Showing posts with label Piracetam. Show all posts
Showing posts with label Piracetam. Show all posts

Thursday 11 May 2017

Tardive Dyskinesia (TD)  - Amino Acids, VMAT2, Diamox, B6 etc

Today’s post is about Tardive Dyskinesia which is a side effect eventually experienced by about 30% of people taking antipsychotic drugs, like risperidone, widely prescribed in both autism and schizophrenia.

Enough money for your lifetime supply of a VMAT2 inhibitor?

Tardive Dyskinesia (TD) is a disorder resulting in involuntary, repetitive body movements, which might think of as tics or grimaces.

It appears that the longer the drug is taken the greater the chance of developing Tardive Dyskinesia.

Tics are quite common in autism and not just in those taking psychiatric drugs.

Tourette’s syndrome is a well-known tic disorder that does overlap with autism, it used to be considered rare, but now 1% of children are thought to be affected.  Some common Tourette’s tics are eye blinking, coughing, throat clearing, sniffing, and facial movements.

People diagnosed with Tourette’s might also be diagnosed with ADHD, OCD or indeed autism.  

We saw in some Italian research that young children with Tourette’s type autism have a fair chance of seeing their symptoms of autism substantially fade away. It was called Dysmaturational Syndrome.

The part of the brain that is thought to be affected in  Tardive Dyskinesia is that same part suspected in Tourette’s and indeed PANDAS/PANS; it is the basal ganglia.  

Avoiding Tardive Dyskinesia

The best way to avoid Tardive Dyskinesia is not to use antipsychotic/ neuroleptic drugs.

It appears that high doses of melatonin and other antioxidants may give a protective effect from developing Tardive Dyskinesia. 

Treating Tardive Dyskinesia

Much is written about treating Tardive Dyskinesia (TD), because nobody yet has found a cure for it, nonetheless there is a long list of partially effective therapies.

Given that the underlying basis of TD may very likely to overlap to some extent with Tourette’s and PANDAS/PANS it is over broader interest.  

A Review of off-label Treatments  for Tardive Dyskinesia 

The Spanish study below gives a good overview of most therapies, but exclude the very recent therapies based on VMAT2. 

All of the studies in the review were small, but you can see that some therapies did seem to help, including:-

·        Vitamin E

·        Vitamin B6

·        Acetazolamide/Diamox

·        Amino Acids

·        Piracetam

I proposed Acetazolamide/Diamox to potentially treat some autism a while back and some readers of this blog do find it effective.

Piracetam is the world’s first cognitive enhancing (nootropic) drug.  It was discovered by mistake when trying to make a cure for motion sickness.

Amino acids may look an odd choice, but in males, and only males, branched chain  amino acids (BCAAs) valine, isoleucine, and leucine in a 3:3:4 ratio appears to be beneficial.  Another amino acid called Phenylalanine is associated with tardive dyskinesia in men but not in women. It is an established fact that an increase in BCAAs will cause a reduction in phenylalanine in the brain, among a range of other effects.

Phenylalanine is a precursor for dopamine (as well as  tyrosine, norepinephrine, and epinephrine). 

One theory is that tardive dyskinesia results primarily from neuroleptic-induced dopamine supersensitivity. So if the BCAAs reduce the amount of dopamine produced, this might explain their effect.


VMAT2 transports monoamines - particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine - from cellular cytosol into synaptic vesicles. Inhibiting VMAT2 will reduce the release of dopamine. 

In some circumstances VMAT2 is necessary for the release of the neurotransmitter GABA. 

Drugs that inhibit VMAT2 appear to help treat Tardive Dyskinesia and one drug Valbenazine/Ingrezza was FDA approved for this purpose in April 2017. Not surprisingly, it is now being investigated to treat Tourette’s syndrome. 

Valbenazine is known to cause a reversible reduction of dopamine release by selectively inhibiting VMAT2. 


Since our regular reader Valentina is dealing with Tardive Dyskinesia, she will probably be very interested in Valbenazine.

The problem is the price. The drug will apparently cost $60,000 a year in the US.

So for the time being it is best to work through the list of very cheap interventions that do seem to be partially effective, at least in some people.

Tuesday 20 January 2015

Treatment of Autism with low-dose Phenytoin, yet another AED

I do like coincidences and I do like not struggling to find a picture for my posts. 

