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Fluoxetine (Prozac) + the visual cortex


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Ugh, sorry about the formatting.. bloody forum.

The Antidepressant Fluoxetine Restores Plasticity in the Adult Visual Cortex

  • We investigated whether fluoxetine, a widely prescribed medication for treatment of depression, restores neuronal plasticity in the adult visual system of the rat. We found that chronic administration of fluoxetine reinstates ocular dominance plasticity in adulthood and promotes the recovery of visual functions in adult amblyopic animals, as tested electrophysiologically and behaviorally. These effects were accompanied by reduced intracortical inhibition and increased expression of brain-derived neurotrophic factor in the visual cortex. Cortical administration of diazepam prevented the effects induced by fluoxetine, indicating that the reduction of intracortical inhibition promotes visual cortical plasticity in the adult. Our results suggest a potential clinical application for fluoxetine in amblyopia as well as new mechanisms for the therapeutic effects of antidepressants and for the pathophysiology of mood disorders.
 

 

 

Source: http://www.sciencemag.org/content/320/5874/385       full text

 

 

Fluoxetine and serotonin facilitate attractive-adaptation-induced orientation plasticity in adult cat visual cortex[/size][/size] Abstract

Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non-preferred stimulus for several minutes. Adaptation of neurons to a non-optimal orientation induces shifts of tuning curves towards the adapting orientation (attractive shift) or away from it (repulsive shift). Here, we investigated the effects of the neurotransmitter serotonin and antidepressant fluoxetine (a selective serotonin reuptake inhibitor) on the modulation of adaptation-induced orientation plasticity. We show that serotonin and fluoxetine promote mostly attractive shifts. Attractive shifts augmented in magnitude towards adapter, whereas repulsive neurons reversed their behavior in the direction of the forced orientation. Furthermore, neurons which retained their original preferred orientation expressed plasticity by shifting their tuning curves after drug administration mostly towards adapter. Our data suggest a pre-eminent role of fluoxetine by inducing and facilitating short-term plasticity in V1.

 

 

 

Source: http://onlinelibrary.wiley.com/doi/10.1111/ejn.12206/abstract

 

 

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Illicit Drug Use and Palinopsia

 

Patients with substance dependence often have perceptual abnormalities, and this is especially common in users of stimulants, cocaine, and hallucinogenics such as LSD, PCP, and marijuana.53 In addition, visual hallucinations have been reported after cessation of cannabis use.62 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) caused palinopsia that persisted for two years, but eventually resolved with fluoxetine treatment.63 Sunness suggested that in her young palinoptic patient, an additive effect from several illicit drugs was the cause of palinopsia.64 Patient #4 presented with a history of multiple substance abuse, though based on his history, it seems most likely that his palinopsia was due to exclusively to LSD abuse.

The most common natural hallucinogens are mushrooms and mescaline, and the most commonly abused synthetic hallucinogen is LSD.3 Approximately one fourth to one third of LSD users will experience some form of flashback phenomena.65 In a study of 123 prior LSD users, 44.3% experienced trailing phenomena.66 LSD exerts an inhibitory effect on the level of synaptic transmission in the brain.67 Patients often describe a “trailing phenomenon” or motion picture frames that remain frozen in space long enough to be perceived individually.66 Gaillard and Borruat concluded that LSD flashback phenomena rarely occur long after the last intake of LSD, though when it does occur, precipitating factors such as ethanol or medication use are often present.62Among other precipitating factors, Kawasaki and Purvin found LSD flashbacks associated with anesthetized tooth extraction and prolonged hot bathing.3

Trazodone and LSD both inhibit serotonin reuptake and interfere with the homeostasis of serotonin levels in the brain, though how the serotonin reuptake inhibitors are related to visual illusion has not been addressed.7

 

 

Source: http://apps.scco.edu/ceonline/courseview.asp?selclassid=10&selID=85&selOrderID=14 

 

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"Improvement of hallucinogen persisting perception disorder by treatment with a combination of fluoxetine and olanzapine: case report." - http://www.ncbi.nlm.nih.gov/pubmed/11386500

 

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From the forum (mixed reviews)

NEUTRAL

ODISA "did nothing for me, neither positive or negative." + "Which are the most common SSRI's reported to have adverse effects? I did for a while, and I didn't experience any effects."

