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In this post, I try to deconstruct what’s going on in people with depersonalization.

I think depersonalization is a disorder that has different underlying causes and people get lumped into the same condition because they have the same symptoms, even though the underlying cause can be different.  It’s the same case with depression.

Beware that different studies will have contradictory findings sometimes because of different patient populations and also because the studies are conducted differently.

What is Depersonalization?

Depersonalization disorder is characterized by a subjective sense of unreality, disembodiment, emotional numbing and reduced ability to get excited.

What Disorders Are Commonly Found Along With Depersonalization

With an issue like depersonalization which doesn’t have too much science in the neurobiology of it, you want to see what conditions go along with it.  Because that can give you more clues as to what’s going on in depersonalization.

Depersonalization is commonly found with anxiety disorders, such as panic disorder. (R)

It can also accompany (RR2):

The symptoms are sometimes described by sufferers from neurological diseases, such as ALS, Alzheimer’s, MS, neuroborreliosis (Lyme disease), etc…(R)

People who live in highly individualistic cultures may be more vulnerable to depersonalization.

Some Key Brain Changes in Depersonalization

There’s a consensus in studies that depersonalization is characteristic of an overactive prefrontal cortex, which inhibits neural circuits that form emotional experience. (R)

An overactive prefrontal cortex inhibits the limbic system, which impairs “emotional coloring” of perceptions and cognitions. (R)

In particular, there is increased prefrontal cortex activation and reduced activation in emotion-related areas (insula/limbic system) in response to negative, arousing emotional stimuli. (R)

The insulae are believed to be involved in consciousness and play a role in emotion, perception, motor control, self-awareness, cognitive functioning, and interpersonal experience. (R)

Normally when you experience something that should be emotionally unpleasing, the limbic system lights up, but in depersonalization, this activation is reduced.

It’s thought that depersonalization is often caused by a biological response to dangerous or life-threatening situations which causes heightened senses of your prefrontal cortex (which is involved in planning, thinking) and emotional neutrality. If this response is applied in real life (non-threatening situations), the result can be shocking to the individual. (R)

So depersonalization can be considered as a hard-wired stress response in reaction to extreme anxiety comprising increased alertness and suppression of emotions by too much activation of the prefrontal cortex. (R)

So we can see how this condition can have an inkling of adaptiveness, such as in really terrible situations where people need to shut their emotions down and act based on reason.

Other studies show activation in the hippocampus and anterior cingulate gyrus. These regions are also believed to be largely responsible for emotion, learning, and memory.  Overactivity in the cerebellar and extrastriate cortex was also found, which are significantly implicated in visual perception and processing.

Compared to the healthy subjects, subjects with depersonalization disorder showed significantly less activity in Brodmann’s areas 22 and 21 and higher activity in areas 7B, 39 and 19. Dissociation and depersonalization showed higher activity in area 7B (area 7 serves as a point of convergence between vision and proprioception to determine where objects are in relation to parts of the body). (R)

The Nervous System in Depersonalization

Many studies show a suppressed sympathetic or fight or flight system.  This will put you in a kind of dazed state.  The fight or flight (sympathetic) and also the rest and digest (parasympathetic) nervous systems in people with depersonalization are not working properly. (R)

Studies have found that cognitive evaluation of emotional sounds is disconnected from their physiological responses to these emotional stimuli. (R)

For example, depersonalization patients rated unpleasant sounds as less unpleasant (i.e. more neutral) as compared to patient controls. (R)

Despite their neutralizing ratings, they showed overall stronger electrodermal responses to emotional sounds than patient controls (R).

