My naloxone trial

5494 Views 37 Replies 5 Participants Last post by teal, Jan 28, 2020

teal

Discussion Starter · Jan 23, 2020 (Edited by Moderator)

I've got six Nyxoid nasal sprays, each containing 1.8 mg naloxone. I used the first of them today, eight minutes ago. To get a smaller dose, I blew my nose right after taking the first dose. Got five more doses left for later.

Why try? In the British Journal of Psychiatry they write.

Nuller et al(2001) found a significant transient beneficial effect of naloxone infusion on symptoms of depersonalisation in 10 of 14 patients studied. This intriguing result suggests a possible role of the endogenous opioid system in the pathogenesis of depersonalisation, and the possibility that anti-opioid drugs may have therapeutic value. To date, this hypothesis has not been explored further in the literature, despite the impressive results from this pilot study.

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· #3 · Jan 23, 2020

Several have tried it on the forum either as injection or nasal spray without effect. Doses of 4.mg have some injected . The "study" has never been replicated. This brings us to what is called the replication crisis in almost all fells. In social psychology under 45% of the "known things" can be replicated. Studies unto 80.years old have been rejected because they cannot be replicated -so the claims of false. In medicine there are also a replication crisis and i would say the many trials in relation to depersonalisation can be severely affected because many trials are so small, have often never been replicated. So, people who trys drugs and post it here becomes a kind of replication or supplement to data. Naloxone do not have it.

"In the past few years, there has been a growing controversy surrounding the validity of a number of cornerstone medical research papers. For example, Amgen, a US biotech company, attempted to replicate 53 high-impact cancer research studies and were reportedly able to replicate only six. Similarly, researchers from Bayer, a German pharmaceutical company, reported that they were only able to replicate 24 out of 67 studies. Moreover, John Ioannidis, MD, Professor of Medicine and Statistics at Stanford University-a strong voice in the replication debate-showedthat of 45 of the most influential clinical studies, only 44% were successfully replicated."

https://www.castoredc.com/blog/replication-crisis-medical-research/

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· #5 · Jan 23, 2020

I was convinced until 10.years ago that the opiopate system was the cause of depersonalisation -particularly the kappa receptor system. I think it plays a part in particularly the emotional numbing. People who could tolerate high doses of naltrexone (more than 100.mg) felt a slight reduction. Some who have tried buprenorphin that has a high affinity for kappa felt some reductions close to 20%. If the kappa opioid system play a signification role the reductions would be much higher on buprenorphin. It is not. Dynorphin are expressed in the medial prefronal cortex and can inhibit the amygdala and anxiety and likely make emotional numbing but other parts of the prefronal cortex is overactive in emotional suppression and will not be affected by it. In theory rTMS could affect these locations too.

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· #7 · Jan 23, 2020

it has a very short half-life. It is a acute treatment for a opiate overdose. It can never be a treatment for a disorder due to it short half-life.

"In one study the serum half-life in adults ranged from 30 to 81 minutes (mean 64 ± 12 minutes). In a neonatal study the mean plasma half-life was observed to be 3.1 ± 0.5 hours."

https://www.rxlist.com/narcan-drug.htm

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· #8 · Jan 24, 2020

teal said:
@Mayer-Gross, yeah, people posting here does indeed become some sort of anecdotal supplement to data. That's why I post.

Well, the trail is likely false and a lie. The half-life of naloxone alone would put question into the claimed effect. Many have tried it here. A person that have had DP for most of his life from Switzerland called "huggybear" had his insurance company to pay for several high dose infusions at hospital without effect. He have deleted his profile and all posts. But, many others have posted their experiences too and none points towards it have any effects. There are many debates going 10.years back in the subject. There is none who have been able to make a replication that could not be viewed as placebo.

