#nmda

[drugsfaq]

Ketamine Daydream

[neurosciencenews]

Research Identifies Brain Chemical Abnormalities in Earliest Stage of Psychosis

Abnormal brain activity in psychotic disorders, such as schizophrenia and bipolar disorder, is thought to stem in part from impaired function of the NMDA receptor. Glutamate and glycine activate the receptor, which is an important mediator of brain signaling for processes such as learning and memory. According to Dr. Öngür, the findings may serve as a marker in the development of future treatments aimed at restoring function of NMDA receptors.

The research is in Biological Psychiatry. (full open access)

[itchyandscratchyanditchyagain]

Do me a favor.

Dip your hand in a bowl of iced water. Hold it under until the ice melts and the water turns to room temperature. Do it. You’ll go numb, tears will strike your eyes from pain but it’s going to get better. First though, you have to remove your hand from the bowl of now-warm water and dip it straight in the hot water.

Now give yourself a slushy. At least a liter worth. Skull it. Let it freeze your brain. That headache, that burn. Feel it.

Hold it there. 

This is how Anti-NMDA Auto-Immune Encephalitis feels.

[celluloyd]

NMDA et magnésium

Le récepteur au NMDA est un récepteur canal à réponse métabolique car provoque une fois ouvert un influx important d'ions calciums (Ca2+). Il peut être régulé par les ions magnésium (Mg2+) qui agissent comme une sorte de bouchon sur le canal empêchant toute circulation d'ions, bouchon qui saute dès que la membrane est dépolarisée. Ainsi, en présence de Mg2+, on peut considérer que les récepteurs au NMDA sont voltages-dépendants en plus de devoir être activés par un agoniste.

Ces schémas ont été faits pour mes ED du Tutorat à partir des cours que j'ai retranscrit quand j'étais en première année de médecine. Ma seule source est le professeur de l'époque, et je peux avoir mal compris certaines choses, faire des approximations fausses, etc même si je fais de mon mieux. Croiser les sources permet d'avoir des informations plus fiables. N'hésitez pas à commenter pour discuter des sujets abordés ! Schémas et explications faits entre 2015 et 2016.

[anishananigan]

Brain: Lost and then Found

59 D. The transcript said, and I shrugged it saying university is always difficult, the same person who would be upset over 89 in high school. A lot of things had changed over the period of 3 months. My friends, lifestyle, attitude, myself. But I felt it was just me growing up. I am still unclear on if it was the claws of a dreadful sickness slowly getting hold of me as I was being oblivious to any change. One night, mid semester of winter 2014, my second year, it was very a cold night I remember because I had two comforters on and I remember thinking “I am an international student what am I going to finish school? Will be able to? What if my Visa expires? What if I fail al the other courses and how do I apply to Ph.D.? how to I register for next years courses” . And I started cursing myself for how I did not think of all this before and by the time I realized how all these thoughts had no premise and had not connection and were easily answerable, it was morning. I had to rush to school. My friend use to pick me on the way I thought of telling him about it but somewhere I still knew I was being irrational, hence decided to figure it out myself. This I believe was the first red flag, keeping quiet, not sharing, not that I am an expert in the field but from personal experience. Once in school walking up the stairs it felt strange. It felt as if the ground was slipping from under my my feet. As if I couldn’t balance myself anymore as if it’s all uneven and not a flat surface anymore. And trying to maneuver the ups and downs I almost tripped 3 times. This felt weird but I though I might be too tired or sleepy as I was up all night. Class was no different hadn’t been for few weeks now. The professors seemed to go faster than usual. I had a hard time recollecting whatever happened in class and the workload just was too much. I would tend to get obsesses so much with one though never got a chance to go to the other. It was the St. Patrick’s day when I first acknowledged I might have a problem. For quite some time the unbalanced feeling was becoming a part of my life however once back from class about to go out with friends for a party I was changing and realized my legs shaking. Uncontrollably. Just shaking involuntarily. I freaked out and for some reason was in denial of this particular event. I disagreed to the fact that this was happening. I convince myself that I am being ridiculous. I went to the party sat there with my group of friends and heard them discuss a lot of things however nothing they said seemed relevant to me or I did not understand why were they talking about what they were talking about. My best friend was discussing about how her boyfriend and her are going through a rough patch (which is very common among girls) and all I could think was “what do I have to do with this? Why is she telling me this? Never mind just keep nodding.” Slowly things started getting worse from professors seeming fast it had now become completely impossible to comprehend anything that the professor was saying and sitting in the class all I could think of was “what have I learned in all these years. I know nothing. My life is useless”, and would get completely obsessed with this idea so much so that I stopped going to school altogether. Once my friends noticed this they wanted to talk to me about it, as they knew it wasn’t like me to miss school and shut off everybody. On more in depth discussion they decided to take me to the hospital and figure out what wrong. I was diagnosed with severe dehydration when I thought “wait, I haven’t been drinking enough water. That must be it.” On coming back home in the car as I was saying rather rambling on stuff that would seem completely illogical to a person I saw my friend tearing up. He started getting emotional and said, “this is not you. I have never seen you like this. It cannot be just dehydration”. He held my hand, “just trust me”. We went to another hospital as we felt like the previous one wasn’t a satisfactory answer where the after 4 vials of blood and 6 blood pressure measurements later I was given a neurologist reference with a presumption that I might be predisposed to having a stroke at 19 years of age. This was based on the idea of me being cognitively troubled and having trouble walking. Again the drive back was painful. Not getting any answers was worse. Being a science student I was desperate for reason for cause for result for a diagnosis. “The doctor is not in today he is on a vacation” the nurse said as my fried clenched his teeth in anger. “why is this happening to her?”. Is it even logical to get a referral for a doctor that isn’t even in town.” All this while I was thinking “Am I going crazy? I am slipping away? I will never be fixed? Is it because I am a bad person?” Maybe if I don’t sit with my legs crossed I won’t be punished?”, and these thoughts seemed completely acceptable to me. I was taken in by the doctors assistant “ push your hand against mine as hard as you can.” She said pressing the hand against mine. She came close to my eye with a device that had a little in it. “look up, right, down, left.”

