Drug info - Clonazepam Used to Treat LSD-Induced HPPD [Archive]

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Powder_Reality

04-07-2006, 01:32

Clonazepam Treatment of Lysergic Acid Diethylamide-Induced
Hallucinogen Persisting Perception Disorder with Anxiety Features
by
Lerner AG, Gelkopf M, Skladman I,
Rudinski D, Nachshon H, Bleich A.
Lev Hasharon Mental Medical Center,
Pardessya and Sackler Faculty of Medicine,
Tel-Aviv University, Israel.
Int Clin Psychopharmacol. 2003 Mar;18(2):101-5

ABSTRACT

An unique and intriguing characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appear during the intoxication, in the absence of recent intake of hallucinogens. Hallucinogen persisting perception disorder (HPPD) is a condition in which the re-experiencing of one or more perceptual symptoms causes significant distress or impairment in social, occupational or other important areas of functioning and may be extremely debilitating. Benzodiazepines are one of the recommended agents for the treatment of HPPD but it is unclear which of them may be more helpful. The goal of our investigation was to assess the efficacy of clonazepam in the treatment of LSD-induced HPPD. Sixteen patients fulfilled entrance criteria. All complained of HPPD with anxiety features for at least 3 months and were drug free at least 3 months. They received clonazepam 2 mg/day for 2 months. Follow-up was continued for 6 months. They were weekly evaluated during the 2 months of clonazepam administration and monthly during the follow-up period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Patients reported a significant relief and the presence of only mild symptomatology during the clonazepam administration. This improvement was clearly sustained and persisted during a 6-month follow-up period. This study suggests that high potency benzodiazepines like clonazepam, which has serotonergic properties, may be more effective than low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD.

OccularFantasm

10-07-2007, 18:52

Abrad

10-07-2007, 19:00

So HPPD is caused by a "blocked liver"?
What are you talking about? Please explain?
If you are going to make outlandish claims please back it up with some evidence.

Lehendakari

10-07-2007, 19:12

like clonazepam, which has serotonergic properties,

What does this mean? Serotonergic properties GABA mediated? Or direct action on serotonin? Anybody has anymore info on that?

Lehendakari

10-07-2007, 19:24

Clonazepam-induced up-regulation of serotonin1 and serotonin2 binding sites in rat frontal cortex.

Wagner HR, Reches A, Yablonskaya E, Fahn S.

Chronic administration of the benzodiazepine clonazepam increased the number of [3H]5-HT (5-HT1) and [3H]SPIP (5-HT2) binding sites in rat frontal cortex. In each instance, binding changes reflected increases in the maximum densities of binding sites (Bmax) with no change in ligand affinities (KD). Increases in binding required continued clonazepam exposure (10 days) at high doses. [3H]5-HT binding was significantly elevated at daily dose levels (i.p.) of 5.0 mg/kg but not 2.5 mg/kg. [3H]SPIP binding was significantly increased at drug doses of 2.5 mg/kg but not 1.0 mg/kg. Binding changes were regional in that they occurred in membranes from frontal cortex but not brainstem. A second benzodiazepine, diazepam, did not affect either binding site at daily doses of 30 mg/kg. These data suggest that serotonin receptor changes seen after chronic clonazepam may occur as a compensatory response to decreases in the presynaptic release of serotonin.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2418653&dopt=Citation

Modulation of 5HT1A receptors in the hippocampus and the raphe area of rats treated with clonazepam.

Lima L, Salazar M, Trejo E.

Laboratorio de Neuroquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.

