Expert: Jacqui - 8/7/2008

Question
QUESTION: hi-

(having been a junky for 4 yrs, yes- harm reduction is a sin in america.. luckily that is behind me now)

question- the PROMETA 'protocol' from Hythiam. around here it costs roughly $15,000 to be treated with Prometa. when told this i just laughed a while... i asked if she'd take a check

she would not

anyway, my husband is trying to get off meth so i've been reading alot about it. prometa is just a combination of flumazenil (for benzo overdose), an antihistamine, and gabapentin, along with some vitamins. SUpposed to work wonders according to nealry all reports (there was no placebo controlled study- but in my opinion if a placebo effect is responsible, hallelujah! fine with me)

i would re-create this protocol for my huz but for the flumazenil, it makes me nervous. It can be bought online from canada but is pretty delicate in amounts before becoming toxic

do you have any info on this protocol, or our situation, that might be helpful?
Just so you know, i have a fair background in medical info and neurochem, and i'm not looking to endanger anyone's life. Just want to help my husband stop endangering his own life, yes?

may i add a random question? what does Santa Claus wear in australia? I've been down there but it was in march, april- no santas around..

thanks very much
L

ANSWER: Hey L,

Great question.  It is fantastic to be challenged by this site!  Anyway, I must admit, I had not heard of this treatment, so have googled it and note it is expesnive and private.  I am always a little bit suspicous about private treatments for drug dependency, as the ultimate aim is profit.  So I did a Medline search (medical access database you may be familiar with given your education on this topic) and found a few mentions, but most for editorial comment in journals, not randomised controlled trials.  It actually reminded me a bit about the ultra rapid detox from opiates with naltrexone which was lauded as the "answer to everyone's heroin problem" then basically failed to meet expectations, and in the worst case, lead to a number of overdose deaths afterwards.  

Anyway, I thought I would transcribe a part of an article from Alcoholism & Drug Abuse Weekly (Jan 21 2008) which might shed some light on it -

"It was in June of 2006 that Nora D. Volkow, M. D.., director of the National Institute on Drug Abuse (NIDA) told Congress that she did not support Prometa because there was no evidence that it worked.  Despite the fact that the director of NIDA questioned the effectiveness of an unproved treatment in a congressional hearing, Prometa treatment did not go back on the bench pending the study results.  Rather, Hythiam, which had brought impressive and reputable scientists on board, continued to market the protocol aggressively.  

But there is plenty of suspicion in the research world about Prometa, "I don't think it ever had a scientific basis," A. Thomas McLellan, Ph.D., CEO of the Treatment Research Institute In Philadelphia, told ADAW last week.  "I don't think it has any kind of promising preliminary evidence, from any kind of research."

Because medications are still new in the addiction treatment field, there's a danger that Hythiam, but marketing its treatment before the evidence is in, could damage the public trust, according to McLellan.  "There are many legitimate companies following the rules, trying to collect evidence and be very sure about what they have before they market," said McLellan.  "In the eyes of the public, all medications are pretty much the same.  So when Prometa comes out with out the evidence, it tarnishes the reputation of medications in general."  He added that: "Responsible clinical facilities should ask hard questions and reevaluate whether they want to continue to be involved in it."

Basically, I would ask myself this.  Would they let an untested drug be used on people with heart problems?  The answer is no.  Unfortunately, when it comes to drugs, people just want a quick fix and don't care enough about the users to test treatments properly.  Imagine if there was some guys marketing a treatment for childhood leukemia, with no randomised trials and experts saying it didn't work, but having the little kiddies lining up to have vitimins and some other stuff mainlined into their arms!  

Anyway, after that tirade I must apologise and get back to the facts.  What concerns me about this treatment is that of the 5 pages of articles on the database, they were all editorials with titles containing phrases like "unproven treatment", "questions of why Prometa funded", "Hythiam under review", etc.  

