# Naloxone/Lamotrigine experiences + substance general.



## Carpacano (11 mo ago)

Recently I went into a frenzy of cure-seeking research and found myself re-reading the wikipedia pages about depersonalization and dpdr. To my surprise i found them totally re-done with some information like rTMS removed (thank god) and some added. The added information in question was about treatment efficacy of naloxone and lamotrigine. So I'm asking: anybody here has had any experience with those two substances? I will very likely try naloxone (and maybe you could to the same) since:
1) It's very cheap
2) Has almost no side effects and is as safe as it can be
3) I already have experience with intramuscular injection drugs
And will report back. I'm not very sure about Lamotrigine (though I will try to talk about it to my psychiatrist) since it's potentially very dangerous.


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## leminaseri (Jul 1, 2020)

Carpacano said:


> Recently I went into a frenzy of cure-seeking research and found myself re-reading the wikipedia pages about depersonalization and dpdr. To my surprise i found them totally re-done with some information like rTMS removed (thank god) and some added. The added information in question was about treatment efficacy of naloxone and lamotrigine. So I'm asking: anybody here has had any experience with those two substances? I will very likely try naloxone (and maybe you could to the same) since:
> 1) It's very cheap
> 2) Has almost no side effects and is as safe as it can be
> 3) I already have experience with intramuscular injection drugs
> And will report back. I'm not very sure about Lamotrigine (though I will try to talk about it to my psychiatrist) since it's potentially very dangerous.


on this forum are already 74357632566 reports that naloxone didnt work


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## Peter (Jun 25, 2018)

> on this forum are already 74357632566 reports that naloxone didnt work


To be fair, people usually do not get naloxone by infusion as in the Nuller trial, but intramuscular or they snort it. This might explain why it hasn't been working that well.


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## 35467 (Dec 31, 2010)

I dont understand the posts reference to wiki. Wiki says that rTMS trails shows the rTMS at the right TPJ might be helpfull to 50%. It really don't point towards naloxone or naltrexone as being a treatment. 

In medicin 50% of findings or cures can not be replicated. There is a reason to 50% can't now as fraud, to small samples, high placebo effect, biases among researchers and patients. Research in depersonalization might have a replication crisis much higher than 50% because research in it is very underfunded. It is very difficult to get money for research and one donor stopping making contributions might close down research totally as it happened with the depersonalization research unit. So, everthing is small in size, no placebo group no follow up. So, it is close to claims. 
The Fuller "trail" is very small 12. patients. It is a pilot study to test the idea that the opiopate system is involved in depersonalization. It is not a trail for a treatment, there is no follow up as if was a trail. It is a pilot study to see if the opiopate system plays a role. It have not be replicated by others to show it findings is false or correct. People read it as a "trail" for a treatment as they also think a trail is a "free treatment" and a "research unit" is a "treatment center"- the narratives says it has to be like that so they think that. 

Naloxone is an antagonist at the opiapate system given to accute overdoses to opioids. It is used to stop people form going into a respiratory crises and sleep to death from an overdose. 

It has to be given I.V and it have a short half-life of close to an hour. That also makes it unusable for a treatment. 

One on this site, one called "huggybear" from Schizerland who have had all his posts and profile deleted wrote some years ago that he had his insurance to paid a serval infusions at a hospital for several hours in the highest dose as in the Fuller study,- felt nothing.


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## Peter (Jun 25, 2018)

> It has to be given I.V and it have a short half-life of close to an hour. That also makes it unusable for a treatment.


Still some people on the Nuller trial had a response lasting more than 24 hours. Even if it worked only briefly, it might give an indication that other drugs working on the opioid system (Naltrexone, nalmefene, buprenorphine) might be worth a try.



> One on this site, one called "huggybear" from Schizerland who have had all his posts and profile deleted wrote some years ago that he had his insurance to paid a serval infusions at a hospital for several hours in the highest dose as in the Fuller study,- felt nothing.


