Since this experience really lead me to do some thinking as to what happened inside my brain and I would also like to give you an idea of why these state was so fascinating to me, I'd like to lose a few words on similarities between the state I triggered to known medical conditions. All of these conditions either involve dysfunctions of NMDA receptors, the frontal lobe or feature symptoms classically associated with frontal lobe dysfunction. I will mostly quote from wikipedia and journal articles, but will skip listing most sources since it's just too much work. It can all be found online though.
The listed symptoms and features are very selective and incomplete! Many symptoms overlap between conditions.
This is a brief summary of the physiological function of the frontal lobe which is part of the cerebral cortex:
http://en.wikipedia.org/wiki/Frontal_lobe#Function said:
The function of the frontal lobe involves the ability to recognize future consequences resulting from current actions, the choice between good and bad actions (or better and best), the override and suppression of socially unacceptable responses, and the determination of similarities and differences between things or events.
The frontal lobes also play an important part in retaining longer term memories which are not task-based. These are often memories associated with emotions derived from input from the brain's limbic system. The frontal lobe modifies those emotions to generally fit socially acceptable norms.
Psychological tests that measure frontal lobe function include finger tapping, Wisconsin Card Sorting Task, and measures of verbal and figural fluency.
Reduce this to a single statement and you will yield something like: The frontal lobe is the chief executive officer in charge of the brain. :D
Since NMDA receptors are insanely complex, I will just give a very rough outline of their function:
http://en.wikipedia.org/wiki/NMDA_receptor said:
The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function. Like nicotinic acetylcholine receptors, they control an influx of cations which is in both cases mediated by ligand binding.
Organic damage to the frontal lobe:
- Examples: Tumors, vascular hypoplasia, aplasia or malformations, ruptured blood vessels, arterial occlusions, other tissue malformations, traumata etc.
- All of these conditions can also be a cause Frontal Lobe Epilepsy, but some symptoms will manifest without seizures.
- An infrequent effect is that of reduplicative paramnesia, in which patients believe that the location in which they currently reside is a replica of one located somewhere else.
→ As you might remember I mentioned that "I [was] crawling on the ceiling". I actually observed my bed from up there and felt that I had switched position from down on my bed to up on the ceiling in an instant
→ I also reported "now I'm here, now I'm there" which was based on the impression of quickly alternating between various locations and the sense of these switches overlapping.
- Emotions that are felt may not be expressed in the face or voice. For example, someone who is feeling happy would not smile, and his or her voice would be devoid of emotion.
→ Most of you have seen people intoxicated by dissociatives and will know their expressionless empty stares very well, even when they are aware of their surroundings.
Simple frontal lobe epilepsy OR psychogenic (non-epileptic) seizures:
- The two diagnoses are very hard to differentiate without imaging techniques and since I showed symptoms most common with both states I will just group them together:
- Seizures occurring in these regions of the brain may produce unusual symptoms which can often be misdiagnosed as a psychiatric disorder, non-epileptic seizure or a sleep disorder
- During the onset of a seizure, the patient may exhibit abnormal body posturing, sensorimotor tics, or other abnormalities in motor skills
- Tonic posture and clonic movements are common symptoms among most of the areas of the frontal lobe, therefore the type of seizures associated with frontal lobe epilepsy are commonly called tonic-clonic seizures.
- Complex automatisms like kicking and pelvic thrusting
→ I was turning around on my bed in a very bizarre and unsettling fashion, without having control over my movement ("the walls were turning and so was I"). The whole body seemed to be involved, especially the lower part of it.
- Dystonic motor movements are usually the first symptom in Frontal Lobe Epilepsy episodes where they are quite brief and
do not affect consciousness.
→ I indeed remained conscious during this brief episode which seemed to begin sometime around the time the involuntary body movement started.
- Repetitive vocal outburts
→ I was "speaking in tongues"
- The person no longer behaves like him or herself; planning for the future, judgment, decision-making skills, attention span, and inhibition can decrease drastically in someone whose frontal lobe is damaged
→ Parallels should be pretty obvious here. Especially my ability to rationally evaluate the situation was severely impaired.
