Well since I posted this I've done a massive amount of research into the phenomenon that is called "opiate withdrawals: and have come to the conclusion that it has nothing to do with withdrawals. What appears to be happening is absolutely fascinating and in fact completely turns on its head almost all of the theories about addiction.
So first things first. What is an opiate addiction, and why do you feel the need to use opiates plus, why do you feel sick a'la "dope sick" when you "stop" taking your opiate of choice. Be it, heroin, buprenorphine, Dihydrocodeine, oxymorphol, oxycodone, oxymorphone, morphine - whatever it is what is actually happening? For years people said it was because your MU receptor was in pain. Others said it was agonist this and partial agonist that and whilst other people said it was a karmic rebalancing. If you get really high apparently you have to pay for it by feeling really shitty. Others said it was because you hadn't put your faith in god and others just said you were weak fucked up junkie.
All of this is so wrong. Utterly fucking wrong. I mean the vast majority of ignores biology completely but the the stuff about opiate receptors is based on truths that have been managled by best guesses and very little empirical data / limited animal studies and a anti-drug coalition of governments , law enforcement agencies, massive parasitic drug rehab industry and many other groups who cynically manipulate drug research to ensure its findings keep drugs illegal, especially hard ones like opiates so as to ensure massive amounts of public money flow into their pockets (and allowing for illegal drug to be sold to the western countries and their illegal incomes to fund illegal wars across the planet).
So around 7 years ago cutting edge research carried out between the University of Boulder and Adelaide, by Professor Linda Watkins and Dr Mark Hamilton discovered something utterly amazing that it has utterly changed the paradigm of addiction and drugs.
It will ultimately lead us to a place where you will be able to take opiates without going into withdrawal. You will be able to take as much as you want and you will not become "addicted" or worse become sick when you stop taking them. And this applies to meth and coke as well!
I'm going to paraphrase/boil/summarise their research but essentially this is the deal.
When you take heroin (this applies to any opiate) your body basically breaks it down into two metabolites. One is called M3G (Morphine-3-glucuronide) and the other is M6G (Morphine-6-glucuronide). All opiates basically do this but its a little different with the synthetic opiates like buprenorphine (suboxone) - its metabolites are called buprenorphine-3-glucuronide and buprenorphine-6-glucuronide.
Essentially though the M6G is the stuff that makes you feel high/blocks the pain and all the other great effects that we associate with opiates.
Now, and this is the really really import bit. For many years it was thought that M3G was inactive. This means they thought it did nothing. This is a good example where the "specialists" just made a guess without any actual evidence to back up their findings.
Oh actually it did and it does something so amazing that once you appreciate it, it will fundamentally change how you view addiction.
See M3G binds to a receptor in your brain. It's a funny named receptor, called TLR4 (Toll-Like Receptor 4).
So what does TLR4 you ask. It's primary job is to activate the 'innate immune system'. See when you get sick proteins, presumably from the infection/injury itself bind to TLR which in turn activates your bodies response. Now when you get a flu virus what happens?
You aches and pains, fevers, swelling, you feel awful right. Well a little bit of this comes from the virus itself but much of it comes from TLR4, from a group of chemicals our bodies make that are called proinflammatory cytokines (PC).
From their wiki page; Due to their proinflammatory action, they tend to make a disease worse by producing fever, inflammation, tissue destruction, and in some cases, even shock and death.
There is also research that suggests that PC's are active in causing depression and anxiety.
Does this sound familiar? Anyone here like to let the straighties know what dope sick feels like. Like when your in supposedly withdrawal? I believe the most common refrain/comparisons used to describe opiate withdrawals is to say something like "its like having the flu but times a hundred".
"dope sick" is actually caused by M3G which is made from the heroin/bupe/morphine/methadone/oxy that you've just taken
But wait a minute chugs. I've been told that my withdrawals are caused by a lack of heroin. That because i got really high god is making me sick. I'm going through withdrawals and an intense desire to re-use because i'm weak and i can't control my urges.
No actually ironically enough the reason why you're going through withdrawals and intense desire to use again is because when you've been high on opiates that drug has simultaneously caused a massive quantity of proinflammatory cytokines to build up (M3G use) whilst the powerful pain relieving power of the drug (M6G) has covered up the pain and discomfort caused by inflammatory agents (PCs)
In chronic habitual drug user the elevated levels of these cytokines are crazy high.