“I have sleeplessness.” I said my first word that day and felt as if I conquered the world, only to realize how low my confidence was now. The assistant did not bother about that remark and looked at my friend, “”She is stressed maybe has some anxiety”. Then looking at the phone she said let me make some calls, “in a low voice she murmured something. “we have a bed for her and will be scheduling an MRI soon.” Next day I was supposed to sit in an exam I screamed and lost all control and started getting all jittery and was shaking yelling at my friend why? You want me to to fail You are pushing me for an MRI in the same day as my exam. What am I going to do? I am losing everything I had.” I see my friend trying to calm me down, the nurse rushing in and then I went to sleep. That was it, for that day. MRIs happened of brain and spine. More vials of blood, more IV more needles still no results. It was frustrating it was testing my patience or whatever I had left of me. MY friends describe my eyes so blank, lips dried and blood oozing out of the cuts, cheeks sunken in until they looked discolored and a smile that was so scary as it was so empty. I was moved from one facility to the other and in that I lost all hope. I decided it was over. There was no answer to my desperation for a diagnosis but by now it the disease had engulfed me such that that I didn’t even know I wanted a diagnosis. I didn’t know how feeling something was. No pain, physical or mental, no expectations except waiting for the lady who came every morning at 6:30 am (as the clock on the wall was the only think I could see) “Morning, stretch your hand. Have you been to the washroom yet?” . “No” the word struggles to come out of my mouth. My friend wakes up “morning, how did you sleep?”. Sleep. Hmm. Wondering when I actually slept last time. All I remembered was my blood being taken and at night a small cup of water with 5 different pills as I force it down my throat and then lay until the next vial of blood is taken from me. I was kept on a stretcher out in the corridor as there was no bed in his facility. According to my friends there were multiple tests done on me but all I remember I seeing a dark empty room with a small red light and I was trying to hold something. A distant voice yelling “if you don’t sit straight we cannot do the test. Please keep you hand still.” It was very faded I couldn’t really understand why was she yelling. Why was I there where was I what is happening? “you’re going to get better, relax don’t move. Let them help you Anisha”.

They are trying to inject something in me. They are plugging something on my head. Are they shaving my head? They are trying to erase all my memories. I am a lab rat. All my friends are with them. I see that man on the computer he is rewriting my life. He is taking away everything from me. He is feeding someone else’s life in me. They are killing me and I start yelling. Why is my friend dancing in the air? What is that group of people beside the waterfall discussing are they conspiring against me? “Maaaa. Mom! I want her! Please my mother. My voice sounds as if I my lungs will burst out. I couldn’t have screamed louder. I push away my friend who was trying to read some religious verses around me and I pull out the plugs off my hair. Banging the table beside me and kicking my legs in the air I roar “MAAA! Where are you! Save me lease I beg you maaaa! Come to me ! MAA, MAA. I was being pushed on the stretcher back to the corridor. I kept yelling and throwing my hands and legs in the air. I remember them giving me some tablet under my tongue and next thing I know I was in a room. Same friend of mine was flirting with a guy whose brother was in the same room admitted for some mental illness. They were talking as I lay there staring at the lights outside it seemed like it was late night. “why she not sleeping” “Am I sleeping?” Suddenly I see this big white monster with red eyes trying to attack me and my friend assisting it in all possible way she could. I screamed and pulled out my IV and punched my friend and started squirming and had this pain all over my body as if something is torturing last thing I remember of that night is 6 very dark soul like thing grabbing me and holding me down and taking me somewhere I didn’t want to go. I wake up apparently I was sedated for 8 hours and it took 6 nurses to achieve that feat. All this seems irrational but it was real very real and it was happening to me and nobody else. Anybody and everybody after that day could tell I was not me anymore. Nothing in me was the same. I was now completely on IV couldn’t eat or walk. Stopped talking comprehending basic information was a rigorous exercise and finally the last straw was when was in my diapers at loss of all control of my body. I thought to myself “Am I even Alive?’

