Wednesday, 16 December 2015

Long Term use of Low Dose Clonazepam and More Science on the Excitatory/Inhibitory Imbalance in Schizophrenia and ASD

A small number of readers of this blog have followed Professor Catterall’s ideas and trialed low dose clonazepam for autism.  

This post summarizes my findings from using it long-term; it would be a good place to collect the findings of other people.

The science part of this blog is courtesy of a reader who highlighted the full-text version of a paper I mentioned.  Perhaps it was the author?

For information on Catterall’s clonazepam research, go to the “Index by Subject” tab and click on Clonazepam.

Before getting to that, I do get asked how I know, for sure, these therapies really do work for Monty, aged 12, with classic autism.  As I told Ben-Ari, the Bumetanide researcher, the best way to convince the doubting public will be to measure IQ, not autism.  If you can add 30 to 50 points to your IQ result, even the sceptics would pay attention.

I am not measuring IQ directly, but I do note things like spelling tests, math tests and handwriting.  The first pleasant surprise was actually reaching the point of sitting the same tests as the NT kids. Piano playing is another interesting proxy.

Monty’s one to one Assistant (and pal) from age 3 to 9 came to visit the other day and could not believe what his handwriting now looks like.  She had spent hundreds of hours with him practicing fine motor skills, like pencil control.  The end result was handwriting, but even then not like that of his peers. 

Cursive handwriting is now great.  Spelling tests and “quick-fire” math tests are also great.

As we now know, 20% of people diagnosed very young with quite severe autism seem to make wonderful progress.  This has happened by 5 or 6 years old, while the brain is still highly plastic.  Spontaneous accelerated development thereafter rarely seems to happen.  Monty started his Polypill therapy at the age of 9 years, in December 2012.

This is a spelling test from school, given to NT (neurotypical) ten year olds and 12 year old Monty (on paper without lines).  It is not rocket science and big brother could probably have got 20/20 in this test when he was eight years old.  But when Monty was eight years old, he was trying to break the windows of my car with his head and his handwriting did not look like this.

I have all the proof I need that modulating the excitatory/inhibitory imbalance in Monty’s autism is well worth the effort.  The effects are reversible if you stop the therapy, as should be the case.


Here I am repurposing an existing drug for a different use, at a dosage so low it is highly unlikely to cause side effects.  This is mirroring the use of the same drug, at similar low doses, in mouse models of autism by Professor Catterall.

Clonazepam at “high” doses is widely used already in people with autism, to treat seizures and extreme anxiety.  

Catterall showed that the drug has a totally different effect at very low doses (less than 10% of normal), via a specific mechanism which he has identified, the positive modulation of the α 2,3  subunits of GABAA receptors. 

GABAA receptors are made up of five sub-units, the strict composition does indeed vary over time, just to make things even more complicated.  The most common GABAA receptors have two αs, two βs, and one γ 2β2γ). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). It is these subtypes of the subunits that Catterall showed to be key.  Clonazepam was one of the substances that he showed to be effective (in mice).

At “high” doses Clonazepam does have side effects, people build up tolerance to it and so take ever higher doses, and then they get hooked on it.

At very low doses the reverse seems to occur.  Over time you become more sensitive to it and need lower and lower doses.  This was a surprise to me.

The other surprise was that slightly above the effective “low dose” you get some anxiety and irritability.  When I first wrote about this I did wonder if this was just a coincidence, but it is not.

My chart from back then:-

Another interesting point was that some other readers found the effective dose was even less than mine.

When you read about the use of Clonazepam at regular, much higher doses, it is clear that there are wide variations in people’s sensitivity to this drug.  So much so that there is standard lab test to measure blood concentration of this drug, so that the clinician can vary the dose to achieve the desired level in blood.

It is not an expensive test and I did wonder if this could be used by clinicians to find the effective low dose in their patients with autism.

It did sound a clever idea, but then I read that even the same blood concentration of clonazepam (at high doses) can have markedly different effects in different people.  Still it is better than doing nothing and would reduce some of the guesswork with dosage.

The effective dose

In my n=1 example, the effective dose started out at 40mcg a day.  The half-life is very long and so you need three days to reach a stable level.

Other people contacted me to say that in their case 25mcg a day was effective and in one case, dosage once every two days was optimal.

In my case 40mcg, now gives the negative effects I has originally discovered at higher doses.

Currently the effective dose is 20 to 25 mcg.

This is a tiny dose, technically sub-clinical, but it really is better than giving none.  I have discontinued on several occasions.  There is cognitive loss, which is then regained when re-starting. 

The incremental cognitive effect is not as great in magnitude as I found with Bumetanide, but in people not using Bumetanide, the effect seems to be much greater.  Put more simply, Clonazepam plus Bumetanide is more beneficial than Bumetanide alone, at least in my case.

At this dose the annual cost of the therapy is one dollar/euro/pound. So it will not break the bank.

Tablets are available as 0.5mg  (giving 20 days of use) and 2mg (giving 80 days of use).  A bottle of 2mg tablets will last someone a few years.

I wish they made 0.025 mg (25 mcg) tablets.

I see no reason why, in ten to twenty years’ time, low dose clonazepam will not be a mainstream therapy for some autism; the only problem is the variability of the effective dosage.


For those diehards who have made it this far, now I move from the Peter-reviewed science to the Peer-reviewed science, but from yet another Peter, Peter Penzes from Northwestern University, close by the Windy City.

Abstract: Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are cognitive disorders with complex genetic architectures but overlapping behavioral phenotypes, which suggests common pathway perturbations. Multiple lines of evidence implicate imbalances in excitatory and inhibitory activity (E/I imbalance) as a shared pathophysiological mechanism.
Thus, understanding the molecular underpinnings of E/I imbalance may provide essential insight into the etiology of these disorders and may uncover novel targets for future drug discovery. Here, we review key genetic, physiological, neuropathological, functional, and pathway studies that suggest alterations to excitatory/inhibitory circuits are keys to ASD and SCZ pathogenesis.

This study really shows how the common genetic dysfunctions in both schizophrenia and autism come together to produce the Excitatory/Inhibitory (E/I) imbalance.  Numerous different dysfunctions result in the same imbalance, some relate to GABA and some to NMDAR, but the end result is the same.

It is a really good paper, mentioning many of the genes we have encountered in this blog, plus many of the pathways like mTOR and even PAK inhibitors.

The study does not cover any therapeutic methods to correct the E/I imbalance, but this blog has those in spades.  They relate to modulating GABAA, GABAB and NMDA receptors.

