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Discussion Starter · #1 ·
Tomorrow the FDA will decide on whether or not to approve ALKS 5461. It is not likely that it does get approved however if it does this is huge for DP sufferers. Considering Yuri Nullers highly successful Naloxone study, it is likely that KOR antagonism could be the answer to MANY of our problems. Everybody keep your fingers crossed. God bless.
 

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Discussion Starter · #3 ·
Could you further elaborate as to why exactly this medication would be a great for us?
it has been speculated that antagonism of the Kappa Opiod Receptor could be very effective in the treatment of DP however this is nearly impossible to selectively antogonize because you would need extremely high doses of naltrexone or nalmefene. A study in 2000 backed up this claim when Yuri Nuller administered Naloxone intravenously to his patients and yielded something like a 60% response rate. This rate could be even higher with ALKS 5461, the first market KOR antagonist.
 

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Discussion Starter · #5 ·
Yes it’s a shame however I know of a fellow DP sufferer who is going to write ALKERMES (the drug manufacturer of ALKS 5461) to do a studies on DP with ALKS 5461 if it is not approved for depression.
 

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I imagine it will get rejected. I do think the reason that THC causes the symptoms of DP (or did with me when I was high) is because it acts on the kappa opioid system:

https://www.researchgate.net/publication/320744792_Antagonism_of_the_kappa_opioid_receptor_attenuates_THC-induced_place_aversions_in_adult_male_Sprague-Dawley_rats

A study on rats showed THC affects were affected by a kappa opioid antagonist. It's believed that CBD has opposing effects to THC and I have found this to be true in my experience. CBD has helped me relax and sleep better, and fingers crossed long term it may help my DP symptoms
 

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Discussion Starter · #7 ·
I imagine it will get rejected. I do think the reason that THC causes the symptoms of DP (or did with me when I was high) is because it acts on the kappa opioid system:

https://www.researchgate.net/publication/320744792_Antagonism_of_the_kappa_opioid_receptor_attenuates_THC-induced_place_aversions_in_adult_male_Sprague-Dawley_rats

A study on rats showed THC affects were affected by a kappa opioid antagonist. It's believed that CBD has opposing effects to THC and I have found this to be true in my experience. CBD has helped me relax and sleep better, and fingers crossed long term it may help my DP symptoms
I believe it will get rejected as well. But this leaves them open to the suggestion that they could do studies for depersonalization. I imagine that there investors won't be very happy so Alkermes may want to take their drug in a different direction.
 

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Discussion Starter · #10 ·
Well I dont know if anyone kept up with the news but it was not approved. They are still pushing forward with studies on depression though and they are conducting studies in many locations throughout the USA. I contacted the people in charge of the study requesting to be a part of the ongoing clinical trial so I might be able to get my hands on the drug.
 

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Why is this thread even a debate? There have been several with heroin addiction and depersonalisation disorder who has been on suboxone/buprenophine with a very low respons as 20 -30% reduction in symptoms. It has a high antagonistic effect on the kappa opioid receptor . It is the kappa opioid system that can shot drown for emotions and the reward system to stress, anxiety and addiction other parts of the opioid system cannot do that so they are excluded. Drugs like naltrexone, nalmefeme and naloxone have either a very short half-life or a very low affinity for the kappa-opioid receptor. The trails done with these drugs where small, not repeated and 20-15.years old. They have never been replicated in larger trails but many on this forum has tried them with no to limited effect effect. Those who have tried drugs like suboxone has had a limited effect. Here is one that had a 20-30% reduction in symptoms with suboxone;

"I wouldn't do it if I were you. I have been on it long term. It's a serious drug. It's what they give heroin addicts to help during the withdrawal process. Most people don't stay on it long term. If you do stay on it long term and want to quit at some point a Suboxone withdrawal is 4x worse than an actual heroin withdrawal. I think it's insanely reckless that people on here are recommending Suboxone/Subutex for depersonalization treatment. These are people who in large have probably not tried it themselves and if so are just being guinea pigs. I highly doubt Suboxone is going to cure or help anyone with DP. If you want to try it that's your call, but if it doesn't help I wouldn't stay on it long term. "