Flumazenil is rarely used for benzo overdose, unless it is in a hospital setting for someone who is clearly not depdendent and has perhaps been given too much.  If it is administered in a benzo dependent person it can bring on serious withdrawal affects such as seizures.  

There is a treatment for amphetamine in Australia that is being trialled with a drug called Modafinil which is a stimulant that improves mood and can be used as an alternative to dexamphetamine.  It is in the early stages so I can't say how it will go.  I don't know if this is available in the states.  

I wish I could offer you some better advice, but I guess this is the problem with drug dependency.  And the bigger issue with amphetamines is that there is not currently a good option like methadone.  Although, perhaps it is a different kind of dependency, and maitenance treatment isn't the way to go.  Cognitive Behavioural Therapy is probably the only tested method for treatment for amphetamine dependency that has a strong scientific base, however I am a psychologist, and I wouldn't place all my hope in CBT!  I guess there are other things to consider and also what your resources are.  I am guessing that if you can access $15,000, you may be able to look at alternatives to Prometa, which might including getting out of the meth environment, psychotherapy, etc.  I would just hate to see you spend that amount of money on something that is unproved and basically dismissed by most of the experts in the field.  Now I know that a bunch of researchers don't know everything about drug use, but between you and I and the lamp post, there are a lot of people in the drug research area that also have personal experience of drug use (although in the US, if they admit it they get hung drawn and quartered), so people often have both perspectives and you are not always faced with the arguments sometimes used by people like Hythiam such as "they are just scientists and they don't understand the pain associated with drug use and how it tears families apart, kills our kids, funds terrorism, makes our president a moron" and whatever other emotional language they can use.  As you know, I adhere to harm reduction which is very much based on research and science and humanism.  However, drug dependency is one of those areas where the anti-science people keep getting heard ... and sometimes I do feel that some people are immune to scientific facts.  But, I have spoken with many families of people who have lost children to drug use who tell me that it is my organisation's fault because we hand out needles.  Whilst I could argue back and say "well sorry madam but the facts are this ..", but there is a time for dry science, and a time for compassion and sometimes we just need to listen to people who think us harm reductionists are evil!  Unfortunately drug use is an emotional issue, and if someone says that they can cure drug addiction, then people WANT TO BELIEVE IT, and this is why people will pay $15,000 for an unproven treatment.

You are obviously very educated and know your stuff.  I would think very carefully about using a treatment like this.  I don't know where you are in the states, but in the past I have been able to refer people to local agencies that might be able to give open and honest advice who also have a local knowledge.  If you would like me to do that, let me know what state and city you are in and I can try to find someone locally who you could speak to.

Anyway, Santa Claus!!!!  He wears speedos (an Australian invention ... kind of our little joke on the rest of the world!) because it is often 40 degrees celcius (over 100 farenheit) at Xmas!  

Please let me know if you would like more info.  I would be really interested in how it goes.  I know I have kind of raved on a bit in this email, but I must say that I really hope that you can work things out.  It can be an enormous pressure on a partner when someone is using.  I would advise that you seek some support yourself, be it from a trusted friend or a professional counsellor.  There are sometims organisations for family and friends of people with drug problems that can be helpful.

Take care, and whatever you do, do it safely!

Jacqui

---------- FOLLOW-UP ----------

QUESTION: tears families apart, kills our kids, funds terrorism, makes our president a moron"

Holy shit, is THAT what made him a moron?? we could get all the liberal meth-heads off the drug forever with that info
<kidding, just got my first good laugh of the day from that>

even better, I'm in Texas- which relates both to Bush joke and your question. Sure, i'm open to recommendations

As for the unproven status of prometa- i went into the Mayo Clinic archives, where prometa was first reported (or whatever word i'm looking for there). After a while i got to the part about how flumazenil affects the GABA sub A alpha 4 receptors. All the other substances i can find that do specifically that are weird poisonous plants (ie, the vietnamese fish berry--- hu?)
not too keen on that, no idea where to get fish berries, i found that endogenous neurosteroids are supposed to help in the GABA department. Ethanol- easy, though potentially it's own problem. so i've been giving him a shot of whiskey with honey and lemon when he's real freaked out.
Then I have one too =)

i'm rambling now, i suspect, will go back to work a while and see what you have to say.
thanks for talking to me about this- i've tried a couple of places here and get no reply- perhaps they think i'm nuts? guess that's ok, i tend to think they are..
L

ps- speedos?? well, i've seen a few guys around beaches that might well have been him..