Luckily the doctors and my friends didn’t think like that. After 2 months of various tests and blood work and spinal tap finally there it was on 30th April my friends came running telling “They have a diagnosis, they have a plan. You’re going to be okay. It is called Anti-NMDA receptor encephalitis”. All I had to say was “hmm”. That’s how it worked because I couldn’t even remember 4 words for 20 seconds anymore. I wasn’t there coherently so I couldn’t understand. To me I was done forever. But then 2 months of psychosis, paranoia, hallucinations cognitive problems and 7 months of IVIG and Methyl prednisone plus another relapse next year with 5 cycles of plasmapheresis, lots of love and support from family and extremely gifted doctors later here I am a B.Sc. graduate in biotechnology with lovely friends to count on. The ghost of NMDA relapse scares me but the possibilities of future keep me going on.

[gdbunit]

[ibogainetreatmentguide]

How Ibogaine Works in the Brain: A Neuroscience Guide

How Ibogaine Works in the Brain: A Neuroscience Guide

How Ibogaine Works in the Brain: A Neuroscience Guide Ibogaine is one of the most pharmacologically complex substances studied for addiction treatment. Unlike maintenance therapies that replace one opioid with another, ibogaine appears to address addiction at the neurological root — resetting the brain's reward circuitry, promoting neuroplasticity, and normalizing neurotransmitter systems disrupted by chronic substance use. This guide examines the three primary mechanisms through which ibogaine acts on the brain, based on current peer-reviewed research. 1. NMDA Receptor Modulation Ibogaine acts as a non-competitive antagonist at NMDA (N-methyl-D-aspartate) receptors — the same receptor system targeted by ketamine. NMDA receptors play a critical role in learning, memory formation, and neural plasticity. In the context of addiction, NMDA receptors become dysregulated through chronic substance use. The brain essentially "learns" to be addicted — forming deep neural pathways that drive compulsive drug-seeking behavior. By modulating NMDA activity, ibogaine appears to disrupt these entrenched addiction pathways. Research by Popik et al. (1995) demonstrated that ibogaine's NMDA antagonism is a key mechanism in reducing opioid self-administration in animal models. Key distinction: Unlike ketamine, which provides acute NMDA blockade lasting hours, ibogaine's active metabolite noribogaine provides sustained NMDA modulation for weeks to months — potentially explaining its longer-lasting therapeutic effects. 2. GDNF Upregulation: Repairing the Reward System Perhaps ibogaine's most remarkable property is its ability to increase levels of Glial cell line-Derived Neurotrophic Factor (GDNF). GDNF is a protein that promotes the survival and regeneration of dopamine-producing neurons — the same neurons damaged by chronic substance abuse. Research by He & Ron (2006) showed that ibogaine significantly upregulates GDNF expression in the brain. This is critical because: - Dopamine neuron repair: Chronic opioid, stimulant, and alcohol use damages dopaminergic neurons. GDNF promotes their regeneration. - Reward system normalization: Rather than artificially stimulating dopamine release (as drugs of abuse do), GDNF helps restore the brain's natural reward circuitry. - Sustained neuroplasticity: Elevated GDNF levels can persist for weeks after a single ibogaine treatment, providing an extended window for neural repair. This mechanism may explain why many patients report that ibogaine doesn't just eliminate withdrawal symptoms — it reduces or eliminates cravings at a fundamental level. 3. Serotonin System Normalization Ibogaine and its metabolite noribogaine interact with serotonin (5-HT) receptors and transporters. Baumann et al. (2001) found that noribogaine acts as a serotonin reuptake inhibitor, increasing serotonin availability in the brain. This has several therapeutic implications: - Mood stabilization: Serotonin dysregulation underlies depression and anxiety, which frequently co-occur with substance use disorders. - Reduced impulsivity: Adequate serotonin levels are associated with better impulse control — a key factor in relapse prevention. - Anti-depressant effects: Many patients report significant improvements in mood and outlook following ibogaine treatment, which may be partly attributable to serotonin normalization. The Multi-Target Advantage What makes ibogaine unique in the addiction treatment landscape is that it acts on multiple neurotransmitter systems simultaneously. Most pharmaceutical interventions target a single receptor system: | Treatment | Primary Target | Limitation | |-----------|---------------|------------| | Methadone | Opioid receptors | Maintains dependency | | Buprenorphine | Partial opioid agonist | Withdrawal on cessation | | Naltrexone | Opioid antagonist | No craving reduction | | Ibogaine | NMDA + GDNF + Serotonin + Opioid | Multi-system reset | This multi-target approach may explain why ib...

