our rats after surgery, right on the incisions. It helps them heal quicker and stops the itching from the staples and scarring.

** I just noticed the "pussy", I mean puss-filled not pussy as in cat or woman related!

OK, back to the topic. First a have some good links so everyone can see what we're talking about. The second link posted, great article in layman's terms (http://www.medicalnewstoday.com/medicalnews.php?newsid=25760) talks about the specific article which can be found at this place. (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRT-4GBM2KH-V&_user=10&_handle=V-WA-A-W-BA-MsSAYZA-UUA-U-AAZWEAZDUD-AAZUVEDCUD-AYBZEDUYW-BA-U&_fmt=full&_coverDate=06%2F07%2F2005&_rdoc=6&_orig=browse&_srch=%23toc%236243%232005%23999849988%23598168!&_cdi=6243&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2f5c79f10f49deaef9dcfaebb2b8bece) I logged out of my institution before accessing this link, so it should be available to the public. Let me know if there are problems. You can also go to the Current Bio site and look it up manually, articles over a year old are accessible to everyone.

Sorry Van I woke up at 3:00 A.m Are you saying endocytosis (the destruction of receptors) is the reason for dependence ? In other words, in the morphine example the cell creates more receptors so I become dependent. And in the methdone example, no or less receptors are destroyed so my dependence doesn;t leapfrog ? I'm not understanding the statistical correlation. Less receptors =more dependence or the reverse. Also, if I understand WD's besine being CNS rebound hyperactivity is a result of a lot mote opiate deprived receptors or is tha a seperae mechanism.

Yes, Dor, it is belived that receptor endocytosis is responsible for dependence and tolerance. This is for a couple of reasons; actually all of my early research was in this area. In someone tolerant/dependent to morphine, we know a couple of things are going on in the body. First, we know that in someone tolerant to morphine, they have more activity going on in a pathway called the adenylate cyclase pathway. Adenylate cyclase (AC) is an enzyme that works with cyclic AMP (cAMP). This pathway is linked to calcium channels on cells (the things that let calcium in and out of a cell). The calcium going in and out can turn on or off this pathway. I talked about calcium channel blockers as 'preventors" of tolerance a while back in a thread I made up.
The second thing we know about a tol/dep person is that their receptors don't seem to recycle or endocytose very often. Endocytosis is important and is normal for receptors. It causes old ones to be eaten up and new ones are created to take their place. The important thing to know is these 2 things are connected to eachother. The reason the AC pathway is put into overdrive is because the opiate receptor is in an activated state (due to drug consumption). So since the receptors are excited by the morphine (as well as the user:D ) it cranks up the AC pathway and it goes crazy.

A third thing we know is that methoadone has 2 different forms called isomers, one is called d-methadone, the other l-methadone. One way to understand the difference is to think of it like your hands. Your right and left hands are identical, and are mirror images of eachother, but not identical, they can't be superimposed on eachother perfectly. This is just like the difference between the d & l forms. Methadone the drug is given as both forms, a mixture. One of the types causes endocytosis, the other doesn't.

The researchers were thinking that maybe if we mix morphine (which prevents endocytosis) with something that causes it, we can prevent tolerance or dependence from happening (by allowing some endocytosis to happen). That is exactly what happened and you can see how they came to their conclusions by looking at the pictures.

If you click on Figure 1, part A is measuring how much endocytosis is happening. If there is a bigger "blob", more of it is happening. If you look at morphine alone, not much same for d-methadone. If you look at high methadone alone, lots happening. When you look at morphine plus low methadone, lots happening. So from that, they know the endosytosis is going on.

in part B, they have labelled actual receptors so they can physically watch what is happening. You can see that the receptors are being broken up (endocytosed) by the little white blobs all over (they are no longer just on the outside of the cell).