Phenytoin (Dilantin) is a drug that appeared in the novel and film, One Flew Over the Cuckoo's Nest, but then it was not used in low-doses.

Today’s post follows from a comment I received about using very low doses of anti-epileptic drugs (AEDs) in autism.

First of all a quick recap.

Clonazepam was discovered by Professor Catterall, over in Seattle, to have the effect of modifying the action of the neurotransmitter GABA to make it inhibitory, at tiny doses that would be considered to be sub-clinical (i.e. ineffective).

Valproate, another AED, was discovered by one of this blog’s readers also to have an “anti-autism” effect in tiny doses of 1 mg/kg.

A psychiatrist from Australia, Dr Bird, specialized in adults with ADHD has just published a paper about the benefit of low-dose phenytoin in adult autism.  The same psychiatrist has also earlier encountered the effect of low dose valproate in ADHD (autism lite).

Significantly, this beneficial effect of sodium valproate appeared to have a narrow therapeutic window, with the optimal range between 50 and 200mg daily. A complete loss of efficacy frequently occurred above a dose of 400mg.

Case presentation

My patient was a 19-year-old man diagnosed in early childhood with ADHD and ASD

a sublingual test dose of approximately 2mg phenytoin was administered

Within 10 minutes of taking the sublingual phenytoin he reported a reduction in the effort required to contribute to conversation and was able to sustain eye contact both when listening and speaking. He was surprised about the effortless nature of his eye gaze and also commented that he had never done this before.

The following day he started taking compounded 2mg phenytoin capsules in the morning in conjunction with his methylphenidate.

After two weeks both he and his mother stated that his communication with the family had improved and there had been no aggressive outbursts.

Over the next four weeks he became inconsistent in taking the phenytoin, and then ceased altogether. His behavior reverted to the previous pattern of poor social interaction; he became oppositional with outbursts of anger and physical violence.

Nine months later he resumed taking the phenytoin, this time as a single 4mg capsule in the morning. After his first dose there was an improvement of his social behavior similar to his previous response, although there was an apparent deterioration in the late afternoon. The dose was increased from 4mg to 5mg and a larger capsule formulated to try and prolong the release of the phenytoin. This appeared to achieve a more consistent improvement in behavior throughout the day, evident both at home and at work. Increases in the dose above 5mg were not associated with any additional benefit. He remained on the 5mg dose of phenytoin for over 18 months and reported that his work performance had consistently improved sufficient to increase his working hours and his level of responsibility. The violence and destruction at home abated. His confidence improved and for the first time he has established and sustained peer-appropriate friendships.

I hypothesize that, in a similar mechanism to the low-dose clonazepam in this animal model of autism, low-dose phenytoin may enhance GABA neurotransmission, thereby correcting the imbalance between the GABAergic and glutaminergic systems.


Now let us look at Phenytoin and see if we agree with Dr Bird's hypothesis that the mechanism is the same as low dose clonazepam. 

The accepted method of action is that working as a voltage gate sodium channel blocker.  GABA is not mentioned.

Phenytoin, by acting on the intracellular part of the voltage-dependent sodium channels, decreases the sodium influx into neurons and thus decreases excitability.

The antiepileptic activity of phenytoin was found during systematic research in animals: it suppresses the tonic phase but not the clonic phase elicited by an electric discharge and is not very active against the attacks caused by pentylenetetrazol.

Phenytoin was the first non-sedative antiepileptic to be used in therapeutics.
It decreases the intensity of facial neuralgia and has an antiarrhythmic effect.

