• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

LDN for reducing opioid tolerance

My sister has been trying adamantane, pure adamantane, and not reporting any ill effects or any incredible effects.

I will try some soon. It seems fairly safe if not effective. In the meantime I ordered some bromantane, which I hope will help with opioid tolerance and also just general beneficial effects on my illness.
I'm trying to find memantine but it's more difficult, maybe a doc will prescribed

My intermittent LDN is not enough to reverse tolerance after binges, but I think it could keep tolerance nil if done often enough. I also think rotating different kinds of opioids may work some, it's done in pain management.
 
debored13

I credit you with the intelligence to know your own mind but my steady opioid us spiraled out of control 6 months ago when my wife left me. The Russians have 'Krokodil' while in the UK we have deoxymorphine-C which is just as potent but not listed on the MoDA and the PDA is just waiting for someone to go 'not guilty' so they have to PROVE that this novel compound is active. It's sure fucked up my life. I just don't want to see that happen to you -you seem like a nice bloke and if their is one thing we like on BL are decent people. After all, they are so are in nature.

Sean
 
Really I guess pure adamantane will not make it through the blood brain barrier, though I am not really competent to make this disclusion.. Memantine is available from some online pharmacies who tend not to require prescription. I have more difficulties sampling bromantane here ...

Ketamine works and is safe when used sparingly.
 
clubcard said:
debored13

I credit you with the intelligence to know your own mind but my steady opioid us spiraled out of control 6 months ago when my wife left me. The Russians have 'Krokodil' while in the UK we have deoxymorphine-C which is just as potent but not listed on the MoDA and the PDA is just waiting for someone to go 'not guilty' so they have to PROVE that this novel compound is active. It's sure fucked up my life. I just don't want to see that happen to you -you seem like a nice bloke and if their is one thing we like on BL are decent people. After all, they are so are in nature.

Sean
Click to expand...
Heres the context. I have a chronic illness thats so severe that id rather be dead than alive with it. There are some possible experimental treatments but in the meantime my quality of life sucks. I am basically bedriddem and in pain most of the time.

I agreee rhat most people chipping could lose control but its just far from the first thing on my mind. I dont have much in the wau of good palliative care docs so i have to figjew out shit that nakes me not wanna kms on my own. Also im bedridden and a carer gives me all my meds. Addiction is about a few tbings, intera cravings and need , and aldo the behavioral patterns that are pathological and come along w that need and feed into it. Im bedridden and very ill so its not like i could go into the street and score or whatever. And i figure i have a year of living left max begorei cant take this anymore. Unless my surgery helps me, itll be lights out. In the meantime im just teying to give myself vacations grom pain and general shittiness.
 
debored13 said:
Heres the context. I have a chronic illness thats so severe that id rather be dead than alive with it. There are some possible experimental treatments but in the meantime my quality of life sucks. I am basically bedriddem and in pain most of the time.

I agreee rhat most people chipping could lose control but its just far from the first thing on my mind. I dont have much in the wau of good palliative care docs so i have to figjew out shit that nakes me not wanna kms on my own. Also im bedridden and a carer gives me all my meds. Addiction is about a few tbings, intera cravings and need , and aldo the behavioral patterns that are pathological and come along w that need and feed into it. Im bedridden and very ill so its not like i could go into the street and score or whatever. And i figure i have a year of living left max begorei cant take this anymore. Unless my surgery helps me, itll be lights out. In the meantime im just teying to give myself vacations grom pain and general shittiness.
Click to expand...

Sorry to hear that - I'm also pretty much stuck in bed. I take opioids to have 4 hours off from being in pain. In my case, totally failed hip replacement and not enough bone to do more surgery. I know how pain just takes over. I hope surgery works for you. I don't know why you aren't being given appropriate analgesia but I didn't either. Doctors are frightened of being sued, maybe?

I know a guy in the US who made fentanyl and got a habit. You can imagine just how BAD a fentanyl habit is. He found MXE was the most useful. If you cannot get that, isophenidine (NDPDA) is pretty good, though I say so myself. Hope it helps with dependence AND pain.
 
Of course having legitimate pain doesn't mean I'm immune to addiction, and if anything just bc of the cost involved and efficiency I try and keep tolerance low and deal with cravings. I will continue LDN but obtain memantine to really help the cravings. I might need a doctor to prescribe the memantine but in the meantime I have some bromantane. I shall be trying this out soon. I also have pure adamantane, my sister has tried it and seemed to get moderately positive effects from it. Also have agmatine.


I have also one other crazy, out there thought. There are studies showing that certain supplements in liposomal form can penetrate cells way more easily making them far more potent. Wonder if this could work for drugs like oxy. There are diy methods to make liposomal drug forms I believe, involving egg yolks or phosphatidylcholine of some kind, and alcohol. People do it for vitamin c, is there any reason it wouldn't work for oxy?
 