But, as i said. There is a replication crisis where at least 50% cannot be replicated in medicine and that is in studies with more empirical data sets. Because all trail in relation to DP is very small the replication crisis might be much higher in publication in relation to depersonalisation. There has been a "studies" with "trials" of lamotrigine with a high response rate and reductions that has been retracted because they where fraud. People do post here with reference to it despite it is openly retracted.

https://www.ncbi.nlm.nih.gov/pubmed/21192145

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· #10 · Jan 24, 2020 (Edited by Moderator)

You often have a placebo effect that might be close to 20-30% in some. So, many will report benefit of anything they do.Many posts on this forum about different things tried that worked is likely related to that. I never read it for the same reason, The awareness of a replication crisis is very recent and that trial goes 20.years back. But, the replication crisis is related to recent publications with a high citations. It can be publication with over 2000.citations. In social psychology it is 80.years old trials with high citations that now is being rejected . So, publication that might seem to have high standards have been published and more than 50% fails. Often are those doing the trials active with a partiality and selective in their perception of data. Many researchers are aware of it now. In the german DTI study of depersonalisation they say that they will avoid certain interpretations due to the risk of failure of replication of data. So, they have been aware of it. We also have our selective perceptions and hopes that do data will perceived in optimist ways there is no basis for.

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· #12 · Jan 24, 2020

As i said the opioid system likely plays a role in depersonalisation but not more than 20-30% of the symptoms. Naloxone can never be a treatment due to its short half-life. If our opioid system is up-regulated it will return very quickly when the effect subsides. I think the trial overestimate reductions and setbacks. The same can be said about the rTMS trials. They do no do a follow up on people in months after to look for setbacks or more reductions. In theory some might in a rTMS have a 40% reduction in symptoms that could make more psychological approaches work and make more reductions.Some could return to the original state within a year. We don´t know. It could be both. The french study will look into that.

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· #13 · Jan 24, 2020 (Edited by Moderator)

Trith said:
How do you know they only had a placebo effect? As far as I know, you need a proper study to rule out the placebo effect, but you also need a proper study if you want to prove it is the placebo effect.

And you say that some have an effect up to 20 - 30% due to placebo. How did you determine it was a placebo effect for specific individuals? Or perhaps you are talking about people who have tried something like homeopathy.

Yes, and there is no control group in most studies to rule that out. But, if you look at the theories based on the opioid system in depersonalisation disorder the prime suspect in the part of the system related to kappa/dynorphin system. The affinity of naltrexone on that system is low. We know that from studies of the drug. It mostly affect the endorphins system in a dose of 50.mg and you need a dose 3-5.times higher to affect the the kappa/dynorphin system. The is simple pharmacology. So, to say that a low dose of naltrexone works is very unlikely as not have any affect at all on the opioid system. I have tried both naltrexone 50.mg and nalmefene 18.mg.

There is a placebo effect in almost everything to many people. People buy experience creams that don´t work and the think they look better ect.

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· #15 · Jan 24, 2020 (Edited by Moderator)

I remember when i first read it stroked me that they had the same surname and there was no other authors. So, family related. The other thing is the claim of being at out-pateint programme with such high numbers a patients in the former Sovjet. The awareness of depersonalisation is very low and so many people ending being referred to a outpatient programme sounds very unrealistic. Their response rate is also much higher than the english data. I think it is all made up.

it can be read here.https://www.researchgate.net/publication/49715384_Lamotrigine_in_the_Immediate_Treatment_of_Outpatients_With_Depersonalization_Disorder_Without_Psychiatric_Comorbidity_Randomized_Double-Blind_Placebo-Controlled_Study

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· #20 · Jan 26, 2020

It is the part of the opioid system called kappa/dynorphin that is thought to make a aversive, numbing and dissociate state. There are no drugs selective for kappa. But, the part of the opioid system that morfin and heroine binds to is called MU or endorphin receptor. It give pleasure, one fells relaxed. "Runners high" is related to that. Naltrexone, naloxone and nalmefene blocks this effect. You cannot get "runners high" on them. Because the affinity for kappa is very low most people will not feel it takes DP symptoms but it may give them a more flat feeling as that endorphin system is taken out.

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· #23 · Jan 26, 2020 (Edited by Moderator)

klonopin is the US tradename for clonazepam. In most of Europe it is traded as "Rivotril". When it is used with success in DP it is in a combination with a antidepressant.