So these people think they were unaffected by a negative event, but their nervous system is elevated.  Therefore, they lose some aspect of their evaluation of their physiological state.   This may be in line with the observation that depersonalization patients have greater difficulties in identifying their own feelings. (R)

This accords with a less active insula in depersonalization, as the insula is involved in the conscious representation of nervous states of the body. (R)

Other studies have found that rather than low sympathetic arousal, depersonalization might be better characterized by abnormal nervous system regulation of emotional responses. (R)

Still, other studies show increased baseline sympathetic nervous activity. (R)

Some examples of nervous system abnormalities:

  • Greater Heart Rate increases to Cold stress (R),
  • Decreased High frequency-HRV (R), which indicates lower vagal tone.
  • Increased Diastolic Blood Pressure during unpleasant orienting responses (a change in the environment that’s less pronounced than a startle response). (R)

The HPA Axis in Depersonalization

One study showed that depersonalization people had less suppression of the HPA axis when given a low-dose of a cortisol-like drug (dexamethasone) and significantly higher levels of morning blood cortisol. (R)

Another study showed that depersonalization sufferers were likewise had less suppression of the HPA axis by dexamethasone compared to a healthy control group.  The more the dissociation severity the lower cortisol response and a blunted stress reaction. Depersonalization people had significantly higher urinary cortisol compared with a healthy control. (R)

Another study showed that base cortisol levels of depersonalized subjects were significantly lower than those of major depression subjects but not healthy controls. (R)

Mindfulness and Depersonalization

The antithesis of depersonalization is mindfulness, i.e. nonjudgmental attention to present-moment experiences. (R)

The more mindful people are, the less depersonalization they have. Dispositional mindfulness was much lower for depersonalization patients. (R)

Mindfulness interventions are regarded helpful for reducing the intensity of depersonalization and increasing emotional awareness. Mindful breathing results in a significant reduction in depersonalization intensity and increased feelings of being grounded . (R)

Improvement of emotional regulation is considered as the therapeutic mechanism of mindfulness exercises. (R)

It is supposed that mindfulness promotes tolerance of negative emotions and improved awareness of the body by directing attentional resources towards physical sensations and breathing, which activates the limbic system/insula and is needed for present-moment sensory awareness. (R) In other words, mindfulness does that opposite as to what’s found in depersonalization.

As a result, depersonalization patients became more grounded by attending to their breathing instead of losing themselves in ruminative self-observation as reflected in a momentary decrease in depersonalization severity. Ruminative and detached self-observation is a core mechanism contributing to the symptom building and maintenance of depersonalization. (R) (probably by strengthening the prefrontal cortex and less limbic activation)

Thus, mindfulness may strengthen limbic/insular processing of emotional stimuli and help overcome impaired self-awareness. (R)

The Suprachiasmatic Nucleus (SCN) and Depersonalization

This is speculative on my part, but I believe problems with the SCN are a significant underlying cause of depersonalization.

People have abnormalities in the prefrontal cortex, limbic system, and HPA axis, all of which are controlled by the SCN.

The SCN connects to areas of the brain responsible for emotion (the limbic system) and also higher order thinking. This is why circadian disruption can cause problems such as ADHD and depression. (R)

The SCN is directly involved in regulating the daily rhythms of the HPA axis hormones involved in stress and also the rest of the nervous system.

All risk factors for depersonalization affect the SCN such as marijuana and psychedelics, anxiety/depressive disorders and neurological disorders are known to have bad circadian rhythms.

This is obvious because people with these disorders often are having wakefulness at night and fatigue in the day.

Damage to the SCN disrupts both the rhythms and the base levels of the HPA axis hormones involved in coping with stress. (R)

SCN has opioid receptors (R), serotonin receptors and is stimulated by glutamate.

All of the preliminarily successful treatments interact with the SCN.  For example, rTMS activates brain regions controlling circadian rhythms. rTMS activates the SCN. (R)

Fluorescent lights, which are hard on your SCN, increase depersonalization symptoms in some rare cases (R, R2).

Other Abnormalities

For the sake of comprehensiveness:

  • Studies show higher cytokines such as TNF. (R)
  • Although I can’t find the source, a book mentions that depersonalization sufferers have lower urinary norepinephrine. (R)
  • According to Dr. Braverman, depersonalization can indicate low levels of brain serotonin. (R)

Drugs and Depersonalization

Serotonin 5HT2C activators can induce symptoms of depersonalization and/or derealization.  Also, opioid and NMDA activators. (R)

The 5HT2A receptor is one that’s responsible for hallucination effects with LSD and psychedelics (R), which are known to also cause depersonalization.

