Autism Spectrum Disorder and the promising treatment with Low Dose Naltrexone by Paula Johnson

According to the Autism Society of America 1 in 54 children are diagnosed with autism, ten years ago it was 1 in 125. There are now over 3.5 million individuals on the autism spectrum in the US alone.1

To varying degrees, depending on the severity of a person’s autism and their age, there are several challenging behaviours that autistic people can exhibit such as:

Aggression and self-injury
Social and communication problems
Repetitive behaviours, obsessions and attention deficits
Psychiatric conditions such as anxiety and depression
Noise sensitivity, sleep issues and mood instability
There is currently no standard treatment for ASD but there are many ways to help minimise the symptoms and maximise abilities.  Treatment generally focuses on highly structured and specialised programs targeting the autistic person’s specific needs. The therapies utilised are: behavioural management, cognitive behavioural, nutritional, occupational, physical therapies and speech-language therapies, to name a few.  And, of course, medication treatments which involves drugs such as the FDA approved drugs for ASD – antipsychotics (such as risperidone and aripripazole) – these treat the symptoms of irritability.  Other drugs used, depending on the age of the child, include SSRIs, Tricyclics, Psychoactive or Anti-Psychotic medications, Stimulants, Anti-anxiety and Anticonvulsants.2  

Endorphins and Autism

Some researchers have suggested that excessive opioid activity in autistic children causes them to engage in repetitive “self-stimulatory” and self-injurious behaviours to further stimulate the pain-induced release of endogenous opiates.  This hypothesis resulted in many trials using the opioid antagonist naltrexone.  The action of naltrexone is to block opioid receptors thus creating a rebound effect of increased endorphin release, which in turn modulates the immune response, reducing cytokines and so reducing inflammation.3 

In several of these trials naltrexone helped to increase socialisation, eye contact, pain sensitivity and a decrease in self-injurious/stimulatory behaviours.  Endorphins are not the only neurotransmitters thought to be involved in autism, serotonin and dopamine are also found in abnormal concentrations which are likely to contribute to the condition.4

The use of Low Dose Naltrexone for children with autism spectrum disorders was studied in the 1990’s with researchers using from 5 mg to 50 mg daily.  Many researchers noted better results with lower doses. 

While not presenting the ultimate answer in the treatment of autism, naltrexone is shown to help alleviate some of the symptoms modulated by endogenous opioids. 

Studies and Trials of Naltrexone in Autistic Children

A double blind, placebo controlled, crossover study of naltrexone by B K Kolmen et al., evaluated the efficacy and safety of naltrexone in young autistic children:

The results were that of the thirteen children studied, eight improved in two or more settings (Home, School and outpatient laboratory).  Of statistical significance were changes in impulsivity and hyperactivity.  Restlessness and initiation of communication in the clinic showed a trend toward improvement.  The conclusion of this study was “Naltrexone offers promise as an agent for modest improvement of behaviour and social communication in young children with autism”.5

A clinical trial on the opioid-immune interactions in Autism showed behavioural improvement accompanied by alterations in the distribution of the major lymphocyte subsets resulting a normalisation of CD4/CD8 ratio. Changes in natural killer cells and activity were inversely related to plasma beta-endorphins levels. The trial concluded that “It is suggested that the mechanisms underlying opioid-immune interactions are altered in this population of autistic children and that an immunological screening may have prognostic value for the pharmacological therapy with opiate antagonists”.6

Jaquelyn McCandless, MD, used a compounded LDN transdermal cream for her private clinical studies of children with autism.  The cream was applied as the children slept.  McCandless performed an eight-week study on fifteen of her autism patients applying 3mg transdermally between 9 and 12 p.m., parents reported weekly on the results.  Eight of the fifteen had positive results, with five of these eight reported as quite phenomenal by their parents.  Mood regulation, cognition, language and socialization were the primary positive responses reported.  Two of the children responded better when the dosage was reduced from 3mg to 1.5mg.  Transitory side effects of insomnia and earlier waking were reported. All children in the study were on well-controlled dietary restrictions at the time of the study.  Dr McCandless concludes that, along with other measures such as strict dietary controls and social support and encouragement, “As an effective, non-toxic, non-addicting, and inexpensive behavioural and immunomodulating intervention, LDN is joining our biomedical arsenal to help more and more children recover from autism as well as helping anyone with autoimmune diseases and cancer”.7