In part C, they are checking out the cAMP pathway to see if it is over-excited or not. To do this, they have tne gene that makes the receptor and they have put a tag on it. The tag is just to see if it is working (making the receptor) and if so, how much is it making. From left to right, you see that with no treatment there is some level of cAMP going on. Next, add morphine and it goes way up. The symbols on top of the bar just tell you that it is a significant difference (statistically). Next is the mix, there is a significant decrease in the cAMP pathway, just like expected. Finally on the far right, you see methadone on its own, no significant increase in cAMP. Kind of a long answer, but I hope it makes sense!

OK, next question about the number of receptors. In the morpine case you've got a bunch of your receptors that are constantly activated, due to the morph. In the methadone case, you get them excited, then they get eaten up and are replaced by fresh new ones. You also have one form of the done doing the opposite, so although you don't have a normal situation going on, it more closely resembles the natural replacement that would happen. If that isn't answering your quesiton, let me know, I could have read it a couple different ways and I'm not sure I'm answering what you're asking.

With the w/drawal question, you have lots going on in that situation. Some are excitatory processes, other aren't. For one thing, you no longer have anything occupying the mu receptors so everything that was causing to happen, is stopped, or slowed way down. Now, you have to depend on your bodies endorphins, which have been slacking off since you've been doing all their work for them. There is also a lot of NMDA receptor activity changing, so it's a big mess and still being worked out!

[dorje]

Thanks for clear answer. My knowledge is on the basis of Physiological Psych not cell pathway activity. Very interesting stuff. I still like Professor Burroughs model of never being able to beat biologic time. WD's being CNS rebound hyperactivity fits that model. Your skin's pores open and close, you take morphine ,they open and close less, you WD, they open and close constantly so chicken flesh or cold turkey.
If this level of research indicates both isomers of methadone worked at cross purposes, why not develop methadone with the right isomer ? Or left depending on your mirror. Also , any way to increase the replacement of receptors to prevent dependence with opiayes in general. Thanks for clear explanations. My theoretical model is Buddhist in that I 'm unclear whether our sense perceptions are mediated by real world or a matrix built on dreams. Like a lightning bolt, a dream, a bubble of air, a wave in the ocean, or a song, so are our separate egos
You working Sunday or getting together with your nice salesman to cop ? Anyhow, thanks again

[vaxn8]

For the isomer question, I think in terms of maintenance you get a better result using both forms. If they gave a junky the purified version that caused endocyosis I don't think user would get the same feeling and they would crave more. There hasn't been a whole lot done with the different forms except in tolerance and dependence work, and a lot of that is fairly recent. If you gave the other form only, I don't think you'd see addicts stabilizing at any one dose, you'd see a constant increase like morphine or heroin. It would be an interesting experiment though, I'm sure there would be no lack of volunteers!

There are ways to effectively increase receptor number. One way is using the calcium channel blockers I briefly mentioned. It slows down the cAMP pathway which gives a similar effect to recfeptor replacement. It's just altering the pathway at a different point and there are many ways to do it. This is a newer idea and another point to attack it. I'm sure this specific group has published more on other drugs that act like methadone does here, I haven't looked into it much yet, but probably will. Personally, i use a Ca channel blocker to keep tolerance down and it does work. I use it to prevent pain from RSD, but it has this added side benefit.

i don't know anything about Bhudda stuff! Is that question (about sense perception) one based in the religion or one you've asked after experiencing it? I guess is it a part of that way of thinking or a result?

I'm working today, actually I've been "on my way" for awhile! Looks like I'm going to be working an all nighter, I meant to start at 7 AM and obviously have found other things to do! I'm not going to be seeing my guy for a while. I'm restocked with rx's and he's going out of town, I think it will be good to cool that off a little!

[lukilu]

Wow Vax , I really like your energy around here and your promptness ! I dont know why, but I always feel like I am typing to a Male and your Female, right ? Dont get me wrong I think its great and really enjoy how you are able to reduce some of the research terminology into something I can sorta sometimes picture in my mental images and I probably should have gone into this field because I like having an understanding of WDs and Tolerance and if I am gonna make Opiates a part of my life, to take whatever tools I can, to try and prevent being Effin Sick or having Huge Tolerance ! It also sounds like you kinda enjoy your work , at times anyway :rolleyes: . Wow ,and you have actually implanted M pellets in mice and made them dependent { any leftover pellets layin around :D } That is just so cool ! So , I probably will have many questions along the way and I saw many more related links when I found that particular article . Oh yea ,the biggy ,if I was to try this at home! How much were they giving to those little furballs did they try different amounts ? Was there always a Ratio of Morph to Meth ? and can we come up with a estimate for 180 pound Male ? You really made my day today, Thanks !