Oxycodone already has excellent bioavailibilty and activity, there's not much to be gained from a liposomal formulation.
 
Wonder if liposomal formulations might be good for other opioids like morphine then. Liposomal opium perhaps ? One can apparently make them with alcohol, phosphatidylcholine and A blender
 
Apparently morphine has a poor intranasal bioavailability, read it should be worse than oral. And that with mixed with some compound of which the name I unfortunately don't remember (but can look up) should make a huge improvisation.

That said, I had good results by extracting crystalline morphine out of the XR capsules in Europe that's doable in the kitchen. So guess not everybody is the same.
 
One can apparently make them with alcohol, phosphatidylcholine and A blender
Click to expand...

I trained under an emulsion chemist, making emulsions/liposomes is not as simple as that. You need careful control of each component. As I understand it liposomes are water-in-oil emulsions so you would also need an oil phase.

That said such a method would probably be appropriate for morphine or any other drug with low BA.
 
But really now that I am off opioids more or less for some days, long enough to flush All morphine metabolites out of my system, I have to say they are a fucking weird bunch of psychoactives. With the morphine all the lingering schizo like positive symptoms are completely gone, I tolerante insane amounts of memantine (a nmda antagonist and dopamine agonist, if anything it should according to theory be psychotomimetic but it is not)

Also I feel my nociception is similar like it was under morphine, just the withdrawal increased everything but by skipping that it's back to baseline minus the mental fog. What remains is a heavy tiredness sometimes and a pretty fucked up sexuality, guess from the testosterone suppressing effect of morphine.

Really I can only recommend to those using opioids but have no experiences yet with dissociatives to give them a try. It's different worlds. Am more interested in selektive kappa antagonism or inverse agonism now, eventually delta agonism.. Always felt I benefit more from the transient excitatory effects of opioids and the permanent inhibitory are like a chemical prison...
 
Hey guys, I have agmatine which many people rave about for potentiating opioids. Any tips on how to use it with opioids. Dosing it before or after , etc? Any major side effects.
 
From wikipedia (granted, not very professional but there are many infos to start with):

Mechanisms of action[edit]
Agmatine was found to exert modulatory actions directly and indirectly at multiple key molecular targets underlying cellular control mechanisms of cardinal importance in health and disease. It is considered capable of exerting its modulatory actions simultaneously at multiple targets.[8] The following outline indicates the categories of control mechanisms and identifies their molecular targets:

  • Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, α2-adrenergic, glutamate NMDAr, and serotonin 5-HT2A and 5HT-3 receptors.
  • Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).
  • Membrane transporters. Agmatine specific-selective uptake sites, organic cation transporters (mostly OCT2 subtype), extraneuronal monoamine transporters (ENT), polyamine transporters, and mitochondrial agmatine specific-selective transport system.
  • Nitric oxide (NO) synthesis modulation. Both differential inhibition and activation of NO synthase (NOS) isoforms is reported[9][10].
  • Polyamine metabolism. Agmatine is a precursor for polyamine synthesis, competitive inhibitor of polyamine transport, inducer of spermidine/spermine acetyltransferase (SSAT), and inducer of antizyme.
  • Protein ADP-ribosylation. Inhibition of protein arginine ADP-ribosylation.
  • Matrix metalloproteases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9.
  • Advanced glycation end product (AGE) formation. Direct blockade of AGEs formation.
  • NADPH oxidase. Activation of the enzyme leading to H2O2 production.[11]
Click to expand...
Well, I was interested before in agmatine as well as sarcosine etc. supplements but either they had no effects in me, or more probably, I was too cautious in that time when there was little information about dosage and effects in human. Pretty many of these hyped "nootropics" / supplements didn't work out for me, so maybe I am a bad example. It's supposedly a neurotransmitter and interestingly one of the few you don't need to take as precursors to be effective? Imidazoline receptors are one of the targets of e.g. clonidine which helps with withdrawal but will make nothing about tolerance development.

It acting on NMDAr's looks promising for sure but need to find binding assays to be more specific. If it binds to other targets much more powerfully, this may be misleading. I think the voltage gated Ca2+ channels are the supergroup of targets where the gabapentins work on, and they are known too at least to help with opioid withdrawal. NO synthesis is involved too, activation of NADPHo is oppositing from DXM interestingly where I had a probably wrong theory that it might be responsible for DXM not sharing the same tolerance as arylcyclohexylamine dissociatives through blocking excessive superoxide production. Guess that one was too easy.

This is interesting:

Neurotransmission[edit]
Agmatine has been discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α2-adrenergic receptor and imidazoline receptor binding sites, and blocks NMDA receptors and other cation ligand-gated channels. Short only of identifying specific ("own") post-synaptic receptors, agmatine in fact, fulfills Henry Dale's criteria for a neurotransmitter and is hence, considered a neuromodulator and co-transmitter. The existence of theoretical agmatinergic-mediated neuronal systems has not yet been demonstrated although the existence of such receptors is implied by its prominence in the mediation of both the central and peripheral nervous systems.[8] Research into agmatine-specific receptors and transmission pathways continues.

