Psilocybin, autism and depression: the psychedelic experience is apparently not needed

 

I like today’s post because it draws together some reader experience, autism research from the 1960s, with modern day lab research and human trials.

A distinct subgroup of our readers fall into what is today level 1 autism, which many think was better described as Asperger’s. Even though cognition and language are not impaired, some can have severe struggles, including anxiety, depression and feeling they do not quite fit in. Remarkably, in some cases just getting an official diagnosis provides a boost, “it's not me, it's my autism”. If that is sufficient therapy, then great.

For the Aspies seeking a better life, some end up looking at their serotonin receptors.

I recently wrote a review of all of them, but the Aspie focus tends to be 5-HT2A.

Rethinking the role of serotonin receptor signaling in improving autism symptoms: Prucalopride for a sub-group?

Incidentally, the mother who prompted that post tells me that her adult son continues to show the behavioral benefit from prucalopride one month later.

5-HT2A was the target of Ivar Lovaas back in 1966 at UCLA in Los Angeles. Lovaas is best known today for his work in Applied Behavioral Analysis (ABA).

Back in 1966 he published this paper:

Modificationof autistic behavior with LSD-25

The study involved a pair of identical autistic twin boys, then around five years old.

The researchers were interested in whether LSD could modify behaviours that were particularly difficult to change in severely affected children.

 

Our reader comments

One of the most notable comments in this blog was written by an Aspie who found a single experience with stimulating 5-HT2A provided a lasting beneficial shift in his mood.

You might wonder how such an effect could occur, like flipping a switch.

The recent research now explains why this likley happened.

 

The 1966 LSD study was tiny and exploratory by modern standards. It cannot establish that LSD was an effective treatment for autism, and the behavioural changes reported were principally observed during the drug sessions. It is therefore important not to read modern ideas about long-lasting psychedelic effects back into the 1966 experiment.

Nevertheless, the study is historically remarkable.

Lovaas was involved in research asking whether altering brain function could alter autistic behaviour.

Then the science took a different path.

 

60 years later we are back to psilocybin – depression in humans, autism in mice

A new study has taken the question into a modern genetic model of autism.

The researchers used mice lacking Cntnap2, a gene associated with neurodevelopmental disorders in humans. These mice show reduced sociability together with hyperactivity and repetitive behaviour.

A single dose of psilocybin produced a persistent increase in social behaviour.

The effect was detectable one day later and remained for at least two weeks. Importantly, the mice did not simply become more active: their overall exploration and locomotion did not show the same change.

And psilocybin did not correct everything.

The hyperactivity and repetitive grooming remained elevated.

This is therefore not evidence that psilocybin "reverses autism."

It is evidence that a brief pharmacological intervention can produce a persistent change in one particular behavioural phenotype in a particular genetic mouse model.

There was another important finding.

The same treatment did not increase sociability in genetically normal control mice.

That suggests something much more interesting than a simple "socialising" effect.

Perhaps the drug is interacting with an abnormal neural state.

 

The 5-HT2A receptor

Psilocybin's psychedelic effects are primarily mediated through the serotonin 5-HT2A receptor.

The researchers blocked this receptor before administering psilocybin.

The persistent improvement in sociability disappeared.

This gives us an important mechanistic sequence:

 

Psilocybin

↓

5-HT2A activation

↓

persistent biological change

↓

altered social behaviour

 

But then came the most surprising experiment.

The mice did not have to experience the psychedelic state

The researchers administered psilocybin while the mice were under light anaesthesia.

The animals therefore experienced the acute pharmacological action of psilocybin while unconscious.

When tested later while awake, they showed the same persistent increase in sociability.

In other words, an awake psychedelic experience was not required for the lasting behavioural effect in these mice.

The psychedelic experience is not itself the fundamental therapeutic mechanism.

It is one consequence of activating 5-HT2A receptors, while another consequence is a longer-lasting biological change in the brain.

 

What could produce a lasting effect?

One possibility is that the brief receptor signal initiates a cascade of molecular and cellular changes.

There is increasing evidence from psychedelic research that psilocybin can influence gene expression, neuronal structure, synaptic organisation and brain network function.

Epigenetic mechanisms may also be involved.

In the Cntnap2 work, the researchers found evidence that DNA-methylation machinery is required for the persistent behavioural effect. 

Researchers found that blocking DNMT1, a key DNA-methylation enzyme, prevented this persistent effect.

Importantly, DNMT1 inhibition did not prevent the acute 5-HT2A-related response.

This suggests DNA-methylation machinery acts downstream of 5-HT2A activation to maintain the longer-term change.