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· #25 · Jan 26, 2020

When I took 2,5 mg of Rivotril I was on Duloxetin 60.mg. It is the drug i tolerate the best. It can give some nausea if one starts with 60.mg at once so 30.mg is recommend the first week.

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· #27 · Jan 27, 2020

It can not be used as a diagnostic tool. I would guess that 20-30% might feel a response.So, if that is your idea,- drop it.

I know a danish women who felt nothing from it except being extremely tried. When it works it is the opposite. You fell much more energy and more present . I had tried other benzodiazepines prior to clonazepam without a similar effect. It could be that i was on other antidepressant. It likely shall be on a antidepressant that also works and you have been on for 4-6.weeks before such effect can be felt. There is no blodtest for any mental disorder and DNA test.

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· #29 · Jan 27, 2020

A very odd way to get a diagnosis. You most have a medical history with symptoms you have reported that are in journals. There are scales for the disorder that can be used. If you had a reduction of 30% on clonazepam it would still be very subjective and not something that can be evaluated from the outside. If there are no psychiatrists in your country aware of depersonalisation then it will change nothing. It the UK it is also very underdiagnose despite there have been a research unit for 20.years. The whole foundation of the charity "Unreal" is not about treatment but to bring awareness of the existence to those who suffer from it and health care professional. You may just be in a situation where it is not there.

Here is the situation in Germany;"However, a German study found a 12-month prevalence of 0.007 based on diagnoses given by clinicians, which suggests DPD is severely underdiagnosed, making research challenging in this population.3 Individuals with DPD experience recurrent episodes of feeling detached from oneself (depersonalization) and/or the external world (derealization). Other clinical phenomena of DPD include emotional numbing and somatosensory distortions.4"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158023/

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· #31 · Jan 27, 2020

So, you are hoping for a conformation that you suffer from this refractory/difficult to treat condition by having a response to a treatment of it that do not formally exist. Sounds very reasonable to me.

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· #33 · Jan 27, 2020

I got better on clonazepam 2.5 mg in 2004. I didn't know i had DP but the effect will go away after some 5-6. months due to tolerance and you likely have to use the same amount of time to get of it and you have been on it. Everybody develops tolerance to a benzodiazepine. We tried to find an alternative among the antiepileptic drugs that also affect the GABA system like gabapentine and topiramat. Because of tolerance and the effect in short in the few it works does that you can not be compered with the treatment of a inflammation.

But, you would also take it without have been on a antidepressant for some time. That would really increase your chances.

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· #34 · Jan 27, 2020

I think the chances on a combination of lamictal and antidepressant is just as high as clonazepam. There should be no problem with tolerance if it works. It is much easier to get a prescription on lamictal than clonazepam. I was by the way offered some years ago to start on clonazepam again by the last psychiatrist i saw . I refused that because if it worked i would develop tolerance to it within 5-6.months.

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· #36 · Jan 27, 2020

But, the majority with depersonalisation who tries clonazepam do not benefit from it,- so it is not a diagnostic tool. When i had such a paradoxical reaction there was thought in neurological causes like epilepsy because nobody knew about depersonalisation. I have never by myself thought i suffered from anything somatic. Some psychtrists had over the time thought it could be a neurolocal condition that didn't had enough clair symptoms yet. So, i was though a examination for that.

But, some will say that since clonazepam works depersonalisation disorder dosn´t exist because it is a anxiety disorder with symptoms of depersonalisation/derealisation. You have go to therapy for anxiety. That is the position among some psychiatrists have here in Denmark.

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· #37 · Jan 27, 2020 (Edited by Moderator)

I do not think that 0.5.mg of clonazepam will make any significant reductions in depersonalisation if it should work. i tried to reduce it from the 2.5 mg i remember and i felt it. My psychiatrist was happy something worked and was ok with giving me it. He said we could go as high as 2.mg -3.times a day. 6.mg in total and see if more symptoms would go away. He had to stop shortly after due to illness

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