Methadone question

[Paulymorphone]

Hello everyone,
I've been in pain management for years and for a couple months was even going to a methadone clinic. I've read a lot about methadone in high doses blocking other opiods taken while taking methadone, but most physicians I've spoken to disagree. I'm on palliative care and just want to be sure I'm getting the most pain relief as possible. I take Methadone 50mg every 8 hours, Roxanol 20mg/ml (morphine sulfate oral liquid) 1ml every 2hrs prn and abstral 800mcg (fentanyl citrate sublingual tablet) every 2 hours as needed. I just want to be sure that the methadone isn't interfering with any pain relief from the morphine or fentanyl. I don't think it is but I doubt myself sometimes. I don't care if it prevents any feelings of euphoria, just as long as its not saturating my opioid receptors so heavily that the other opioids can't get to them.

Thanks for any and all input!

 

[sekio]

Methadone will outcompete morphine for mu opioid receptors, but fentanyl will outcompete methadone.

It's probably the best you can do. I do seem to recall that morphine does actually have some secondary painkilling effects that are not related to its direct agonism at mu opioid sites. Even if the methadone is outcompeting morphine at mu opioid receptors, the methadone is a pretty strong activator of them, so it will still provide analgesia.

 

[Erikmen]

IME methadone will not interfere if you are using Fentanyl in the indicated dosage above.
As for the others meds, I believe it will shut the euphoria for sure but will keep you pain free.
I had used Fentanyl before with breakthrough pain medication. But switched them all to methadone.

 

[endotropic]

I think it's worth pointing out that methadone is a high efficacy opiate, so even if your receptors are saturated with Done you should still get maximal pain relief.

 

[serotonin2A]

If you are taking a high dose of methadone then it will limit the response to fentanyl. Chronic use of opioids produces mu-receptor desensitization and downregulation. The other factor is that both drugs compete for the same binding sites. It is possible to compensate for this by giving high doses of fentanyl but there will be a ceiling on the response and the doses required may produce respiratory depression.

 

[endotropic]

^True, just like taking a high dose of any strong opioid will limit the analgesic response to any other opioid over time. He's better off than if he was taking a weak partial agonist like Buprenorphine, which would prevent other opioids from binding without producing much activation itself.

 

[Keif' Richards]

Someone please correct me if I'm wrong, but ~150mgs a day is definitely enough to block other opioids. The actual dose at which opioids are blocked by methadone is a little dubious. The concencus in the medical community is 80mgs (two different clinic doctors), but some people say as low as 40mgs seems to block other opioids.

 

[Paulymorphone]

Well i know that fentanyl citrate...subsys, abstral, lazanda does help my pain even on 150mg q24 done, just unsure about the morphine....I dunno....I always get scared to stop taking methadone

I have gone down to 100mg to 120mg of methadone per day though...

 

[dopamimetic]

I would strongly recommend to try adding a NMDA antagonist like memantine (that standard dose of 20mg is related to its primary use against alzheimer's and might be to low for full efficacy. In studies up to 60mg were used - of course for such a dose some titration is required) or, if possible / available in your country, ketamine . The use of ket in low dose and orally is still rare despite its potential and positive studies existing). Other option is dextromethorphan, which is available without prescription and also works for some.

NMDA antagonists have quite potent pain killing effects on their own which are not directly related to the opioid system and they also help countering tolerance as well as some potentiation of opioids.

Good Luck !

 

[Paulymorphone]

I highly doubt I could gain access to memantine. I've never done DMT but ive done a ton of ketamine. What is the comparison. And how many oz. Of robitussin dm max strength would a 350lb man have to swallow for any experience like ketamine.

 

[serotonin2A]

Someone please correct me if I'm wrong, but ~150mgs a day is definitely enough to block other opioids. The actual dose at which opioids are blocked by methadone is a little dubious. The concencus in the medical community is 80mgs (two different clinic doctors), but some people say as low as 40mgs seems to block other opioids.

100 mg methadone should definitely block euphoria induced by most opioids but I'm not sure about analgesia. Many people do not think that fentanyl is very euphoric but it definitely produces analgesia, so there may be distinct dose-response functions for euphoria and analgesia.

 

[Paulymorphone]

Hey guys, I saw my palliative care doctor today. I asked him about the methadone preventing the fentanyl and morphine from producing the same amount of analgesia.....he said that it will not and that (I may noy be saying all this correctly) methadone works on the NMDA receptor while morphine & fentanyl affect the mu receptor....also something about the "cappa' receptor.) I took 80mg of methadone at 3pm. About 30mins ago I had about 140mg intramuscular morphine 800mcg sublingual abstral and 1600mg lazanda nasal spray. I feel great. Out of all the different forms of fentanyl, lazanda is the best by far, I've tried abstral, patches, actiq, subsys, now lazanda. I have not tried Fentora, Onsolis...or any other form. But I only have the trial, lazanda is the most expensive one and I bet medicare will decline the prior authorization. I was able to walk today (with 4 prong cane) for the first time in a long long time after using 800mcg lazanda. It was awesome!