1. Clonazepam is one of the most potent benzodiazepines known to decrease the activity of the central serotonergic systems. The acute and subchronic administration of clonazepam reduced serotonin (5HT) turnover rate in the hippocampus of the rat, as determined by the ratio of the monoamine and its metabolite, 5-hydroxyindoleacetic acid. 2. The modulation of 5HT binding sites and 5HT1A receptors by the administration of clonazepam for various periods of time were studied in the hippocampus and the raphe area by experiments with radioligands. 3. The density of [3H]5HT recognition sites increased in the hippocampus of clonazepam-treated rats in a dose- and time-dependent manner. This increase was impaired by the simultaneous administration of the 5HT agonist 5-methoxy-N,N-dimethyltryptamine. The affinity of this binding did not significantly change. This observation might indicate an increase in some of the 5HT receptors or an increase of the uptake site. 4. The binding parameters for [3H]DPAT, Bmax and Kd, decreased in the hippocampus but not in the raphe area of clonazepam-treated rats. It seems that the presynaptic reduction in 5HT function, resulting in the decrease of its availability at the synaptic space, modifies the corresponding 5HT recognition sites. 5. These changes could be related to the anxyolitic activity or the withdrawal symptoms of benzodiazepines.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7689737&dopt=Citation

^^ HPPD is very real, it only happens in a few individuals but it should not be ignored

darawk

11-07-2007, 00:36

Powder_Reality

11-07-2007, 03:28

Its funny all the diseases they make up. HPPD may be my favourite. If only these people realised its jus some acid stuck in their livers and gallbladders and not a disease. Oh well, i guess some people do enjoy feeling sorry for themselves or need to blame failures in their lives on something. i would imagine this would do well for those people. I do have quite the prediction for this scenario however. As clonazapam wrecks your liver, it would probably lower anxiety for a select few people, and in the long run actually worsen the symptoms of a clogged liver, er i mean hppd. Any other effects of hppd are just post traumatic shit, ehich you could get if you have a bad trip and are emotionally weak. LSD doesn't cause diseases, it doesn't fry your brain, it doesn't mke you crazy. Isn't this one of the things they made up in their original reefer madness style tactics to say all drugs make you crazy in the head.

First of all, I really hope that you're just kidding about LSD getting clogged in someone's liver and gallbladder.

I don't really think that doctors "make up" diseases per se. However, I'm sure there are a lot of people out there who have been diagnosed to have a certain disease when in fact they didn't. I'm guessing that at least 25% - 50% of the people who are diagnosed as being depressed don't actually suffer from depression (just have some of the symptoms because of poor diet, lack of exercise, etc). The whole ADD/ritalin explosion a few years back is proof that certain disorders can gain "popularity" in the medical community. For every 1 person that actually had the disorder and needed medication, another 10 probably received a wrong diagnosis and a ritalin prescription (maybe more).

But HPPD has been shown to be a real (albeit uncommon) disorder. SWIM suffered from the symptoms of HPPD for about a year. His symptoms included visual static and depersonalization/derealization, among others. This was not a very severe case, and pretty much disappeared with time. However, other people have had much more severe cases of this disorder which lasted for much longer. Although I should also point out that quite often HPPD symptoms are more likely to occur in people who have a family history of psychological disorders/diseases (SWIM himself has OCD, which runs in his family on his mother's side).

I believe I remember Nagognog making the analogy of HPPD symptoms being like opening a door in your mind that shouldn't have been opened. Someone who is suffering from HPPD-like symptoms needs to abstain from all further drug use until that door closes again. SWIM says that this is a very good way to describe the psychological symptoms of HPPD. As far as the physical symptoms go (visual distortions, etc. ), I don't think any real conclusions have been made yet. HPPD is a relatively new phenomenon (and with good reason, most of the chemical psychedelic drugs of today have only been used recreationally/gained popularity in the last half-century or so.

Well, I'm kind of rambling on here, so I'll wrap up my post here. Yes, HPPD is a real disorder, but it is not very common, and certain people are more likely to develop symptoms than others. And as far as doctors "making up" HPPD, let's just put it like this: not much is known about HPPD presently, but there are quite a lot of people out there who share similar symptoms that have been linked to excessive psychedelic drug use or unpleasant drug experiences. Hallucinogenic Persisting Perception Disorder is just a name that has been given to these symptoms in order to label it. I'm sure that in the future we'll have a better understanding of why these symptoms occur, but for now we're just going to call it HPPD and give anecdotal evidence of why it happens and how to treat it.

BTW, has anybody else noticed that there has been a lot of discussion about HPPD on the forum lately?