Low dose clonazepam is modulating GABAA , as does Bumetanide and as should Acetazolamide (Diamox).  More of that in 2016.


  1. Would low dose clonasepam and bumetanide help someone who shows some positive results from gaba-b agonist Baclofen? Or would those be better suited for someone with nmdar hyperfunction? Because from what I understand, baclofen/cinnamon/d-cycloserine would improve nmdar hypo function symptoms whereas low dose clonazepam/bumetanide/memantine would help those with nmdar hyperfunction? Or do these symptoms overlap? The only thing I have responded to is baclofen, and initially it helped a great deal. Especially about 5 hours after my morning dose of adderall (perscribed for my adhd symptoms). But I have come to a point where baclofen only produces dizziness and fatigue, whereas before it gave me cognitive/social/mood/anxiety benefits. Maybe it is time to taper off baclofen for a while to let my gaba-b receptors upregulate(maybe gaba-b antagonist fasoracetam could help this process?). I am an early adult and baclofen'a loss of effectiveness is bringing me back to my original anxious/startle-prone/poor-sociability state, and things are seeming to spiral downhill in my brain. I am at a loss of what to do at this point. Any help/suggestions would be greatly appreciated.

    1. I would give the Baclofen a break, tolerance to it is a known problem. If you can find two or three treatments for the anxiety, you can rotate them. I am informed that other anxiety treatments that can be highly effective are Propranolol and pregnenolone/progesterone cream, the latter is affecting GABA the former is not.

      You could also try the Russian GABAb drug, Pantogam, which is sold online. This might not have the tolerance problem of the Baclofen.

      You certainly could try bumetanide and low dose clonazepam, I have no feedback as to how they work in anxiety for Asperger's. They are safer than Baclofen.

      So there are plenty of things to try. Let us all know when you find some effective solutions.

  2. HI You don't need to post if this won't be helpful to others, and I will need to re-look at your other posts on this, but I thought that low doze clonazapam was actually negative for some from your posts? Not just a non-responder. And, if I recall, using lorazapam would not offer same benefits if you are a responder? What are the big cog. areas of improvement specifically like spelling, handwriting, piano playing. The reason I ask is that my child has always been excellent at all those, so wondering if this helps that part of the brain -- would there be other area impacted? Thoughts? Thanks!

    1. It all depends where on this spectrum you are. If your child is great cognitively, it certainly is not classic autism. The E/I imbalance is present in HFA and Aspergers, but it may be of different origin. You cannot link a drug to specific skills like handwriting, but you can to cognition generally. If you want to recreate the Catterall effect, Clonazepam is what you need. If you do not have that underlying dysfunction, there will be no effect. You have to identity where your child has issues, many people with HFA suffer anxiety, whereas most with classic autism do not.

  3. About 4 months ago I started giving my 8 yo a tiny dose of clonazepam. After some trial and error we settled on every second day as the best frequency. It has definitely brought about changes. Many thanks to Prof Catterall for his research.

    Almost immediately I noticed more creativity. He is better able to entertain himself now and find things to do. Like many children with autism he never played with toys imaginatively, but now I have noticed him play creatively with cars and even set up little races.

    His general demeanour is happier and he is more easy going.

    He is more likely now to sit and do his desk work independently. Whereas before it was always a huge effort to get him to do his work, and he would need to be prompted and guided.

    He seems to speak in a more appropriate voice now. Whereas before he always spoke so softly people couldn't hear him.

    Interestingly, I have also noticed that his handwriting has improved tremendously. Approximately one year ago it was almost illegible.

  4. Interestingly enough I just read a paper on dopamine signaling that is somewhat ancillary to this discussion in that the research group that produced the paper showed via modeling and experiments that a small amount of amphetamine boosted the stable states (as they called it) for making cognitive decisions, but too much amphetamine caused disruptions in cognitive decisions. Amphetamine of course boosts dopamine release in the brain. Here is the press release (I have not read the papers).

    What I find interesting here is this idea with impacting cognitive states with the right dose to get the desired effects, when traditionally in the field of psychiatry the assumption with drugs was if a patient was not responding, they just needed a higher dose (the more is better approach).

    I have had great success so far (cognitively especially) with Bumetanide plus another intervention I have mentioned here dealing with serotonin, but what also seemed to make a big difference lately is Picamilon which is a very old supplement/drug that is thought to work by getting GABA past the blood brain barrier via its bond with Niacin (Picamilon is a synthetic chemical bonding the GABA and Niacin together) which then hydrolyzes in the brain releasing both agents to do their work independently (increasing blood flow plus all the cognitive and behavioural effects of increased GABA signaling in the brain, including lethargy).

    Now the strange thing is that other GABA analogues such as L-Theanine had a very, very, very bad manic effect on my son (this was pre-Bumetanide) and I was also paradoxically confused by Picamilon as it seemed to make him more alert but more hyper (GABA is typically sedating). Perhaps Reduced GABAergic signaling in the brain (new paper):

    is a response to the brain reacting to the depolarized steady state of GABA interneurons in the autistic brain as suggested by Ben-Ari due to problems with chloride homeostasis. Also, perhaps treatments which shift the polarization of inhibitory interneurons such as Bumetanide may open the door to GABAergic signaling drugs not having the paradoxical effects they have on many with autism where they cause stimulatory behaviour rather than the opposite which is the intent. I decided to give Picamilon another go and it seems to have for whatever reasons given a boost on top of Bumetanide. Picamilon is no where near as potent as the wide range of GABAergic drugs on the market (including Clonazepram) which is why I prefer that route since the clearance rate of GABA in the brain is about 20 times more than what can be recirculated back in, whereas many GABAergic drugs can stay floating around in the brain much longer, possibly leading to known side effects as well as perhaps many others not explored in the developing brains of children.

    Last but not least, the only bad thing (if you call it bad) about my son lately with his latest gains is he has a new behavior where he walks up to random kids on the playground or at the speech therapy waiting room and gives them hugs. While on the one hand, I am happy he is being more social, on the other hand, this behavior needs to be shaped to the proper context fast before something bad happens between him and another stranger who might not understand his intentions (and most people don't want random hugs from strangers anyways even if the intentions are understood). Of course, I am always a few feet from him at all times whenever he gets near other kids in a public setting (always have), but when he goes for a hug, he often does it so fast I can't do anything even though it is harmless.

