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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, March 7, 2012

The Merits of High Dose Loperamide for Opioid Withdrawal

Basic:

Loperamide, best known as the active compound in Immodium AD, is a synthetic opioid widely used as an over the counter antidiarrheal agent. It was originally controlled under schedule V of the US controlled substance act, due to initial occurences of mild physical dependence and withdrawal symptoms, but is no longer classified as a controlled substance.

Loperamide and other opioids relieve diarrhea by reducing wave-like movements (i.e. peristalsis) of the intestines and allowing time for the body to absorb moisture from intestinal waste. This allows feces to take on a thick, nugget-like form, rather than gooey diarrhea. The constipating action involves the same mechanisms as conventional opioids; loperamide acts as an agonist at mu receptors in the gut. Mu receptor activity in this area produces primarily an anticholinergic response - leading to the inhibition of secretions and smooth muscle functions; or in very high doses, additional side effects such as dry eyes and mouth, sore throat, vision problems, and urinary retention.

Loperamide is highly lipophilic and unable to dissolve in water, which adds to its appeal as a non-prescription compound.  Dissolution of the compound in the gut is very slow. Peak levels are reached in around 5 hours after oral administration. It has a half life of 11 hours. It is metabolized by the liver and excreted via the feces (main kinetic pathway is N-demethylation via cytochrome P450 enzymes).

Use in Preventing Opioid Withdrawal

Loperamide has a limited ability to reach the central compartment when taken in typical doses, so its action on the CNS is insignificant in this setting. Accounting for its limited psychoactivity is its very slow dissolution (~5 hours to reach peak plasma levels), its limited bioavailability (~40%), and a metabolic efflux of loperamide from the CNS (a process in which therapeutic concentrations of loperamide present in central fluid is pumped back out of the central compartment). 

The aforementioned limitations are primarily pharmacokinetic or metabolic in nature and have been overcome with the use of high dosages or the concurrent administration of a metabolic inhibitor of P-glycoprotein (the aforementioned transport protein). Both measures have been found to be somewhat succesful in overwhelming the metabolic function that limits the central activity of the drug. 

With very high doses of loperamide, sufficient to accumulate in the central compartment (spinal cord and brain), marked narcotic effects have been reported. In addition, abstinence suppressing properties have been widely reported in opioid-dependent subjects; who frequently use the drug to reduce, or alleviate altogether, opioid withdrawal syndrome in the abscence of conventional narcotics.

Its effects are unique in some respects but similar to typical opioids in other respects. Most users report a "body buzz" - consisting of a heavy, warm, or weakening sensation in the arms, legs and neck, similar to that produced by poppy tea or plain morphine. Also common is dry and itchy skin, this itching is often particularly intense and may require the use of antihistamines. CNS effects (aside from relief of withdrawal) may include a mild sense of well being or an increase in mood, talkativeness, sedation or sleepiness, analgesia, miosis, emesis and respiratory depression.

It is important to note that loperamide has very limited recreational value; mainly because the risk to benefit ratio in the context of recreational use is extremely unfavorable. The only possibly justified use of such high doses remains temporary alleviation of abstinence symptoms - and even in this case, the risk/benefit merits of this self treatment are questionable.

Risks and Adverse Events:

Such uses of loperamide are not without risk. Loperamine is a synthetic compound of the phenylpiperidine type. Very little is known about its action on CNS and brain tissue, and little is known about the potential for neurotoxicity with either the parent drug or its metabolites, though it shares structural attributes with methadone and meperidine, or more significantly, a neurotoxic meperidine analogue MPTP; a compound linked with irreversible symptoms of parkinsonism. The lack of such known neurotoxic properties with loperamide could very well hinge only on its lack of CNS activity in normal doses - though there have not yet been reports of loperamide-induced parkonsinism to the author's knowledge. However, with its high lipophilicity and slow elimination profile, accumulation of loperamide in the CNS and soft tissue organs could present a real issue, especially in the astronomical dose ranges used in these opioid tolerant & dependent populations; opening up the possibilities of hepatic and renal issues, the aforementioned neurotoxicity, and delayed acute toxicity (overdose). The constipating action itself raises some issues of concern with extended high dose use. 

Deaths have been reported in connection with loperamide, anecdotally and in the literature. One such case described a death in which the cause was ruled as "combined loperamide and ethanol intoxication". There have been anecdotal reports of pancreatitis associated with loperamide. Known adverse events include paralytic ileus or bowel obstruction, toxic megacolon, perforated colon, anaphylaxis, septic shock and death.

Whether or not the short term benefits of high dose loperamide are worth the potential risks, remains up to the individual user. The author however does not reccomend anything of the sort.