The finding points to a molecular mechanism whereby a brief drug exposure can produce behavioural effects long after the psychedelic experience has ended.

This suggests that a short-lived pharmacological signal may be converted into a longer-lasting change in gene regulation.

We do not yet know that psilocybin permanently rewrites the epigenome in these mice.

Nor do we know that the behavioural change is caused by a permanent epigenetic modification.

A more cautious model would be:

 

brief 5-HT2A stimulation

↓

intracellular signalling

↓

changes in gene regulation and possibly epigenetic state

↓

altered capacity for neural plasticity

↓

changes in neural circuits

↓

persistent change in behaviour

 

The important word is persistent, not permanent.

 

Could this matter for depression in autistic people?

This brings us back to humans.

Depression and persistent low mood occur in some autistic people, and this may be a particularly interesting population for psychedelic research.

Psilocybin has already produced persistent antidepressant effects in studies of people with major depressive disorder.

But there is an important unanswered question:

 

Would an autistic person with depression respond in the same way?

We do not yet know.

Autism is heterogeneous, and depression in an autistic person need not have exactly the same biological basis as depression in a non-autistic person.

Nevertheless, the new mouse findings make the question more interesting.

The drug did not simply increase sociability in every animal.

And now the experiment has returned to humans

The circle is becoming particularly interesting because researchers are now asking the same mechanistic question in humans.

A Stanford Phase 2 study, SPACE, is investigating psilocybin administered under general anaesthesia in people with major depressive disorder. The rationale is to suppress the noticeable psychological effects of psilocybin, making it possible to investigate whether effects can occur without the conscious psychedelic experience.

This is not an autism study, and it is small and experimental.

But scientifically it is fascinating.

Can separate the pharmacological action of psilocybin from the subjective psychedelic experience?

If lasting antidepressant effects were observed despite anaesthesia, that would provide important evidence that the biological action of 5-HT2A stimulation can produce therapeutic effects independently of the psychedelic experience.

 

From LSD in autistic humans to psilocybin in autistic mice and depressed humans

This brings us back to the historical arc.

1966 — UCLA

Lovaas and colleagues studied LSD in autistic children.

The question was whether changing brain function could modify autistic behaviour.

The following decades

Lovaas's research increasingly concentrated on behavioural intervention.

The question became whether changing the environment and learning experience could change behaviour and development.

2026 — autism mouse model

Researchers can now manipulate the biology much more precisely.

They can alter a specific autism-associated gene, activate 5-HT2A receptors, block the receptor, examine molecular pathways and administer the drug while the animal is unconscious.

And they find that a brief exposure to psilocybin can produce a behavioural effect that persists after the drug and the psychedelic state have disappeared.

2026 — depressed humans

Researchers are now taking the question back into humans.

Can psilocybin produce a lasting antidepressant effect without the person experiencing the psychedelic state?

The historical arc is therefore almost a circle.

 

Why did they choose the CNTNAP2 model and how this relates to Pitt Hopkins

The researchers did not choose the Cntnap2 mouse because it represents autism as a whole. They chose it because it is an established genetic model with a measurable reduction in sociability. Cntnap2-knockout mice show reduced social interaction, together with hyperactivity and repetitive behaviour. This gave the researchers a way to ask a very specific question: can psilocybin change an abnormal social phenotype?

The result was quite specific. Psilocybin increased the mice's preference for the social stimulus without significantly increasing their general exploration or movement. It also did not correct the hyperactivity or repetitive grooming.

The researchers also tested genetically normal mice. They did not show the same beneficial increase in sociability. This is important because it suggests that psilocybin may interact differently with a brain that already has an altered neurodevelopmental state, rather than simply acting as a general social enhancer.

 

Why is this relevant to Pitt Hopkins?

CNTNAP2 is particularly interesting in relation to Pitt Hopkins because biallelic CNTNAP2 mutations cause a Pitt-Hopkins-like neurodevelopmental disorder. Classical Pitt-Hopkins syndrome, however, is caused by alterations in TCF4.

There is also a biological relationship between the two genes. TCF4 is a transcription factor that can regulate CNTNAP2 expression. Thus, CNTNAP2 sits within a neuronal gene-regulatory network that is relevant to Pitt-Hopkins biology.

This does not mean that a Cntnap2-knockout mouse is a model of classical Pitt-Hopkins syndrome. The primary genetic abnormalities are different, and the findings cannot be directly extrapolated from Cntnap2 mice to people with Pitt Hopkins.