    1. I would not worry too much about the hugs in the playground, more typical problems are going up to random kids and hitting them. I expect it will settle down.

      In some older posts I looked at the idea of switching GABA back to inhibitory and then giving GABA a "boost". Using a tiny dose of Valproate, as suggested by another reader, you can achieve this. The response is similar, with hugging and hand holding.

      GABA is supposed not to cross the BBB. Valproate is not fully understood, but is considered to "increase GABA".

      Picamilon is interesting, as is Gabapentin.

      Low dose Clonazepam is doing something very specific, it is modulating the receptor's response, it is not "increasing GABA".

    2. Tyler, what dose(s) of Picamilion have you tried?

    3. Tyler, when I was trialling clonazepam daily with my son he was alert but extremely hyper, constantly fidgeting, pacing up and down. I was pleased when the hyper ness relaxed on a lower dose.

      Are you suggesting that clonazepam is potentially unsafe? What do you mean when you say " many GABAergic drugs can stay floating around in the brain much longer, possibly leading to known side effects as well as perhaps many others not explored in the developing brains of children." You have succeeded in making me feel worried.

      The dose that I give my son is tiny but as a parent of course I wish I didn't have to give any drugs at all.

    4. Nina, Clonazepam is well studied and at doses 20 to 200 times your dose it can be habit forming. As I mentioned above, after using it for a long time at these low doses, I actually need even less. All drugs need careful thought. If you google Picamilon, refered to above, you will see that the FDA in the US want to ban it. Ponstan the NSAID in a recent blog is OTC in Australia and NZ and is seen as safe, it costs $8. In the US Ponstan is rarely used, costs $200+ and is claimed to have troubling side effects.

    5. I was speaking to my compounding pharmacist yesterday who is making up 25mcg clonazepam capsules for me. He said that he was used to making up mcg doses of it, mostly for people who were weaning off regular doses of clonazepam. He said that it appeared that the micro doses were very successful for this.

    6. Peter, I have been using the standard recommended dose of 250mg. The hard thing here for me is efficacy as my son won't do pills and I have to mix it in drinks so how much gets absorbed/degraded before it even gets into the brain is something I just don't know. The other thing about Picamilon is it has a half life similar to Bumetanide, and NAC so I give it all together in a sweetened drink usually twice a day. Picamilon anecdotally produces a relaxed alert state in myself and I have done up to 4x the recommended dose (for myself) just to see if there were any major problems since my son is about 1/4 my size and higher dosages didn't seem to do any more than the lower dosage.

      And to Anonymous, GABAergics are not substances to be taken lightly. Picamilon in theory could be considered straight GABA, except that it uses a Niacin molecule to piggyback through the blood brain barrier where it hydrolyzes into Niacin and GABA at that point. It is one of those compounds that has no patent on it, so there is not a whole lot of modern research behind it because we all know how medical research is funded these days, especially as in the USA the budget for the National Institutes of Health keeps getting slashed each year (and they fund most of the independent pure science medical research whereas the health care industry which comprises a mammoth 20% of our GDP funds the somewhat biased and selective research with respect to drugs for profit).

    7. The other thing about Picamilon is it often gets lumped together with other over-the-counter GABA supplements like Phenibut which you could consider a true GABAergic like Clonazepram in that it affects specific GABA receptors directly and can also be habit forming. That is where most of the impetus for idiotic politicians wanting to ban the substance and other substances in the "supplements" category. At least I don't live in Europe where even common vitamins are banned for over the counter use. Only in America do you have a push for legalized Marijuana (which has been recently proven to have disastrous long-term effects now, especially on adolescents and teenagers), but at the same time having politicians trumping up fears about people overdosing/abusing supplements. I wonder where they get their campain financing from. We don't have a functional health care system for the majority of people in the United States, so not everyone can deal with complex issues by going to a doctor as the visits to the doctor are often far more costly than any generic prescribed drugs.

      Also, high-dose or low-dose is a matter of perspective for any drug (independent of how you word it). I don't know what dose if any makes sense for autism with respect to weighing the long-term benefits versus the long-term outcomes, just I am very cautious about GABAergics. I am not a doctor, but like probably most of us parents in this situation with limited realistic options, we all have to try and do our best and part of that means being cautious.

      Personally, I think Picamilon is safe in a normal person and as I said before I got paradoxical results before Bumetanide and linking the two together is just my personal hypothesis which is the best I can do at the moment. Maybe once I read a dozen or so scientific papers about Clonazepram I might change my mind about the low-dose thing, but I will certainly take a look at it because there is some very compelling research lately suggesting that some of the problems with inhibition in the autistic brain might not be to GABA levels directly, but GABA signaling somewhere and who knows maybe low-dose GABAergics do the trick in this regard. Really, I don't know as this is just speculation. Either way, finding a doctor to prescribe low-dose experimental Clonazepram therapy to my son would probably going to be a next to impossible feat at his age, so even if I was all aboard for this treatment, I would have some of the practical problems that I had with Bumetanide when I looked at it several years ago when there was a lot of news about the treatment (it was one of the more widely reported research findings in the mainstream media at the time). Really, for Clonazepram I would probably have to go to a psychiatrist and tell him/her I have extreme anxiety due to being a parent in this situation (which would actually be true) and that I would like to try the GABA route of treatment and then use the prescription to treat my son. Even then it is a controlled substance with a lot of risks if someone else knows what is going on and snitches on you.

    8. Hi Tyler,

      I have a very supportive family physician. If you would like to contact me in private, you could get my email from Peter?

  5. For those wanting to try this but unable to get Clonazapam, supplementing menthol (aka mint) could be an easy to obtain over the counter alternative.

    Mint/menthol activates GABA A receptors. It also blocks voltage-gated sodium channels and voltage-gated calcium channels.

    It has already shown promising cognitive and memory-enhancing effects (eg

    For those who like to read up on mechanisms see this and many others

  6. Hi Peter,

    I didn’t know that you can check clonazepam blood level, it could be helpful.

    I found various doses of Clonazepam to be effective, but for most of the time it was not more than 20 mcg daily. Anxiety and sleep problems occurred with higher doses. These behaviors were so distinctive that I learned to recognize them very easy.

    Clonazepam is metabolized with the enzyme CYP3A4. From what I’ve read, some adults who use Clonazepam for other purpose than autism, take advantage of that and use other drugs that block CYP3A4 to increase Clonazepam blood concentration and effects. Some drugs are minor CYP3A4 inhibitors, but I think their effect may be significant when you use low dose Clonazepam with narrow therapeutic range for autism. It saw typical anxiety when gave Omeprazol for a few days and with Acetazolamide, which was also suggested to be a weak CYP3A4 inhibitor. That’s why I stopped Clonazepam now for a while. I think in case of low dose Clonazepam use it is worth to consider even minor drugs interactions.