ANSWER: Hey L,

I am loving getting your questions!  Anyway, Texas ... mmm ... bloody big state, but as our new (left leaning) Prime Minister recently said, it isn't as big as Queensland (Australian state) and I don't think George Dubya was impressed (men talking about how "big" something is often makes them nervous!).

Anyway you are clearly able to answer your own questions and know way more than I do given that we dont have Prometa in Australia.  I am wondering about the GABA link though because amphetamine works on dopamine receptors (hence the hypothesised link with psychosis given that there is a potential link between dopamine and schizophrenia - the dopamine hypothesis).  Anyway, so not sure what the GABA link would be trying to do.  If it is about being a "blocking agent" like naltrexone, then I guess they don't have a history of being very successful in the long term.  If it is about just getting through the withhdrawals, then maybe there is something to it ... although as they often given benzos to people withdrawing from drugs, giving the opposite doesn't seem to make much sense.  

I must admit, I believe that methadone works because it satisfies cravings and lets people address the other issues in their lives.  Other treatments are really just focusing on the physical and not why there was a dependency in the first place.  Given that, I am the first person to say that sometimes people become dependent on drugs because they like them, not becuase they are a sad case or nut bag, or whatever.  Unfortunately, once you have found out how great they are, you can't wipe this memory (although I am sure there are some anti-drug types out there trialling a treatment where they bash people over the head like in the bugs bunny movies so that they can forget that drugs ever existed, and given that they don't need evidence for some drug treatments it would probably get a run!!).

Seriously, I think you are doing extremely well.  You sound like you care very much for your husband, and your support is something that can't be bottled!  Keep it up.  If he is over the physical, then it is just going to be a day to day struggle and about finding support, and looking at other alternatives to enjoy life.  I have searched for some agenices that might be able to give you some info, but their response may be based on their philosphy (ie: the harm reduction ones will probably say what I have said) but they might be worth a go ...

Well I just "googled" harm reduction and texas and got a big zero, so that isn't very inspiring. I googled drug treatment (which I am sure you  have already done), and found this site:

http://www.usdrugrehabcenters.com/drug-rehab-centers/texas-drug-rehab-centers/

But I am a bit concerned at which ones are private and which ones aren't.  

I have to go now, but I am having lunch with one Australia's harm reduction gurus who is part of the international harm reduction association.  I will ask him if he knows anyone in texas who could give you some information.  

Otherwise, I can only reiterate, support, support, support.  Most people stop using at some point.  And make sure you get time to yourself so that you don't get burned out!

Best of luck, and please keep in touch, your questions are very inpiring!

Jacqui



---------- FOLLOW-UP ----------

QUESTION: hello- middle of the night here, sopardon me if i'm fuzzy

i do have a question, perhaps more clear than the ones so far. hope you don't mind the back and forth?

first, to clarify: in my opinion the GABA link is to minimize withdrawal effects. It is given on the first couple of days and then again at 21 days, when cravings are shown to have another spike. My huz took a dopamine drug while in a brief stay at a psyc hospital (in attempt to quit)- the first night he was home- a mere 4 days after he went in, ha- he lost it.  completely freaked out, screaming, then crying, AGITATED. which i later read is a major side effect of ...wellbutrin, i think it was. I believe the flumazenil is supposed to counteract the sort of dopey thought process and excessive sleeping of the first week- which would make sense considering these are alot like benzo OD.

these are just my guesses- always potentially wrong (disclaimer)- as i try to tie information together. I agree that people want to market you a cure-all pill for drug problems, and i also believe they don't want to give you too much info on how those cure-alls work...

why would that be, you suppose??

