Clonazepam, variously marketed as Klonopin, Paxam, Rivotril and Rivatril, belongs to the benzodiazepine class of drugs which also includes diazepam, better known by the brand name Valium.

Benzodiazepines work by binding to specific receptors on nerve cells which enhances the potency of the body's main inhibitory (calming) neurotransmitter, GABA. These drugs are therefore used in conditions where there is overexcitability of the brain and central nervous system such as epilepsy/seizures, anxiety and panic disorders, and sleep disorders including restless legs syndrome (RLS).

Clonazepam is a potent benzodiazepine whose effects have a rapid onset but also wear off relatively quickly. This is in contrast to diazepam which is less potent and generally slower to take effect but also remains in the body for longer and its effects therefore have a longer duration.

All benzodiazepines are considered to be effective and have low toxicity but they are also known to lose their effectiveness over time, thus requiring increased dosages to produce the same benefit. They also bring a risk of dependence and are thus usually prescribed for short periods or on an "as needed" basis only.

Finally, it is worth noting that a number of specialist physicians have used clonazepam as part of a comprehensive treatment approach for chronic fatigue syndrome (ME/CFS). The most notable of is Dr. Paul Cheney who believes the brains of ME/CFS patients are in a state of chronic overactivation which besides contributing to symptoms can be damaging to brain cells over time. Dr. Cheney has used clonazepam/Klonopin to return brain activity to within normal ranges.

RxList entry for clonazepam

Naltrexone is a member of a class of drugs known as an opiate antagonists. It blocks the effects of opiate drugs such as as heroin and morphine and as such is often used as part of treatment programs for addiction to these drugs. For this purpose the dose is usually between 50 and 150mg daily.

When used in low doses (1.5 to 4.5mg daily) however it has entirely different effects and is being used "off-label" to treat people with autoimmune diseases including multiple sclerosis (MS) and Crohn's disease, as well as environmental illnesses including chronic fatigue syndrome (ME/CFS), fibromyalgia, irritable bowel syndrome (IBS) and autism. It may also be effective in mood disorders such as depression and bipolar disorder for reasons that will become apparent.

Low-dose Naltrexone (LDN) therapy was developed by Dr. Bernard Bihari, a neurophysician in New York, USA. Dr. Bihari is qualified in Internal Medicine, Psychiatry and Neurology. LDN has been used in the USA since 1985 but has only recently started to be used by doctors in the UK and mainland Europe.

LDN is thought to work by temporarily inhibiting the action of endorphins (the body's own opioids) which has the rebound effect of stimulating the body to produce larger amounts of endorphins. The diseases treated with LDN typically involve abnormally low levels of endorphins. Restoration of normal levels of endorphins by LDN should have the effect of reducing pain and increasing mood, energy and an individual's general sense of well-being.

However, these are not the only effects of LDN  - perhaps more important are the effects increased endorphin levels have on the immune system. Increased endorphins have been shown by Dr. Bihari and others to stimulate the immune system, specifically producing an increase in the number of T lymphocytes. In particular, LDN appears to restore normal levels of T suppressor cells - these cells normally prevent the runaway immune reactions that lead to autoimmune and allergic diseases. Additionally, LDN is thought to restore a normal balance between the Th1 and Th2 branches of the immune system which would be expected to reduce the production of antibodies against the body's own tissues (autoimmune disease) and environmental antigens such as pollen and mold (allergies). An abnormal dominance of Th2 immune activity has frequently been noted in environmental illnesses and LDN would therefore be expected to be beneficial. Also of importance is evidence that LDN restores numbers of Natural Killer (NK) cells - an important part of Th1 immunity - which have consistently been shown to be low in chronic fatigue syndrome and other environmental illnesses.

In summary, the effects of LDN on the immune system in theory reduce abnormal reactions to the body's own tissues and allergens and increase the ability of the body to fight infectious agents including viruses, bacteria and yeasts/fungi (e.g. Candida).

The introductory dose of 1.5mg LDN is usually taken for the first 2 weeks of treatment, then increased by 0.5mg every 2 weeks until the individual finds the dose that suits them best (up to the maximum of 4.5mg). If there is an increase in symptoms when taking a higher dose it might indicate that this dose is too high. Lowering the dose should result in improvements becoming apparent.

LDN only stays in the system for 4 hours and most people take it before bed as the temporary blocking of the effects of endorphins can be uncomfortable whilst awake (e.g. increased pain, lowered mood). However, some people find taking LDN at night causes disturbed sleep so taking the dose in the morning is preferable for them.

Groups promoting LDN, whilst noting a patient's symptoms more initially become more severe and sleep disturbances and constipation may occur, suggest these effects or usually last only a couple of weeks and then improvements will be seen in most cases. They do caution that clinical trials have not been performed on LDN however so the possibility of long-term side-effects cannot be ruled out.

For more information see www.lowdosenaltrexone.org and www.ldnresearchtrust.org