 

NEGATIVE

g29  DP/DR more intense and worsen visuals, specially halos around objects and trails. (I left the treatment in the second day)"

 

jay "The only thing i had a big problem with was" + "First doctor I had (in England) just said I had depression and put my on, which turned into a nightmare. "

 

 

Memnoth "Speaking with personal experience on both questions, (brand name Prozac) worsens visual snow permanently, after 5 days of treatment it increased my symptoms by 300%. Taking amphetamine while having visual snow appears to only worsen the symptoms during comedown, 5 years of sporadic amphetamine use have not worsened my symptoms permanently as far as I can tell. "

Kellen "I took a 20mg dose of before bed and the next day I was fried. Like I was seriously tripping. I know 20mg is really low but why does it hit me so hard?" CONTEXT: Kellen talking about his sensitivity to drugs.

 

 

Puppeteer "Was prescribed, had a bad reaction to it which may or may not have been related to HPPD"

 

se7ven "have quit now, because the dp/dr got much worse." + started on 20mg 4 weeks ago and upped my dose to 40mg 3 days ago. it has only helped whit my depression. no wisual effected and a low effect anxiety. seriously feeling that im crazy all the time. suffering from bad dp/dr. considering to start klono to get my life quality back. 

 

2muchmandy "I used to be on and it made me feel shiiit." +  "only time I came close was on. It just killed all emotions I had, that stuff was horrible"

 

Lucid "was on.... that turned into 4point restraints, suicide watch..."

 

Emily "I tried once it brought on dp which made me have a panic attack."

 

findacureformyson "We tried to increase his to 20m a few weeks ago and he freaked out, wanted to kill himself and harm others and had a major panic episode for three days."

 

 

David S.Kozin (may be him quoting someone else's experiences from the old board) now since prozac in november of 2007 [/size]Major flaoters again. Colors brighter again. trails again.MAJOR DR againand a lot of emotional instability, up and down, emotions are all over the palceheadachesanxiety, major major major anxiety again. Insomnia again. Halo's around objects again. Slight afterimages (they are not as bad this time) -trails -weird street lights and car lights (when dark, especially in the morning, sometimes i see the light of cars stretch about double the car size with a transparent rainbow around, not overwhelming thou) -some color spots appear once in a while, mostly blue -conversations can be uncomfortable because my vision gets weird, sort of out of focus but its clear, damn hard to explain, makes me feel like i'm standing in a weird position or something. -some songs replay in my head, not only after hearing them anymore, reading the name of the song is enough now -irregular heartbeat(went to the doctor when i first got it, turns out i have 3 different heartbeats) -no anxiety -no panic attacks -looking down at my arms and hands, they look weird,arms are long, wrists are small and hands are big (saw a picture of that here, probably why i see it now) -bullshit dreams that don't make sense, at all

 

POSITIVE/

Hannahb00 I am posting this to let you all know or anyone suffering from this that I am 22 now, have been totally clean and sober for one year (a little over) and am on Lamictal 50MG;; and my HPPD has seemingly disappeared." + "Im on PROZAC and LAMICTAL. 50MG. not using any ofther drugs and my HPPD has seemed to have dissapeared. I live a normal {for the most part lol} and productive life! I can go to work ! "

 

3rd_tour_of_duty "I've been on Prozac for 15 years, on clonazepam for 6 months which helps with the larger bouts of anxiety/dp/dr. Prozacs not very effective and I'm going to need a decent alternative soon but it keeps the wolf from the door in the depressive aspect of my condition." + "It helped me loads many moons ago mate. But everybody's different. " + "8 months after I first got it and I responded well not knowing what the hell was wrong with me, just that mentally I was far from 'normal'. With the Ssri and exercise I had it if not on the ropes then pushed back a fair bit. Allthough i was far from 100% life was bearable. Years later it caught up with me again though after a build up of stress and various other things, although I dunno if it was that or just the Prozac 'pooping out' on me as I've heard. "

