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Monday, 21 October 2013

Piracetam for Autism, Comrades





Piracetam was first synthesized in 1964 by a Romanian scientist called Corneliu Giurgea, who was highly unusual.  He was educated in then communist Romania, followed by research in Russia and then at the University of Rochester in the US, before ending up in Belgium, eventually as the Head of Research at drug firm UCB and being a Professor at a Belgian university.  How this was possible under the strict form of communism followed in Romania,  I do not really understand.

Anyway, Giurgea was clearly very resourceful and he decided to invent a new class of drugs, to be called Nootropic.
He stated that Nootropic drugs should have the following characteristics:
1.     They should enhance learning and memory.
2.     They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
3.     They should protect the brain against various physical or chemical injuries.
4.     They should increase the efficacy of the tonic cortical/subcortical control mechanisms.
5.     They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

Piracetam was soon followed by other drugs developed by competitors.
This class of drug seems never to have been licensed in the US, but was used widely in the Soviet Union, Eastern Europe and some western European countries.
As seems all too common in medicine, nobody knows for sure how Piracetam works.  There are many proposed mechanisms and I was attracted by one of them.

Autism in Ukraine
The internet does give the impression of giving you all the answers.  Often it gives you far too much information, much of it of dubious quality.  In reality, you are only seeing what is written in English, and although it is the international language of science and medicine, you will never see the majority of Russian, Japanese and Chinese knowledge/research.  Medical practice varies widely between Western medicine and the others.
In Japan for example, the MMR vaccination has been banned since 1993 and Prozac, the anti-depressant prescribed in huge quantities in the US, is a banned substance.  
So it was not a surprise to find only passing references to apparently widespread use of Piracetam for autism in the Ukraine, going back for decades.  I have no doubt if you could access the Russian research you would find studies on this.

Side Effects
There is no shortage of drugs prescribed in the US for autism, such as Ritalin, Prozac and Risperidone.  I have no doubt that they have some very good qualities; however they all have very real side effects, some of which are permanent.  Giurgea was very wise to only consider drugs with very few side effects and low toxicity.

In the 50 years since he synthesized Piracetam, one thing everyone seems to agree on, is that either it has no side effects, or it has very minor side effects.

Does Piracetam work?
In the 1970s there were numerous studies on Piracetam in a wide range of neurological conditions.  Today Piracetam is extensively used “off label” as a treatment for many of those conditions.  Does Piracetam work in autism?

I guess the doctors in the Ukraine must think it works.  Dr Akhondzadeh, a researcher into autism, ADHD, and other mental health conditions in Iran, found it to be effective.  Kelly Dorfman of the Development Delay Resources in Pittsburgh thinks it is effective for learning disabilities and dyspraxia, but less so for autism.
Olga Bogdashina, President of the Autism Society of Ukraine, notes that piracetam is widely used as an autism treatment in the Ukraine. Having conducted her own small-scale study, she found that piracetam improved the attention spans and mental capabilities in the majority of participating children. She also says that her autistic son became more sociable and flexible and less aggressive on the supplement. She does warn that during the initial phase of treatment, hyperactivity and tantrums may increase. However, researcher Stephen Fowkes notes that these side effects are only common with high doses, and asserts that they are rare with standard doses (both cited in “Letters to the Editor, Autism Research Review International, 1996).

I thought Bogdashina’s name was familiar.  I read her book on sensory issues in autism.  It is a good read, but it does not really tell you what to do.


Piracetam’s claimed possible methods of action
·        It is NOT a sedative or a stimulant

·        Piracetam is a positive allosteric modulator of the AMPA receptor.

·         It is hypothesized to act on ion channels or ion carriers; thus leading to increased neuron excitability

·         GABA brain metabolism and GABA receptors are not affected by piracetam.

·         Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes

·        Furthermore, piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes.

·        Piracetam is thought to increase cell membrane permeability

·        Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+).

·        It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains.

·        Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria.