There is another important difference. Reduced social motivation is a clear phenotype of the Cntnap2 mouse, but it should not automatically be assumed to be the principal social problem in Pitt Hopkins syndrome.

People with Pitt Hopkins can have profound communication and social-communication difficulties, but many also actively seek attention, enjoy being with other people and show considerable social interest. In other words, the ability to communicate socially and the motivation to engage socially are not necessarily the same thing.

This means that if psilocybin were investigated in Pitt Hopkins, increasing social motivation would not necessarily be the most appropriate primary outcome.

Instead, researchers could ask whether it changes social communication, spontaneous communication, mood/affect, anxiety, repetitive behaviours, adaptive functioning or other measurable Pitt Hopkins phenotypes.

 

The research question

The Cntnap2 finding nevertheless raises an intriguing question for Pitt Hopkins:

If 5-HT2A activation can produce a persistent improvement in a behavioural phenotype caused by disruption of CNTNAP2, could it also modify some downstream consequences of TCF4 dysfunction?

The next logical experiment would therefore be to test psilocybin in a Tcf4 haploinsufficient Pitt Hopkins mouse model.

Researchers could examine not only behaviour but also the underlying biology:

• Does 5-HT2A activation alter the synaptic abnormalities associated with TCF4 deficiency?
• Does it affect gene expression or epigenetic regulation?
• Does it alter neuronal plasticity?
• Are any behavioural effects persistent after the drug has disappeared?
• Does the effect require the conscious psychedelic state, or could it occur under anaesthesia as in the Cntnap2 experiment?

The most interesting possibility would be a downstream compensation: the TCF4 mutation would remain, but a transient pharmacological intervention might alter some of the neuronal consequences of that mutation and allow the system to function differently.

 

Pitt-Hopkins is already being approached through epigenetics

There is an especially interesting parallel here because Pitt-Hopkins researchers are already testing an epigenetic strategy in humans. The RVL-001 trial, being conducted by Unravel Biosciences with the Pitt Hopkins Research Foundation in Colombia, is testing Vorinostat, a histone deacetylase (HDAC) inhibitor, in people with genetically confirmed Pitt Hopkins syndrome. The current exploratory study is small and is designed to examine safety and efficacy, as well as changes in the transcriptomic profile.

Vorinostat is approaching the problem from a very different direction than psilocybin. Rather than activating 5-HT2A receptors and potentially initiating downstream changes in neuronal signalling and plasticity, vorinostat directly alters epigenetic regulation by inhibiting HDAC enzymes, thereby changing how tightly DNA is packaged around histones and influencing gene expression.

There is a particularly strong rationale for this in Pitt Hopkins. In Tcf4-haploinsufficient mice, HDAC inhibition with vorinostat normalized abnormalities in hippocampal long-term potentiation and memory recall. Molecular studies also found changes in gene expression and DNA methylation associated with the treatment.

This creates an intriguing contrast:

Pitt-Hopkins genetic defect → TCF4 haploinsufficiency → abnormal gene regulation

Vorinostat: attacks the problem directly at the epigenetic/transcriptional level

versus

Psilocybin: 5-HT2A activation → intracellular signalling → potentially altered gene regulation/plasticity → possible downstream compensation.

 

In other words, these are two very different ways of trying to change the functional consequences of the same developmental genetic disorder.

The important point is that neither approach corrects the underlying TCF4 mutation. Both are attempting to modify downstream consequences of TCF4 deficiency.

 

Gene therapy

As was discussed in the recent post on gene therapy, there is now a fundamentally different approach being investigated in Pitt Hopkins: gene therapy.

Pitt Hopkins is caused by loss of function of one copy of TCF4, so gene therapy attempts to address the problem at its source. The investigational therapy MZ-1866 uses an AAV9 vector to deliver a functional copy of TCF4 to the brain.
It is being tested in a Phase 1/2 first-in-human clinical trial. The first participant was dosed in February 2026.
The current study is investigating safety and tolerability as well as potential clinical effects.
Unlike vorinostat or psilocybin, this approach is attempting to restore the missing genetic function itself.

Conclusion

Some Aspie readers of this blog have already established that a single dose of Psilocybin can produce long lasting improvements in social behavior. They skipped the mouse models and adopted the Nike approach.

The LSD trials in children in the 1960s assumed that the psychedelic experience was the therapy, now we see that this is not the case. You can sleep through it and still get the long lasting effect.

The beneficial effect in CNTNAP2 mice does indicate that the experiment should be repeated in the closely related Pitt Hopkins model. Of course, it should also be checked in idiopathic autism models like the BTBR and the maternal immune activation (MIA) model

In the prenatal valproate (VPA) model, psilocybin was previously tested and it did rescue the social-behavioural abnormalities. 