 

CMM "Once I took the, it was like the world came back. Colors were nice, I had hope inside of me and all the vision stuff went away. I was my old self again, well 98% to it. " + " I spoke with Dr Abraham through email and phone. He said nothing about the beta blocker. He also said prozac has never helped nor made hppd worse. "

 

 

Chris "I'm considering going back on [fluoxetine]. It did nothing for me HPPD-wise, but I felt generally better on it. Definitely the best SSRI I have taken."

pokeypup 'Success with prozac' http://hppdonline.com/index.php?/topic/1259-succes-with-prozac/?hl=prozac n.b didn't help visual symptoms

 

 

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Not Prozac, but another SSRI:

Young, C. R. (1997). Sertraline treatment of hallucinogen persisting perception disorder. Journal of Clinical Psychiatry, 58(2), 85-85. [/size]

Reports the case of a 22-yr-old man who presented with hallucinogen persisting perception disorder and symptoms of mild depression 6 mo after discontinuing the use of LSD. Antidepressant treatment was begun with sertraline, until a target dose of 100 mg was reached. Mild exacerbations of the LSD-like phenomena were noted for 2-4 days after each dosage increase. Within 1 mo of reaching the target dose the perceptual disturbances decreased until they had almost completely remitted, and the depressive symptoms also improved. It is hypothesized that hallucinogen persisting perception disorder is serotonergically mediated, and that sertraline initially exacerbates the perceptual disturbances, but attenuates them after chronic administration

 

 

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New Onset LSD Flashback Syndrome Triggered by the Initiation of SSRIs [/size]

 

Interestingly, one subject in the Bonson et al study reported an increased response to LSD when taking it concurrently with fluoxetine. In contrast to the other subjects, this patient had initiated the SSRI treatment much more recently, only 1 week prior to the intensified hallucinatory experience.[/size]

There are several possible explanations for these flashback responses to acute SSRI therapy in patients who are concomitan tly abusing LSD. First, these individuals' reports could reflect the somatic, hallucinatory, and sympathomimetic sensations that patients sometimes report following initiation of SSRI treatment in the absence of LSD. It is possible that individuals who use or have used hallucinogenic drugs are more sensitive than non-users to these SSRI side effects (1). An alternative explanation is that initial SSRI therapy potentiates the effects of LSD, since acute fluoxetine administration has been shown to increase the LSD-induced suppression of serotonin raphe neuron firing (8). This suppression normally results in a disinhibition of target neurons in the visual and limbic systems, accounting for the changes in mood and altered visual perception associated with LSD. Increased inhibition of raphe firing by co-administration of an SSRI with LSD could therefore result in enhanced hallucinogenic effects of LSD due to disinhibition of visual and limbic system neurons. Thus, the aforementioned individual in the Bonson et al study may have had an increased response to LSD during initialfluoxetine therapy due to a potentiation based on the similar initial effects of both drugs (1).

 

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096346/

 

Fluoxetine Method of Action

 

Fluoxetine's mechanism of action is predominantly that of a serotonin reuptake inhibitor.%5B90%5D%5B91%5D Fluoxetine delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Fluoxetine may also produce some of its effects via its weak 5-HT2C receptor antagonisteffects.%5B92%5D In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.%5B93%5D%5B94%5D[/size]

 

 

Molecular Target Fluoxetine Norfluoxetine SERT 1.0 19 NET 660 2700 DAT 4180 420 5-HT2A 200 300 5-HT2B ≥5000 ≥5100 5-HT2C 260 91 M1 870 1200 M2 2700 4600 M3 1000 760 M4 2900 2600 M5 2700 2200

 

 

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I am tempted by this study that shows fluoxetine promoting visual cortex neurogenesis, but it seems risky business. My HPPD has calmed down quite a bit (I can function at 60-80% now), but I am by no means a full recovery. I wonder if the adverse reactions to Fluoxetine on the forum are because the trial was too short and/or perhaps the HPPD too aggressive at the time. Perhaps there is a way of targeting Fluoxetine more specifically or administering it with something else, i.e the positive report above of fluoxetine + lamotrigine, seems like an interesting pairing. I like the idea of something stimulating the brain and something inhibiting it at the same time, finding the correct cocktail, so to speak. Has anyone found any other substances that promote plasticity and neurogenesis in the visual cortex? 