...and the owner of the former site repersonalization.com responded to naloxone. However lamotrigine worked for him as well, so he sticked with that.


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## 35467 (Dec 31, 2010)

Have tried nalmefene and naltrexone myself. I could not tolerante such high doses need because the affinity to kappa it very low. Felt nothing. I think Joe Perkins could tolerante a very high dose for a long time without effect. One with a heroin addiction here was shifted from metadone to buprenorphine and felt a 20% reduction. The opiate system likely plays a role but not the whole explanation of it. When studies are so small in size, with almost no follow up, no placebo controlled and no replication by others,- you can not conclude much either for or against. There will always be a placebo response of 30-40% felt reduction in some when the trial is active and some weeks after.


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## leminaseri (Jul 1, 2020)

Mayer-Gross said:


> Have tried nalmefene and naltrexone myself. I could not tolerante such high doses need because the affinity to kappa it very low. Felt nothing. I think Joe Perkins could tolerante a very high dose for a long time without effect. One with a heroin addiction here was shifted from metadone to buprenorphine and felt a 20% reduction. The opiate system likely plays a role but not the whole explanation of it. When studies are so small in size, with almost no follow up, no placebo controlled and no replication by others,- you can not conclude much either for or against. There will always be a placebo response of 30-40% felt reduction in some when the trial is active and some weeks after.


got a question for you. do you think the dpdr from which people can recover in a few years is fundamentally (maybe biologically) the same „illness“ as someone who got this for 20 years? and do you still think that the anancasm of one person with dpdr is a factor that the symptoms persist?


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## 35467 (Dec 31, 2010)

difficult to say if those who recover is more recent, have a more anxiety related condition that depersonalization is just a response too. There are some recent German structural brain scans that point towards that the condition becomes more "imprinted" into the brain with more white mater indicating som abnormal networks. Over and underachieve parts of the brain also changes in size like a muscle is over or under used. They also point some networks related to obsessive-compulsive thinking. Some more psychoanalytical models finds this obsessive feeling of "incompleteness" to be precent prior to the outset. In their model the brain makes a "solution" with depersonalization that becomes destructive instead of a brake,- and the brain starts to obsess about depersonalization instead of incompleteness. 

The medial prefrontal cortex is found overactive in some studies with depersonalization. It is a location too deep to stimulate with normal rTMS but after 2015 a deep coil was developed and the medial prefrontal cortex have been tried in research in depression. 1/3 with depression respond to it, many with OCD and PTSD also see a response. A Recent trial with functional brain scan in depression found that those with depression who responded also had new connections between the medial prefrontal cortex and precuneus. These two locations are also the two central hubs in the default mode network and is related to the feeling of the self. So, those who respond gets a more integrated default more network. The precuneus is also found as abnormal in many brain scans studies. A location that can only be stimulated with a deep coil. So, there are some locations never tried in depersonalization but I would say the medial prefrontal cortex is strong candidate as it is related to both obsession and the default mode network.


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## leminaseri (Jul 1, 2020)

Mayer-Gross said:


> difficult to say if those who recover is more recent, have a more anxiety related condition that depersonalization is just a response too. There are some recent German structural brain scans that point towards that the condition becomes more "imprinted" into the brain with more white mater indicating som abnormal networks. Over and underachieve parts of the brain also changes in size like a muscle is over or under used. They also point some networks related to obsessive-compulsive thinking. Some more psychoanalytical models finds this obsessive feeling of "incompleteness" to be precent prior to the outset. In their model the brain makes a "solution" with depersonalization that becomes destructive instead of a brake,- and the brain starts to obsess about depersonalization instead of incompleteness.
> 
> The medial prefrontal cortex is found overactive in some studies with depersonalization. It is a location too deep to stimulate with normal rTMS but after 2015 a deep coil was developed and the medial prefrontal cortex have been tried in research in depression. 1/3 with depression respond to it, many with OCD and PTSD also see a response. A Recent trial with functional brain scan in depression found that those with depression who responded also had new connections between the medial prefrontal cortex and precuneus. These two locations are also the two central hubs in the default mode network and is related to the feeling of the self. So, those who respond gets a more integrated default more network. The precuneus is also found as abnormal in many brain scans studies. A location that can only be stimulated with a deep coil. So, there are some locations never tried in depersonalization but I would say the medial prefrontal cortex is strong candidate as it is related to both obsession and the default mode network.