- Motor symptoms of seizures in the medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions are accompanied by emotional feelings and viscerosensory symptoms.
- Fear is associated with temporal and frontal lobe epilepsies, but in FLE the fear is predominantly expressed on the person's face whereas in TLE the fear is subjective and internal, not perceptible to the observer.
→ Fear set in very abruptly as it would during a seizure. There was a specific moment in which i realized my "brain broke" which caused a great deal of fear, as did my explanation attempts (demonic affliction, irreversible batshittedness).
- Geschwind Syndrome
→ See below for a thorough evaluation of the link between the dissociative experience and what has been coined 'Geschwind Syndrome'
Autosomal dominant nocturna frontal lobe epilepsy::
- Very similar to simple focal frontal lobe epilepsy, but a genetic pathogenesis has been identified.
- Clusters of nocturnal motor seizures, which are often stereotyped and brief (5 seconds to 5 minutes)
- A minority of individuals experience daytime seizures
- They vary from simple arousals from sleep to dramatic, often bizarre, hyperkinetic events with tonic or dystonic features.
- Affected individuals may experience aura.
- Retained awareness during seizures is common.
- Fear is a very common occurence
- Psychiatric comorbidity may occur
- I mostly mention this illness because of the distinct pathomechanism of the disorder compared to Frontal Lobe Epilepsy. It is caused by gain of function mutations in genes which code for nicotinic acetylcholine receptor subunits. This leads to a hyperactivity of these receptors which in turn causes NMDAr modulation and increased dopaminergic activity in certain areas of the brain. In fact, α7-nAchRs and NMDArs form a complex through protein-protein interactions. Both are critical for some critical neuronal processes like LTP and LTD. It's just something to keep in mind because it shows how the causes for very similar symptom complexes can vary while still sharing downstream pethomechanisms. The exact nature of the interaction between NMDArs and nAchRs are still subject to speculation. Enlighten me if you know more.
- It is worth noting that while I am on antiglutamatergic dissociatives I become extremely sensitive to nicotine. It will simply (functionally) throw me back in time to when the dissociative effects were still much stronger to the point of me diving off into a hole again after it had seemingly ended. This further hints at an intricate relationship between nicotinic acetylcholine receptors and NMDA receptors.
- Some forms of psychosis can be treated successfully with antagonists to α7-nAchRs.
- Ketamine's metabolites show inhibitory activity at the α7-nicotinic acetylcholine receptor which may contribute to the clinical effect of ketamine.
- Both Dizocilpine and PCP have binding sites on nicotinic acetylcholine receptors, the former being a non-competitive inhibitor
- These and a number other findings sufficiently indicate an involvement of nAchRs in the dissociative experience
Cotard delusion:
- Central symptom is a nihilistic delusion which is the conviction of an object or a concept being non-existant
- The most common nihilistic delusions concern body parts or the entire body (86%)
- Another common delusion denies the own existence (69%)
- Guilt is present in 63% of patients
- Hypochondriacal delusions are very common (58%)
- Delusions of immortality occur in 55% of patients
- Depression is reported in 89% of subjects
- Anxiety is present in 65% of patients
→ This type of delusion seems only distantly related to the posted experience and it isn't too closely linked to frontal lobe disorders either, but I still think it is of interest since it seems to be a common theme in very stressful drug experiences. It also commonly co-occurs with depersonalization which I find is deeply linked to the dissociative experience (more on that later) and depersonalization disorder.
→ The symptoms remind me a lot of how people often explain their psychedelic and dissociative experiences. The theme of 'having died' is probably the most common interpretation seen in the most severe and subjectively overwhelming intoxications with said substance classes
→ I had a very striking feeling of being observed by loved ones from inside my brain which caused a great amount of guilt or was caused by it. "Everyone was there to see the pitiful scrambled mess I had become." were the words I chose. This feeling accompanied the entirety of the experience before the full-on psychotic break occured. I apparently came to the dreadful realization I would never return reflected by "They were standing in my mind saying their goodbyes."