https://www.dpselfhelp.com/forum/index.php?/topic/54131-suboxone/?hl=suboxone

But, depersonalisation is a disorder of cognitive regulation of emotions with many brainstructures involved. This emotional regulation emotions starts at the prefrontal cortex and one structure can use dynorphin in the inhibition of anxiety, stress and addiction is the medial prefrontal cortex and it has been found to be active with other structures in the prefrontal cortex in functional brain studies of depersonalisation. So, emotional inhibition is also done by other structures in the prefrontal cortex that will not be affected by a opioid antagonist. But, these debates are kept alive by ignorants . You can inhibit that response in the medial prefrontal cortex with rTMS and some trails have done it in with people with cocaine addition. But, the right ventrolateral prefrontal cortex that is active in emotional regulation might not be a supressor by itself but likely to mobilised other structures in the prefrontal cortex to regulate emotions. To use rTMS at the right VLPFC will inhibit the instruction to regulate emotions given to other areas in the prefrontal cortex including the medial prefrontal cortex. A selective kappa antagonist if it existed would not cure depersonalisation disorder. It would likely give a reduction in symptoms of 20-30%

The role of the ventrolateral prefrontal cortex but also the angular gyrus in cognitive regulation of emotions can be read here.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801480/
 

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Why is this thread even a debate? There have been several with heroin addiction and depersonalisation disorder who has been on suboxone/buprenophine with a very low respons as 20 -30% reduction in symptoms.
If there were a study on DPDR showing a 20-30 % reduction in symptom severity following ALKS 5461 treatment, then that would be valuable, if not as a treatment then as a clue to which mechanisms are at play.

It would also be valuable to repeat the Russian study on Naloxone, seeing how many would benefit and to what extent. If it'd have no effect on all, that would also be a clue. At the time of writing the British Medical Journal writes the following about treatment of DPDR
"A study of lamotrigine as an adjunct therapy reported dose related benefits, as did studies using opiate antagonists"

https://www.bmj.com/content/356/bmj.j745.full
 

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Totally irrelevent. The right VLPFC cortex that is active in depersonalisation works as a switch to other regions in the prefrontal cortex. We know that from basic research of different areas in the prefrontal cortex and functional studies of depersonalisation disorder. To inhibit the right VLPFC with rTMS will stop all inhibitions of emotions by the all areas of prefrontal cortex, including those areas that works though the opioid system. To inhibit the right VLPFC reduces depersonalisation with 45% on average -especially emotional numbing -but not dissociation.

The study with lamotrigine only mentions a reduction of 30% in 56% of those who tried. On this forum i would say that the response rate in lower among those who have tried.
 

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The study with lamotrigine only mentions a reduction of 30% in 56% of those who tried.
And this was as an adjunct to an antidepressive, I suppose. Which doesn't say much about lamotrigine monotherapy.

To inhibit the right VLPFC with rTMS will stop all inhibitions of emotions by the all areas of prefrontal cortex, including those areas that works though the opioid system. To inhibit the right VLPFC reduces depersonalisation with 45% on average -especially emotional numbing -but not dissociation.
I take it it's this study you're referring to. "20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44%" It does look promising. Even though it's based on only seven patients.
 

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There was a trail with lamotrigine as mono-therapy prior to that without any response.https://www.ncbi.nlm.nih.gov/pubmed/12680746

Yes, the sample size is small. They didn't have any funding for a larger trial. Since 2016 there has been no funding for research at the depersonalisation research unit. Staff is highly reduced.

But, we have functional studies of depersonalisation disorder and we have basic research into models on how the brain regulates emotions. So, we have an idea of the role of the right VLPFC is. We also know that numbing and dissociation might involve two related networks and that is the reason that people can get numbing reduced but not dissociation or dissociation reduced but not numbing.

Here is one who had rTMS done a the right VLPFC after mapping with a MRI-neuronavigation was used;

"So today, my VLPFC was targeted at 1HZ per second I believe? Point is, it fucking worked. Probably a 20-30% reduction in numbness. I particularly noticed when I was driving I looked at the clouds-and they looked like they used to. Really. I have tried tons of meds, and none of them has ever produced an effect remotely close to what I'm experiencing now. There really is something to this, and I'll definetly be continuing with more sessions. More to follow!"

https://www.dpselfhelp.com/forum/index.php?/topic/54723-starting-tms-next-thursday-over-tpj-and-vlpfc/?hl=vlpfc
 
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