    Verapamil is also considered CYP3A4 weak inhibitor. I added Clonazepam and established the best dose after I had been already using Verapamil. Did you see any relation between Verapamil dosing and Clonazepam? I would not be surprised that when one starts with Clonazepam and then add Verapamil, Clonazepam dose needs to be adjusted, at least in people so vulnerable to increasing the dose as my son is.

    Do you understand why such behaviors occur with higher Clonazepam doses? I saw exactly the same once for two days when my son was off Clonazepam also.

    1. Hi Agnieszka, I do vary the Verapamil dose slightly, since he benefits most during the pollen season. As you say this will affect the metabolism of the other drugs. I am now giving slightly less Verapamil and I do need to give less Clonazepam.

      The very good news is that there is no tolerance at these tiny doses, which would have meant this could not be a long term therapy.

      The bad behaviors at slightly higher doses is not something that Catterall noted in the studies on mice. This is something that needs to be known since it might cause a trial to fail, when in fact it means the dose is just slightly too high. As to why it happens, I cannot say other than it does not surprise me. We are fine tuning something very specific and we ideally want a good effect, or no effect. It turns out that with increasing dosage, it goes no effect, good effect, bad effect, no effect and then at much higher doses a totally different effect.

    2. Thanks. I wonder if the trial has already started. I can't find any information apart from what prof. Catterall said at the end of SFARI webinar.

  7. So I read the paper on peppermint and there were no positive findings in the paper. Basically, the authors concluded their hypothesis was incorrect and that peppermint did not do anything for cognition or memory. I read the whole paper so maybe you accidentally posted the wrong link.

    The second link you posted from PubMed on menthol research was much more interesting.

  8. Also Nat I did a lot of reading on menthol because it sparked my curiosity. Well, in addition to being an allosteric modulator of the GABAa receptor, menthol is also a 5-HT3 antagonist which is suggested as being downregulated prenatally leading to social impairments. Ironically, it seems to have been investigated as a treatment for autism because the other side effect of blocking/downregulating the receptor is decreased anxiety. My reading on it all is that this is all very complex and paradoxical in the sense of maybe decreasing anxiety like behaviors, yet increasing social impairments.

    While searching through the search pages for "5ht3 receptor autism" on Google, I came across this link on the third page:

    Anyways, thanks for the posts Nat, though the question begs for discussion whether ingested menthol would be a good or bad substance with respect to autism symptoms, especially with respect to this discussion at large.

  9. Hi Tyler,

    yes I posted that first link as the first one I came across (I really need a PA to keep my files in order :) Although it reported a negative result it does reference several positive studies so is a good starting point imo.

    In our N=1 it has been a very positive ‘intervention’. So far. Long story short ds has recently developed a taste for fresh mint, and has been eating whole bowls of fresh leaves, just 'snacking' on them (I have no idea how much he consumes in weight but can go through a large bag of leaves in 2-3 days, or finish off a small supermarket pot of the 'grow your own herb' in an afternoon). We have recently had a nice big leap in cognition and fluency and tone of speech (just acting and speaking in a more ‘typical’ way all around), and I have been trying to figure out why and to match it to different things we have been doing. We have introduced one or two new supplements and changed dosages of some of the old ones etc but the thing that probably matches this recent sudden jump is this new mint craze. His food fads come and go so I doubt the love of mint it will last long enough for us to notice negatives developing, but I'll report if any.

    PS Peppermint (oil) is often recommended and used for IBS and all sorts of gut/digestive problems, but ds hasn't had any gut issues for many years, so I doubt the effects here would be linked to 'calming' the gut or any such thing.

    1. Another paper I read last night (on menthol) suggested that at least in the gut that menthol upregulates antioxidative stress mechanisms, in particular enzymes for glutathione and superoxide dismutase. No idea if this effect is global throughout the body or restricted to the gut (can't find anything saying it is not the case), but this study found stress responses to be upregulated including HSP-70 which is relevant in some research to autism.

      I also came across a patent on menthol and autism that listed Henry Markram as one of the contributors (which I thought was odd). Henry Markram is famous for his work with spike timing dependent plasticity (STDP) and also notorious for having a son with autism and promoting the "intense world theory" to name a few other things. I then looked up research related to him and menthol and came across this paper:

      Basically, it covers some of the same stuff found in other papers I found on menthol and its effects on various neural receptors plus some other things. You can read it yourself if you like since it is open access.

    2. Thanks Tyler, that second paper looked at Cinnamaldehyde alongside menthol and a several other natural compounds, concluding:

      "Interestingly, several different AIS produce qualitatively similar effects both on single neurons and on larger-scale network behaviour. This suggests the existence of a common mechanism of action that could be shared ..."

      We also supplement cinnamon. The two (cinnamon and mint) could easily be working in synergy here!

  10. Hi Peter,

    I do think that the behavioral regression that I am seeing in my daughter the last week or so is due to allergies. For the first time, I noticed a loss of cognition, in math class and in following directions. 'Foggy' response. Interestingly though, unlike with the usual summertime allergies, verapamil and bumetanide are not taking care of it. Sytrinol is the one that appears to work. Stops the behaviors in about 10 minutes.

    1. I am glad the sytrinol helps. It is good to have various options.

  11. Hi Peter,

    I was trying to find an old post of yours on exercise, but the search wouldn't work. So here it is. Very interesting paper, but surprisingly, even when it first came out in 2013, it hardly got any press.

  12. Hi Peter,

    just passing to say I'm glad for you and your kid.

    And thank you, I've been following your blog for about 18 months, and my kid is better and in a good trend largely due to pointers you published.



  13. Hi Peter and RG,

    I have a question about Bumetanide, potassium and ketogenic diet so addressed it to you, but maybe other readers also have some experience with that.

    Some update on Acetazolamide (Diamox) in addition to Bumetanide after a few weeks: my son has got Diamox almost all days in December. The aim was mainly to address headaches, but it does have clear impact on autism. I am calling this “What happened to your son?” phenomenon as we’ve got many unprompted comments from teachers about his achievements recently, for example calls from his assistant just to tell me that he answered the teacher questions addressed to the whole group for the first time in his life, done educational tasks without mistakes and on time etc. He is with kids 2-3 years younger, but their tasks are very challenging for him. The other therapist put it quite straightforward: “I don’t know what you started giving him now, but please give it always”. She didn’t know about Diamox.