........ Also Dorje , Thanks for asking some great questions on topic ! You saved me from tryin to figure out how to phrase a couple things .

.............................. Lukilu

[orangejuice]

Vaxn8: Yes, when i first noticed the wound, it WAS pussy...or puss filled. As soon as i noticed it, i washed it out. Apparently it was very painful to him then, but i managed to clean it out with peroxide, and used neosporin, the kind with the pain releiver in it. It works well on his wounds, and does something for the itch too because he scratches the hell out of any wound he has making it tough to help it. I have been giving zippo 250mgs of amox 2 and sometime three times daily. I was wondering if that would make him sickly feeling. I like to keep it twice a day in that case. I'd say that he weighs roughly 12 or 13 lbs. Thanks for your help again.

[lukilu]

Hey OJ would you mind keeping this thread on topic . I understand your concern for your cat maybe you could PM Vax with your Questions .
.................. Thanks Lukilu

[orangejuice]

if you want vaxn8, for the sake of this thread, and how i always seem to hijack em, you can pm me about this ^ . that is, if you want to. Either way it doesnt matter, it looks like i have no regard for thread etiquitte :( sorry again people.

AGAIN sorry luk, i understand we all want our threads to be looked at for what they are and not anybody else's issues. Sorry sorry sorry, i posted this ^ several hours ago to divert it. That shows that i wasn't trying to steal the show from you. so dont think thats the case. I dont kno what else to say. Dont worry your topic is still at large and we do care about it. :) It happens to everyone sometimes.
Have an outstanding day. If you want you can post something in one of my threads if it makes you feel better.:o

-daniel

[lukilu]

OJ . Nah . thats not it . Its just alot easier to follow the thread if its on topic . I have a hard time paying attention and easily distracted so , Yeah it happens and not a huge deal . just asking thats all ;) .

...........Lukilu

[vaxn8]

I will answer the other questions once i get my experiment up and running. I do want to say one last thing about the cat- in case any one comes across it in a search. Cats need 0.5 mg/pound so for a 12 pound cat, that's 6 mg! I'll write ya more OJ on how you can divide it up, I just wanted other to know that 250 is a bit on the high side!

[Curio]

:o sorry for continued off topic Lukilu: :o

I wanted to post this just so anyone interested can have a safer understanding should they wish RE: medicating their animals (other than our typicals...say a coupla monkeys, some good-sized gorillas, etal !!)

OJ:
Just FYI as Vaxn8 mentioned, even 250mg given once a day is itself much too high of a dosage for a cat, unless your cat weighs up around an average sized human, lol..

anyway, it's great he's feeling better but smaller animals are generally given meds by weight,
i.e. #_mg per #_kg (or per #_lb)

here's a couple of decent links I found:

http://www.lowchensaustralia.com/health/med.htm
http://www.diamondpaws.com/health/drugs.htm
http://www.merckvetmanual.com/mvm/htm/bc/tphm29.htm


I think amoxicillin is around 5mg per pound per day....if you wanted to space the dosing (which I think is almost always better for antibiotics administered to anyone, feline or human), you could divide that in half, giving each half 12 hours apart for an am/pm dosing, just to keep the therapeutic levels up in the blood. Usually the treatment period is same as people, anywhere from 5-14 days average length of medication therapy.