 But as I dug a little deeper, I found from 1995:-

We report here that carbamazepine and phenytoin, two widely used antiepileptic drugs, potentiate gamma-aminobutyric acid (GABA)-induced Cl- currents in human embryonic kidney cells transiently expressing the alpha 1 beta 2 gamma 2 subtype of the GABAA receptor and in cultured rat cortical neurons. In cortical neuron recordings, the current induced by 1 microM GABA was enhanced by carbamazepine and phenytoin with EC50 values of 24.5 nM and 19.6 nM and maximal potentiations of 45.6% and 90%, respectively. The potentiation by these compounds was dependent upon the concentration of GABA, suggesting an allosteric modulation of the receptor, but was not antagonized by the benzodiazepine (omega) modulatory site antagonist flumazenil. Carbamazepine and phenytoin did not modify GABA-induced currents in human embryonic kidney cells transiently expressing binary alpha 1 beta 2 recombinant GABAA receptors. The alpha 1 beta 2 recombinant is known to possess functional barbiturate, steroid, and picrotoxin sites, indicating that these sites are not involved in the modulatory effects of carbamazepine and phenytoin. When tested in cells containing recombinant alpha 1 beta 2 gamma 2, alpha 3 beta 2 gamma 2, or alpha 5 beta 2 gamma 2 GABAA receptors, carbamazepine and phenytoin potentiated the GABA-induced current only in those cells expressing the alpha 1 beta 2 gamma 2 receptor subtype. This indicates that the nature of the alpha subunit isoform plays a critical role in determining the carbamazepine/phenytoin pharmacophore. Our results therefore illustrate the existence of one or more new allosteric regulatory sites for carbamazepine and phenytoin on the GABAA receptor. These sites could be implicated in the known anticonvulsant properties of these drugs and thus may offer new targets in the search for novel antiepileptic drugs.

So not only is it possible that phenytoin can modulate the behaviour of the GABAA receptor like Dr Catterall did with Clonazepam, but carbamazepine is yet another known AED with this effect.

So I expect someone will also go and patent low-dose carbamazepine for autism.

We potentially now have a wide range of low dose AEDs for autism.

·        Valproate (1000 to 2000 mg for adults as AED) at a dose of 1-2 mg/kg

·        Clonazepam (up to 20 mg for adults as an AED)   at a dose of 1.7mcg/kg

·        Phenytoin (up to 600 mg for adults as an AED) at a dose of 0.05 mg/kg

·        Carbamazepine (up to 1,200 mg for adults as an AED) no data for the low dose!

We also have two other drugs that are used as AEDs in high doses and have been used in autism with much lower doses.  I do not have any evidence to show that they affect GABAA receptors.  I think their method of action is unrelated to GABA, or sodium channels.
·        Piracetam (up to 24 g as an AED) at a dose of 400 to 800 mg

·        Vinpocetine (up to 45mg for adults as an AED)  at a dose of 1 to 5 mg

Both Piracetam and Vinpocetine are classed as drugs in Europe and supplements in the US.  Both are also used as cognitive enhancers. Both have numerous possible modes of action.  They may not help with behavioral problems, but may well improve cognition.

Interestingly, a clinical trial is underway to look at the cognitive effect of moderate doses of Vinpocetine in epilepsy.

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.

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.




Sunday 29 September 2013

Autism in Iran: Piracetam, Periactin & Pentoxifylline

This may sound like a very odd subject for my blog.
In 2002 US President George Bush first used the term “Axis of Evil” to refer collectively to Ian, Iraq and North Korea.  Later that year the then-Undersecretary of State John Bolton gave a speech entitled "Beyond the Axis of Evil"; in it he added three more nations to be grouped together: Cuba, Libya and Syria. Finally, in 2005 Bush’s Secretary of State came up with “Outposts of tyranny” to refer to Cuba, Belarus, Burma and Zimbabwe.

Many readers of my blog are from the US and may think that not much good can be going on in Iran.  The reality is quite the reverse, at least in the field of autism.

In spite being under all kinds of economic sanctions, Iran has generated a substantial body of insightful research.  There are 75 million Iranians which is just under the population of Germany.  I do not recall seeing much German research into autism. 

One particular researcher, Shahin Akhondzadeh, has done several very interesting studies. His CV lists 128 research papers, including autism, ADHD, schizophrenia, Alzheimer’s and other conditions.  He also writes about herbal medicine for mental health, which I know is popular among readers of this blog, so I included links to some of those papers.

Piracetam, Periactin/ Cyproheptadine & Pentoxifylline

Akhondzadeh is unusual in that he actual makes repeated clinical trials of existing drugs that the science shows could be effective.  In the case of autism he trialled three interesting drugs (with similar names):-

·        Piracetam

·        Periactin/Cyproheptadine

·        Pentoxifylline

Unfortunately his three trials combined them with an anti-psychotic.  But I think it is still interesting to look at the net impact of each of the three drugs.  I did just that.