28 comments:

  1. what is the incidence of accidental overdose using loperamide moderated doses, combined with a history of tolerating such doses ( 20mg-30mg) est. and would it occur as a cns shut down, with or without seizure, quickly and without other drugs consumed by person.

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  2. The good thing about Loperamide is that once it activates it shuts the withdrawals off for almost two days. You have to experiment with it to find your comfortable dose. It's the best thing to come clean. You may not believe this, but I'm more comfortable on Loperamide than I was on Oxycontin. Oxy would only hold off the withdrawal, demon/flu, for a few hours before I'd have to pop another 40 mg. F..k that! I'm sick of being SICK! Get your old life back, you deserve it! Hey, look at the bright side...you and me sailed off into the sunset where hardly anyone else has been..., or ever will go...it was fun dude...now it's time to respect ourselves and retire. We can always talk about those good 'ol days. They can't take them away.

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    1. I agree. I just want my life back. And I just had major back and hip surgery. It doesn't really help the pain but I'm dealing with it. The loparamide has helped and I'm on day 3 no other drugs.

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    2. I'm going to try this tomorrow

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    3. I'm going to try this tomorrow

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    4. Be very careful when using loperamide. My addictive nature almost killed me (again). I was using loperamide at one point in very high doses achieving full agonist effects while in a work release program as to avoid dirty urine screens. I was having severe side effects, blurred vision, blood red eyes, vomiting. This was over every other day use of about 3 months. I had severe withdrawals upon cessation from loperamide. I began having extreme blood pressure spikes, heart pounding etc. I was taking at first 40 2mg tablets and in the end reached 200+ tablets. I ended up in the cardiac unit for 3 days having horrifying blood pressure spikes head pounding, very pale,vomiting, elongated QT intervals, basically on the edge of death. Thank god that doctor put me on a morphine reduction and I entered a buprenorphine program and have been away from heroin/loperamide etc for 2 years now. I am completely stable living on my own. Be careful and seek professional help. I would strongly recommend some Medically assisted treatment if your having trouble with relapse etc. I cannot condone loperamide, as I foolishly learned its potentially fatal ability to induce Torsades de pointes and other frightening heart arrythmias. It is now making its way into the news with other cases of cardiac complications directly resulting from abuse/high dose loperamide use. I feel for all those out their on the front lines, fighting with the demon of addiction. Hope is always there friends, good luck.

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  3. Good idea, we've over sailed these waters.

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  4. Currently released case studies are showing a connection between severe heart problems and high dose or mega dose loperamide over the long term. You won't see me doing this. I like my heart!

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    1. You wont give a damn about your heart when you are curled up in a cold sweat with what feels like the worse flu youve ever had combined with depersonalization AND the runs all the while feeling like you weigh 1000 lbs. Do the math on not being able to move fast due to atrophy and having the runs...It says LONG TERM...you only do the lope tactic for a few days. Either until you are clean and thru the worst of it OR until you next script.

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    2. You are an idiot if you take this, my 25 year old daughter took imodium from advice of people on the net . And I've been in a ccu for 10 days watching her heart be shocked over and over agin because of the tachycardia, the screaming isn't like anything I've ever heard from a human.
      This shit is rediculas

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    3. You are an idiot if you take this, my 25 year old daughter took imodium from advice of people on the net . And I've been in a ccu for 10 days watching her heart be shocked over and over agin because of the tachycardia, the screaming isn't like anything I've ever heard from a human.
      This shit is rediculas

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    4. Sorry but your duaghter is an idot for listening to everyone on the web, and you are an idot for not teaching your daughter how to properly discern good info and bad info.
      People on the internet say to take like a whole bottle full. I took 4 pills my first time and my stomach hurt, which was obviously a sign that I was very intolerant to it. Some people have different tolerances. Im sorry about your daughter, but you never ever trust peoples word om the internet. Do research. Whenever testing an unknown drug you do threshhold tests to check for sensitivity. Obviously they didn't tell your daughter that.

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  5. I've brought my oxy withdrawl down to tolerate levels with just 8mg of loperamide and an occasional glass of tonic water. The quinine in the tonic water inhibits the action that expels loperamide from the CNS.

    The tonic water tastes pretty nasty, so I use flavoring. If you really can't stand the taste you could probably boil or evaporate it. The quinine is in salt form and should be left behind in the container albeit in small quantity.