I have a client who got infected with a weird strain of mold and suffered from hallucinations.  Well, mold is a type of fungus and the psychedelics are also often fungi.  I wouldn’t be surprised if the mold worked on the 5HT2A receptors.

A low-dose ketamine, which stimulates glutamate and NMDA, mimics depersonalization disorder. In particular, increased glutamate in prefrontal cortex is thought to be partly responsible for depersonalization. (R)

Opioid blockers such as naltrexone  have shown some promise in the treatment of dissociative symptoms (need a high dose of naltrexone). The mu and kappa systems, in particular, have been implicated in symptoms of depersonalization. (R)


A low inflammatory diet (see lectin avoidance diet) is always the first thing to try – to see if food is causing inflammation.

As discussed, mindful breathing reduced the severity of depersonalization. (R) See my post on the benefits of the benefits of Mindfulness Meditation.

In a Russian study with naloxone, 3/14 people had their depersonalization symptoms disappear entirely and 7/14 showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the opioid system in depersonalization. (R)

Interestingly, there’s increased expression of peripheral opioid receptors observed during rat inflammation (R), but I haven’t seen any studies showing this to be the case in the brain.

Magnesium is nature’s natural NMDA blocker and NMDA over-activation in the prefrontal cortex is one underlying cause of depersonalization.  Load up until you get diarrhea and then back off.

LLLT  may be helpful. The problem with using light therapy (LLLT) is that the parts of the brain that need stimulation most (the limbic system) are the inner areas, so it won’t get enough of a dosage.  Light therapy can help reduce excessive glutamate in the prefrontal cortex, but it will also increase metabolism.

ICES – This will bring blood flow and oxygen to various brain regions that you put it on.  As opposed to LLLT, this will more effectively reach the limbic system and activate it….and you can bypass your prefrontal cortex by putting it on the side of the head next to your ears.

Studies show lower metabolic activity in certain areas of the limbic system.  Getting more oxygen to your brain with ICES can help, especially when combined with LLLT.

Ultrasound – I put this thing on my prefrontal cortex once, and it shut it down.  It’s as if all ruminating thoughts were gone and I was so relaxed for a few days, even more so than general.  But it also diminished my analytical thinking, which came back after a few days.   So the effects seem to be temporary.  If I had sleep problems or depersonalization from an overactive prefrontal, I would use it selectively and smartly to deactivate my prefrontal….But I haven’t seen anyone use this on their head.

Rhodiola is a good supplement to balance the HPA axis, help with your SCN, increase serotonin and reduce anxiety and depression.  It seems like a good all around supplement in this condition.

Cannabidiol reduces dysphoria and depersonalization provoked by THC while contributing its own antianxiety, antipsychotic, pain-relief, anti-nausea, anti-cancer, antioxidant, and neuroprotective effects. (R)  Cannabidiol is a very safe drug, but it’s expensive.  I’ve taken it, but only noticed a small effect.  I think the manner in which you take it is key.

A recently completed study at Columbia University in New York City has shown positive effects from transcranial magnetic stimulation (TMS) to treat depersonalization disorder. (R)

In patients with depersonalization, a single session of right-sided rTMS to the Prefrontal cortex significantly increased arousal capacity, which is good in combatting emotional numbing in depersonalization. (R)  I don’t recommend this approach unless it’s a last resort.  Better use softer approaches first.

A 2011 study involving lamotrigine (an epilepsy drug that reduces glutamate) demonstrated efficacy in treating depersonalization disorder in a double-blind placebo-controlled trial. In particular, 26/36 lamotrigine-treated patients responded by week 12 versus only 6/38 in the placebo-treated participants. The study is not a good one because patients were allowed to take up to 4 mg per day of clonazepam for insomnia and hydroxyzine, which is also an anti-anxiety. (R) But at least we see a 3 drug combo could be helpful for most of these people. 