Anyway, my question is about how long the brain takes to readjust itself back to (ahem) 'normal'. to start making its own dopamine again, to smooth out functionally. this is another thing where some sites say Years, some say 4-6 weeks, some just want to scare you- etc etc

anyone ever study that? i know everyone's bound to be different, but a ballpark idea would be handy..

That's all i've got for the evening- my step kids have been in town for several days and i'm fairly beat! unless i come up with something else from your reply, thanks again for talking to me about all this. and just as add'l knowledge, i've a degree in psyc and rehab, 'physiological psych' having been my favorite. then i worked at a bar. then i taught myself to make stained glass.  it's a weird path huh? i'm also an allexpert in the spinal cord injury/neurology category.. broke my neck once. so- surely our paths will cross again, one way or another?

i aim to get back to australia one of these days.

thanks again- fight the good fight
leslie

Answer
Hey Leslie,

Big apologies for taking a while to reply.  Work was chaotic on Thursday (police activity in the suburb where I work, making running a needle and syringe program difficult, and some local dentist decided that he doesn't like the fact that we exist, so spent the whole day in damage control PR, whilst interviewing nurses for jobs, giving statements to the coroner because a client overdosed and died and ... god, now I am raving!  Anyway, had Friday off and decided to not even look at a computer!

Firstly, wondering if you have ever thought to join the good fight and hook up with a harm reduction movement.  There is apparently one in Texas - Austin - but they are running on a MySpace page, so I am thinking that they are small time!  

I ran a literature search on Flumazenil and came up with some interesting info:

- much of the research on flumazenil is around its use in benzodiazepine overdose in a clinical setting

- when I ran a search on "flumazenil and amphetamine" I didn't get any articles about using the drug for amphetamine withdrawal treatment and all of the research that did mention amphetamine and flumazenil in the one abstract (there were about 9 articles) under this search were animal studies and not related to amphetamine treatment.

- all articles were bloody technical ... but none seemed directly related to the topic at hand.  The mention of flumazenil and amphetamine in the same article abstracts were not directly related (ie: they just both happened to be mentioned in the same abstract, but not about having an effect on each other), so I have absolutely no idea why Prometa is marketed to do what it does!  I just dont get it!

I would be very happy to send you some articles, and if you can think of a way I can communicate my email address to you without posting it on the site, then I am happy to do it (I don't want it up on the site as it is a work address).  Actually I haven't ever offered to give my email (I was asked for my phone number once!)  Just want to keep my private email private, but like I said, if there is a way ...  I am on facebook ... (Jacqui Brown)

As far as it mediating the drowsiness associated with speed withdrawal, my opinion is this:  There are many drugs that reduce withdrawal effects, but that is all they do.  They don't stop people from wanting to use again.  If you are coming off heroin, you can take high dose codeine and it will reduce the withdrawals, but once all of that is over, there is everything else to deal with.  As I said earlier, I am quite an advocate for methadone, but only because it gives people time to deal with other stuff.  I have no illusions that it "cures" drug dependency and I am becoming more and more of the belief that taking drugs to cure drug dependency isn't really going to work.  Perhaps nothing works!  Perhaps it is about the process of going through the process!  

