01 June 2007
Can we alter brain chemistry to cure mental illness issues would such interventions raise? The government debate on brain science, addiction and drugs.
In late 2007, the Academy of Medical Sciences will publish the results of its public review of the social issues raised by brain science and in particular drugs and addiction. The review is a response to a 2005 government report Drugs Futures 2025?1 The RSC took the opportunity to highlight the challenges this area of research poses to chemists in collaboration with other disciplines.
Our knowledge in the area of brain science is progressing, we now understand more about the chemical and biological basis of addiction and have started to improve treatments. There are developments in medicines for mental illness and we know more about psychoactive substances that can affect normal brain activity.
Drug addiction has become one of the most significant social problems of the last decade. The social and economic cost of drug abuse in terms of crime, absenteeism and sickness is now estimated to be in excess of £20 billion a year. But research into the complex area of addiction has far to go.
In a normal brain dopamine is continuously released at low levels as a trigger to nerve activity. It binds to receptor sites on nerve cells which trigger a central nervous system response. It is then removed by being absorbed into the receptor cells.
When addictive drugs such as opiates are taken more dopamine is released in the brain, which has a mood enhancing effect. In addition, drugs such as cocaine will hinder the re-uptake mechanism keeping dopamine levels elevated.
After removal from the brain, the user will feel the urge to take more of the drug to replicate the euphoria. The continual over stimulation of the dopamine system eventually causes the brain to change, and higher doses are needed to achieve the same high, as well as the physical symptoms of withdrawal if the drug is removed.
Treating addiction chemically
Crack-cocaine is highly addictive because it has one of the shortest half-lives of commonly abused drugs. When smoked it has an immediate effect on the brain with a very high peak concentration followed by a fast decrease. The see-saw pattern exaggerates the need for the next fix.
Dampening this see-saw effect is the key to the chemical treatment of drug addiction. Current treatments use agonists or antagonists, which respectively stimulate or block the receptors affected by the abused drug.
Agonists such as methodone stimulate the same pathways as the addictive drug. Antagonists such as naltrexone, block the pathway so that the abused drug no longer gives the desired high. Such treatments are not always successful because they lead to severe cravings and withdrawal symptoms that often lead addicts to stop treatment.
Partial agonists such as buprenorphine only partially stimulate the brain's opiod receptors. A ceiling is reached which stimulates enough to prevent withdrawal symptoms, but reduces the high experienced after taking drugs such as heroin. The drug is also longer lasting, as it is deposited in the body's fat tissue.
The holy grail for treating addiction is to find a drug that will work for a range of addictive substances and over long periods of time to allow greater intervals between doses (to decrease the risk of non-compliance).
Considering the economic and social cost of addiction, basic scientific research into new drug therapies is poorly funded. The RSC made this point in its submission to the Royal Academy of Medical Sciences.
For successful treatment, drug dependence needs to be considered as both a physiological and psychological phenomenon. Treatment of addicts is ultimately unlikely to succeed by purely chemical means and a combination of psychological, social and pharmaceutical treatments is likely to be the most successful approach.
In fact, the UK needs to provide more quality treatment to addicts before we can even assess what really works and look at the best direction for future therapies. A comprehensive comparative study into success rates of present pharmacological and behavioural treatments is needed.
Vaccinating against addiction
Another interesting direction for treating addiction is the use for vaccines. Cambridge based Xenova Group plc are developing therapeutic vaccines for the treatment of cocaine and nicotine addiction. These vaccines are designed to prime the immune system to produce anti-cocaine or anti-nicotine antibodies.
On entering the bloodstream, the addictive substance binds to the antibodies. The resulting large complex cannot cross the blood-brain barrier, so the usually pleasurable stimulus is absent or reduced. Such vaccines will provide benefit to those who wish to stop using cocaine or nicotine, but could also be used as a preventative treatment.
However vaccinating against addiction remains controversial. For example, who would receive vaccinations? Would the process be voluntary or coercive? Would parents be able to vaccinate their children at an early age? Would this be an infringement of human rights? Do we have a right to 'get high' and experience altered states of mind? All these issues are for society at large to consider.
Understanding mental illness
Scientists have understood something of the chemical imbalances underlying mental health problems, but making meaningful chemical measurements in the brain has not always been easy because of the small size of synapses and the inaccessibility of the brain.
Recent breakthroughs are now advancing knowledge. In 2006, University of Michigan scientists developed a sensor that will monitor levels of neurotransmitters in a patient's brain. The device has enabled them to study chemical changes associated with behaviour and disease.
Last year, researchers at the University of Cambridge identified specific biomarkers for schizophrenia. The team looked for psychosis-associated changes in the fluid which circulates around the brain and spinal cord. Their results showed that levels of some proteins and peptides were elevated in schizophrenic patients. They also saw characteristic changes in samples taken from patients with depression.
The identification of specific biomarkers could redefine the diagnosis of psychotic disorders, which is currently very subjective. Biomarkers may also help to distinguish between different mental health conditions which is not always possible to do at present.
The future potential of the discovery of biomarkers for mental illnesses is immense. Improved treatments and preventative medicines might all develop from such early research.
Chemists are using a wide range of approaches to develop therapies for neurodegenerative diseases that are becoming more prominent in our aging population. The latest research into Alzheimer's disease (AD) provides an excellent example.
Swiss scientists have examined the physiological activity of an unusual compound isolated from the bluegreen algae known as Nostoc, a common type of pond scum. Nostoc produces nostocarboline, a compound which shows promise as a drug candidate for Alzheimer's and other neurodegenerative diseases.
Nostocarboline acts by blocking the brain enzyme cholinesterase. Cholinesterase is involved in memory and cognitive processes. By blocking this enzyme the worst of the AD symptoms are reduced.
Collaboration is key
In responding to the Royal Academy of Medical Sciences, the RSC has emphasised the importance of collaborative research between the chemical and biological sciences to enable further advances in brain research.
The advances science can provide are likely to lead to new treatments for mental illness, addiction and may even lead to ways of improving normal brain function. The Royal Academy consultation is a welcome chance for society to examine and steer future progress in these areas.
02 March 2007
The Academy of Medical Sciences call for submissions on brain science, addiction and drugs.
Contact and Further Information
Dr Ellen Friel
Programme Manager, Life Sciences
Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 0WF
Tel: +44 (0) 1223 432440