In an LDN Research Trust documentary, “The LDN Story”, Dr Brian Udell, specialising in paediatrics, has parents who go to him with children who are not developing normally and the conventional medical community don’t have answers for them.  Dr Udell has been using Low dose Naltrexone with his autistic patients since 2008 and says it’s been very successful in some variations of autism. He has found it effective in aggressive and disruptive behaviours in particular, there are also reports from parents that the children “don’t get sick like they used to” and for that reason alone they will continue with LDN.8 

Brian D. Udell, MD, in his chapter in the LDN Book,9 gives a case study of a patient, Jacob, who was helped enormously by Dr Udell’s LDN protocol.

Experience of a Selected Patient:  Jacob, a three-year-old boy, was brought to Dr Udell by his parents after being told that their son had ASD by a neurologist. His medical history showed a steady increase in symptoms from the first months with significant sleep disturbance and incessant screaming diagnosed as gastroesophageal reflux which required Proton Pump Inhibitor medication. Jacob continued to have extreme episodes of vomiting up to three times a day. At 18 months he could not tolerate solid food. At 2 years old he was diagnosed with speech delay and there were other repetitive behaviours such as staring, head banging and running in circles.  Sensory issues, such as his little sister crying or the flushing of a toilet, could set him off in a fit of punching and kicking.  He did not want human contact, not even with his mother. All of this was consistent with ASD and so a protocol was started with routine laboratory testing of blood, urine and stool which resulted in supplements targeted at improving gastrointestinal health and energy.  After an allergy panel was run and gluten and casein were removed from Jacob’s diet the parent’s reported that the vomiting had stopped and he was now able to tolerate foods of differing textures.

The aggressive behaviours continued and the parents were reluctant to take the specialist’s advice to administer Ritalin or Prozac.  Reluctantly they did agree to administer Dr Udell’s LDN protocol, applied as a transdermal cream in the late evening.

Communication and social interaction improved from that point on and Jacob was able to return to a neurotypical classroom in a public school.  Jacob is now somewhat famous for his ability to play the piano with ease!  Jacob’s story, as told by his parents, can be found on YouTube10 and at the LDN Research Trust website.11

We are excited about “The LDN Book Volume 2” book tour which launches in Chicago, Illinois, USA on October 14th 2020.12 In this new volume there is a wonderful chapter on the uses of LDN in Pediatrics by Vivian F. DeNise, D.O. ABAARM, FAARFM, the first section concerning Autism and LDN.




2. Eunice Kennedy Shriver National Institute of Child Health and Human Development,

3. LDN Research Trust, “How Low Dose Naltrexone Works”,

4. “IB5. Clinical Applications: Endorphins and Autism”,

5. B K Kolmen et al., “Naltrexone in Young Autistic Children: A Double-Blind, Placebo-Controlled Crossover Study”, Journal of the American Academy Child and Adolescent Psychiatry, 34, 2 (Feb 1995): 223-31.

6. R Scifo et al., “Opioid-immune Interactions in Autism: Behavioural and Immunological Assessment During a Double-Blind Treatment With Naltrexone”, Annali dell'Istituto superiore di sanita, 32, 3 (1996): 351-9

7. Jaquelyn McCandless, MD., “Low-Dose Naltrexone (LDN) for Mood Regulation and Immunomodulation in ASD”, (April 2006):

8. LDN Research Trust Documentary, “The LDN Story” –, Dr Udell begins at 23:26 minutes.

9. Linda Elsegood, ed., “The LDN Book – How a Little-Known Generic Drug – Low Dose Naltrexone – Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression and More”, Chelsea Green Publishing, White River Junction, Vermont (Feb 2016) Chapter 8.

10. “The LDN Story” YouTube, Jacobs Story at 33:00 minutes.

11. “The LDN Story”,

12. The LDN Book Volume 2 book Launch and Tour,