Jatelka

11-07-2007, 06:18

There are a few interesting articles in the archive on HPPD...

http://www.drugs-forum.com/forum/local_links.php?action=jump&id=171&catid=32

http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1142&catid=68

http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1342&catid=65

http://www.drugs-forum.com/forum/local_links.php?action=jump&id=1011&catid=18

FlamingoEDIT: If anyone can find the full articles for the abstracts listed in this thread can they upload them to the archive please?

OccularFantasm

11-07-2007, 21:20

Well let met read all of these things, and you did make some of the same points i was going to make powder_reality, so we are not on totally seperate ideas here. I think the entire use of the DSM IV for anything whatsoever is rediculous. This is a major part of my argument, so i am interested to see what other people may think about that. I don't really see the big deal with hppd however. Also i was not trying to say lsd clogs your liver. That would be pretty absurd. What i was getting at is previous heavy drug use can cause a sluggish liver in which it take longer to detox harmful chemicals, or even not so harmful chemicals. This happened in my pet turtles own experiance, not by a medical study or something. I have also had all the lil things on the list for HPPD since I was born, so that makes me possibly a little irrationaly on the side of it being a disease. Also from what I've found thus far anyway, there is no even suspected chemical inbalence yet associated witht his disease. Like I said however, i need to do a little more research here, make sure I read all the related threads ont he forum, and then i will come back n make a nice neat paper explaining my argument. I fear when I do things without organizing it it can be quite hard to decipher.

Also, I must say I do not fully understand how that extract from pubmed supports claims for hppd. I am not saying that I ignorantly disagree, I just don't understand.

Note the 'heavy drug use' was legitiment and legal, and that is why it is I and not swim. I wasn't going to incriminate myself.

OccularFantasm

11-07-2007, 22:16

On a seperate note, wikipedia classifies flashbacks and HPPD as different things, whereas the first article in those listed here on one of those posts, indicate that HPPD is merely flashbacks when they interfere with ones life. Is there a larger difference that I can not seem to find? I don't see the correlation of colorblindness or visual snow or halos or depersonalization as being even slightly related to LSD, psilocybin, or any other drug use. The actual flashback of seeing events which happened can be seen entirely with post traumatic stress disorder. It is well known that hallucenegenic use is an intense emotional experiance, so is it really surprising people could have these experiances. It just seems as though I am missing something really important here to make the argument make sense for the validity of hppd.

As for the part when swim mentioned of his pet turtles experiance, after that silly turtle took some lsd, he did have the feeling of being on lsd come on and off for a while. After swim detoxed his liver n gallbladder however, this phenomenom dissipated entirely. this was swims idea on that portion. It is not to say that is why all the cases happen, but I would have to say probably at least half. Lsd doesnt harm the liver, but past use of way too many pills very much could, or perhaps heavy heroine or alcohol use. This would cause a scenario where you do have lsd stuck in your liver. (See I wasn't talking fully out of my ass.:))
The fact the clonazapam works against such symptoms does however make perfect sense to swim, regardless of all that new research. the flashbacks are part of an intense emotional experiance, and clonazapam acts to help quell emotional unsteadiness. Its main mechanism acts on gaba if swim isn't mistaken, which is used solely for anxiety. this would thus lead to a reduction in symptoms, or as far as HPPD is concerned, since the disease is only considered real if it negatively affects your life, it would take away the scary or bad parts thus making less of an impact on ones life and thus would eliminate them from having said disease. I've still got more to read up on, as I don't like making points unless I have seen all the different points of views on the subject.

Also, if anyone sees a flaw in my arguments, or sees a part that doesnt make sense, please make a fuss about it. I am very interested in the other side of this. I would imagine not many people if anyone share my point of view, as I concocted it myself, but would imagine at least some parts might be viewed as at least plausable.

Abrad

11-07-2007, 22:26

As for the part when swim mentioned of his pet turtles experiance, after that silly turtle took some lsd, he did have the feeling of being on lsd come on and off for a while. After swim detoxed his liver n gallbladder however, this phenomenom dissipated entirely. this was swims idea on that portion. It is not to say that is why all the cases happen, but I would have to say probably at least half. Lsd doesnt harm the liver, but past use of way too many pills very much could, or perhaps heavy heroine or alcohol use. This would cause a scenario where you do have lsd stuck in your liver. (See I wasn't talking fully out of my ass.)