→ While I am far from being an expert in the field, I (and many others I guess) have strong doubts about Cotard delusions actually being a clinical entity of it's own with a specific pathomechanism. The brain regions involved are subject to variation and it co-occurs with countless psychiatric and neurological disorders. I personally look at it as a subconsciously fabricated delusion which serves the self as an explanation to a variety of difficult to integrate psychological phenomena. Generally, the temporal lobe seems to play a larger role than the frontal lobe, this much has been shown.
In fact (this goes a little off topic) I would go as far to describe all psychotic hallucinations and delusions as being an expression of a huge number of experiences which are of such emotional gravity, are so alienating, scary, pleasant or plain fascinating that the mind starts to come up with explanations that it can entertain, however strongly they are in opposition to how the world around the delusional person explains them (usually with a broken brain).
This could be the delusions of being the messiah, voices forcing their version of the truth into your ear, the assumption to have died, the idea of being possessed, the creeping feeling of the world having turned against yourself (which it obviously
really has in most cases of acute schizophrenia!), the list goes on and on. Each of these can be explained as an expression of their underlying distress and if you ask me, the way the vast majority of modern psychiatry (as big as a fan I may be of the meds) explains delusions and hallucinations is a fucking tragedy. One day we will laugh about it and I really hope to be able to contribute to that. I already do as a patient lol.
Depersonalization disorder:
- Depersonalization disorders are conditions that involve disruptions or breakdowns of memory, awareness, identity, or perception.
- People with dissociative disorders (which depersonalization disorder is classified as) use dissociation, a defense mechanism, pathologically and involuntarily. Dissociative disorders are thought to primarily be caused by psychological trauma.
- Depersonalization disorder often co-occurs with Cotard syndrome, deja-vus and reduplicative paramnesia.
- Sometimes misdiagnosed in patients with frontal lobe epilepsy
- The regional cerebral blood flow ratio is decreased among patients with dissociative identity disorder in the orbitofrontal region bilaterally. It is increased in median and superior frontal regions.
- Can be a reaction to organic brain damage (see organic frontal lobe damage section above)
- However, and this is what makes this condition so interesting, frontal lobe involvement is not a necessity for depersonalization to occur (but usually can be observed) which hints at an overlapping with downstream processes of other disorders I listed.
- Even more remarkable is the fact that depersonalization disorder
commonly co-occurs not only with Cotard syndrome, but also with deja-vus und reduplicative paramnesias!
→ As a child I experienced frequent mild depersonalization without ever having seen a doctor about it, often coupled with an intense sense of deja vu. The state reminded me of (or was identical to) a state I experienced in a specific type of recurring nightmare. The nightmare was so strange in nature, that I still lack the words to describe it today. It was characterized by two forces battling and me being caught in between.
Now, over 20 years later I experience this state again, first on diphetidine, then on 2-methoxy-dipehtidine! I have described it in detail in the Big and Dandy Diphenidine thread. I could willingly step in and out of the state. This was profoundly impressive to me, since it showed how similar processes are apparently involved in both depersonalization as well as the dissociative experience. I cannot stress enough that this state was essentially identical to the one that haunted me in my dreams and the much milder one I experienced during waking hours.
Neither Ketamine, nor MXE, PCP or DXM or any other dissociative have ever allowed me to enter this state (despite hundreds of experience), but it has occured frequently on diphetidine and 2-methoxy-diphetidine. To me this is absolute proof that diphetidine has a novel mechanism of action and no pharmacological paper could convince me of this not being the case, no matter how hard the authors would hammer their case! Unfortunately I am not aware of much research being conducted on the two substances. They have however been shown to show differences in action to dizocilpine.
First manifestation of Anti-NMDA Receptor Encephalitis:
- Behavior changes are a common first symptom. These changes often include increased agitation, paranoia and psychosis
- Other common first manifestations include seizures and bizarre, often rhythmic, movements mostly of the lips and mouth but also including pedaling motions with legs or hand movements.