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  6. I successfully withdrew from tramadol by using the loperamide on its own for just a few days. I didn't use humongous doses like I've seen, either. I needed 36 mg the first day, 24 the next, 20 the third day. The fourth day I felt fine. I'd been taking 400 mg of tramadol for two years, and I've never seen anyone post they got off it that fast or easily through any other method. I did have zolpidem for three nights as well. I wouldn't push loperamide intake too far or for too many days -- it can carry its own horrid withdrawal. And that seems to happen fairly often from the reading I've done, people trading pain med dependence for loperamide dependence. I took Metamucil and was able to have bowel movement, by the way. I wouldn't take that much loperamide without good stool softeners or the Metamucil.

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    1. It's a long shot, since this is anonymous, but did you have stomach pain or any other negative side effects with the lope dose at 30+mg?

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    2. I usually take 90 mg or more, and I'm in the same boat with the tramadol withdrawals. Yeah, it gets a little uncomfortable, feels like a big bubble inside you. But it goes away after a couple hours. Totally manageable. take it with stool softeners and some fiber supplements, otherwise you'll regret it.

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  7. Please watch this interesting video before even considering loperamide. If it's even mentioned in the same sentence as MPTP, stay away! It may not kill neurons as fast as MPTP but if it leads to parkinson's at some point your life, you will be pretty screwed...

    http://www.youtube.com/watch?v=KsBphHpOfd4&feature=youtube_gdata_player

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    1. I have frequent loss of llegs. They will buckle and shake to the point thAt I cannot work. This is after a 200mg bottle throughout the day
      Stopped taking that and im back to Gabapentin. What is happening to my legs

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  8. I take about 400mg a day... I can see how it starts to weaken the body down.. I have lost a decent amount of muscle strength. To the point where my arm starts to shake when i hold something as light as a cup of coffee too long

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    1. That is in fact caused by heart arrhythmia, common at those dosages. The effect is known as syncope, and is the sign of a serious problem. I would start a strict taper now, because it will eventually stop your heart.

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  9. I like what you said even though it is an old post.

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  10. I like what you said even though it is an old post.

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  11. I lost my 18yo son on 1/28/2015 due to a toxic level of loperimide(22ng/ml) that caused a lethal cardiac arrhythmia. Such a tragic loss of a wonderful young man. I urge folks not to take this drug. We did not know he was going through opiod withdrawl and that he took the loperimide to help him feel better. If I had known I would have taken him to the hospital. Now we have to live our lives without our sweet Lee.

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    1. I am so sorry to hear about your son. My sister is afraid the same thing happened to her son on Nov 17, 2015. He had actually been having seizures for about 8 months and was prescribed several medications to combat the seizures, low blood pressure and other things. She is waiting on autopsy results to find out the exact cause, but the medical examiner called her yesterday asking if her son was ever addicted to drugs. They mentioned finding the loperimide in his system but that had not been mentioned on any of medication list they had been given. She did find OTC medication to treat diarrhea laying around the house on different occasions. Her son told her it took it to help with diarrhea and help him keep weight on. Most of our family suffer with IBS so she didn't think anything of it. Now we are all left to wonder, if loperimide is the culprit for his death. He just went to bed that evening and when she went to wake him the next morning, he was gone.

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    2. That is AWFUL...im so sorry to hear that. Absolutely devastating :'( just one question though... was 22ng really the lethal dose? because i looked it up and thats not even as much as half of an immodium...

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  12. I'm sorry to hear about ur son but one will try just about anything to relieve this pain,especially when they're having to do it by themselves

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  13. Just got the autopsy results back from my girlfriend and mother to my now 4 month old twin girls. Loperamide(immodium) toxicity. Go to a doctor or facility for treatment. Self medicating is not the answer.

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  14. I've now read several different posts on this subject. There will always be pros and cons regarding " is it good or bad " I myself have tried the as they say mega dose but what people must understand is we are ALL different and need to figure out for themselves what is there own " mega dose " no one should jump in and start a crazy high mg. I'm sorry but doing that is just plain stupid. Yes I understand the urge to make it all stop or ease up. Hell there's nothing worse then withdraw and I gave birth to two children pretty much all natural due to the blocks not working and let me tell ya. That was a piece of cake compared to withdraw. My point being is if you're going to try this method,don't go balls out and take a psycho mg dose. Start off at the lowest possible treatment and see how it affects you. Remember it's better to take less then it is more. Less you can baby step your way to the proper mg your body needs. To much and you've screwed yourself only causing more misery. I have muscular dystrophy along with a novels worth of other chronic conditions. So believe it or not Peppe I totally understand the "make it all just stop" monster that drives us to do stupid things we read about or heard is the wonder cure. So in closing I leave you with this. Do your homework,and don't jump in with eyes closed.stick your toe in and go from there. For those who have suffered the ultimate tradjity of losing a loved one. I'm without words and my heart lays heavy with sorrow.

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