Note

Psilocybin is the main psychoactive compound found in “magic mushrooms.” It is converted in the body into psilocin, which produces the psychedelic effects. Research using purified psilocybin therefore studies the key active psychedelic component rather than the whole mushroom.

Fine tuning Social Behavior in Autism with an existing pediatric drug, Desmopressin?

 

There are two closely related hormones, vasopressin and oxytocin, that have been extensively researched in autism. 

With oxytocin you can modify social-bonding behavior. You can increase oxytocin in the brain either via a nasal spray containing oxytocin, or you can add a specific bacterium to your gut that triggers a signal to the brain to produce more of its own oxytocin.  The latter is my preferred method, because you can produce a mild long-lasting effect throughout the day.

Oxytocin has a very short life and it does not cross the blood brain barrier.

There is even a new study in the works that will compare these two methods of treating autism.

 

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients.

Methods

This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0–24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13–24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24.

Discussion

This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients. 

My conclusion was to add two drops of L.Reuteri DSM 17938 (Biogaia Protectis) into the liquid part of my son's Polypill therapy. That way there are no extra pills to swallow and in theory the bottle should last 50 days, so I am not forever looking to buy more.  If you want a bigger effect, just add more drops.  The producer suggests a daily dose of 5 drops for babies, to promote GI health - the original intended purpose.

When it comes to Vasopressin it looks like you cannot avoid a nasal inhaler, unless you want to try transcutaneous electrical acupoint stimulation (TEAS).  There is a debate as to whether Vasopressin and its analogs (man-made modified versions) can cross the blood brain barrier and to what extent. 

There are 4 previous posts that looked at Vasopressin. 

https://epiphanyasd.blogspot.com/search/label/Vasopressin 

The Vasopressin showing good results in the trials at Stanford is the injectable pharmaceutical version of the hormone made into a nasal spray.  This kind of spray could be made easily at a compounding pharmacy.

It turns out that a synthetic analog of vasopressin, called desmopressin, has been widely used for over 40 years to treat nocturnal enuresis (night-time bed-wetting) among other more serious conditions.

 

Desmopressin in Autism 

“Nocturnal enuresis is common in individuals with but to our knowledge, there are no reports that desmopressin enhances social functioning in ASD (or in any other clinical population). This may be because desmopressin is typically administered at bedtime (so prosocial effects would be less evident) and orally (oral desmopressin does not cross the blood-brain barrier). The most likely explanation, however, is that desmopressin acts selectively on AVPR2, rather than on AVPR1A”

 

From:

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

 

Desmopressin N=1 example 

I was recently contacted by the father of a young boy with autism who has been prescribed Desmopressin nasal spray by his neurologist.

The father noted major positive behavioral changes from the first dose.

This is of course great news.

Desmopressin is a widely available drug, seen as safe, and that is why it is prescribed to children.

In the US the nasal spray version is no longer widely used for children and they use the oral version.

In some countries it is used for people with MS (Multiple Sclerosis) with nocturnal enuresis.

 

Desmopressin Shortage

Before readers get too excited, Ferring Pharmaceuticals, the big producer of Desmopressin nasal sprays did voluntarily withdraw its brands (Minirin, DDAVP Nasal Spray, Desmopressin Acetate Nasal Spray) from the market in August 2020 due to a quality problem. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetate

  

There is now a shortage and so what was an easy to obtain drug, may be more difficult to get.  There is a Pfizer version called Presinex.  

From the above paper on vasopressin for autism:-

Vasopressin benefits 

“In conclusion, the present pilot study determined that 4-week intranasal AVP treatment compared to placebo enhanced social communication abilities, diminished anxiety symptoms, and reduced repetitive behaviors in children with ASD. On nearly all behavioral measures, participants with the highest pre-treatment blood AVP concentrations benefitted the most from AVP treatment, suggesting that pre-treatment blood AVP concentrations may be useful for setting dosing guidelines for this medication. Last, intranasal AVP treatment was well tolerated with minimal side effects in this pediatric study population. These preliminary findings suggest that intranasal AVP treatment has potential to enhance social abilities in an ASD patient population characterized by currently intractable social impairments” 

Transcutaneous electrical acupoint stimulation (TEAS) to raise vasopressin 

“there is evidence that nonpharmacological interventions may facilitate endogenous AVP release, for example, electroacupuncture stimulation increases brain AVP concentrations in rats. Transcutaneous electrical acupoint stimulation (TEAS) therapy improves social functioning and anxiety symptoms in children with ASD, particularly in those with the largest post-treatment increase in blood AVP concentrations. The authors of this prior report theorized that increased AVP signaling may be the mechanism by which the prosocial and anxiolytic benefits of TEAS treatment were achieved” 

 

Vasopressin with Bumetanide  - take great care

A while back, one reader did ask me about taking intranasal Vasopressin with Bumetanide.  His doctor in California thought this might not be wise since the two drugs have opposing effects.

