How do you classify ‘long-term’ cannabis use?
We classified ‘long-term’ cannabis use as being regular, at least weekly, cannabis use for over 12 months. This is the period of time that’s used in the DSM-IV psychiatric diagnostic manual to classify substance use disorders. In our study the average duration of at least weekly use was just over four and a half years.
What prompted your research into long-term cannabis use and motivation?
We were really interested in exploring the link between smoking cannabis and mental health problems like schizophrenia.
It’s been known for some time that smoking cannabis regularly, over a long period of time increases the risk of mental health problems like psychosis. Importantly, the risk is higher the younger people are when they start smoking cannabis. However, we’re not sure how cannabis increases the risk of psychosis.
Based on research by Dr Oliver Howes, who I work with at the MRC Clinical Sciences Centre based at Hammersmith Hospital in London, and Professor Shitij Kapur, who works as the Dean of the Institute of Psychiatry, we know that people who have schizophrenia have a tendency to have raised levels of dopamine production in a part of their brains called the striatum.
We’ve worked together in a clinic based at the Maudsley Hospital in London for people with schizophrenia that aren’t getting better with treatment, so it’s very important to us to understand how different risk factors for psychosis affect the brain.
Around 1 in 3 British adults have tried cannabis and in the USA almost 1 in 20 people will at some point abuse or become dependent on cannabis, so the effect of cannabis use on the brain is quite relevant to a large number of people.
Professor Valerie Curran and Dr Celia Morgan from University College London are experts in the field of understanding how drugs affect the brain and have been conducting a large study with hundreds of cannabis users for a few years now. We thought that it would be a good opportunity to join forces!
Of course schizophrenia isn’t the only mental health problem associated with smoking cannabis, there’s also depression and low motivation levels. Dopamine is a really interesting neurotransmitter as its involved in signalling reward and punishment in the brain, which also relate to motivation. So we thought we’d look at that too.
What did your research involve?
We included 19 young adults who smoked cannabis regularly and 19 age and sex matched control subjects who didn’t smoke cannabis. The cannabis users in our study experienced a transient increase in psychotic-like symptoms when they smoked their own cannabis, but they didn’t have a diagnosis of schizophrenia.
We measured psychotic-like symptoms by observing cannabis users away from the laboratory, in the environment where they normally smoked cannabis such as their own home.
During the study we took detailed information about the amounts and types of different drugs, including alcohol and tobacco, that people had used as well as taking a sample of the cannabis they smoked for chemical analysis.
In order to measure how much cannabis people were using we asked them “how long does it take you to smoke an eighth of cannabis”, as an “eighth” is the normal unit of sale for cannabis in the United Kingdom, being about three and a half grams.
All of our subjects had a Positron Emission Tomography scan, or PET for short, which uses a compound that’s labelled with a small amount of radioactivity, called a radiotracer, so that it acts like a “dye”. The radiotracer we used is [18F]-DOPA, which is a radiolabelled version of L-DOPA, the chemical precursor to one of the main neurotransmitters, dopamine.
The radiotracer was then injected into an intravenous cannula placed in the arm of our subjects. The PET scan then measures the amount of radioactivity emitted from the brain. With our technique, we had to measure how much of the [18F]-DOPA was going in to the striatum in the brain, compared to another part of the body where there isn’t much dopamine.
We chose the cerebellum in the brain as we’ve previously shown that we can get repeatable measures using this technique. We then used another method for analysing the PET scans, called a voxelwise analysis, to confirm our results.
What were the results of your study, were you surprised by them and how do you think they can be explained?
Our main hypothesis was that the cannabis users in our study would have increased dopamine production in the striatum. This was based on findings of studies into people who have schizophrenia and related mental health problems.
Instead, we found they had reduced dopamine production – which was quite surprising to us initially – although, this does make sense in terms of studies of users of other drugs.
Interestingly, we found that cannabis users who met diagnostic criteria for abuse or dependence had the lowest levels of dopamine production. This makes sense to us in terms of regular, long-term cannabis use “blunting” the brain’s dopamine system.
We also found relationships between the lowering of dopamine production and both the amount of cannabis people were smoking and old people were when they started smoking the drug. These dose-effects suggest cannabis use is the underlying reason for our findings, but we can’t say cannabis is the cause without doing a prospective study.
Why did you only look at cannabis users who have had psychotic-like experiences while using the drug and not all cannabis users? Do you think your results would apply to cannabis users in general?