Modafinil used alone has been reported to be effective in a subgroup of individuals with depersonalization disorder (those who have attentional impairments, under-arousal and excessive sleepiness). However, clinical trials have not been conducted. (R

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  • Cindy Marshall

    Hi Georgie, My name is Cindy and I have been dealing with DP for the last 10 years. I have done a ton of research and I am presently writing a book for DP sufferers. It’s rare to meet someone who has been dealing with this for so long. Would you be open to the possibility of chatting through email? Would love to get your ideas and share mine. Thanks, Cindy [email protected]

  • Danielle

    I have ADD and depersonalization. I wouldn’t be surprised if it is linked. The longer I suffer from this the more I feel it has something to do with each other.

  • cawion

    Take care with Lion mane, it raise Kappa Opioid, as mentionned in the article…

  • Red

    NEJC–the fact that mindfulness can worsen depersonalization or other types of dissociation is actually a sort of “dirty secret” in the meditation world, an elephant in the room that no one wants to talk about. When you consider that many of these techniques were, in fact, designed to foster a feeling of “no-self” in the practitioner, it’s not exactly surprising. I would not recommend that a person who experiences depersonalization spend a lot of time “neutrally observing” their emotions.

    I *would* recommend that anyone who’s interested in this subject Google Lorin Roche and/or the Skeptic Meditations blog to find out more about the potential psychological risks of mindfulness and other forms of meditation and how they can worsen dissociative disorders.

    BTW, new studies and meta-analyses of existing literature are showing that much of the hype over mindfulness as a magic panacea is unwarranted.

  • Nejc

    I made mistake, this 2017 study is the correct one:

  • Nejc

    Please note that depersonalization is only a subtype of “dissociation”. I believe this article could be upgraded by studying dissociation articles (e.g. NCBI).

  • Luka

    My depersonalization is unduced with orgasms. There must be some chemical pathway.

  • Nejc

    Meditation is mentioned but mindfulness meditation often makes my depersonalization worse. This was also ecknowledged in an old study (NCBI: I would still try some other types of meditation (OM mantra meditation, guided imagery, those from Meditainment, …). Let me know how it effects you.

  • Sam

    In my opinion, having gone in a different routes to self-hacking and why I’m so impressed by this site – the problem is not the HPA-axis, low t3 or cortisol levels or any of the other symptoms that the body produces, those are usually the symptoms. And the body usually knows how to auto-correct and naturally heal itself, the same way that a cut on an arm will form a scab and the scab will harden and peel off leaving no sign of an injury. All those self-correct once the healing starts.

    For these psychological challenges there are some profoundly powerful techniques.

    EMDR will remove all major and minor traumas. Minor traumas are like a person has had small stone pebbles and debris in their shoes since childhood and added during adulthood, they’ve been walking for years ignoring the fact that it has changed the way they walk, their gait, and their posture. In life, it’s their outlook on life. EMDR will remove the trauma, no matter how big or small with just the movement of a hand in front of the client and the wisdom of a clinician asking the appropriate questions. We are here talking about phobias, depression, anxiety and other PTSD effects that can include war memories, terrorists attacks, physical violence, any sexual abuse, grief from breavement, disassociation, attachment disorders, divorce ect, ect. One to six sessions is all it takes.
    How it works, well it seems to instigate the power of REM sleep whilst asking the client to bring up the trauma/upsetting event and it starts processing to a healthy memory.

    Other techniques that can complement it are…

    Hypnosis, so that powerful inner states can be accessed and used to bring strength and stability and inner confidence, not to mention creating positive visualisations for the future. Anyone can do self-hypnosis.

    Time-Line Therapy Meta Meditation: The mindfulness of meditation not only allows the person to live in the present moment, reduce all measures of stress but also to be able to release and choose the thoughts that they want to entertain. In addition to mindfulness, meta meditation is known as loving-kindness meditation, which simply means focusing one’s mind on someone we love – then thinking of someone else we love and building that feeling up and then giving that feeling to oneself if we have a poor self-image/self-esteem or self-perception. Then moving that feeling to people we feel neutral about and finally that we may actually dislike, giving them compassion, forgiveness, kindness, Do it at night, before going to sleep but especially – if possible – by using a family album. This changes a person’s perception of who they are and reconnects them to their innate self.