 

 

Also, some other things to think about regarding serotonin (maybe not all that good for you):

 

http://raypeat.com/articles/articles/serotonin-depression-aggression.shtml[/size]

http://www.dannyroddy.com/main/things-are-getting-trippy-serotonin-and-lsd

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Nice comprehensive post syntheso!
 

 

These effects were accompanied by reduced intracortical inhibition and increased expression of brain-derived neurotrophic factor in the visual cortex

Increased BDNF is good, but I'm not so sure about intracortical disinhibition.. seems to be exactly what perpetuates HPPD in the first place.
Maybe the 5HT2C antagonism is in part responsible for these effects.. But you've tried 5HT2C antagonists to no avail, right?

This article may be interesting by the way. Perhaps TrkA agonism is involved? Seems to be NGF mediated..
This may also be of interest.
And a bunch of interesting articles

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Nice comprehensive post syntheso!

 

Increased BDNF is good, but I'm not so sure about intracortical disinhibition.. seems to be exactly what perpetuates HPPD in the first place.

Maybe the 5HT2C antagonism is in part responsible for these effects.. But you've tried 5HT2C antagonists to no avail, right?

This article may be interesting by the way. Perhaps TrkA agonism is involved? Seems to be NGF mediated..

This may also be of interest.

Cheers mate.

My thoughts are the same as yours. On one hand, potentially helpful, on the other, not. This is why I mention that perhaps when someone's HPPD becomes less aggravated (when the brain gets better at inhibiting) it could be useful for a full recovery, or, if taken with something that is globally quite inhibitory (i.e AED's; thinking more along the lines of Levetiracetam and Lamotrigine), it could just be a good combo. Or maybe L-DOPA, as increased serotonin would decrease dopamine. 

How do we get increased BDNF in the visual cortex without the cortical disinhibition?! 

Maybe the 5HT2C antagonism is in part responsible for these effects.. But you've tried 5HT2C antagonists to no avail, right?

Perhaps it is. But it seems more likely, given that 5-HT agonists have resulted in HPPD, that it is the access to serotonin that allows the visual cortex to be manipulated, not the blocking of it. I would be worried that giving more access to serotonin would just further manipulate the visual cortex in a destructive way. Though, plasticity/neurogenesis would be required reverse damage to that area. I do not have the motivation to do this now, but it would be worth seeing if any other SSRI's exhibit the same effects (Setraline, as noted above seems to have some clinical implications for HPPD). And if so, in what ways they differ, looking at binding affinities. I have read that there are lots of 5-HT receptors in the visual cortex, hence why agonising them produces such visual phenomena.

You're right I did try Cyproheptadine, which I think binds to all/most 5-HT receptor subtypes + many other actions (inc. anticholinergic). I only managed it for two days though, because I had horrible nightmares which I just couldn't hack (which is strange considering it is used to treat nightmares). Given the upregulation/downregulation idea, chronic use probably would have been required to see results for that to work. I also thought perhaps there could be a serotonin syndrome (too much serotonin) in HPPD, which if were the case, presumably I would have seen immediate benefits. Though, maybe I would have needed inverse agonists for that. Idk...

I'll read through those articles now. Hope you are well mate!

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Regarding NGF.. yes, ever since I heard about it, I just want to drop loads of that into my eyes! It is just so expensive :(

Perhaps that is the answer to my question 'how do we get increased BDNF in the visual cortex without the cortical disinhibition'. Would increased NGF increase BDNF as well (edit; it seems so)?

Time to find a NGF stack.

Edited by syntheso
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