We now continue your daytime matinee without further interruption, heh heh:p

[orangejuice]

sorry luk, but reading these posts have worried me, and i have a need to post. I appreciate the information vaxn8 and coma!!!!!!!!! I feel really dumb for giving him that much, just guessing! I figured that since this bottle was for fish then it wouldnt be too strong, but then again, it said to add 2 tabs to every 5 gallons of water. I kno now that youve given me the correct inforamation. I cannot thank you enough. Im just worried that ive harmed my cat. He seems fine right now, ill lower the dose immediatley! :( God... thank you again yall. and sorry luk. This definitly warrants points you two. Sadly vaxn8 you gotta wait till i spread em around, but i owe you!

[dorje]

Add my thanks to others for elucidating interesting research, Here's the tip on the Buddha (from Naked Lunch " In India, where the man has no sense of time " I've got a meet long about the first or second monsoon" The Buddha says " I'm tired of this noise. I'm going to make my own, ya dig?"... "Jeez ,boss what an angle."

As Betrand Russell mentioned there is no external evidence that our sense perceptions reflect anything real. In short, he questioned and certain types of Buddhisn allege that ordinary experience is the false assumption of the externality of relations. It's not that there is nothing out there but that it's illusory as in a trick. It appears differently than it is...
My reference is Tibetan Buddhism , Karma Kagyu lineage. Vajrayana
This is not my beautiful wife...this is not my beautiful car.

[SuperJunky]

I'm pretty sure that opiates act like speed to felines because there opiod/dopamine systems are wired differently. Paradoxical stimulation, but the dopamine is always prevelent in cats. Not 100% sure thoug. Does any one know? I wold suggest finding out before you give your cats some done though.

I apologize for dropping off the face of the earth, you'll all be hearing from me again.

[Paregoric Kid]

it's a good combination, whether it does that or not. but it might be true, especially if tolerance is controlled by the NMDA receptor.

[vaxn8]

LL- Yes, I am female for real. I'm glad you're understanding it. One of my grad advisors told me that if I could explain my work to someone totally out of the field, then that is when I completely understood it. Not sure that I always do that, but I try.

It was a very hard field to work in while using. Part of the time I wasn't using anything at all, and for the last stretch of time I was and it made it very difficult. I did enjoy what I was working on, but there were times when I wasn't feeling very good and would have much rather given the shot of whatever I was working with to me instead of wasting it on a mouse! That wasn't my major reason for leaving that lab, but I think if I would have stayed there a whole lot longer, I would have found a way to get myself in serious trouble, so it's good that I left. I love what I'm working on now, I work on hemorrhagic fever viruses which is cool work.

For the paper you posted, for part of the work, they were dealing with HEK cells (human embyonic kidney cells), so the doses were expressed as a concentration, which isn't helpful to figure out a human dose. Actually this was something I meant to mention and forgot. When they gave the actual drugs to actual rats, they did it by i.c.v injection (intracereb.-vascular) that's right through the skull into the brain. Not a way to dose a human obviously! They did say their dose was equivaltent to the 80% MPE, which means it's equivalent to a rat dose that equals 80 percent of the maximum possible effect. That I can convert to a mg dose and we could scale from there. I've doing this inbetween incubations, so i'll be in and out while I'm doing this. A ratio will not be helpful here because of the differences in animal vs. human dosing. We can calculate a pretty close approximation though. I'll let ya know.

[lukilu]

Vax , Yea , No problem on taking your time on this one and Im not about to put a needle thru me noggin although ,I had no problem with the other end {Not a mettle one anyway } :rolleyes: ! It seems like we just arent sure of all the different mechanisms that are at work with Dependance and Withdrawals But with Proglumide/CCK , Calcium Channel Meds and Maybe Methadone Looks like some possibilities . I have Proglumide and Methadone, but I know you mentioned Calcium Blockers or something you were taking , can those be gotten over the counter and do they have any side effects which are unpleasent ?
Thanks again for your time and now I can tell your Female and Friendly:D !
......................Lukilu

[HistoryofMadness]

Hey OJ would you mind keeping this thread on topic . I understand your concern for your cat maybe you could PM Vax with your Questions .
.................. Thanks Lukilu

ha good luck, you may as well be herding cats... you will learn eventually around here to go with the flow!:D