·        Bumetanide (a diuretic) makes you pee more.

·        Vasopressin (the anti-diuretic hormone) makes you pee less.

The real problem is the risk of low sodium, hyponatremia.  This is always a risk with vasopressin and the risk might well increase if you took Bumetanide.  The risk is going to be dose dependent.

If you take Vasopressin and then drink large amounts of water this will disturb the volume of fluids in your body and in particular it will lower the level of sodium.  This may lead to seizures and ultimately worse.

Bumetanide does disturb the level of electrolytes, but nearly all the change usually occurs in Potassium, this is why you need to add back potassium via diet and add a supplement.  Sodium is not normally a problem, but always check all electrolytes when taking a blood draw.

If someone adds vasopressin to their existing bumetanide therapy, the doctor should definitely monitor the level of sodium.

In most people’s diet, sodium is one thing you are likely to have too much of and it is very easy to add a bit more sodium if the blood test suggests it is necessary.  In extreme cases of low sodium you need to use a special re-hydration drink, or an intravenous saline solution.  Monty has a relative who keeps going to hospital for the latter.

The diuretic action of Bumetanide is a side effect of the "autism effect" and so if you can reduce the diuresis of bumetanide that would be good thing.  Researchers are trying to find a better-bumetanide and their goal is to have no diuresis.

If combining vasopressin with Bumetanide is accompanied by both reduced diuresis and a matching reduction in fluid intake, this might actually work well.  Clearly, extra care needs to be taken and what might be perfectly safe in one person may not be safe in another person.

  

Conclusion

I do have to give a big thank-you to our reader who shared his experience with Desmopressin and to the neurologist for suggesting it.

Desmopressin looks like one of those autism therapies that needs only a very short trial to determine whether it is beneficial.  This is a big advantage.

You would hope the Stanford vasopressin researchers make a short trial of Desmopressin, just to compare the effect.  They probably will not.

All you have to decide is whether it is going to be the left nostril, or the right nostril.  With intranasal insulin there was a problem with irritation inside the nose, so alternating left and right sides might be best.  You hold your breath and then squirt the spray; the objective is not to breath the spray into your lungs.  An easy mistake to make.

Note that I am referring to the 10 mcg/0.1mL Desmopressin nasal spray.  The one used to treat kids that wet their bed at night.

There is also a much more potent 1.5 mg/mL version, called Stimate in the US.  This is used to treat von Willebrand’s Disease (Type I) and hemophilia/haemophilia.  You do not want that version.  This version is 15 times more potent than the anti bed-wetting variant. 

I have been suggesting to Aspies living in the US that they give Vasopressin a trial to counter the social deficits that some find troubling.  I think they are able to obtain this via a compounding pharmacy, with a helpful doctor’s prescription.

I think outside the US your doctor will think you are mad if you ask for a specially compounded vasopressin nasal spray, or indeed a compounded  oxytocin spray.

For people unable to get the intranasal vasopressin prescribed/compounded, Desmopressin is on option to discuss with your doctor. Maybe time to develop a bed wetting problem?

The Aspies in the Netherlands have the legal option of a tiny non-hallucinogenic dose of Psilocybin once a month, which seems an effective way to target Serotonin 5-HT_2A receptor-mediated pathways and so improve social behavior. What caught my attention was that the effect of this tiny dose lasts a month and it can also be used to treat severe, otherwise untreatable, cluster headaches.

Psilocybin is the fancy name for magic mushrooms.

Psilocybin is also legal in Brazil and not surprisingly in Jamaica.  It looks like the US is moving in the same direction - medicinal magic mushrooms!

FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder

The “medical” dose of Psilocybin is a tiny fraction of the “recreational” dose and is only taken when the effect of previous dose fades to zero.  It is not a crazy idea at all, just not currently a legal therapy in most countries.  More than half a century ago Lovaas was researching something very similar at UCLA, but using LSD.

All told, there are several potential ways to fine-tune social behavior in autism. Sulforaphane is yet another option.

 

Why is the evidence for Early Intensive Behavioral Intervention for Autism so weak?