 

[Nagelfar]

It's Kappa (as in the Greek letter) and Kappa antagonism is better than agonism for alleviating nociception (unlike the Mu receptors, where you want agonism). And yes, methadone is also an NMDA antagonist while morphinan type opioids (morphine, vicodan, oxycodone.... but not Fentanyl) are not (though the reverse stereoisomers of them are). I don't believe Fentanyl types have affinity for those glutamate receptors (NMDA) either.

This is probably a reason why methadone withdrawals are so harsh. NMDA antagonism is a kind of dissociation anesthesia. NMDA antagonists like PCP & ketamine are used in veterinary anesthesia to sedate pets under the knife. Coming off of it is an over-load extra-associative type of nociception.

 

[adder]

Kappa antagonism is better than agonism for alleviating nociception

Do you have a source for that? I've never heard about kappa antagonists producing much analgesia (perhaps some weird ones do to some extent but then again it may be due to secondary effects like increased catecholamine levels). How would you explain analgesic properties of drugs like nalbuphine or butorphanol which are very weak partial mu agonists at best (certainly weaker than buprenorphine)? It's true kappa activation counteracts some of the effects of mu activation but I guess it's mostly related to euphoria caused by the latter and not analgesic effects. I can imagine 14-hydroxy analogues like oxycodone or oxymorphone are held in high regard by some people and perceived as more speedy because their efficacy at kappa receptors is lower than morphine's.

On the other hand there this: http://www.ncbi.nlm.nih.gov/pubmed/9584625, which is surprising to me. Still, even for opioids like morphine this effect is probably negligible.

 

[Paulymorphone]

11 to 13 years ago I used to use ketamine quite regularly...ages 19 to 22. When I didn't have it I used to have extreme anxiety but there were no physical withdrawal symptoms. A lot of people don't like it because of the circumstances under which they did the drug, for instance I remember being at a club where this girl tried it for the first time and went into a K-hole, and must have had eaten recently because of the vomiting, something it rarely did to me. I used to get the best effects from it using it in a completely dark room, lying flat and comfortable and unmoving, while focusing on a computer screen doing a high Def version of a super colorful psychedelic thing along with trance music. If I didn't use it in those conditions, or in combination with mdma lol, it felt like a waste. It also seemed to provoke in me some amazing things, like I was conversing with God or a future version of myself. It became important to write down these things while on the drug because it was impossible to recall what it was afterwards.

 

[Nagelfar]

Do you have a source for that?..... On the other hand there this: http://www.ncbi.nlm.nih.gov/pubmed/9584625, which is surprising to me. Still, even for opioids like morphine this effect is probably negligible.

You found it yourself.

Basically Kappa seems to be dysphoric in studies, which doesn't help analgesia to any degree. Buprenorphine is an antagonist at kappa & mixed agonist & antagonist at mu. Norbuprenorphine is a full agonist at mu; I'm uncertain if it is still an antagonist at kappa but if it were that would probably be a most efficacious combination.

 

[Paulymorphone]

You guys all seem very intelligent in the fields of biology, pharmacology, & chemistry. Anyway my insurance is still not covering the TIRF Transmucosal Immediate Release Fentanyl (Subsys, Abstral, Fentora, Lazanda, Actiq, Onsolis) formulations so the drug representatives just keep giving me trial after trial package. I think the pharmacy messed up but I didn't say anything because they gave me a ton of Fentora 800mcg (169 tablets) and 15 1600mg Subsys (30 800mcg sprays, but each one is in a pack of two). Anyway, what I have noticed is that the faster whatever medication you're taking absorbs, the more effective it is. For instance, the lazanda is a spray in the nose & subsys is a spray under the tongue; these both absorb very fast and kick pain in the butt and sometimes make me a little bit sleepy. Abstral, Fentora, and Actiq (I've never tried Onsolis, apparently it has all kinds of regulations making it a nightmare for patients, doctors, pharmacies, and courier services) take a lot longer to dissolve and don't work nearly as well as Subsys and Lazanda. So my question is this: would it be alright to powderize the fentora and then place it under my tongue so it absorbs faster, more like the subsys? And does crushing it interfere with the system in the fentora that makes it fizz like pop rocks candy? Or maybe I'm thinking of another kind of candy lol. Anyway, thank you very much for considering my question.