    This all happened when he got 60-150 mg Diamox daily with 0.5 mg Bumetanide daily and peaked with coming back to 2x0.5 mg Bumetanide. It seems like he needs at least 120 mg Diamox for headaches and with this doses it’s hard to get his K+ over 3.5, while I know that he feels best at K+>4.5. The diuresis issues got better after few weeks and this is not a problem now.

    When I quit Bumetanide for a few days some behaviors reemerged, the same I noted to be alleviated by Bumetanide a year ago, including sensory issues I was happy not to see and my son was happy not to experience for many months.

    If other readers consider Diamox, please don’t feel discouraged by potassium issues in my son as he needed especially high dose of potassium even before, for most children it’s not a problem.

    Now I have been offered a ketogenic diet to be started in my son at hospital setting by a doctor who doesn’t mind introducing this diet while he’s on Diamox. And my question is: have you done any dietary modifications for potassium intake? Can I expect an impact from food potassium (those who has hypoKPP sometimes doubt it)? Only recently I started to explore this area, but well… my son will eat a banana only when he is extremely hungry. RG, did modified Atkins diet influence K+ levels in your daughter? Had she already been on Bumetanide when you started? Do you supplement potassium? I can’t imagine keto diet if you have to give a child potassium rich foods like dried and fresh fruits. How can this be managed? I know what doctors do in adults on loop diuretics with hypokalemia: add potassium sparing diuretic spironolactone, but I think might not be a good idea because of diuresis. I would appreciate your comments!

    1. I wonder if your Diamox effect could also be achieved by a higher dose of Bumetanide, or perhaps there is a limit to how far Cl- levels can be affected via NKCC1 and that it may need a different ion transporter to "finish the job". This latter option seems plausible to me, so I will test it in January.

      I try briefly try spironolactone, but concluded that K+ was a better option, in our case. Your case is different and if K+ levels are more affected spironolactone may be the best option.

      According to Johns Hopkins, the benefits of the ketogenic diet can also be achieved with the Modified Atkins Diet, which is easier to implement.

    2. My oldest son is only 6 but he has had accident issues at home and school so often over the last year or so that all of our furniture is ruined (him doing gymnastics onto the couch has not helped either). Some days at school he would have 3 accidents a day. My best guess from what I know about enuresis which I have read probably a dozen or so papers on alone, is that hyperactivity in the motor cortex is the main issue here (something which is also pretty standard in brain imaging studies with autism as well not to mention issues in pretty much all sensory/motor cortices). The other guess is ADH (antidiuretic hormon) which is also known as vasopressin in the brain which at least in the brain is generally atypical among the autistic population as well, but really I think my son's issues deal with the well-documented inhibitory problems in that area of the brain in particular.

      So ironically after giving him bumetanide now for about three weeks, his accident problems though not gone completely, are down probably from 3 or more a day to maybe once a day or sometimes none a day.

      As far as potassium goes, I would just go with potassium gluconate to supplement. You can also use a product called Nu-Salt or another one I think called No-Salt which is a potassium chloride salt substitute on foods which it makes sense to sprinkle it on. Potassium Gluconate is largely tasteless (at least the NOW foods brand we use) so you can easily mix it in drinks as well.

    3. I can't tell about higher dose of Bumetanid vs Diamox, tried to increase it few months ago, but my son did not tolerate it. He felt unwell and urination was unbearable for him then. Yes it can be MAD, but I realized that his diet is not really high in potassium and switching to MAD can also result in even lower potassium intake.

    4. Spironolactone would seem well worth a try.

    5. Hi Agnieszka,

      We were already on the MAD before Verapamil and then Bumetanide. If Peter's blog had been where it was then as it is now, I might have tried other things first, such as Diamox and Bumetanide combination, PEApure, etc before going on the MAD. Inherently, the MAD/Ketogenic diets are so restrictive that one has to come in with added supplementation. Which is not necessarily a bad thing in my opinion, because they are more measurable and controllable. One never knows with food sources how much is absorbed and bioavailable. I think our kids all have various things that are off, and it is just better to address it with supplements than food.

      So far, my daughter's potassium levels have been ok, borderline normal, but then, she drinks so much water that chloride is also low normal. Blood acidity is something we have to constantly watch for, she seems to need the water to keep it normal. This is also the reason I have hesitated with the Diamox since it increases acidity. If you start the diet, I would be very interested to see how it goes.

      There are many papers on the ketogenic diet for migraines. Did you see the last one I linked to, it talked about adenosine being one of the reasons for the success of the ketogenic diet. I wonder if supplementing with uridine might do that instead.

      If you son has a chronic issue with low potassium, have you run a cardiology work up on him. If everything is fine with that, I would just go ahead, supplement with as much potassium as needed to bring it up to normal and then start the diet.

      Typically, magnesium runs low on the diet, as well as calcium. Some kids may also need carnitine. Magnesium has been our biggest problem, my daughter already has a tendency to run low and the MAD drives her need even higher. Where it is potassium for your son, I think it is magnesium for us.

    6. Agnieszka, one more thing. Are you going to start the diet inpatient at the hospital, for three to seven days? That might be very good, as the potassium and acidity can be monitored there and you will know within a few days how things are going. If it is an option, then take it.

  14. Hi and thanks to all of you for comments.

    Peter, what dose of Spironolactone did you use? I remember that I asked you before about this, but I can’t find now. Spironolactone has been suggested to reduce neuroinflammation:
    Otherwise, I think that preventing hypokalemia with dietary modification and supplement would be perhaps safer. Having read the recent paper about omalizumab I had one thought: “how many pills can a polypill have…”.

    Tyler, thanks for suggestions with K+ supplement. Potassium gluconate syrup available where I live tastes extremely awful. My son in addition to autism has recurrent migraine-like symptoms, with some features of periodic channelopathies, that’s why a few months ago I applied things people with hypokalemic periodic paralysis do: drinking K+ supplement at once instead of over several hours, low-sodium salt, K+ before carb meal or exercise. All made my son feel better despite he never had serious hypokalemia. It’s like Peter wrote here about his experiment with K+ and sensory issues.

    Interesting what you wrote about Bumetanide and urinary control as I had the same experience. I’ve been told recently that for some professionals it would be difficult to accept treating autism with a diuretic, even after Bumetanide gets approved, what about treating enuresis with a diuretic then?