[lukilu]

Oh HOM ! Thanks for clueing me in on your secrets ........:rolleyes: .... but I like to go with the WOLF:cool:

......................Lukilu

[lukilu]

Vax , I was able to find a thread you started about Channel Blockers and Tolerance and see you listed NIFEDIPINE and NITRENDIPINE as Ca2 channel blockers also ,a Chinese Herb called "Denshen" {Salvia Miltiorriltza } That HOM has mentioned as working to Potentiate Pod Tea I beleive ! Can you when you get a chance tell us more about the 2 Meds you mentioned and any side effects one should be worried about if taking them and what dosages are safe for you ?
,,,,,,,,,,,,,,, Lukilu

[dorje]

I believe Vistaril is used to potentiate Demerol and can be had by telling the Doctor you itch. Plus it control itching. Hydroxyzine pam 25mg vcap VI #120, Van-do you know mode of action? I know this is no calcium channel blocker. Probably an antihistamine to stop itching but it works ( cross potentiation /)

[halfalien_s4]

vax8 u and i would probably have a lot to talk about....im a storm-chaser by trade but also a microbiologist and my favorite out of all of it is level 4 virology. i almost became a doc and worked for the CDC but the first wreck i was in sort of blew the doors off the med school thing. i know you said you woreked ina lab. i remember all my lab expiriences as well. i dont go as much as i used to because of pain but im way into it. right now im studying nesseria menigitis. sorry to highjack the post everybody!

[halfalien_s4]

and yes hydroxyzine pam (vistaril) is a poteniator, so is hydroxysine hydocholride (attarax)....ive taken it for yrs on and off....its good for itching, anxiety, and nausea....

[lukilu]

OK, Looks like we are getting somewhere again ! We now have, thanks to Dorge and H Alien. that Attarix and Visitril Both used for Nausea and Itching Potentiate certain Opiates . Is it possible Half Alien since you have a backround in the Jargon they use to write medical research reports , you could tell us the mode of action in laymen terms of Visitril or Attarix on Potentiation of Opiates ?

.....................Lukilu,

[orangejuice]

OK, Looks like we are getting somewhere again ! We now have, thanks to Dorge and H Alien. that Attarix and Visitril Both used for Nausea and Itching Potentiate certain Opiates . Is it possible Half Alien since you have a backround in the Jargon they use to write medical research reports , you could tell us the mode of action in laymen terms of Visitril or Attarix on Potentiation of Opiates ?

.....................Lukilu,

Dont get upset again, but im about to change the subject again. :D i love doing that. about the....
AH just joking! lol, i was gonna see if you'd get pissed because i posted in here again. It's not worth ruining this thread for you though. Im going to pm the people that helped me with my pussy issue. ;) everythings great now. Later. Stay cool lukilu

[dorje]

Did not know you had a problem with pussy. You see you learn stuff everyday on this forum .Problem as in old W.C. Fields line The only problem I have with pussy is getting some ..or other problems ? How is cat. Juice ? BTW Look at 7 repeat threads and alert DD to newcomer fish or you can handle. Peace, love, dove, brother in arms

[orangejuice]

Yeah, every guy's got pussy problems sometimes, unless your antony or someone like that lol. Nah, the cats doing great, i just now like one minute ago posted in a thread talking to you about whats going on with tha "zip man" (cats name zippo) umm cant remember the name of thread already even though it was only a min ago lol.
Yeah, i just got home from work at 6, and thats what im doing, trying to catch up on some threads. What did you mean about the 7 repeat threads and alert dd to newcomer fish ?? Later, broski.

[dorje]

Check out Myrrh thread not double but 7 posts from newfish. DD locked and loaded just not online

[lukilu]

Well , It looks like weve got ourself alittle Passive Agressive Little A Holes on here that are bent on Effin around and Screwin up peeps Threads ! But dont get me wrong , I understand if you havent got a LIFE its a poor fools way to get Attention and give no respect . Now, im not actually pissed off, sorta dissapointed , thats all ! So I will start another thread with the relavent Info and see what happens !

