Of cannabis and psychosis
Weed, puff, dope, skunk, marijuana, blow, pot, hash. Cannabis has many different names and is the most commonly used illegal drug. A recent study in Australia revealed that 60 per cent of teenagers had tried it by the time they were 20. Yet despite its reclassification in the UK from a Class B to a Class C drug in January 2004 – making possession an illegal but non-arrestable offence – some scientists are concerned that its use can lead to psychosis, and schizophrenia in later life (see Box).
Why the concern now?
Cannabis has been used for thousands of years for its medicinal and therapeutic effects. The Chinese in 6000BC used cannabis seeds for food and 2000 years later were making fabric out of hemp (the plant Cannabis sativa) (Hemp clothing is available today from selected suppliers.) The first written evidence that cannabis was used for medicinal purposes comes from China in 2727BC. Today a synthetic cannabinoid (cannabis-like molecule), nabilone (1), is available for treating chemotherapy-related sickness, associated with cancer, on a named-patient basis. Current, medicinal uses of cannabis include:
- to improve spasticity (muscle flexibility) in patients with multiple sclerosis (MS);
- to treat neuropathic pain (sometimes known as phantom limb pain) common to people who have had a limb amputated;
- to treat chronic (long-term) pain associated with cancer;
- to stimulate appetite (eg for AIDS patients).
One UK firm has been at the forefront of these applications. GW Pharmaceuticals has a special Home Office licence to grow cannabis and produce a drug called Sativex. The company has been granted a licence for Sativex to treat patients with MS symptoms in Canada, but the UK medicines regulatory agency has yet to approve its use. A decision by the UK agency earlier this year asking GW Pharmaceuticals for more clinical evidence before approving the drug was met with dismay from the MS Society. The charity believes there is convincing evidence that cannabis can significantly improve the quality of life of MS patients.
Chemists at GW Pharmaceuticals extract high quality active ingredients, delta-9-tetrahydrocannabinol (THC) (2) and cannabidiol (CBD) (3), from its specially grown cannabis plants. The two active ingredients are administered in carefully calculated doses, to avoid the side effects desired by recreational users, via an under-the-tongue spray. THC and CBD work by attaching to cannabinoid (CB1) receptors in the brain. These receptors can also be blocked by molecules such as the weight loss drug sibutramine (Reductil), which are also cannabinoids.
A psychotic connection?
Just under 20 years ago research done by Swedish chemists at the Karolinksa Institute in Huddinge suggested that cannabis use could result in long-term mental health problems. They discovered that men who had smoked cannabis before they did National Service (aged 18–20) were six times more likely to be hospitalised with schizophrenia (see Box). Although the researchers could not determine which came first, cannabis use or the tendency to get schizophrenia, the work prompted further research in this area.
More interesting results have come from a recent study at King’s College London. Professor Robin Murray and his team found a three-fold increase in the likelihood of developing schizophrenia with recreational use of cannabis. The link grows stronger the more cannabis is smoked and if there is a genetic predisposition to mental illness, ie a family history of mental illness. Adolescents who had displayed disturbed thought processes before the age of 11 but did not smoke cannabis had a 25 per cent risk of developing psychosis. However, this increased to 50 per cent once they had smoked cannabis.
The big problem with this kind of research has been determining cause and effect. Does the cannabis cause the psychosis or do people who have a tendency to develop psychotic symptoms have a tendency to use cannabis? In 2000, a study was published which was designed to ans- wer this question. David Fergusson at the University of Otago, Christchurch, New Zealand found an increase in psychotic symptoms of up to 150 per cent in people who regularly used cannabis in contrast to non-users.
Yet as cannabis use has increased, the number of people suffering with schizophrenia hasn’t increased at the same rate. Going back to the predisposition argument, more research from chemists in New Zealand published this year has thrown light on possible genes involved in schizophrenia. COMT is an enzyme produced by a gene, and is responsible for breaking down the neurochemical dopamine. (An overproduction of dopamine in the brain is thought to lead to psychotic symptoms.) COMT comes in two forms, which break down dopamine to different degrees, and a double dose of the ‘bad’ form increases the likelihood of a cannabis-smoking teenager developing psychosis 10-fold. One good and one bad COMT increases the risk slightly. For those with two good COMT enzymes, cannabis smoking does not affect their mental health.
It is also worth noting that different forms of cannabis cause different effects. This appears to offer another insight into the psychosis link. Research done by Professor Cyril D’Souza and his team at Yale University published last year indicates that 9-THC could be the principal cause of temporary schizophrenia-like symptoms. Their work suggests that the cannabinoid receptors could be involved in the mechanisms underlying schizophrenia.
Despite the long history of cannabis use, the wealth of clinically researched evidence is strangely minimal. Researchers from the University of Birmingham, writing in the medical journal The Lancet last year, concluded that more evidence is needed to establish whether cannabis causes mental health problems. Fiona Salvage
Psychosis and schizophrenia
One in 100 people fall victim to schizophrenia. This debilitating illness, which affects the chemistry of the brain, is ignorant of gender, race and culture, and social standing. The illness strikes between the ages of 15 and 45, with little obvious warning. While symptoms vary from patient to patient, they will all experience psychosis. This means their perception of reality is altered, they are unable to distinguish between real and unreal thoughts. Their thought processes are so disordered, they find it difficult to cope with the bare essentials of daily life. Making a cup of tea for example, can become impossible. In a psychotic state, patients have been known to jump into a lion’s den or try to walk across a busy motorway, with no appreciation of the consequences. In the extreme, schizophrenic patients experience hallucinations both visual and auditory, as well as delusions, such as feelings of persecution. Some people will experience a psychotic breakdown, and not go on to develop schizophrenia, which is characterised by several psychotic episodes throughout the sufferers’ lives. Many people suffering with schizophrenia also have ‘negative’ symptoms, they become withdrawn, often pre-occupied with their own thoughts and find it difficult to communicate. They lose their self-esteem, as well as interest in work, friends and family. No one knows what causes the illness, though many factors – genetic, environmental, and alcohol and drug abuse – may play a part in a person’s risk of developing the illness. There are a plethora of drugs available for treating some of the symptoms of schizophrenia, which have varying degrees of success (see InfoChem, 2001, no 67, All in the mind). Kathryn Roberts