but then we have some people (even if its limited) who recovers also after 10+ years without a specific treatment. just with things like meditation or lifestyle changes. do you think they reach a shift in their brain what makes that possible or it is a psychological thing? 

my second episode of dpdr was triggered by major depression and anxiety (obsession about becoming psychotic). i took antidepressants, which eliminated my anxiety but the dpdr was still there. im taking the medication for 20 months now and im tapering slowly because i dont like the side effects. i hope that my anxiety comes back because this seems the only way how i can hope for a recover, EVEN if my outset is quite recent. sure my very first bout of dpdr was triggered 11 years ago but my symptoms were very different. i dont think that both episodes came from the same issue


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## Peter (Jun 25, 2018)

leminaseri said:


> got a question for you. do you think the dpdr from which people can recover in a few years is fundamentally (maybe biologically) the same „illness“ as someone who got this for 20 years?


Not necessarily, since other mental disorders can also be both episodic and permanent (like depression or psychosis) and I am not aware of evidence that this indicates a fundamental difference. There is evidence that depression and psychosis can become more severe with each episode and the likelihood of the symptoms becoming permanent rises with each subsequent episode. This might also hold up for depersonalization disorder, where the course patterns "permanent" and "initially episodic, but later permanent" are the most common courses.



> Have tried nalmefene and naltrexone myself. I could not tolerante such high doses need because the affinity to kappa it very low. Felt nothing. I think Joe Perkins could tolerante a very high dose for a long time without effect. One with a heroin addiction here was shifted from metadone to buprenorphine and felt a 20% reduction.


Someone on Longecity was cured while taking buprenorphine. Currently only combining buprenorphine with naltrexone (similar to ALKS-5461) might be the safest and most cost effective way to block the kappa-opioid-receptors.



> but then we have some people (even if its limited) who recovers also after 10+ years without a specific treatment. just with things like meditation or lifestyle changes. do you think they reach a shift in their brain what makes that possible or it is a psychological thing?


They exist, but they are not as common as many people want to believe and in most cases it is difficult to draw conclusions from their recovery stories, especially regarding the direction of causality between the things they did and their recovery. Maybe their symptoms got better by themselves and this made them change their lifestyle?


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## Carpacano (11 mo ago)

Mayer-Gross said:


> I dont understand the posts reference to wiki. Wiki says that rTMS trails shows the rTMS at the right TPJ might be helpfull to 50%. It really don't point towards naloxone or naltrexone as being a treatment.
> 
> In medicin 50% of findings or cures can not be replicated. There is a reason to 50% can't now as fraud, to small samples, high placebo effect, biases among researchers and patients. Research in depersonalization might have a replication crisis much higher than 50% because research in it is very underfunded. It is very difficult to get money for research and one donor stopping making contributions might close down research totally as it happened with the depersonalization research unit. So, everthing is small in size, no placebo group no follow up. So, it is close to claims.
> The Fuller "trail" is very small 12. patients. It is a pilot study to test the idea that the opiopate system is involved in depersonalization. It is not a trail for a treatment, there is no follow up as if was a trail. It is a pilot study to see if the opiopate system plays a role. It have not be replicated by others to show it findings is false or correct. People read it as a "trail" for a treatment as they also think a trail is a "free treatment" and a "research unit" is a "treatment center"- the narratives says it has to be like that so they think that.
> ...


