Low Dose Naltrexone: Can It Work?

Editorial Note: The Low Dose Naltrexone post from Osama Mustafa earlier this week is quite striking. Many will read it and be persuaded. Others will read it and think such low doses of a drug cannot do anything.

And yet others will read the following few words and begin to doubt where they may have been persuaded before – Osama has a business selling Herbal Medicines. For many this alone will produce the appearances of a conflict of interest and the apparent conflict will make them doubt his report. Is this fair?

The answer to some extent hinges or whether herbals or very low dose treatments work. Clearly if these “alternative” treatments don’t and can’t work, then claims that they do would seem likely to be based in some conflicting interest. But if they can work, what then? Do those who advocate for high dose allopathic treatment have no conflicting interests?

From humors to tonics

From Hippocrates to the French Revolution, the dominant treatment approach for any disorder, physical or mental, was humoral. There were four humors – phlegm, choler, bile and melancholy – and treatment aimed at increasing or reducing one of these.

The treatments also typically involved efforts to reproduce what the body appeared to do when faced with illnesses – it sweated, developed diarrhoea, bled or we drooled. So treatments were designed to get us to sweat or purge or pass water or drool or to bleed us. This was pretty rational, even though we might now call many of these effects “side-effects”.

In the 18th century John Brown from Edinburgh broke from the traditional humoral approach to therapy. Rather than talk about four humors Brown’s view was that the same disorder could arise from either an excess or a defect of a basic vitality.

He linked most disorders to the nervous system where he thought the basic substrate was irritability. The excitability and irritability of nerves had just been discovered in Edinburgh.

To cure maladies therefore Brown suggested that problems stemming from a deficiency of irritability could be treated by tonics while other problems linked to an excess of irritability might be treated by sedatives.

This is in very close to a Yin and Yang theory of treatment. It naturally extended from herbs and metals and other such medicines to the food we ate and climate. Red meat and nuts, or anything that interfered with sleep, were seen as tonics – to be taken in certain conditions and not others.

Tonics and sedatives today

When the psychopharmacological era opened up in the 1950s with the discovery of the antipsychotics and antidepressants we had broadly-speaking tonics that included psychoanaleptics, psychic energisers and stimulants on the one side and sedatives and later tranquilizers on the other side.

Among the most intriguing discoveries of early psychopharmacology, one that has since been eclipsed, was that brain systems such as the reticular activating system could produce the same outcome by stimulating or by sedating.

Anaesthesia for instance is classically induced by sedatives but it can also be induced by drugs that stimulate such as ketamine or phencyclidine.

These insights linked to another idea that was born with Carl Jung in 1909 – the idea of introverts and extraverts. For Jung, these terms referred to people who solved their problems in their head – introverts – as opposed to people whose problems became a problem for others also – extraverts. Introverts have phobias about illnesses – extraverts actually have the illnesses but nothing shows up on laboratory testing.

This idea was taken further by Pavlov in 1924 who, faced with dogs who had what he termed traumatic neuroses following a flooding in his laboratory in St Petersburg, found that some responded to stimulants while others, who appeared to have exactly the same condition, responded to sedatives. Pavlov suggested this was down to the temperaments of the dogs – their personality types.

Hans Eysenck in the 1950s married Jung and Pavlov when he proposed that successive layers of neural inhibition produce the personality types of extraversion and introversion. To map these, he produced the Eysenck Personality Questionnaire that has led on to the Cloninger Tridimensional Personality Questionnaire and most other personality questionnaires we have today.

Eysenck showed that introverts and extraverts could be distinguished for example on the basis of their response to sedatives. Studies have shown in fact that your degree of introversion or extraversion can predict the dose of anaesthetic agent needed to induce sleep for surgery.

This line of thinking came to a full stop for almost 50 years with modern psychopharmacology but with the ever widening spread of ADHD (aka extraversion) and interest in ketamine as an antidepressant these ideas may all be forced back on the agenda – See Ketamine – Convulsions and Depression.

What we have lost

So back in the nineteenth and early twentieth centuries, doctors and patients essentially saw what we would now call side effects as the benefit that a treatment brings whereas we see them as side effects. The immediate reaction is that you cannot get a much better definition of progress than that.

Except….

Take the case of Ebenezer Maurice from Festiniog, admitted in August 1875 to the North Wales Asylum at Denbigh. He had become agitated (maniacal). The treatment involved soothing him with bread and milk for breakfast and supper and beef tea for dinner. Once the agitation resolved, he was given meat to fortify him. But he became agitated again, and when he did the meat was withdrawn and he was put back on bread and milk. It is clear from the record that both staff and patients expected these interventions to make a difference.

The key point here is that patients and doctors then were aware of the effects of meat and nuts on things like sleep. If someone now were to approach their doctor and say they thought eating meat in the evening was interfering with their sleep they would likely be dismissed as daft. Incorrectly.

While we have gained much, we have lost much also. Treatments aimed at curing some core problem are now administered with no sensitivity to the 100 other things they do. We may have reached the point where we are now killing more people than we cure.

Comparing the data from the North Wales Asylum with modern services in North Wales it shows that we kill far more now through our therapeutic efforts than we did in 1875, 1900, and 1950. (Mortality Data in BMJ article here).

On your bike?

Sometimes to get safely from A to B, all you need is a bike. But in medicine now we rarely use anything less than a top of the range vastly over-powered sports car even to just drop around the block. Sports cars are great to have but we have close to forgotten how to ride bikes. At the end of the day which could we more readily live without?

There is every reason to think that it makes sense to know what herbs and foods in general do – because they do do things. If we think they don’t do things its because our powers of observation have been dulled.

Low dose?

There is another even more complex story here. It is almost certain that many of the drugs we now use do a huge amount of other things at a fraction of the dose used conventionally. This is true for many of the older antidepressants where 10% of the usual dose can improve sleep and appetite, stop people wetting the bed or a range of other things.

The most striking claims in this area come from Josef Knoll who has demonstrated a range of striking effects of drugs like selegilene at 5% or less of the conventional dose – effects that are of much greater benefit than found with the so called full dose.

If a lot of reasonable people offer convincing reports of significant benefits on an off-patent drug like Low Dose Naltrexone, whose interests are served by dismissing these claims?