    Thanks RG for explanations. Yes the diet would be started at the hospital. In fact it’s the first thing for years that has been offered to my son for autism and this doctor is a gem. She says that she treats many children on Topiramate (also being carbonic anhydrase inhibitor) together with ketogenic diet without problems with blood acidity. My son had cardiology work up when started Bumetanide - everything was ok.

    Before I was thinking about some “light” version of ketogenic diet, more or less as is suggested here:
    I discussed it with the other reader here, but personally never managed to introduce even the simple idea of some coconut oil for breakfast in my son. He is allergic to gluten and milk protein, that would make MAD or KD more difficult, but there’s a case report by Martha Herbert describing huge progress of a girl on such diet, so it seems possible. I can’t find the paper about ketogenic diet, migraine and adenosine - could you link it once more? While I was looking for it I found your another comment about your daughter drinking huge amount of water when she’s unwell. This sounds familiar to me as my son drinks lots of water during his periodic headache episodes. I don’t know if this is a kind of OCD or anything else that can be biochemically explained.

    1. Agnieszka, I used 25mg of spironolactone once a day, at that time I was giving bumetanide 1mg once a day. I saw that paper suggesting its use for different reasons in autism. It did not seem to have any advantage in our case, but we have K+ at 5.0. It does seem from other feedback that high normal is the best place to have K+.

    2. Hi Agnieszka,

      Here are two papers:

      Specifically migraines:

      When I started the diet, I did it without dairy, my daughter is gluten free anyway. It is only recently that I added the yogurt, more for the probiotics than anything else. She drinks a water that has a good amount of calcium. It is quite easy to do the diet without gluten and dairy.

      You could start with the MCT oil diet, which is the KD with the MCT oil added in. Adding it in, did nothing for us. There are studies that have shown that it is the C10, capric acid/decanoic acid that are important in mitochondrial disorders and epilepsy. I have not been able to find an mct oil with a higher ratio of capric acid. If you would like to go this route, I think you should consider a combination with coconut oil like this:
      Scroll down to a link for diet guidelines and faqs and there you will find a recommendation for mixing 16oz met oil with 12oz coconut oil and then building up from 1tsp of this mixture. She found the combination with coconut oil necessary and not mct oil alone, I think because of the capric acid.

      Two points are interesting from the study you linked to: one, that it seems to be the milder autism kids who had the best response; second, that the researchers postulated that it might be the increased concentration of gaba that contributes to the effectiveness of the kd. It seems that it is the apsergers/high functioning subgroups who do well with baclofen and other gaba supplements anyway. For many of the others gaba might still be excitatory and therefore, an increase may not help much. I think this might be the case with my daughter.

      Its great that you can start the diet at the hospital. Maybe they can also do a 24 hour EEG alongside?

  15. Agnieszaka, I also wanted to send you this link on decanoic acid:

    1. Speaking of fats and mitochrondria, here is some very recent research on stearic acid (highest concentration in cocoa butter but also high in many meats) and its effect as a signaling molecule for mitochondria in terms of improving its function:

    2. Thanks for the links, I will read the papers and also more about Spironolactone. I can see this drug has been used by DAN in a dose as low as 3 mg.

      RG, in the Greek study about KD they wrote: “the higher improvement was seen in children with lower initial Childhood Autism Rating Scale scores, although they belonged to the severe autism group.” and also that “The increase of ketone bodies maintains the synaptosomal content of γ-aminobutyric acid (GABA) at a higher level”. Maybe when inhibitory function of GABA is restored with Bumetanide then ketogenic diet is one of the possible ways to have “more GABA” available in the brain as in the title of Peter’s most recent post?

      I have just read this study once more and think it’s odd that they used KD intermittently and also the effects did not disappear for at least half a year after the diet was quit. It is quite old study, submitted in 2002 and I wonder how are these kids doing now as adults and if they still use KD.

      With regard to 24h EEG, my son had this test. In all his EEGs epileptiform discharges were found in sleep only and usually they were considered minor. He was seen by 3 neurologists and no one diagnosed epilepsy in him.

    3. hi tyler this is intereting... would you supplement with stearic acid supplements, then?

    4. Hi Tyler-- thanks for sharing. Would you supplment with stearic acid then for mito dysfucntion?

    5. Hi Agnieszka,

      There are many children who leave the KD/MAD successfully. They seem to remain seizure free the rest of their lives. The most famous one is the movie producer Jim Abrams son, who literally had no seizures after he left the hospital. I do see a few parents come back after a couple of years or so after having left, their children have had one or more breakthrough seizures. The statistics say that it is harder to gain back the success second time around. Most parents these days seem to do a wean from KD to MAD to Low Glycemic Index Diet and then out.

      Except for a few not very comprehensive studies, there is very little about long term effects of the ketogenic diet. Even people like Peter Attia seem to go in and out of ketosis. Most of the doctors who personally are on the diet seem to have this approach. In my experience it is difficult to maintain ketosis, without constant measuring and adjusting (though dietitians will tell you differently). I just found out that my daughter had no blood ketones at all in a recent lab, even though her diet had not changed. I am still troubleshooting.

      We had very good success the first month of the MAD. No seizures, undesirable autistic behaviors cleaned up, speech was up. We had three more such intervals in the last year and a half. The diet could not prevent allergy or stress provoked seizures. or the catamenial. At this point, there are only two reasons I am staying on the diet: one, weight loss, my daughter had gained a lot of weight with puberty, and it is the MAD that helped her lose it, about 50lbs. Second, I want to try the Diamox and increase the bumetanide and see if that combination with the diet will help. Also, bring back the NAC. My daughter has had a very good response from day 1 of the bumetanide, so I don't know why the MAD with increased gaba would have helped, she was not on bumetanide at that time. I have to think that it might be other effects, such as adenosine, ppargamma etc.

      I am looking at additions like the coconut oil and glyceryl triacetate, which have been shown in studies to help with epilepsy and in other purine disorders like canavan disease.

    6. Thanks for link Tyler.

    7. Hi RG

      Thanks for all information, it made KD/MAD more familiar to me. At the moment I realize that not trying this would be unreasonable. I am a bit afraid about weight loss as my son is skinny. Once I had to consult dietician how to make him gain weight after switching to gluten free diet.