- Some other symptoms typical during the disease onset include impaired cognition, memory deficits, and speech problems (including aphasia or mutism).
- The symptoms usually show as psychiatric in nature. In many cases, this leads to the illness going unnoticed.
- It is important to note one distinguishing characteristic of Anti-NMDA Receptor Encephalitis is the concurrent presence of many of the above listed symptoms. It is extremely unusual that patients have only one or two symptoms- the majority of patients experience at least four symptoms with many experiencing six or seven over the course of the disease.
→ There really isn't much left to say here. Pretty much all these symptoms occured during my experience and many can be commonly observed in intoxications with antiglutamatergic dissociatives.
-As they recover, many will have symptoms of frontal lobe dysfunction (poor attention and planning, impulsivity, behavioral disinhibition, memory deficits), which improve over months.
→ Go figure! :D
Schizophrenia:
- Obviously I cannot give this psychiatric diagnosis the amount of attention it deserves, so I will limit myself to pointing out some features of schizophrenia
- Because many of the problems that patients with schizophrenia have involve the regulation of their behavior, the regulation of their perception of their cognitive apparatus, the ability to organize behavior so that it fits the contextual environmental context – these functions which are thought to be served by the frontal lobe suggest that the frontal lobe is not really working that well in schizophrenia.
- Compromised signaling through the N-methyl-D-aspartate (NMDA) receptor has been linked to positive, negative, and cognitive symptoms of schizophrenia.
- Studies in postmortem brain have identified altered expression of several structural and signaling molecules of the postsynaptic density (PSD), including the abundantly expressed protein PSD-95, which binds directly to NR2 subunits of the NMDA receptor and regulates its trafficking, membrane expression, and downstream signaling.
- The density of the GAD67+/NR2A+ (the latter is an NMDAr subunit) neurons was decreased by [~50%] in schizophrenia. These findings raise the possibility that glutamatergic innervation of inhibitory interneurons via the NMDA receptor in the prefrontal cortex may be selectively altered in schizophrenia.
- A lot of this has really been established and there are many striking abnormalities in the prefrontal cortices makeup of schizophrenic patients, eventhough a direct causative relationship between NMDAr's and the changes seen in the frontal lobe are a matter of ongoing debate.
Demonic possession:
- Obviously not a medical diagnosis, but it still would be the most plausible explanation for my symptoms in most cultures (and so it was for me, at least I alternated between that conviction and the classical 'I have gone bad shit theme')
- Apparently some shamanistic cultures explain psychotic states as being a sign of great distress due to a person being afflicted by ghost like entities and finding himself inable to cope with the situation. Overcoming the psychosis marks the birth of a healer and psychotic breaks are therefore viewed as one of the most fortunate events in the life of a person. Truly a very interesting subject! Additional literature:
http://themindunleashed.org/2014/08/shaman-sees-mental-hospital.html
- Science dominated societies really are the only institutions which deny the possibility for a person to become possessed by independent beings. A book I read on this listed many dozens of cultures and religions which view a number of phenomena during which a person loses control over his body as an expression of possession by spirits, ghosts, angels, demons or gods. Sometimes this is considered fortunate or necessary, other times it becomes a collectively celebrated event (very similar to the ecstatic dancing we can see at psychedelic festivals), while some religions view it as intrinsically bad (e.g. catholicism).
-Possession was my explanation as well and has been twice before during and after similar events. At least I alternated between the 'demonic entity theory' and the 'clinical nutcase explanation'. Interestingly one of those 'possessions' happend during full-blown mania while I was at a Dead Can Dance concert in a sleep-deprived state, without drugs being involved. The experience was ecstatic and mystical in nature and I explained it with being possessed by benevolent ancestral spirits instead of demons. The first time it happened on DMT and ketamine in a group of people who saw me suddenly start to dance in a bizarre robotic fashion while remaining seated, I interpreted this as some undefined entity, likely a ghost, neutral in nature and taking control of me cause I'm high as fuck. Afterwards I had the sense of having become psychotic and never returning for a very short amount of time before the DMT wore off.
