NEUROTOXICOLOGY THEME
This theme is about understanding the effects of drugs and chemicals on the brain and nervous system.
This is important because of increasing concern about the effects ofexposures to chemicals on the brain and nervous system and the potential that this has to cause short-term (‘acute’) or longer term (‘chronic’) clinical effects, especially in children and young people.
Descriptions of individual projects:
Developing methods to identify emerging recreational drugs
Misuse of drugs is common and can sometimes result in clinical symptoms severe enough to require admission to hospital for treatment. And some people die from misuse. In recent years, drug misuse has increasingly involved new synthetic chemicals, called Novel Psychoactive Substances (NPS). These drugs have also sometimes been referred to as ‘legal highs’, but it is important to point out that currently all of these substances are now illegal.
These NPS cause particular challenges to health services because a large number of new chemicals emerge each year and there is very limited information about unpleasant or dangerous (‘toxic’) symptoms that people may develop after using them. A further problem is that the precise chemical that has been used is often not known and can be found out only by chemical analysis of the substance that has been used or analysis of samples taken from those who have been affected. Such analysis is not part of routine NHS care and is not available to those health professionals managing those who have been affected.
This project is involving people who have come to hospital with severe toxic symptoms after drug misuse where it is suspected that an NPS has been involved. With their consent (or the agreement of a personal or professional representative), brief clinical details and samples of blood, urine or oral fluid are collected. These are then sent to a research laboratory and the substances responsible are identified. Currently, more than 20 hospitals across England, Wales and Scotland are participating in the research.
Using these methods, we’re identifying those NPS most commonly causing severe toxicity and we’re monitoring how these patterns vary across the country and over time. We’re also trying to find out what harmful effects are being caused by which drugs.
We’re publishing our results in medical journals and passing them on to government agencies responsible for public health and drug misuse and directly to health professionals managing affected patients.
Models of In Vitro Neurotoxicology
We’re developing new methods to help us understand the effects of drugs and chemicals on the human brain. The human brain is composed of many different types of brain cells, which are unevenly distributed throughout the brain because different parts of the brain have different functions. But it is not generally possible to study the effects of drugs and chemicals in the intact human brain. For this reason, we have developed a method to make human brain cells using stem cells. Stem cells are special cells that can be programmed to transform into any cell in the human body. In this research we’re transforming these stem cells into various types of human brain cells. We can then study the effects of drugs and chemicals on these cells to better understand their effects on the human brain.
Using these methods, we’re analysing the effects of NPS on brain cells which have come from stem cells and have shown that some NPS can damage these cells. We have also seen differences between NPS in the severity and type of damage that can be produced.
The analysis we are conducting in the laboratory will allow us to gain a better understanding of the effects that NPS can have on the human brain, both in the short and longer term.
Organophosphate Exposure Levels from Domestic and Occupational Use
Pesticides are exceptionally useful chemicals and are used in many different types of ways to kill or repel unwanted pests in our homes.
Products containing pesticides are licensed and regulations and guidelines on use are in place to limit exposure to levels that should not damage our health. However, the extent of pesticide use in UK homes is unclear. Furthermore it is unclear if guidelines are followed and this may increase the risk of exposure to levels which could possibly damage health.
The first part of our study was to collect information using an on-line survey on the different types of pesticides people use in their homes, how frequently they are used and if there may be any factors that increase use in a household such as pet ownership. We also asked people about how they stored pesticides and if they followed the guidelines on use. All this information will be published and shared openly on-line so it can be viewed by the public and used by other interested parties including public health professionals.
The second part of the study is to determine if use of pesticides in the home is related to levels of pesticides in our bodies. We have used the information collected in the first part of the study to identify the most commonly used combinations of pesticides used by our participants. We will collect urine from participants and information on their pesticide use, and assess the urine for the breakdown products of the most commonly used pesticides. This information will allow us to determine the levels of pesticides in people’s bodies.
Finding something when it isn’t there – identifying exposure to carbon monoxide
Perhaps as many as 4,000 people a year end up in hospital following exposure to carbon monoxide, a colourless, odourless gas which is often released from faulty heating systems. Symptoms of carbon monoxide poisoning are however very non-specific and often overlooked. One problem with finding out if someone has been exposed to carbon monoxide is that by the time poisoning is suspected, the carbon monoxide has been expelled from the body and can no longer be detected. This means that we have no real way of finding out how many people are actually affected by carbon monoxide poisoning and if there are long term health effects. What is needed is a specific test that can tell us if someone has been affected by high levels of carbon monoxide, even if the carbon monoxide has long gone – in effect a carbon monoxide fingerprint.
To try to identify a carbon monoxide fingerprint (in scientific terms a “biomarker”), we have been funded by the charity the Gas Safety Trust ( to run a series of experiments. We will first take blood samples from healthy volunteers and then expose the blood cells in the lab to carbon monoxide. Any changes in the blood cells will then be determined using sophisticated laboratory methods. We will then be able to see how long these changes last in the cells after the carbon monoxide has disappeared. If some of these changes last for several hours, then we might be able to use them to detect carbon monoxide in blood samples from people who have been exposed. Having this test would mean that we can find out how many people are affected by carbon monoxide exposure each year, and if there are long term effects in those people.
Further details about this research is available here