One to one autism therapy is pricey – is it worth it?

Only a handful of countries widely apply behavioral interventions to treat toddlers diagnosed with autism.  Behavioral interventions include Applied Behavioral Analysis (ABA), Verbal Behavior (VB), Pivotal Response Treatment (PRT) and the Denver model.

Even after several decades, the published evidence that these interventions actually work is quite weak.  This explains why most countries do not readily provide public funds for ABA.

In the US, efforts are being made to diagnose autism at younger and younger ages, because the child can then benefit from these “proven” interventions, that other countries do not believe work.  Who is right?  

You can read Manuel Casanova’s perspective at the end of this post.  He is not such a fan of expensive US developed therapies and concludes:-

"spending time with your children and group socialization, in my experience, have provided the most favorable outcomes"

Does ABA work?  If so, why can’t you prove it?

From my personal experience, behavioral intervention was very beneficial as a teaching method, but it does not make autism go away.

In today’s study the aim was to determine if behavioral intervention is cost effective.  The conclusion based on all the studies considered is that there is no conclusive evidence that behavioral intervention is cost effective.  So logically the countries that do not widely fund it, like the UK, can be reassured that they are on the “right side” of the argument.

My view is that is that autism is so heterogeneous you can prove almost nothing, with any degree of certainly.  It is always going to be a case of ifs, buts and maybes.  This also very much applies to clinical trials of drugs to treat autism.

Why did ABA ever catch on in the first place?  People want hope and the more expensive something is, the more people want it.  Forty hours a week of ABA is very expensive and nice to have, if someone else is paying.  

We saw in an earlier post that Lovaas (the founding father of ABA) later admitted to selectively retiring non-responders from his clinical trials, to improve the apparent success of his methods.  This pretty much means you have to ignore all his data and his papers should be retracted. 

Many parents want curative treatments for autism.

Lovaas claimed that ABA is curative and that the treated kids end up like typical kids.  Sadly, this is an exaggeration.

Is two years of ABA cost effective for severe autism?  I guess it depends whose money is paying for it.  Is two years of ABA going to be life changing for a person with severe autism?  Unfortunately, even after 20 years of ABA, that person will likely still have severe autism, if you have not treated their underlying biological problems.

Some parents rave about ABA and make comments like “after two years of ABA my son now makes eye contact”.  Great, but would you pay $120,000 of your own money for that?  I think not.  Should your local government regard that as money well spent?  I think they should be more demanding; the results of just $1,000 spent on the right personalized medicine will be much more impressive.

Today most people currently being diagnosed with autism have mild cases.  If they can talk and do not have intellectual disability (ID) / mental retardation (MR), they will likely see little benefit from 40 hours a week of discrete trial training.  It would be a huge waste of money and probably just annoy the child.  

Many children with mild autism need a different kind of therapy, they need to learn social and emotional skills they may not naturally possess - how to make friends, how to avoid making enemies and so how not to get bullied at school.  This will only be effective started very young, before being a victim becomes a badge of honour.

Interventions based on early intensive applied behaviour analysis for autistic children: a systematic review and cost-effectiveness analysis

Autism is a lifelong condition that affects how people understand the world and interact with others. Early intensive applied behaviour analysis-based interventions are an approach designed to help young (preschool) autistic children. This approach is often delivered on a one-to-one basis, for 20–50 hours per week, over a period of several years.

This project obtained and analysed the original data from studies of early intensive applied behaviour analysis-based interventions, to determine whether or not these interventions are beneficial. It also investigated whether or not the interventions represent good value for money.

The results suggest that early intensive applied behaviour analysis-based interventions may improve children’s intelligence, communication, social and life skills more than standard approaches. However, some results could be inaccurate or incorrect, and there was no evidence about other important outcomes, such as the severity of autism and where children went to school. Most studies lasted for around 2 years, which means that it is not known if early intensive applied behaviour analysis-based interventions have meaningful long-term benefits.

It was not possible to fully assess whether or not these interventions provided value for money, as the benefits of early intensive applied behaviour analysis-based interventions were unclear, although the available evidence suggested that they did not. Early intensive applied behaviour analysis-based interventions may, however, provide value for money if their effects were to last into adulthood, or if receiving early intensive applied behaviour analysis had a large impact on the type of school children attended.

Future studies of early interventions may be helpful, but should consider looking at which components of early applied behaviour analysis-based interventions are the most important, rather than at whether or not they work better than other interventions. Future studies should also follow best current research practice and evaluate outcomes that matter to autistic people and their families. 