      I checked potassium and it’s now much better after simple dietary changes, although all these new things to eat are probably not to be used in KD/MAD…

      This is interesting what you wrote about immediate bumetanide response in your daughter as it usually takes a few days to see the effect. In my son mood and sociability changed visibly for better also from the first dose of bumetanide. But he was on some low dose of valproate then as he was finishing withdrawal. I remember I asked Peter whether it is typical to see bumetanide effect so quickly or it was just coincidence. Maybe it happens when one adds bumetanide to previous GABA-ergic intervention (KD or drugs). I also wondered how possible that my son didn’t react badly to valproate which main action is to increase GABA. But it’s perhaps as your wrote about MAD - this drug also has many actions.

      The paper about adenosine and KD is very interesting. Have you already tried uridine? I recall one thing about adenosine. Once I was trying to figure - ineffectively - what is the mechanism(s) of “fever effect” and how to use it in practice, I tried to find ways to boost anti-inflammatory interleukin 10 production, which some of ASD children were found to be deficient. It was suggested that adenosine 2A receptors agonists (and adenosine itself) increase IL-10 and it has already been tested in other conditions:

      IL-10 peak is typical for fever and also ketone bodies are sometimes found in urine of febrile children. I wonder if you have ever seen “fever effect” in your daughter?

    8. Hi Agnieszka,

      If weight loss becomes worrisome, in the kd there are a few options. One would be to supplement carnitine, the second might be to also add in more calories/fat. My daughter does not like sweets at all and does not mind taking some oil or fat straight from an ounce cup, so I don't usually cook keto breads or ice cream. Many parents do though, the favorite seems to be an ice cream pop or other sweet as dessert at every meal. Can be dairy free. I also have a recipe for a high fat bread that is pretty good. If you need them later, I could send you recipes.

      It is very interesting that your son also had an immediate response to bumetanide. Did he maintain the positive response after you weaned him off the valproate? Then, it could be the verapamil that both our kids take that could be responsible? The known similarities between valproate and the KD are inhibition of sodium channels, reducing aspartate in the brain and some effects on the potassium channels, though that part of the KDs action appears conflicted and controversial. I also saved this part from a paper:
      "Alterations in the expression of ion channels or in the machinery of synaptic transmission would be expected to influence seizure susceptibility. Indeed, a recent microarray study of gene expression in the hippocampus of rats fed a ketogenic diet for three weeks revealed changes in the transcripts of a total of 39 genes that encode such proteins [39]. Most transcripts were reduced in animals receiving the diet, including the voltage-dependent calcium channel subunits γ4 and α1D, the ClCN1 chloride channel, the KCNH3 and KCNE1-like potassium channels, P2X3 and P2X7 purinergic receptors, and synapto-tagmins 6 and XI. Other transcripts were upregulated, including subunits of the ionotropic glutamate receptors GluR2 and KA1, the KCNN2 potassium channel, the SCN1a type Iα sodium channel subunit, and the glutamate transporter EAAC1".

      I have not started the uridine, since I don't have the high dose powder yet. I have written to the only person who is selling it for a quality assay.
      From all that I have seen, in epilepsy, it is the higher doses that have been used, upwards of 50mg/kg, with most around 150mg/kg.

      I have never been sure of the fever effect in my daughter. She has always been quiet and calm during a fever but I thought that was due to tiredness. It is very interesting about the adenosine, I am keen on exploring this further.

      Have you been able to find a good neurologist to interpret your son's EEG? I don't yet, but hopefully the person I am going to see later this month might. Have you seen this:

      and this:

    9. Agnieszka, Peter,

      I also wanted to mention that Sytrinol seems to boost the effects of bumetanide, along with having its own additional effect. My daughter has been taking it for about two plus weeks now, and has become less inhibited socially. We went to a party for New Year's Eve and she sat through it all calmly, and actually seemed to enjoy quite a bit of it. Also, she has not been physically affectionate with anybody other than me these last few years, not even her father. Now, suddenly, she has been giving him kisses and having him swing her up and around, things she used to love to do earlier. Also, up until puberty, she used to be a very active child, loved sports, but changed literally overnight, where it has been hard to even get her to go for a walk. Now, I see the old enthusiasm back, is ready to go out, would like to go ice skating again etc. Fingers crossed, this lasts.

  16. Agnieszka, the other day we were at the Apple store, and my daughter was quite happy playing around on their display computers, when suddenly she had a mini seizure, lasting a few seconds. As is usual, her face got pale and she became exhausted and tired and was slumped against me. I gave her a bumetanide and within ten minutes, she perked up and back to normal. Have you tried giving a dose of bumetanide as soon as your son starts a migraine?

    Btw, does he have auras, is he able to tell you?

  17. Hi, thanks for all comments. It's good to hear that your daughter is doing well on Sytrinol.

    The papers about EEG are interesting. I think that as a noninvasive examination it is underused in autism reasearch. Personally I couldn't find a neurologist who would investigate my son's EEG more than to say it's not (yet) epilepsy.

    I have never tried an extra dose of bumetanide for migraine, but a typical daily dose does not work for this. With regard to acetazolamide, this paper seemed quite familiar to me:

    It's about a girl with monthly headaches since the age of 3 and only after 13 years, when she developed full-blown hemiplegic symptoms, she had genetic testing done and acetazolamide was introduced, which quits her migraines at aura phase.

    My son is not able to tell me about aura, his speech is very limited. Before bumetanide he was not even able to tell or show us that he had headaches. But yes probably he sometimes had aura, I saw him plugging his ears shortly before such headache while he is not usually sensitive to sound and it was not loud then.

    I wonder what do you think about the ideas from the paper below: triheptanoin and acetyl-L-carnitine as metabolic treatment for epilepsy:

    1. Hi Agnieszka,

      That paper is very interesting. I have Diamox in my queue. After low dose clonazepam and vitamin a. Please see my comment on Sytrinol, have you tried it yet?

      The triheptanoin is interesting, I think a lot of effort is going into duplicating the effects of the kd. About the acetyl carnitine, there are several parents on the MAD seizure forum who find that it increases seizures. The same with carnitine.

      My daughter is on 1mg of bumetanide once a day, and that by itself is not fully stopping the seizures. An extra dose as needed seems to help, her face brightens about ten to fifteen minutes after taking it, and she become more cheerful. It also helps with recovery after a seizure. That and two tablespoonfuls of MCT oil, alleviates post epileptic irritability and stabilizes her quickly.