·        But in the brain, it also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.

In 2005 there was an interesting review carried out in Poland; it is very readable.

"Piracetam is generally reported to have minimal or no side effects. It is interesting to note, however,  that piracetam is occasionally reported side effects of anxiety, insomnia, agitation, irritability  and tremor are identical to the symptoms of excessive acetylcholine/glutamate neuroactivity. In spite of these effects, piracetam is generally not considered to be a significant agonist or inhibitor of the synaptic action of most   neurotransmitters. The piracetam-type nootropic drugs might exert their
effect on some species of molecules present in the plasma membrane. It would seem that they act as potentiators of an already present activity, rather than possessing any neurotransmitter-like activity of  their own."

It would seem to me that we have come back to the vagus nerve and the Cholinergic system

I learnt in that post that there are two main classes of acetylcholine receptor (AChR), nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR).  Mostly it seems to be the nicotinic type that is targeted by medical science, but piracetam has an effect on the other type of receptor.  This would explain excessive use of piracetam causing symptoms of too much acetylcholine.
If this is indeed the case, that would add yet another method of “correcting” the known biomarker of autism that is “diminished acetylcholine and nicotinic receptor activity”.  Of all the methods I have so far investigated, this might actually be the safest;  it is certainly inexpensive.

Effect on Comorbidities
My method of separating fact from fiction in autism now includes looking at the effect of therapies on the principal comorbidities of autism.  Most genuinely effective drugs seem to work across many comorbidities.  Epilepsy is the most prevalent comorbidity.
 


"CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage. "
Note:  Unverricht–Lundborg disease is the most common form of an uncommon group of epilepsy called the progressive myoclonus epilepsies.


Conclusion
Piracetam seems to be a safe supplement/drug that improves mood and reduces aggression (and SIBs).  I thought it was worthwhile testing and indeed I was not disappointed.  The dosage suggested is 50-100 mg/kg, but the optimal dose seems to vary by child.  If you follow my vagus nerve/neuroinflammation/ cholinergic way of thinking, then Piracetam would be acting (via acetylcholine) to reduce pro-inflammatory cytokines and hence reduce inflammation in the autistic brain.  This would mean that Piracetam would be a useful tool to control autism flare-ups, be they triggered by pollen allergy, intestinal inflammation, or even stress.  I shall use it as such.

As for why Piracetam seems more effective in the Ukraine than in Pittsburgh - that I can answer.  Much of what passes as autism in Pittsburgh, would be completely ignored in Kiev.  It would not be diagnosed as autism; only if it is disabling would it be called autism.  If you have "autism-lite", the symptoms are mild and you probably do not need Piracetam and it would likely have little effect.   The same would apply for the majority of ADHD/ADD cases, outside of the US they would not be diagnosed as such.
If you are on Ritalin for your severe ADHD, you might want to try Piracetam.  If you Google ADHD and Piracetam, you will find adults using Piracetam to avoid the side effects of Ritalin.
If your child suffers from SIBs (self-injurious behaviours) then Piracetam, along with nicotine patches, would be well worth investigating.

 
 
 

 


 

7 comments:

