New life for naltrexone and autism?

During the very earliest days of the life of this blog I posted about the opiate antagonist naltrexone (ReVia®) and some research on its history with autism in mind; in particular, the various emerging speculations on low dose naltrexone (LDN) (see here). Today I'm following up that entry based on the results of a systematic review by Ashok Roy and colleagues [1] on the value (or not) of naltrexone for "attenuating the core symptoms of autism spectrum conditions in children".

"Yadwigha in a beautiful dream" @ Wikipedia 

The authors report: "Naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in majority of the participants. It is likely that a subgroup of children with autism and abnormal endorphin levels may respond to naltrexone and identifying the characteristics of these children must become a priority".

I am not unhappy with this statement. Realising that autism is probably better represented by the plural 'autisms' and, as with just about every intervention put forward for the autisms, there is not one-size-fits-all measure, it makes good sense to seek out those best- and non-responders to something like naltrexone therapy. The fact that the authors also talk about "abnormal endorphin levels" as potentially being one guide for responder status harks back to the work of Gillberg and colleagues [2] from decades ago. I've also talked before about how other interventions such as the use of a gluten- and casein-free (GFCF) diet (which may very well be related to any naltrexone effect) seem to also affect more peripheral functions over core behaviours when it comes to autism (see here).

As odd as it might sound that a drug more normally used for the management of opioid dependence or alcohol dependence should potentially affect the presentation of at least some autism, there is perhaps some logic to its use. Opioid, by the way, refers to drugs such as morphine and codeine which bind to the opioid receptors we all have and produce various effects, most famously analgesia (pain relief) or in the case of abuse of such drugs, euphoria (happiness and wellbeing) at least for a short time. Naltrexone and other opioid antagonists produce an effect by blocking those opioid receptors, such that opioids cannot bind to them and so don't carry their prescribed effects. This similarly applies to our own internal opioid system including the endorphins. This euphoria blocking effect has also been put forward as a possible counteraction to the placebo effect too [3].

Of course one has to accept that one of three potential scenarios may be related to autism if one is to believe that naltrexone might seriously affect the presentation of symptoms for some:

1. that autism, some autism or its comorbidity, may have an element of opioid involvement to underlying biochemistry as per the Gillberg endorphin findings or even speculations that something like the opioid-excess hypothesis [4] may show involvement to cases, bringing in the GFCF diet angle. I hasten to add that I am not insinuating that autism is due to opioid addiction or anything like that.
2. that some autism may have an element of immune system involvement in light of the proposed action of something like LDN on inflammatory processes [5] and the preliminary signs of an effect on some cases of inflammatory bowel diseases such as Crohns disease [6] which might yet be relevant to other autism research (see here).
3. that any effect is purely epiphenomenal; just coincidence or a placebo effect, bearing in mind the Samokhvalov paper [3].

I'm not on this occasion going to offer any particular opinion about those options. I'd like to think that scenarios 1 and 2 are the more likely options in light of some [limited] results under double-blind, placebo-controlled conditions [7] for naltrexone acting on autism, but echoing the sentiments of Roy et al, there is much more investigation required in this area.

I do find the topic of naltrexone and autism to be a particularly interesting area of research. As also mentioned in a previous post on drug refractory aggression and autism, naltrexone continues to find favour for aiding some people on the autism spectrum, with the promise of so much more. You will be hearing more from me on this topic in future, particularly on some of our own research which has just cleared the peer-reviewed hurdle with drug delivery methods in mind...

Now, some music to liven things up... AC/DC and a very famous guitar riff...

---------

[1] Roy A. et al. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2014 Mar 4.

[2] Gillberg C. et al. Endorphin activity in childhood psychosis. Spinal fluid levels in 24 cases. Arch Gen Psychiatry. 1985 Aug;42(8):780-3.

[3] Samokhvalov AV. et al. Naltrexone may block euphoria-like placebo effect. BMJ Case Rep. 2013 Aug 7;2013. pii: bcr2013010098. 

[4] Shattock P. & Whiteley P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. 2002 Apr;6(2):175-83.

[5] Younger J. et al. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Feb 15. 

[6] Segal D. et al. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2014 Feb 21;2:CD010410.

[7] Willemsen-Swinkels SH. et al. The effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study. Biol Psychiatry. 1996 Jun 15;39(12):1023-31.

----------

Roy A, Roy M, Deb S, Unwin G, & Roy A (2014). Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. Journal of intellectual disability research : JIDR PMID: 24589346