.................. lukilu

[dorje]

Thanks for correction. No life as yet. I think the visuals as Kyuss said are what provoked reaction. I thought I was having vertical nystagmus (sp?) Hell, I am having vertical nystagmus. Too much Vitamin K not enough compassion. So alls well that end's well.

[orangejuice]

I think fate has me dammed here. Shit hitting the fan? id better hide. i think im the a hole here :((

[kyuss]

Hes a killer. ill have to find the picture of him shooting up the hood.



something like this??

http://www.mobango.com/uploads/thumbnail/84828.gif

[orangejuice]

lol yeah, exactly. I have that picture too. Funny thing is he really looks like that. exact colors i mean. No shit. Yeah sometimes he makes that face too lol.

[kyuss]

lol yeah, exactly. I have that picture too. Funny thing is he really looks like that. exact colors i mean. No shit. Yeah sometimes he makes that face too lol.

hahaha
that's cool
I use that gif
as my avatar on another forum

[orangejuice]

yeah it is, i think a pic of him is in this thread near the beginning. not a good one though. I wont post another one, im already kinda being looked down on a little bit by a couple because i keep ruining threads because i talk about something else sometimes. I think im the only one though.:rolleyes: :confused-

[vaxn8]

Vax , I was able to find a thread you started about Channel Blockers and Tolerance and see you listed NIFEDIPINE and NITRENDIPINE as Ca2 channel blockers also ,a Chinese Herb called "Denshen" {Salvia Miltiorriltza } That HOM has mentioned as working to Potentiate Pod Tea I beleive ! Can you when you get a chance tell us more about the 2 Meds you mentioned and any side effects one should be worried about if taking them and what dosages are safe for you ?
,,,,,,,,,,,,,,, Lukilu
Nifed/Nitren are the 2 big, more famous ones there are many, many ca channel blockers. It is more than just blocking the channel, it is a certain voltage gated type of channel. My brain is way too dead for this, I'll write more about this after it recovers. I worked all last night and all day today, so I'm a walking (or typing) zombie.
I don't know herbs at all. I know H mentioned a few in my ca thread and jacky writes about them all the time. I don't mess with them. I have nothing against them, I'm just more familiar with the non-herb drugs.
The Ca drugs are taken at the rx'd dose, more on that later but it is a normal dose, not excessive or anything. It does lower blood pressure (that's why most people take them) so that is something you have to pay attention to.
I believe Vistaril is used to potentiate Demerol and can be had by telling the Doctor you itch. Plus it control itching. Hydroxyzine pam 25mg vcap VI #120, Van-do you know mode of action? I know this is no calcium channel blocker. Probably an antihistamine to stop itching but it works ( cross potentiation /)
Yes, vistaril and hydroxyzine both potentiate opiates, but it is more of synergistic reaction than anything. I wrote a lot about that in Cube's potentiator thread last month, or the month before. Phenergan would also be included here. It's still argued about how this all works. Some groups say that by supressing some of the bad effects of an opiate (nausea/vomiting) you get better action of the drug. It also contributes to sedation, which gives the appearance of being a potentiator. You also have the antihistamine action, which decreases the itching side effects of the opiate.
vax8 u and i would probably have a lot to talk about....im a storm-chaser by trade but also a microbiologist and my favorite out of all of it is level 4 virology. i almost became a doc and worked for the CDC but the first wreck i was in sort of blew the doors off the med school thing. i know you said you woreked ina lab. i remember all my lab expiriences as well. i dont go as much as i used to because of pain but im way into it. right now im studying nesseria menigitis. sorry to highjack the post everybody!
That's really cool HA! i used to only with with level 4's, now the virus I'm concentrating on is a 3. I'd much rather work at level 3 than 4 anyday!
OK, Looks like we are getting somewhere again ! We now have, thanks to Dorge and H Alien. that Attarix and Visitril Both used for Nausea and Itching Potentiate certain Opiates . Is it possible Half Alien since you have a backround in the Jargon they use to write medical research reports , you could tell us the mode of action in laymen terms of Visitril or Attarix on Potentiation of Opiates ?
.....................Lukilu,
Luk- H is right, trying to keep everyone on topic is like herding cats! Every topic goes on and off, don't let it get to ya! BTW, I couldn't figure out who you were talking to when you kept writing half alien, I was reading that whole username as one word and didn't see the alien in it. MOA of antihistamines is above^
Dont get upset again, but im about to change the subject again. :D i love doing that. about the....
AH just joking! lol, i was gonna see if you'd get pissed because i posted in here again. It's not worth ruining this thread for you though. Im going to pm the people that helped me with my pussy issue. ;) everythings great now. Later. Stay cool lukilu
OJ- glad to hear the pussy is doing better:D
thats all ! So I will start another thread with the relavent Info and see what happens !