Economic evaluation

Using National Institute for Health and Care Excellence decision rules to benchmark the results of the cost-effectiveness analysis and adopting a £30,000 (USD 40,000) per quality-adjusted life-year threshold, these results indicate that early intensive applied behaviour analysis-based interventions would need to generate either further benefits or cost savings to be considered cost-effective.

Implications for service provision

Although individual participant data meta-analyses have shown small to moderate improvements in child cognitive ability and adaptive behaviour for early intensive applied behaviour analysis-based interventions relative to treatment as usual or eclectic approaches, all of the identified studies were at risk of bias, limiting the strength of conclusions that can be drawn from these results. Furthermore, results from individual studies varied considerably, with some showing no relative benefit of early intensive applied behaviour analysis-based interventions. 

Conclusion

For cases of severe autism, if you can afford intensive (and expensive) 1:1 intervention of any credible kind (Floortime, ABA, Denver etc - whatever works best in your case) it makes sense to use it.  It should improve skill acquisition and will make the parents feel better.

None of these interventions are curative, the child will still have autism.  When you no longer pay for the 1:1 intervention, the effects most definitely will start to fade away.  Don’t mortgage your house to pay for ABA.

Nothing stops you making your own 1:1 intervention program using family, friends and volunteers.  This does not cost much and is sustainable over many years; it is likely to be much for effective that 2 years of "professional" therapy.

I do find it odd that in the US there is free early intervention for toddlers and then provision just stops, as if it suddenly is no longer needed.

If you use ABA to teach a child to tie shoe laces, he/she will retain the skill as long as you keep buying shoes with laces.  If you do not practice/apply the skill for 6 months, do not be surprised if it has to be re-taught.

Our final ABA consultant was very experienced, she worked for 10+ years in the US before moving home to Athens, Greece.  She told me that in her experience all children with autism benefit from ABA, but the level of progress they make varies widely.  If a child does not respond to ABA, it very likely is not being done correctly.  ABA should be seen as fun, not like a punishment. If your child hates ABA sessions, they have no chance of working.

I come back to my earlier recommended strategy. Find your most effective novel medical treatment, which will inevitably be a polytherapy and combine this with a method of learning that works best for your particular child.

Then just keep going and let time do its work.

In countries like the UK, with free health and education provision, the government does not generally pay for early intervention because their medical advisors do believe it to be cost effective, which really means they think it does not work and so do not want to pay for it.  The cynic might just say they do not want to fund it. 

The idea was supposed to be that by investing upfront in ABA during the early years, you save money later on, by having a more functional child and then adult who requires less expensive provision.  Unfortunately, there is absolutely no proof this is true.  

If you go from early intervention, to an ABA special school and then ABA college, things clearly did not work out.

In the US early intervention is assumed to be very effective and the current idea is that doctors should hurry to diagnose autism before 24 months so as to get into the intervention program as soon as possible.  Where is the evidence to support the US view?  Are US outcomes any better?

We saw in recent research from UC Davis that looked at outcomes over time in autism that the best outcomes are not associated with any particular therapy.  The best outcomes happen because of the biological characteristics of that child, rather than any amount of behavioral intervention.

I expected the UC Davis study to show a relative benefit for those who received ABA therapy, but it did not.  We do have to take note.  I am actually pro-ABA and have spent a vast amount of money on this kind of therapy and 1:1 instruction.   

Ignoring treating the biological dysfunctions in autism while spending hundreds of thousands of dollars on 1:1 therapy and special education does not make a lot of sense.

Here is a relevant excerpt from a recent post by the neurologist, autism researcher and autism Grandfather, Manuel Casanova, from his Cortical Chauvinism blog: -

AUTISM: HOW CULTURE INFLUENCES OUTCOMES

Despite marked differences in geography, non-Westernized countries see autism as a social responsibility rather than a medical condition.  These countries offer a collectivist perspective that downplays individuality and prioritizes maintaining relationships within a given group of people.  In this regard, I have often marveled as to how vastly different countries, like Colombia and the more desolate regions of Eastern Russia (Siberia), share similar perspectives regarding autism. Indeed, due to a lack of resources, interventions in these countries are usually parent-mediated and heavily influenced by cultural norms.  Lack of personnel trained in behavioral analysis has been supplanted by art and music instruction.  Classes are provided in group settings where outperforming other members is not seen as conductive to the overall benefit of the group. Members are encouraged to adopt the norms of the group while teachers emphasize cooperation and nurturing. Students arrive early to school to participate in team building exercises.