You have to look at the data and compare the impact after 8 weeks to be consistent and you have to adjust for the fact that in the Periactin/Cyproheptadine trial at week 0 the placebo group was out of line with the trial group.
Net improvements:-
Piracetam                                        7 points on ABC

Periactin/Cyproheptadine           7 points on ABC

Pentoxifylline                                 3 points on ABC

This tells us that Piracetam and Periactin had the greater incremental impact over the antipsychotic and that the change was 7 points on the aberrant behaviour checklist (ABC).  The ABC is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54. It is a 58 item checklist. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech.




I have written about this drug in my recent post on Serotonin.  Periactin is an old first generation H1 antihistamine that happens to have additional anticholinergic, antiserotonergic properties.  It is the effect on serotonin that appears to reduce aberrant behaviours in autism

Periactin is available OTC in the UK.  In the US it is sometimes prescribed to increase appetite.
The link to Akhondzadeh’s full study is later in the post.



Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB; struck by its apparent ability to boost mental functioning in even healthy individuals and by its safety, they coined the term nootropic to describe it and other substances. Piracetam (trade name "Nootropil") was launched clinically by UCB in the early 1970s, and currently is in use in many European countries.

Piracetam is a cyclic derivative of the neurotransmitter GABA.

Akhondzadeh writes:-

In addition to serotonergic abnormalities, the strongest evidence implicates the glutamatergic and GABAergic systems are important biochemical factors in autism. One current hypothesis is that autism is a hypoglutamatergic disorder. This hypothesis is based on neuroanatomical and neuroimaging studies and supported by similarities between symptoms produced by N-methyl-D-aspartate (NMDA) antagonists in healthy subjects and those seen in autism. If there is deficient glutamatergic transmission in autism, the most logical treatment would of course be a glutamatergic agent. In the treatment of schizophrenia, that has many similarities with autism either D-cycloserine (glycine agonist) or Piracetam showed promising results. Indeed, autism and schizophrenia have some similarities regarding the role of serotonin and glutamate in their pathophysiology.

Piracetam is a member of the nootropic class of drugs, which have cognition enhancing effects, it appears to modulate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acids)-sensitive glutamate receptors positively and has been used in many countries in the management of dementia. Although its mode of action is not certain, it is said to protect the cerebral cortex against hypoxia and has been used following trauma or surgery and in a variety disorders including senile dementia and behavioral disorders in children. In addition, it is used in the treatment of dyslexia and some type of myoclonus in adults. Indeed. Piracetam is the most studied nootropic in children.

Piracetam was freely available in the US as a supplement until three years ago.  You will see on the web that people were using it, combined with another supplement called choline, to improve their mental functioning.  It had been shown to work in rats, as you can see in this trial.
In the Ukraine it seems that Piracetam has long been given as a therapy in autism.  No mention of choline.

The full study is listed later in this post.


Pentoxifylline is a drug that targets the immune system, well established to play a key role in autism.  It is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF  and leukotriene  synthesis, and reduces inflammation and innate immunity.

So it would be fair to classify it as an immunological treatment for autism.

It is hard to find much about Pentoxifylline and autism.  It was trialled in the 1970s in Japan.

Japanese Journal of Child Psychiatry, Vol 19(3), 1978, 137-144

Describes the successful use of Pentoxifylline (150–600 mg/day) with 3–15 yr old children with abnormal behaviour (e.g., self-mutilation, aggressiveness, and hyperkinesis) and with autism. It is noted that while the drug was effective in reducing symptoms of autism, developmental factors in the disorder should not be ignored. (English abstract)

Unfortunately I gave not found the full text version of Akhondzadeh’s study on this drug.

Autism in Iran

A paper actually entitled “Autism in Iran”, makes very interesting reading and was co-authored by  Akhondzadeh.


Links to my selection of Akhondzadeh’s Research


Herbal medicine and women's mental health


Autism spectrumdisorders: etiology and pharmacotherapy

Herbal Medicine in the Treatment of Alzheimer’sdisease

Cyproheptadine in the treatment of autism 

Authors: GUDARZI S., YASAMYM. and AKHONDZADEH S Eur. Psychiatry, Vol.17, Year. 2002, Page: 230-231,    NO ABSTRACT

A Double-blind Placebo Controlled Trial of Piracetam


All three drugs would seem worthy of further investigation, but particularly Piracetam and Periactin.  Both seem to be widely used with children and were/are OTC.