The theory is the kappa-opioid system that should inhibition emotions and give a state of anhedonia and depersonalisation . The affinity for naltrexone for the kappa system is low so you need a high dose above 150.mg to have a partiel effect.
There is another problem. There has been several brain imaging studies of people with depersonalisation with the model that areas in the prefrontal cortex makes the inhibition of emotions and the insula, the in the structure in the brain that gives the sense of self.
3.structures are very active in this inhibition of emotions in DP; The right ventrolateral prefrontal cortex, the right dorsolateral prefrontal cortex and the medial prefrontal cortex. The ventrolateral prefrontal cortex is regarded as the most potent of the 3 in DP
if one tries to locate kappa opioid receptor in these structures that can inhibit emotions and anxiety only the medial prefrontal cortex can do that. So, if the inhibition of emotion in the other structures is likely with the current knowledge not done by the opioid system and antagonist will not have any effect on their inhibition. There might be people with depersonalisation where the medial prefrontal cortex makes a large inhibition and have some larger effect but in general the right ventrolateral prefrontal is the most potent in DP. It might explain that some have a high response, some partial and some none response to a opiate antagonist. It only affect one of the structures.
You can in theory try to inhibit them with rTMS. I don't think all can be tried in one session. The right VLPFC and the right DLPFC could be tried in a trail.
The medial prefrontal cortex is a part of the "default mode network" that is the network the brain is in when is not exposed to stimuli and at rest. The brain is self-reflective. That is likely to be disrupted in depersonalisation and other strutures related to the network is also very hyperactive active in DP. So, to work medial prefrontal cortex with rTMS one should properly look at depersonalisation as a abnormal and hyperactive "default mode network" that makes the brain highly self-reflective, introspective, defensive to emotions with difficulties to make shifts to other networks that is extroverted towards the world. There is no publications indicating the the medial prefrontal cortex has been tried in depersonalisation like there is for the right ventrolateral prefrontal cortex and the right dorsolateral cortex so I think it is extremely difficult to get someone to work with as it is untried unless it is tried with by researcher with knowledge of DP. There is either no publications where depersonalisation is viewed in from the view of the "default mode network". But, i know that someone has expressed an interest in that perspective. So, it might come in the future. There is a rTMS trail with depersonalisation in France with inhibition of angular gyrus that is a part of the "default mode network". The Temporo-parietal junction( TPJ) is also a part of the "default mode network" and rTMS trails have some significant effect in 50% when neuronavigation for location is used. To include the medial prefrontal cortex with either TPJ or angular gyrus might normalise the depersonalisation more. But, in rTMS trails it is one locations only and not two. If normalisation of a network two location might be more potent. https://en.wikipedia.org/wiki/Default_mode_network
I told my psychiatrist about different studies, and he agreed to give me different things, including naltrexone.
I had told him about that study where they gave low doses of naltrexone to people experiencing trauma related dissociation symptoms. 11 out of 15 felt some improvement. The objective of the low dose (2 to 6 mg /day) was that they can still dissociate if they need to as a protection in case of trauma induced stress. They give descriptions of recovery that felt promising, so I wanted to try the low dose like them before moving to higher dosage.
My prescription is 25 mg/day, because there is no lower dosage on the market, so I cut it in pieces of 6 mg by myself. I took the first one this morning and it did reduce my derealization. The world was more vivid, but I still felt kind of detached from it, it was not full 3D, but I still got more connection to the atmosphere of the place, and had a walk outside just to enjoy the effect. I would say I had -20 to -25% of derealization symptoms. But it is hard to estimate because I might have forgotten a bit what reality feels like after the years, so I might underestimate how far I am from reality, and overestimate the improvement. And I am still full of mental BS default mode chatter.
Also I was surprised by how fast the pill was acting. I felt the very first effects after literally less than 5 minutes.
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