We looked at cannabis users who were sensitive to the psychotic-like effects of cannabis as epidemiological studies indicate that this group of cannabis users are most at risk of developing enduring psychotic symptoms, such as those seen in schizophrenia.
We didn’t find a relationship between dopamine production and increase in psychotic-like symptoms, so we think the effects we saw would apply to cannabis users in general.
Has dopamine been proven to be linked to motivation?
Some very good scientific studies in animals demonstrate that brain cells that use dopamine play a key role in signalling the “motivational salience” of stimuli.
The way that I think about this is that for animals, including humans, one of the key functions of the brain is to decide when something in the environment is important for our survival. This could either be pleasurable things like food, which we would seek out, or unpleasant things like feeling pain, say from an injury, which we would want to avoid.
If the dopamine system is “blunted”, it may create a situation such that pleasurable things feel less pleasurable and unpleasant things feel less unpleasant, such that motivation would be impaired, as occurs in long-term, regular cannabis use.
How did your results compare to previous research?
Our results extend previous research studies in people who used to smoke cannabis that have found altered patterns of dopamine receptors, and a similar relationship to the one we found between the age that people started smoking cannabis and an effect on the dopamine system.
Our findings that dopamine production is particularly reduced in people who abuse or are dependent on cannabis fits in well with previous research on other drugs of addiction.
Do you think your results support the existence of the ‘amotivational syndrome’ in some cannabis users?
It has been known since research studies in the 1970s that people who smoke cannabis regularly can lose interest in their working lives or studies, i.e. have loss of motivation, and I don’t think that’s very controversial.
The controversy centres around whether this loss of motivation is part of regular cannabis use due to chronic intoxication or whether the “amotivational syndrome” exists as a separate entity.
Either way, our results provide a biologically plausible mechanism which could explain the mechanism underlying the loss in motivation associated with regular long-term cannabis use.
How was your research funded?
Our research was funded by a grant from the Medical Research Council (United Kingdom) to Dr Oliver Howes, a National Institute of Health Research Biomedical Research Council grant to King’s College London, and a Medical Research Council (United Kingdom) grant to Professor Valerie Curran and Dr Celia Morgan.
Do you have plans for further research into this field?
Yes, we’re doing some additional analyses on our study looking at both motivation and other possible mechanisms underlying the link between cannabis and psychotic-like symptoms.
My colleagues at University College London are continuing their research into how the chemicals in cannabis affect the brain and I very much hope to collaborate with them again.
Dr Howes has a research programme at Hammersmith Hospital investigating the chemical changes associated with a range of mental health problems, which I’m actively involved in.
Where can readers find more information?
I’d point readers to the main article itself which is published in the journal Biological Psychiatry. This should be made freely available to the general public in due course.
If people would like further information about some of the mental health issues raised like cannabis and schizophrenia, the Royal College of Psychiatrists has some really useful information on its website (www.rcpsych.ac.uk).
If readers are concerned about their own or a loved one’s mental health I would recommend they speak to their family doctor or psychiatrist.
About Dr Michael Bloomfield
Michael studied Natural Sciences at Corpus Christi College, University of Oxford taking specialist papers in Pharmacology, Systems Neuroscience and Behavioural Neuroscience. Whilst an undergraduate he was tutored in Physiology by Professor Chris Ashley and in Pharmacology by Professor Trevor Sharp. He also studied the History and Philosophy of Science and Technology.
Michael then continued his studies at Oxford, studying Clinical Medicine. Whilst at medical school Michael studied Psychiatric research in Melbourne, Australia, and studied evolutionary theories of schizophrenia under Professor Tim Crow.
Michael completed his early medical jobs in London and in the Channel Islands, where he worked as a flight doctor on Jersey’s air ambulance.
Michael began his specialty training in Psychiatry in London before taking up a Medical Research Council Clinical Research Fellowship with Dr Oliver Howes at the MRC Clinical Sciences Centre within Imperial College’s Hammersmith Hospital campus.
Michael is also a Visiting Research Fellow at the Institute of Psychiatry. He has worked as an Honorary Specialty Registrar in Psychiatry in the TREAT clinic for treatment-resistant schizophrenia at the Maudsley hospital with Dr Howes and Professor Shitij Kapur and in Psychotherapy under Dr Anne Patterson at Chelsea & Westminster Hospital.
Michael is a trainee associate of the Royal College of Psychiatry, a young fellow of the Royal Society of Medicine and a trainee member of the British Association of Psychopharmacology, the European College of Neuropsychopharmacology and the Schizophrenia International Research Society.
Away from London Michael is a qualified aeroplane pilot and enjoys travelling.