Yeah, just like rTMS, it's a shot in the dark since studies about it are very limited. I think I'll try naloxone anyway, since I've read it's safe, and won't hurt to try at all since it's so cheap. Regarding use, i guess it _can_ actually be usable for treatment because it can either be administered intramuscularly and snorted. If I try, i'll do the former and report back, but I don't have any expectations. Having them utterly destroyed by rTMS taught me this lesson already.


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## Peter (Jun 25, 2018)

> Yeah, just like rTMS, it's a shot in the dark since studies about it are very limited.


I would say we have to work with what we have, of course not without taking notice of the associated problems.



> Regarding use, i guess it _can_ actually be usable for treatment because it can either be administered intramuscularly and snorted.


I might not work if you do not get by IV.



> Having them utterly destroyed by rTMS taught me this lesson already.


What effect did TMS have on you? Which area was targeted?


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## Carpacano (11 mo ago)

Peter said:


> What effect did TMS have on you? Which area was targeted?


None. In fact, It made things worse (but It was probably just nocebo). I think it was the right temporoparietal junction.


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## Peter (Jun 25, 2018)

By the way, my dear friend leminaseri. In Germany there is an opportunity for you to try naloxone infusions:
rTMS + Ketamin und tDCS + Ketamin | Depressionsbehandlung mit rTMS-Neuromodulation Praxis Dr. Tamme (wege-aus-der-depression.de) 

The only catch: You have to pay for them yourself.


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## 35467 (Dec 31, 2010)

There is a recent Chinese evaluation of possible targets for rTMS in depersonalization. It is partly based on all brain scans . They point towards the medial prefrontal cortex as the strongest candidate . It is a location never tried, as all research is done prior to 2015 where a coil that could stimulate this area was developed. This coil is approved to clinal use last year for magventure machines . One can see the diffrent locations in the article and I expect that 80% would be non-responsive. There is a need for a better understanding of networks involved. Many locations have to be tested and people be scan before and after to see changes. There likely is variations in locations people will respond to. It is seen in other conditions like depression and obsessive compulsive disorder. Potential Targets for Noninvasive Brain Stimulation on ... - MDPIhttps://www.mdpi.com › pdf


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## Peter (Jun 25, 2018)

> There is a recent Chinese evaluation of possible targets for rTMS in depersonalization. It is partly based on all brain scans . They point towards the medial prefrontal cortex as the strongest candidate .


Since several studies suggest that topiramate dampens prefrontal activity I wonder whether it could be used to treat depersonalization disorder.


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## 35467 (Dec 31, 2010)

No. I have tried topiramate in very high doses prior to its was known I had depersonalization. I responded by accident with 30% to clonazepam and my psychiatrist and I knew that it was only a matter of time before tolerance would become a problem. So, we tried anti-epileptics that worked on the GABA system like to topiramate or gabapetine. I told a neurologist about the doses I had tried in topiramate and he was surprise I could tolerate it. But I lost of lot of weight.

There is overactivity/overregulation in the prefrontal cortex in almost all depressions and obsessive compulsive disorder. You don't use anti-epileptics to normalize that as it don't work.


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## Peter (Jun 25, 2018)

> I told a neurologist about the doses I had tried in topiramate and he was surprise I could tolerate it. But I lost of lot of weight.


So you did not have cognitive problems, like difficulties finding words? This could mean that topirmate did not dampen your prefrontal cortex. Some people who take topiramate react with increased prefrontal activation, possibly due to a compensatory effect.



> I responded by accident with 30% to clonazepam and my psychiatrist and I knew that it was only a matter of time before tolerance would become a problem. So, we tried anti-epileptics that worked on the GABA system like to topiramate or gabapetine.


Clonazepam might have a special mechanism of action regarding depersonalization other than GABA, since other benzos often do not have the same effect. Apart from that Gabapentin doesn't seem to affect the GABA system directly.


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