Due to its ability to pass through open cationic channels, agmatine has also been used as a surrogate metric of integrated ionic flux into neural tissue upon stimulation.[22] When neural tissue is incubated in agmatine and an external stimulus is applied, only cells with open channels will be filled with agmatine, allowing identification of which cells are sensitive to that stimuli and the degree to which they opened their cationic channels during the stimulation period.

Opioid liability[edit]
Systemic agmatine can potentiate opioid analgesia and prevent tolerance to chronic morphine in laboratory rodents. Since then, cumulative evidence amply shows that agmatine inhibits opioid dependence and relapse in several animal species.[23]
Click to expand...
 
one problem with a lot of the small molecule neurochemicals is they are way too polar and too metabolically labile to work as good drugs.

I would expect sarcosine to exist in some charged form no matter the pH, for instance. Either a zwitterion (carboxylic acid deprotonated = negative charge, amine protonated = positive) in neutral solution, the amine would be positively charged in acid solution and the carboxylate would be charged at basic pH. And usually charged compounds are unable to cross the BBB.
 
Well, I got my memantine. What should I know about dosinghg dear, side effects and interactions?


Semi unrelated, but relates to pain management, after some research on bioavailability I'm trying to get my doctor to switch to intranasal oxytocin rather than the sublingual troches I've been prescribed for years
 
How does oxytocin feel? I've wondered about this for longer, never actually bought some though.. the research appears to be unconclusive, some say it improves anxiety and specially social anxiety but some also tell about worsened aggressivity etc. and last but not least there were/are nasal sprays of oxytocin available which are only used to induce birth and don't have mental effects listed ...

The usual dose is 20mg/d, well for Alzheimer. This might be enough to lower tolerance. For withdrawal you will need more, but be cautious it has a huge safety with people tolerating about 8-10x the recommended dosage w/o apparent ill effects but it certainly is a powerful dopaminergic with all implications for mania and compulsion, even worse while w/d when there's high NE. Maybe memantine+clonidine would make a good combo for painless opioid w/d.

Really I can't push this topic enough given the huge pain and general problemacy about opioid dependence and withdrawal.. with NMDA antags opioids loose much of their fears, an almost painless and problemless withdrawal is possible - unsolved question remains for how long you need to continue them afterwards and whether the suppression of craving is permanent (it probably isn't, and will come back after stopping the antagonist, but afaik w/d intensity and longevity are relevant factors for relapse so still not too bad). Might be that for heavy heroin habit a stronger one than memantine is required but I dunno. DXM is good too if you don't get psychotic reactions like I have, and strangely while it's a strong SNDRI it, in moderation is less stimulating than memantine.

There are actually sedative arylcyclohexylamines, I remember one of the briefly available 3-MeO-PCxy (not PCP/PCE) to be sedative - another one heavily psychotic - such one would be the ideal choice for withdrawal, maybe even of GABAergics(?), imho.
 
Morphine tolerance appears to be mostly(?)/completely(??) peripherally mediated, with peripherally selective NMDA antagonists able to block tolerance development. That's remarkable and given the age of the paper, once more weird that we don't see this used. Source
 
Memantine really isn't that of an anticholinergic. It only antagonizes one subtype of nicotinergic ACh receptors, you feel less from smoking yeah but when taken alone I didn't get anything at many times the recommended dosage. DXM is effective too btw in sub-dissociative dosages and to me memantine heavily fucks up sleep while DXM doesn't. It's a stronger psychotomimetic though if you are susceptible to that sort of effect (or can provide you with some nice nighttime visuals).

For sure that's the primary downside of opioids and unfortunately here dissos tend to make little, the euphoric effects might be based on excitatory opioid transmission to which tolerance develops very fast and ultra low naltrexone for example blocks these even but to manage tolerance against pain killing effects seems to be possible.

Maybe you could try ket together with clonidine, an effective antisympathomimetic which shouldn't interfere with it?

From all what I've read, CWE seems to work but never done it and might be wrong about it.

Thanks for the report link :)
 
dopamimetic said:
Maybe you could try ket together with clonidine, an effective antisympathomimetic which shouldn't interfere with it?
Click to expand...
I do actually have some clonidine. But the cause of my blood pressure issues is sort of a mystery. I've tried beta blockers and prazosin, which is more similar to clonidine, and felt pretty bad from them, which made me think the sympathetic nervous system issues are compensating for low blood volume. When I get saline infusions my bp actually lowers. So I'm not sure clonidine wi help but I'll try a small dose of it. If that doesn't work I'll ask my doc to start me on losartan or a calcium channel blocker. Then I may feel more comfortable using ketamine or kratom which mess with my bp some.
 
You must log in or register to reply here.
Top