So based on SWIMS personal experience he came to the conclusion that half of HPPD cases are caused by LSD being stuck in the liver?
I'm sorry OF but I do think that you are talking out of your ass.

OccularFantasm

11-07-2007, 23:55

Just of curiousity, how is it less likely for this to be the cause of a portion of the disease, for which there is no current explanation. I think any theroy is worth mentioning and considering when there is no evidence to support the contradictory claims. Also, can you find any other times where it has been reported of such symptoms subsiding. I searched a lot and found nothing. It seems to me that people beleive in this becuase of the lack of scientific evidence against it, as opposed to a scientific backing of evidence. I can see where not having a bunch of medical studies backing me up could evoke feelings of rejection from the brain, however it should be consistant. There is no evidence to support claims made int he DSM IV. None. And to what would anyone attribute the fabled hppd to. Is it seratonin for no reason being pushed out in excess in certain receptor sites for no reason; and then to say that it is because of lsd or mushroom use. I just can't buy that, especially since I have all the symptoms of hppd and pshcadelics, get this, actually can alleviate symptoms. I need more than being in one old outdated book and having some random study on rats with which we cannot communicate to beleive this crazy theroy. The entire pointof psychiatry is get the customer, i mean patient, to take certain drugs. After a while, the drugs create a further imbalence, coupled with being told the patient is sick. Therefore, this section of medicine will never go broke.

If you can find me reports of people with whatever chemical change this is, show me the changes, make it a worldwide study, and show how the chemical is responsible for the alteration of personality and for the inhibition of normal functioning. Also think about this, drugs have had a war against them for 30-40 years now. If there was actual negative evidence against phsycadelics, don't you think it would be out and more prevalent. Also don't you thinkt he percentages would be more elevated. After all, probably 80 per cent of people have done various pschadelics. Also, almost every study done to show that of a medical illness in psychiatry is rediculously unreliable.
For example the study for people diagnosed with schitzophrenia after smoking weed. It is not made up for people who got schitzophrenia from smoking weed, it was peopel whom have smoked weed before, and have at some later point been diagnosed with schitzophrenia, may the diagnosis be repealed or not. I wouldn't be surprised if swim was one of those lil tallys. Or how about the study where LSD causes chromosome damage. They did manage to make a complete study on it, which many people believed, mainly from their lack of knowedge on the subject. All I'm saying is even if some remote part of the idea of hppd is true, the entire thing together certainly is wrong.

Also, an ass can be a good thing. Many a novel idea have come from someones ass. I think this theroy is far far supperior to almost any other in all of psychiatry. It actualy encompasses trouble in ones head with torble in ones body, an issue most often overlooked, especially in the United States.

And on even another note. What about HPPD symptoms caused by antipsychotics? These are far more intrusive and common than that of safer drugs like lsd and psilocybin, yet it is never published or talked about. Perhaps it could be as simple as u screw around with ur chemicals in rbrain too much and it may take them awhile to get back to their ground state. That first article I read actualy partially supports my claim about the flashbacks being that of emotional unsteadiness. Also in that same article you will see how selective and unrelaible their test selections were. First off, all the people were from a psych ward. You don't even want to know the shit they force down their throats. Secondly, they only chose people whom would make their argument more plausable. Anyone whose effects were not that desired by the tester were thrown out. So thats one study discarded entirely. I still havent read the rest yet so i am not yet able to comment on such things.

As far as I am concerned, my theroy is just as valid as those made by the DSM IV until there is suffcient evidence against it. I guess until then I'll call it my hypothesis. I think even in the event of me being completely and 100% wrong, a study showing such is very much needed. From all the research ont he topic I could find, to my surprise, not one handled anything concerning either the liver nor the lymph nodes (the two major detoxing things). I think the correlation could wind up being shocking to many, however without a study like myself, I am afraid it may be more ass talk. Then again, the world being round was ass talk for hundreds of years. But I think, even if the percentage is wildy low, that my idea about the liver would be rersponsible for some percentage of the hppd patients. I was just using half as an arbitrary figure.