    2. RG thanks for the information about Sytrinol, glad to read that it helps your daughter so much. I have PPARy on my list of targets also, but haven’t tried yet. Have you seen what dr Kelley wrote about carnitine and seizures? “An occasional immediate sign of the effectiveness of carnitine in children with more severe, non-AMD complex I deficiencies is hyperactivity or even increased seizure activity. (...) hyperactivity stems from increased cerebral energy availability and, therefore, that long-term benefit from carnitine supplementation can be anticipated.” What do you think about this? He advises to begin with very low dose then.

      My son experienced extreme hyperactivity on carnitine long ago before I learned that, so I quit carnitine then.

      I wonder if this can be expected also with other mitochondrial support drugs suggested by dr Kelley? His remarks relate only to carnitine, but I think I saw the same effect few days ago when I tried MitoQ.

    3. Agnieszka, seizures are tricky business. I see what Dr. Kelley is saying, but I am not sure that I feel like playing around with it. Whenever my daughter has seizures, starting immediately to about three days later, her speech and prosody improves, awareness, much more normal behavior. When I mentioned this to her neurologist, he said he has
      heard similar reports from a few other parents as well. I thought it was to do with the Nmda receptor and LTP. Could you send me a link?

      For how long is the hyperactivity expected to last? Are you going to push through it?

      It seems that some degree of mitochondrial dysfunction exists in all neurological disorders. Are you giving the MitQ every day at full dose? What do you think of MitoSpectra? The price is in the stratosphere, but easy enough to make up our own in a similar ratio.

    4. Agnieszka, Peter, it appears that excess bdnf can cause seizures, particularly catamenial which I am interested in, and migraines.

      Is there anything specific that can be done about it?

      Agnieszka, I am sorry I forgot to save the bdnf migraine papers, but they can be easily found.

    5. Regarding mito I just want to add a suggestion . I have aspergers and recently found that Peters companion blogger Paul Whiteley has a company, Analutos, which offers affordable metabolic tests. I have ordered their amino acids test, which can give hints if mito issues are present.



    6. I have no idea how long would the hyperactivity last, at the moment I quit MitoQ: everybody needs to sleep sometimes… What I know is such reaction is consistent in my son and as benefits could also be seen, I will have to figure what to do with that. I think in such situations it pays to have practical experience and if I was to speak with only one doctor from the US it would be dr Kelley. The quote was from the paper that is linked here in Peter’s blog in the Regressive Autism part, but it’s clear from the text that he knows much more.

      I used half a capsule of MitoQ every day and then every other day. It’s still more than the dose of coenzyme Q10 suggested in dr Kelley's paper, in which you can also find the dosage of other mitochondrial enhancers. I created a simple calculator to count each dose per kg easily, you can use it and the ratio seems the same as in MitoSpectra:

      It would be difficult to go low dose carnitine using this combination supplement though.

      As far as BDNF I don’t know at the moment. I remember one father described in another blog the same what you said about temporary improvements related to seizures. It is odd as when my son had these episodes regarded as migraines, his awareness and speech improved much for few days just as in case of your daughter seizures.

    7. Hi Agnieszka, thank you very much for the spreadsheet. I am tempted to try it, because over the last few days my daughter's energy levels have gone down a lot, she is unable to stand or walk for any reasonable length of time. At the store, she tries to sit everywhere, and the other day, she just lay down on the aisle. Yesterday, she wanted to go to the gym, and I was happy thinking her energy levels were up, but dad reported that she had only wanted to go there to play with the timer on the treadmill. She walked for 15 minutes, came back home and had a tonic clonic seizure.

      She was also irritable after the seizure and the usual magnesium and vitamin c that I give did not help. Or the sytrinol. I have a new MCT oil by Viva Labs, I gave her two tablespoons of it and within a few minutes, she calmed down and became cheerful. The NOW brand mct oil that I used before had no such effect. Maybe you could try it with your son when he has the headaches? There are plenty of studies out there about the neuroprotective effects of mct oil.

      Have you been able to consult with Dr. Kelley? He left Johns Hopkins last year, and I was told that he was joining Boston Childrens, though they have no information for him there. If you find any information for him, please do let me know.

    8. Hi RG, I couldn't find this thread once again. How is your daughter now? Is she more energetic? I saw similar behaviors in my son and they were usually triggered by inflammatory conditions, even minor and sometimes undiagnosed. The last time such thing happened it was with the tooth problem. For dentists it was considered cured, no infection, just some residual inflammation which was to resolve on its own. But at the same time my son had no energy at all: went sleeping on the floor during his classes. Things improved within hours after solving tooth problem.

      Knock on wood, headaches decreased from at least week per month to 30 minutes with Diamox.

      Have you tried to e-mail Dr Kelley?

    9. That's great Agnieszka! I guess I really should be adding in the Diamox, I have been sidetracked with other things like Vitamin A, but that became more complex and so I have stopped it.

      How did you resolve the tooth inflammation? Its interesting, because my daughter's tiredness went away after a few days and she is ok now. Though a low grade irritability has come back after the vitamin A trial. Her vitamin D levels were already borderline low, maybe it went down further.

      I don't have an email for Dr. Kelley, do you?

    10. The tooth inflammation resolved with tooth removal, so nothing really innovative. It was molar milk tooth after peridental abscess treatment. The dentist did not want to pull out the tooth as she did not see a reason why minor inflammation could affect the behavior so much and also she thought that it would be impossible to do this without general sedation (just because of autism, M. was really cooperative). Both reasons show how "cognitive distortions" prevent children with autism from proper medical care. We went to another dentist who made an X-ray and pulled the tooth in 5 minutes. Guess where I met this clever dentist before... at parental meeting at the ABA center...

      I have found only this one, perhaps it's outdated as you say dr Kelley left this institution.

  18. As the effective dose for clonazepam has dropped from 40mg to 20-25mg, what would you say is the recommended dose /kg now?

    In your original post you had it at 1mg/kg, I'm guessing it's now 0.5mg/kg?

    It would seem the "safest" way here would be to go low and slow at around that level and expect the dosage to be effective after a couple of weeks given the half life?

    1. The half life is long, but it takes about three days to reach a stable level.

      The dose most people seem to using is 0.025 mg, which is a tiny amount.

      The effective dose does seem to be influenced by other drugs being used.

      My dose is 0.0012 mg/kg.

      If you are slightly too high there should be some anxiety/negative effects within a hour or two of taking it.

      If the dose is too low there is no effect good or bad.

      If the person is not a responder, there should also be zero effect. The dosage is far below that for which the drug is normally envisaged.


Post a comment