This leads me to...
The frontal lobe's involvement in Geschwind syndrome and it's proposed role in religious experiences:
- Geschwind Syndrome, also known as Gastaut-Geschwind, is considered a personality disorder that is characterized with five primary symptoms:
- hypergraphia
- hyperreligiosity
- atypical sexuality (usually hyposexuality, but sometimes patients present with hypersexuality)
- circumstantiality (unnecessary details and irrelevant remarks cause a delay in getting to the point)
- intensified mental life
→ Let's just look at me during the experience and during the days after the experience:
→ Hypergraphia: Check. This thread should be more than sufficient to demonstrate that I present this symptom
→ Hyperreligiosity and Circumstantiality: Check. The obvious demonic possession explanation I suggested to myself; The conversation to my friend the next day during which I had some profound revelations covering neurophilosophy, physics, metaphysics and how the knowledge in these areas in combination with the whole of my experiences forms all my religious beliefs. I was so excited during this conversation that I at times had difficulty breathing. The circumstantiality was extremely apparent that night, eventhough you might not find that much of it in my written words.
→ Intensified mental life: Check. Well... Do I have to elaborate on this?
→ Atypical sexuality: Check. I've experienced hyposexuality for 2-3 days after dissociative experiences, especially after MXE and Ketamine use, but on the other hand I get insanely horny after using pcp, diphetidine or 2-methoxy-diphetidine, moreso than on any other drug out there. I actually went to see a whore one day after using MXP which I have never done before in my life. Definitely worth it though.
- These symptoms present themselves in association with patients that have a certain kind of epilepsy called temporal lobe epilepsy. Personality changes seen with people with TLE are chronic not acute. Changes in personality develop and become more noticeable over time. The symptoms are interictal, meaning they occur between seizures.
→ If we look at the dissociative experience as an event similar to a frontal lobe seizure and keep in mind that Geschwind syndrome occurs between seizures, there's a good chance that common neurological processes are involved in dissociative intoxication and temporal lobe epilepsy.
- When a Christian speaks in tongues (glossolalia), there is a decreased amount of activity in the prefrontal cortices. Since the frontal lobes are utilized for attention focusing tasks; a decrease in neural activity leads a glossolalia practitioner to feel like they have less control over their actions.
- Religious experience can be replicated using magnetic fields: the sensed presence of a 'Sentient Being' can be reliably evoked by very specific patterns of weak (<1microT) transcerebral magnetic fields applied across the temporoparietal region of the two hemispheres. Dr. Persinger from Laurentian University, found that 80% of healthy non-religious people will feel a sensed presence within the room if you stimulate a person’s temporal lobes with magnetic fields.
- Every medical student is taught that patients with epileptic seizures originating in the frontal lobe can have intense, spiritual experiences during the seizures and sometimes become preoccupied with religious and moral issues even during the seizure-free of interictal periods (Geschwind Syndrome).
- There are hundreds of case reports and multiple studies which support this pattern of frontal lobe seizures triggering religious experiences
Now, I have yet to go into detail between the molecular processes which above listed phenomena and diagnoses share with the dissociative experience, but I am convinced there are plenty. The understanding of dissociatives' pharmacodynamics and the entailing downstream processes are highly likely to facilitate a better understanding of both the illnesses I listed as well as the physiology of the human mind as a projection of neurological processes (or could neurological processes be merely a projection of our immaterial minds?). This gain in knowledge should be reciprocal in nature which is why I think we should at least pay some attention to the obvious similarities and overlapping we can observe between known phenomena and illnesses instead of focussing merely on the drug pharmacodynamics alone despite the possibility that we can see common patterns in the listed pathophysiological processes and those effects caused by a drug.
Hoping for some input, but not expecting any. In fact I'd be more than content if a single person even bothers to read this rant. :D