  1. Thank you for this insightful article I have never heard of nootropics until I read your article here.. I commented before I believe on a blog about sensory overload and rare adhd caused by low potassium levels.. I have a rare (supposedly) disorder named Andersen tawil syndrome and believe it goes through five generations of my family.. Even though my potassium is not considered low I become very ill when my levels are below 4.5 and feel well at 5.5.. over the course of 53 years of life with hypokalemic illness I feel I have lost a lot of my mental sharpness.. and have described my symptoms as brain fog to the 9nth degree.. I think perhaps the Piracetem might be something I ought to try.. when I read the research about Viagra being helpful for oxygenation I was curious about trying that but with cost and likelihood that my doctor wouldn't prescribe it for my off label use anyway I gave that up.. Some of the individuals I have met have had some success with mestinon for some of there issues exacerbated by hypokalemic symptoms even though our levels are almost always wnl.. another friend has recently undergone a thymectomy and has had substantial improvement with this surgery .. have you ever given consideration to the role of the thymus in autism? My daughter has a dual diagnosis of PP possible Andersen tawil syndrome and Aspergers syndrome.. Even though my potassium is always within normal levels (so far) I ingest on an average of 100 meq of khlor con daily along with 80 mg of accupril (potassium sparing) to hold my levels artificially higher along with a low carb diet as even small shifts of my potassium lower can cause horrendous brain fog.. muscle pain muscle weakness and paralysis.. I agree with your new focus on endocrinology in my very ill family members many are very short and many are very tall .. but many also both extremes have various levels of physical and nuerological deficits varying from sensory integration problems to adhd .. so very many complex issues.. I am also curious about mitochondrial issues as others I have met often exhibit severe gastroparesis along with mitochondrial issues.. and ps.. most of us are descended from sick royal ancestors with the Habsburgs being at the top of the family heap poor Charles had supposedly Renal Tubular Acidosis and pituitary issues I believe.. I continue to read your research and I believe you are definitely on the right track.. One more thing I wanted to mention for me sodium is one of my worst triggers,, plus even minor fluctuations in my potassium in the downward direction can trigger me so for me along with the potassium in massive quantities the ace inhibitors sugar and refined carbs can trigger a worsening of my symptoms.. so even though considered a good source of potassium potatoes.. bananas and sweat potatoes the carb load completely negates the potassium content in my case.. thank you again

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    1. The problem with testing electrolytes and hormones is that you are limited to the blood. What is happening in the brain may actually be the opposite, so Free T3 thyroid hormone can be high in the blood but low in the brain. My son has high serotonin in the blood, but I am pretty sure it is low in the brain. I am discussing this with an Endocrinologist, and I am getting her to point that she can see my logic that there is central hormone dysfunction (inversion) in autism. I am reading about Magnesium and here again it seems that low brain levels of magnesium are common in many neurological/psychiatric conditions; because of the blood brain barrier, low brain magnesium may be accompanied by normal or even elevated blood levels.

      I have not considered the thymus (yet).

      It really looks like there is complete failure to maintain the homeostasis of hormones and intra/extracellular levels of electrolytes in the brain. It is amazing the brain continues to function. Na, K and Mg are all interrelated so it is logical that Na is not good for you. But Mg should help maintain your K levels.

      The thing I like about Piracetam is the lack of virtually any side effects. So you cannot do any harm, unlike many other drugs that do actually have some benefits but have side effects. Piracetam is cheap and does have a positive effect, as do the nicotine patches incidentally. If you want to increase the effect of Piracetam you add choline. This done by both researchers and "cognitive enhancers".

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  2. No wonder it is so difficult for members of my family to quit smoking.. we need the nicotine perhaps.. I definitely plan on switching to e cigs or patch at next appointment to help me in this endeavor..

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    1. Interestingly, the nicotinic receptors in the cholinergic system function in one (good) way when given a low level of stimulation; but at high levels the effect is completely lost. So it looks like 2-3 cigarettes a day may have a genuine health benefit. If you smoke 20 then the receptors are overloaded and you lose the anti-inflamatory benefits, but you get the "high".

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  3. Piracetam is to be in theory- a "Cognitive Enhancer". I have an Autism Spectrum Disorder, though I have no idea what this medication would do to me. I bought some Piracetam, Choline, and fish oil off the web... We shall see rabbit.

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  4. Hi Peter, and thanks again for this fantastic site. I've finally been diagnosed with adhd inattentive with autistic traits, although I'm absolutely confident dyspraxia/DCD is the most appropriate description.

    I'm currently trying 2mg of Bumetanide daily. Do you think it has any effect on the DCD spectrum of autism? I have yet to try piracetam.

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    1. I think you can just try it and see. It seems that about half of people with autism respond to Bumetanide.

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