    Meditation – Mindfulness: It keeps you in the present moment, allowing a powerful sense of the present moment.

    Havening: If you can’t get an EMDR practicioner, this is quite brilliant off-shoot of EFT will put you right. EFT works but it usually works after the stressful feeling, thought or physical sensation has occured. It’s rather like bolting the barn door once the horse has bolted. Havening removes the phobias/depression/anxiety and other PTSD effects by calling up the memory and then distracting it whilst flooding the brain with a host of chemicals such as serotonin. And the person is back to who they were. The only problem is that the person may be confused by the sudden return to reality and normal thinking processes, without the sudden feelings of fear, anxiety, apprehension. This will set you free and can be used before EMDR to give you stability and perspective.

  • Georgie

    This is the most informative and helpful site I have EVER seen…. For the first time in the 13 years that this vile condition has ruined my quality of life, you have finally brought me HOPE. While I know it will take time, for the first time I am confident that I will feel “awake and alive” one day !!! Seriously, I cannot thank you enough.

  • Sandy

    Hi – Amazing site!!!

    I have successfully treated my depersonalization disorder with EMDR therapy. Of course, i had already read a Book about this disorder which helped me identify my state of being due to abuse and conditioning. Then I went to hypnotherapy to reach my child self and then i made a list of major teaumas, experiences and time periods of stress and negativity in my life. EMDR unlicked me from this diordervand after addressing the major traimas, smaller ones came to the surface. My life has completely changed and my health has improved. (Also check for mildew/mold/fungus in your environment for all emotionsl, mental and physical and spiritual issues.) thank you for all the work you have invested in this website! Invaluable information!

  • Jerzy Roginski

    Would you recommend supplementing with some l tryptophan before sleep as well for this issue? I already use magnesium and niacin and Phosphedylserine. Also what’s your opinion on lions mane mushroom? I don’t know if it was 5htp that caused my depersonalization or if it was because of my bad lsd experiences. But I will follow these guidelines. I also have Chaga, reishi mushrooms to. Please let me know what you think

  • Ron

    Wondering if depersonalization could co-exist with ADD or executive functions issues since the former is associated with an overactive prefrontal cortex and the latter with an underactive prefrontal cortex. I am guessing it might be possible since different PC areas may be involved. Appreciate any views from Joe or others!

  • fakesens

    Very thorough and interesting look at this condition.

  • Dylan

    Great job man!

    I personally think depersonalization is related to HPA-axis dysfunction, as you mentioned, and possibly low t3 and or cortisol levels. I think low or high cortisol (high which would cause cortisol resistance), would lead to the inability for cells to utilize hormones. I think high or low cortisol is the root cause. I personally think the hpa-axis dysfunction is usually caused by constant stress from a pathogen (like lyme).

  • Deltrus

    Putting ICES on that spot above/slight in front of the ears is really good for team-based video games. Makes me happy and forgiving when normally I get a bit stressed out, emotionally blunted and unfocused.

    I tried putting it on my prefrontal cortex beforehand, and I didn’t perform very well at all in game. Poor focus, poor self control, poor synchronization with things as they were happening.

    I think ICES above the ears might be very good for people who have adhd. It seems like the prefrontal cortex being overactive can lead to people being in their own world while also being susceptible to noxious stimuli.

    I think previously I was over analyzing the physical sensations ICES gives me. Now I think they should be completely ignored. They give rise to psychosomatic patterns and placebo.

    1. Joseph M. Cohen


  • Neville

    Great article, but I’m confused on why you recommend Rhodiola Rosea, which lowers cortisol, for depersonalization when you show studies that say depersonalization is actually correlated with low cortisol?

    1. Hlad

      Rhodiola rebalances hormones.

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