Anyway, in answer to your other question about how long it takes for the brain to 'get back to normal', I found the following which I have transcribed (because I think you understand these things better than I do!):

"Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter" (From Brain Research Vol 1131, no 1)
ABSTRACT:
Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transport (DAT) function.  The resultant potentiation of dopaminergic neurtransmission is associated with psychostimulant addition.  Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphnidate (Ritalin) and benzotropine in CHO cells expressing wild type DAT; cocaine potency also decreased in DAT-expressing non-neuronal COS-7 cells and neuronal N2A neurblastoma cells.  In contrast, the DAT substrate (+)-amphetamine did not display this DUIP fluctuation.  In parallel experiments, no fluctuation was observed for the apparent binding affinities of these 5 drugs.  The DUIP decrease appeared to correlate with an increase in cell surface DAT expression level, as measure by Bmax values and confocal microscopy.  The fact that the DUIP profile of amphetamine divergd from that of the classical DAT blockers is consistent with the idea of fundamental difference between the mechanisms of abused psychostimulant DAT substrates and inhibitoris.  Identification of the cellular factors that underlie the DAT inhibitor DUIP fluctuation phenomenon may be relevant to anti-psychostimulant drug discovery efforts.

After typing all that, I kind of realise it doesn't answer your question at all, but thought that rather than deleting, I would leave it as it is interesting and in the ball park of our discussion.

After trawling through a multitude of articles, there appears to be little evidence off long term damage to the dopamine receptors after dependency to amphetamine or methamphetamine.  So, my answer to your question is that I can't answer your question.  I have been asked this before with regards to cocaine, and the answer I gave was this:

__________________________________________________________
Hi M,

I had a chat to a friend of mine who is expert in this stuff, and basically cocaine works to decrease the reuptake of dopamine, meaning that you have more swirling around your brain.  Over time, there may be a reduction in activity at the receptors, but there is no evidence that this is permanent.  

Brain chemistry is extremely complex, which I am sure you are aware, and the interaction between internal and external stimuli is difficult to separate.  So, someone having reduced pleasure after a cocaine dependency could be hypothesised to be about reduced receptors, or a lingering memory of how good it was before when they were using coke.

So I am really sorry but I can't really give you a definitive answer.  However, a quick literature search didn't yield any particularly mind blowing studies.  Also, my guess would be that if there was solid evidence that cocaine dependency reduced your ability to enjoy sex forever, then the US government would've made a television commercial about it (although they manage to say things about drug use without any evidence anyway).

If you are a student or have access to a university journal database you might like to run a search on 'dopamine and cocaine'.  Although, I have always found those neurochemistry journal articles hard work!

Good luck and stay safe (whatever you do)
Jacqui
__________________________________________________________________________

As you have probably noticed, I tend to type then look for more info, then add more answers.  As I have been answering your question, I have been running different searches on my university database and basically 'dumbed' the question down (took out the work receptor and dopamine) finding:

One study in rats found that the more amphetamine that was given (poor little rats ... or lucky, depends on your view I guess!) the greater the sensitivity to the affects and withdrawal of amphetamines.  This is pretty logical I guess, the longer you are on it, the worse the come down/withdrawal will be!

I also found some stuff on other drugs for amphetamine withdrawal.  Amineptine (a tricyclic antidepressant) has shown good effects - but the research is a little old (1999).  Also newer research has examined reboxetine.  I must stress though that you should ALWAYS GET MEDICAL ADVICE regarding this kind of stuff.  Do you have a doctor you can talk to about this stuff?

You said you were thinking of coming to Australia again ... you have been here before???

Anyway, Leslie I guess the psychologist in me keeps saying psychotherapy.  It isn't worth doing in the midst of withdrawals, but might be worth considering at some point.  You know, drugs have been taken for years and years and people will continue to take them.  What is the answer?   Maybe there isn't one!  You said that you used to be a "junkie" (funny, it's only the junkies amongst us who can say that!  bit like the "n" word for african americans!)  - anyway, what did you find helpful?  Most people do eventually stop using, and your husband will too probably.  Can you guys afford to go away for a bit, just so that he can get some distance between him and the meth?  Somewhere relaxing (I am thinking beach), just take it easy.  Sometimes the best treatment, isn't really treatment at all, it is love, massage, relaxation, sunshine and more love.  Am I getting soppy now?  

Keep in touch, I find your questions incredibly interesting, although I can't seem to answer them!

Stay safe ...

Jacqui