I have often marveled at the achievements of troupes of autistic children performing autochthonous musicals and their accompanying choreography.  Adopting the norms of the group have served them far better than any Westernized behavioral intervention.  Participants in these groups seem genuinely happy; in part, given the sense of achievement at contributing to a piece of artistic expression.  In addition, the structured activities in such groups offer norms that minimize uncertainty.  Participants feel a sense of security in a group that fast becomes their extended family.

Autism is a medical condition but, without a cause that we can target, treatment options have remained symptomatic.  This is one of the reasons for looking at other countries and learning what has worked for them.  Indeed,  I believe that we can gain from adopting the cultural perspective of other countries to benefit our own children. Whether it is an improvisation on an autism chair, electroacupuncture, or using a zen bowl, spending time with your children and group socialization, in my experience, have provided the most favorable outcomes.

Manuel is one of a very small group of thoughtful researcher-clinicians, who have been working in the field of autism for decades, like Dr Kelley from Johns Hopkins and that psychologist Dr Siegel who wrote the Politics of Autism and revealed how Lovaas really did his "research". 

Manuel's researcher son-in-law is interested in precision medicine and drug re-purposing, I guess driven by his own young son's rare genetic "autism", NGLY1 deficiency. This very severe condition leads to the body not being able to breakdown and remove damaged and misfolded proteins.  You would think that reducing Endoplasmic Reticulum (ER) stress, that produces misfolded proteins, might be useful. This was covered here, along with a long list of possible therapeutics:-

https://epiphanyasd.blogspot.com/2019/12/er-stress-and-protein-misfolding-in.html

Some readers are following the details of the Covid-19 situation.

The Indian Experiment rather than the Swedish Experiment

A recent study suggests that more than half of the 6 million slum dwellers in Mumbai have had Covid-19; another 6 million do not live in slums. Government research showed that in the capital Delhi 23% have Covid-19 antibodies.

Mumbai slums have an extremely high population density, extreme poverty and so not much social distancing. So they show what Covid-19 does with no serious intervention, better than Sweden does.  Mumbai has reported 6,200 deaths in total.

You can extrapolate from the data (57% of slum dwellers and 16% of non slum dwellers with Covid antibodies) for the total 12 million population of Mumbai.  4.4 million had the virus and 0.14% died.  In the worst case scenario, when everyone finally gets infected in the next few years, there would be another 7.4 million with the virus and another 10,800 deaths.  The death/mortality rate for the city would be 0.14%.  (In reality it will probably be less than 0.14%, because some people will not get the virus)

The 0.14% Covid-19 mortality rate compares to the 2.5% mortality rate of the 1918/9 global flu pandemic; worse still that flu pandemic affected fit young people the most, making the demographic impact huge. 

The crude death rate from all causes in the US is around 0.8% each year (just 0.7% in India).  That puts the 0.14% from Covid-19 into some perspective. If Americans are as healthy as Indians and India did not under-report the number of Covid deaths in Mumbai (both are big ifs), you could apply the 0.14% mortality from Covid-19  to 330 million Americans and get 460,000 people. I think the realistic number would be higher, given deaths to date in the US.  

I think the world has been very lucky to have been affected by a pandemic that has such a low mortality rate.  It could easily have been 20 times worse, perhaps next time?  In the Middle Ages, the Black Death killed hundreds of millions of people - a truly apocalyptic pandemic.

There is no certainty that a vaccine is going solve the Covid-19 problem, indeed the UK government is buying 12 different vaccines, in the hope that one is effective.  Vaccines are often least effective in older people, who are main risk group for Covid-19.

If no vaccine turns out to be 90% effective, the Mumbai slum dwellers and the Swedes will have been the smart ones.


Controlled Infection vs Vaccination

If I was a dentist I would be seriously worried about Covid-19. I would favor a small infection today, caught from my party-going offspring, rather than in two year's time catch it while peering into a stranger's mouth during an hour long procedure, and get a huge initial exposure, leading to a more severe infection.  The fact that Mumbai policemen, London bus drivers and of course doctors and nurses without good PPE have had so many fatalities does suggest the amount of virus you are initially exposed to is a critical factor to the outcome.  This would be logical anyway.

I am really glad at least my older son and myself have had Covid-19.  If I was a dentist, I would be hugely relieved. A few months ago we assumed Covid-19 was both highly infectious and often deadly, now we know the reality.  If you are youngish, slim and healthy the risk is very low.  Many in rich societies are old, overweight and in poor health.

I did take my younger son Monty, aged 17 with autism, for a visit to the dentist two months ago and I really felt sorry for her.  She was wearing a mask, but that is no guarantee of her safety.