Seriously, we're not writing a book, don't let it bother you. Every topic does this and covers more than one thing.
OK, the things I'm supposed to remember to answer are .... more about Ca2+ blockers, and calculating a done dose, is that it? Did I miss anything?
night all, I need sleep! night OJ, night pussy, g'night Dor, and good night John-boy

[orangejuice]

g-nite vaxn8. :)

[lukilu]

Thanks Vax For that last bit of Info ! ...... I will take the relavent information and start a new thread later . I was hoping this could be some kind of a Sticky ,but as far people going off topic, that I can understand have done it myself ! If a person here asked me respectfully, I would back off . To me this Topic is seroius ! and there are a bunch of Needy Attention Seekers that have found a way to get attention by disrespecting others and Im starting to see more and more of it and its kinda annoying . Nothin wrong with pointing that out ! Who knows, maybe they will get a clue and find something outside of the Internet to interest themselves . Thats all . Not a huge deal, but one, none the less!

................................ Lukilu:cool:

[orangejuice]

This is starting to get way wild. If it makes you feel better, im going to sleep now, so i can get up and GO TO WORK in the morn. But first, we'll be up front with this, i mean why not? Beating around the bush isn't something i think is very efficient, but whatever floats your boat. Im smart enough to kno who you've been refering to all night.
If anyone is interested and thinks any topics about methadone is serious, its me. If you haven't noticed, despite of the past few days, the majority of my posts are about methadone. Everything methadone, methadone this methadone that. I like it any way, sideways frontways backwards, down the hatch, white, orange, dry, wet, potenitation, cocktails, and reducing tolerance. EVERYTHING Its my DOC, and since i was 14 ive been interested in it. So i hope you dont have yourself thinking that nobody cares or wants to hear what this thread is about, again. just because, 99% of all threads here get changed in one way or another, doesn't mean that nobody here at opiophile cares about everything opiate, does it? GOD i hope not. This is the first time i've seen a matter like this taken so serious, and really don't understand, but ok. About 20 posts back, i apoligized numerous times, and said i would stop moving an inch off of topic. And i did. I came home from work and as i do every single day, i do what i need to do, then get on here and see whats new/ whos responded to what etc. Some reason, i keep reading these sort of posts referring to needy attention seekers, and what not. lol. This is almost turning into an elementary school thing. I get sad whenever things get this way around here, whether im involved or not. This place means more to me than you'll ever kno.
But theres one thing that you DO seem to kno, and thats about me "not having anything to do outside of the internet".... .... what?! haha I dont think we've ever spoken before this thread, lukilu, and all of the sudden you seem to kno ssoo very much about me. How is that so? Is it possible? Is it because i got a lot of posts for my time here? What else could it be???? I type and respond pretty fast when im online. Would you like me to change that for you? Im very confused.
You let ONE person "annoy" you, after reading a handful of posts that just happened to be about different things, and it "annoys" you so bad that you have to stop talking about your important thread constantly, and MAKING SURE that i kno i've "done wrong" or "annoyed" you. I got the point YESTERDAY lukilu, and as far as im concerned this shit was over then. Im just wondering, did i break a rule or something? maybe let me in on that one if you will.
I'm done playing this game, there are other, better "games" to be played. I just wanted to make sure i made myself clear on all of this before i turned in. If you have any other questions, concerns, or complaints, please do not hesitate to post them here! If not, chill out, and get back to your life. Im sorry it was all so ground moving and you had to put your life on pause to let me kno repeatedly that you wanted YOUR thread TALKED about NOW. Have a blessed night, sleep tight, dont let the bed bugs bite. GOod luck with your opiate cocktail reducing tolerance. I kno i'll be researching it. Thats what i do, learn and share about methadone. But im just a needy attention seeker, what do i kno. ;)