In a opiate naive individual, someone who doesn't take opiates regularly the levels of PC's are very low so the pain relieving effect of the opiate last long enough to avoid from feeling any discomfort.
So to summarise. When you take your last shot/pill/hit before going cold turkey that is actually going make your dope sick worse. Its actually going to elevate your proinflammatory cytokine levels. When the pain relieving effects of M6G expire you're hit with the full force of the other effect of the opiate.
As people can attest the time frames also make sense. It can take a good three days for M3G to be metabolised out of your body. Depending on your metabolic rate and other factors it can take upwards of another 5-10 days for the cytokines to be metabolised out as well. This is the usual length of time it takes to get through dope sickness. Which is how i describe it now seeing its not actually "withdrawals".
So a few things. Imagine if heroin didn't have M6G. And you shot it up - and all it had was M3G. You'd go straight into "withdrawals" although it wouldn't be called withdrawals. It would be called dope sick.
Second thing. There is a large body of work that suggests that people who are exposed to stress hormones, cortisol, during early childhood and in the womb have subtle changes made to their brain. The Glia, where TLR4 lives, is apparently different in the brains of those exposed to stress hormones. It also causes significant issues with how our body produces dopamine (the neurotransmitter that helps us be good boys and girls by giving us focus and attention to learn and be obedient.
Now imagine a situation where TLR4 is being activated by some sort of malfunctioning part of the brain during early childhood A small trickle of these PCs have, per the research I've read, all sorts of problems. Depression, anxiety, combined with low dopamine and serotonin levels would create children with all sorts of behavioural problems. ADHD, poor attention in class, inability to focus, depression, anxiety and all sorts of other problems.
You wouldn't know that you're feeling sick, or can't focus because that's how you've always been. If you come from a childhood full of stress and abuse I'd imagine this is even worse.
This explains the wide differences between drug users. Its clear that people have suffered terrible abuse tend to be the most dysfunctional when it comes living and drug use. They have the biggest tolerances to drugs and require massive amounts (why because they've already got elevated levels of these proinflammatory cytokines).
And this has all be confirmed in animal studies. In one of the papers that Hutchinson wrote he basically created for the first time ever, animals addicted to opiates from birth. And he did it by causing physical stress/pain to the mothers before and just after giving birth. He then went and cured the rats from their opiate "addiction" by giving them ibudilast.
And its not just drug use. Overeating, gambling, overspending, excessive fitness/sports power games, and any other habit forming behaviour can create powerful neurotransmitters that alleviate the pain and discomfort caused by this problem.
We weren't born with a choice. We were born in pain. We were born suffering. All of this is confirmed by the very fact that a treatment designed to suppress TLR4 function - ibudilast - is not just working with opiate users but its also working with amphetamine addicts (and most likely cocaine users). In fact there is evidence that suggests it will work with alcohol addiction.
It suggests that there is a universal pathway to addiction and that addiction is primary response to pain and discomfort caused by the build up of incredibly toxic proinflammatory cytokines.
Anyway ibudilast is going to destroy the rehab industry. What I don't understand is why they don't replace morphine/opiate painkillers with M6G. The research shows that pure M6G is a superior agonist (because its not produce any of those nasty inflammatory agents).
Just one last point. Its clear that the researchers are playing a very careful game, making sure they don't pisss off the government but equally working hard to publish and get the research translated into a real world medication. See Hutchinson and Watkins make a huge effort to downplay the massive significance of their research. They tend to use conservative language and description that are in some ways old fashion and quaint. They talk about the research in the context of "withdrawal" and "addiction" when it reality addiction has nothing to do with a compulsion to use drugs without control.
Addiction is when you'll suffer an immense amount of pain if you don't take drug X. So you take it at all possible cost to avoid the huge amount of pain and discomfort that non-taking the drug will cause. Yes there is a degree of wanting to just get high and party but for the most part most people just want to live without pain - just be fucking normal.
So yeah I can't wait for ibudilast to come onto the market. It's going to change alot
references
1.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783351/
2.
http://www.ncbi.nlm.nih.gov/pubmed/25386959
3.
http://www.ncbi.nlm.nih.gov/pubmed/17982582
4.
http://www.medicaldaily.com/cure-meth-addiction-fda-fast-tracks-human-trials-ibudilast-244892