[ibogainetreatmentguide]

How Ibogaine Works in the Brain: A Neuroscience Guide

How Ibogaine Works in the Brain: A Neuroscience Guide

How Ibogaine Works in the Brain: A Neuroscience Guide Ibogaine is one of the most pharmacologically complex substances studied for addiction treatment. Unlike maintenance therapies that replace one opioid with another, ibogaine appears to address addiction at the neurological root — resetting the brain's reward circuitry, promoting neuroplasticity, and normalizing neurotransmitter systems disrupted by chronic substance use. This guide examines the three primary mechanisms through which ibogaine acts on the brain, based on current peer-reviewed research. 1. NMDA Receptor Modulation Ibogaine acts as a non-competitive antagonist at NMDA (N-methyl-D-aspartate) receptors — the same receptor system targeted by ketamine. NMDA receptors play a critical role in learning, memory formation, and neural plasticity. In the context of addiction, NMDA receptors become dysregulated through chronic substance use. The brain essentially "learns" to be addicted — forming deep neural pathways that drive compulsive drug-seeking behavior. By modulating NMDA activity, ibogaine appears to disrupt these entrenched addiction pathways. Research by Popik et al. (1995) demonstrated that ibogaine's NMDA antagonism is a key mechanism in reducing opioid self-administration in animal models. Key distinction: Unlike ketamine, which provides acute NMDA blockade lasting hours, ibogaine's active metabolite noribogaine provides sustained NMDA modulation for weeks to months — potentially explaining its longer-lasting therapeutic effects. 2. GDNF Upregulation: Repairing the Reward System Perhaps ibogaine's most remarkable property is its ability to increase levels of Glial cell line-Derived Neurotrophic Factor (GDNF). GDNF is a protein that promotes the survival and regeneration of dopamine-producing neurons — the same neurons damaged by chronic substance abuse. Research by He & Ron (2006) showed that ibogaine significantly upregulates GDNF expression in the brain. This is critical because: - Dopamine neuron repair: Chronic opioid, stimulant, and alcohol use damages dopaminergic neurons. GDNF promotes their regeneration. - Reward system normalization: Rather than artificially stimulating dopamine release (as drugs of abuse do), GDNF helps restore the brain's natural reward circuitry. - Sustained neuroplasticity: Elevated GDNF levels can persist for weeks after a single ibogaine treatment, providing an extended window for neural repair. This mechanism may explain why many patients report that ibogaine doesn't just eliminate withdrawal symptoms — it reduces or eliminates cravings at a fundamental level. 3. Serotonin System Normalization Ibogaine and its metabolite noribogaine interact with serotonin (5-HT) receptors and transporters. Baumann et al. (2001) found that noribogaine acts as a serotonin reuptake inhibitor, increasing serotonin availability in the brain. This has several therapeutic implications: - Mood stabilization: Serotonin dysregulation underlies depression and anxiety, which frequently co-occur with substance use disorders. - Reduced impulsivity: Adequate serotonin levels are associated with better impulse control — a key factor in relapse prevention. - Anti-depressant effects: Many patients report significant improvements in mood and outlook following ibogaine treatment, which may be partly attributable to serotonin normalization. The Multi-Target Advantage What makes ibogaine unique in the addiction treatment landscape is that it acts on multiple neurotransmitter systems simultaneously. Most pharmaceutical interventions target a single receptor system: | Treatment | Primary Target | Limitation | |-----------|---------------|------------| | Methadone | Opioid receptors | Maintains dependency | | Buprenorphine | Partial opioid agonist | Withdrawal on cessation | | Naltrexone | Opioid antagonist | No craving reduction | | Ibogaine | NMDA + GDNF + Serotonin + Opioid | Multi-system reset | This multi-target approach may explain why ib...