[lukilu]

There you go thinking its all about you . I wasnt just refering to you . Yea , you were one of them . I wont get back into it because , Its been done before . and Like you said its gettin old and im done pointin it out for now ! Have a great night !

................Lukilu

[lukilu]

All righty then , I looked and I looked for something on Rules about staying on Topic but Guess What ......... There arent any :( . So ,even if you ask, it dont mean shhit !

... Now , I will say this .I have been in WD,s from Subutex for the last Week and have noticed Quite a bit of Anxiety , Frustration , Hairy Trigger Finger .. Well most of you know what thats like :mad: and since no Moderators or anybody agreed with my Dissapointment with others not respecting to" keep it on Topic " I can only assume , I was to hard on people here and said some things that I should have kept to myself . So for that, I apologize to anybody I offended ! Hope you had agreat day OC:D
.............Lukilu

[halfalien_s4]

vistarl and attarax are both anticholaragenics, but vistaril is used more than attarax. attarax is used primarly for severe itching from like say hives....i had it for that once when i had the beginning of a anaphalactic reaction to the antibiotic keflex. the doc also added steroids. but visaril is used a lot with pain medication demerol and morphine. in fact, more often than not a concoction of demorol, visteril, and phenergran will be given for severe migraines. like vax said it has an antihistamine effect for itching, antiemetic effect for nausea, and an antanxiety effect for the patient as well. visteril and attarax are only slightly different, attarax being geared more toward itching....let me know if i can answer any more questions for ya!

[halfalien_s4]

vax what virus may i ask are u concentrating on right now?

[Dilaudid]

Hello opiophiles,

You can also reduce tolerance in many ways:

_Use a delta opioid receptor agonist (like TAN-67)
_Use an non competitive NMDA antagonist (like a little K)
_Use an stereospecific competitive antagonist in very little doses (like naloxone who can prevent total saturation of your receptors with an agonist)

A little methadone or pentazocine (NMDA antagonist, agonist-antagonist µ, weak µ antagonist) and even little Ketamine (especially S(+)-Ketamine) with your DOC can help to prevent tolerance.
Like you can see there are many ways to reduce or to prevent opiate tolerance.

[Chipper]

SWIM has been testing this very idea by lately adding 0.5~2.0 mg Methadone to every pt. of H.

SWIM will get back to you with their findings.

[Chipper]

After some rigorous testing, SWIM could not authenticate the claim. Appolgies.

[OxyContinuously]

So anyway, regarding the methadone/morphine study, let's look at it from a common sense point of view. Methadone is stronger than morphine in the sense that it takes precedence at the receptors. it is also an opiate. i think the two concurrently would only serve to raise the total tolerance very quickly and painfully. Methadone is long acting so sticks around the body longer, wheras morph is shorter and is eliminated quicker. it just seems to make sense that if you mix methadone and morphine concurrently, you are certainly NOT reducing tolerance, but in fact you are raising it, and raising it very high due to the long duration and relative potency of methadone. Plus, there's morphine involved which just serves as another drug to add to the total cumulative habit.

OxyC

[Chipper]

I am still going with this one .. how much is a "small" amount of methadone? Is my 0.5-2m6 (now with about 50 mg street H) compatable with their study?

I am trying this again with 1 mg methadone prior to use and another 1mg one day later. In othet words, do you think that this is ratio is similar to their experimental mix?