Also, as for reasoning of the whole liver thing, most people whom have used acid didnt do it as their first drug. It is usually done after a person has done heavy drinking and/or a lot of other drug use. This is the case for any person that swim personaly knows who has done lsd or mushrooms, which is probably 50-70 people. Swim doesn't know anyone who did lsd as their first drug. Also please do not discard legal medicines as drugs. All perscription drugs wreck your liver: every single one; with the possible exception of pills to help your liver (which most liekly attack your kidneys instead). These include pills for depression, ADD, insomnia, or any other overly perscribed pill. In fact solely taking those drugs too much can cause some symptoms of HPPD to occur. Even over the-counter-drugs destroy your liver. Why do you think every drug commercial on tv is for people unless they have somethign wrong with their liver. People assume there is only toruble there if there is renal failure from being old or sirosis(sorry bout that spelling) of the liver, the latter being from alcohol abuse. In fact, Americans have worse livers thanany other population in the world, even those africans who drink blood and eat tree bark soup. With all of this, isn't it much more probable that is is the body having trouble getting rid of some garbage than some random craziness sweeping the nation. Theres clearly got to be some sort of reasons for people beleiving not as I do on this subject, and it is those very reasons i am interesting in hearing. I don't care that it goes against what is currently in the books, I want a real reason.

For some reason i feel as though a giant article is going to be posted right below here explaining point by point how I am wrong. I don't expect to be all right with my inital ideations, but i do wish to alter it slightly if necessary as I think it needs to be added to american psychiatry. Well I have written enough, I'll wait for more responses.

Powder_Reality

12-07-2007, 04:16

For some reason i feel as though a giant article is going to be posted right below here explaining point by point how I am wrong.

Don't worry, I'll refrain myself :D

But I absolutely have to point out that I highly doubt 80 percent of all people in the world have used psychedelic drugs. Even if you count marijuana as being a slightly psychedelic drug, I still don't think it would reach 80%.

But on to the main point: OccularFantasm, are you basically just saying that you have a theory about what causes HPPD (the liver hypothesis) and that it's just as plausible as any other theory because little is presently known about HPPD?

I'm completely for people having ideas about unknown things, and I love reading about them. But I think I have to disagree with your hypothesis. I don't know much about biology, but the liver essentially filters different drugs/chemicals, correct? If that's true, then why would your liver hold on to these chemicals instead of just flushing them out/getting rid of them? Even if someone had a very damaged liver, I still doubt that this would effect the duration/after-effects of other drugs that are taken later in life. This logic reminds me of all those urban myths about ecstasy/LSD staying in your spine forever (and you can get high by cracking your back :rolleyes:), etc. If your theory was true, wouldn't that mean that everybody who has ever taken any kind of drug (whether it be LSD, alcohol, or Tylenol) would always feel like they were under the influence of those drugs all at once?

And yes: antipsychotic meds and other drugs all have unpleasant side effects. But HPPD (as far as I can tell) has only ever been linked to psychedelic drug use. Most (if not all) of the stories I've read about HPPD involved people who had an unpleasant psychedelic experience and developed HPPD symptoms without even knowing what they were. It's possible for people to develop placebo symptoms if they know a lot about a certain disorder, and some HPPD cases have probably been completely psychosomatic. But like I said before, essentially all of the HPPD stories I've read about (including SWIM's) involved people who developed symptoms without even knowing what HPPD was.

So in closing: no, we don't know that much about HPPD presently. Most likely because it isn't a very common occurence and only a small minority of people are prone to it. However, we do know (through anecdotal evidence) that it is most likely caused by unpleasant/difficult psychedelic experiences and is more likely to happen to certain people (ex: people with a family history of psychological disorders). We also know what the general symptoms of HPPD usually include. Besides that, further research is needed.

Lehendakari

12-07-2007, 18:22

whoops! Mods delete this!