How cannabis and cannabis-based drugs harm your brain
July 23, 2018
Science Daily/Lancaster University
Long-term use of either cannabis or cannabis-based drugs impairs memory say researchers.
The study has implications for both recreational users and people who use the drug to combat epilepsy, multiple sclerosis and chronic pain.
They found that mice exposed to the drug long-term had "significant ... memory impairments" and could not even discriminate between a familiar and novel object.
There is little understanding of the potential negative side effects of long-term cannabinoid exposure, though it is already known that heavy, regular cannabis use increases the risk of developing mental health problems including psychosis and schizophrenia.
More and more people are using the drug long-term due to its legalisation in several countries, while more potent varieties are available for recreational users.
Researchers from Lancaster and Lisbon Universities studied the effects of the cannabinoid drug WIN 55,212-2 in mice and found that:
· Long-term exposure impairs learning and memory in the animals
· Brain imaging studies showed that the drug impairs function in key brain regions involved in learning and memory
· Long-term exposure to the drug impairs the ability of brain regions involved in learning and memory to communicate with each other, suggesting that this underlies the negative effects of the drug on memory
Dr Neil Dawson, the lead researcher from Lancaster University said "This work offers valuable new insight into the way in which long-term cannabinoid exposure negatively impacts on the brain. Understanding these mechanisms is central to understanding how long-term cannabinoid exposure increases the risk of developing mental health issues and memory problems."
He also highlighted the relevance of the work to those using cannabinoid-based therapies to treat medical conditions.
"Cannabis-based therapies can be very effective at treating the symptoms of chronic diseases such as epilepsy and multiple sclerosis, and dramatically increase the quality of life for people living with these conditions. We need to understand the side effects that these people may experience so that we can develop new interventions to minimise these side effects."
Professor Ana Sebastiao, lead researcher at the University of Lisbon, said: "Importantly, our work clearly shows that prolonged cannabinoid intake, when not used for medical reasons, does have a negative impact in brain function and memory. It is important to understand that the same medicine may re-establish an equilibrium under certain diseased conditions, such as in epilepsy or MS, but could cause marked imbalances in healthy individuals. "As for all medicines, cannabinoid based therapies have not only beneficial disease-related actions, but also negative side effects. It is for the medical doctor to weight the advantages of the therapy, taking into consideration quality of life and diseases progression, against the potential side effects."
The research was published in the Journal of Neurochemistry and was conducted as part of the European Commission Horizon 2020 funded SynaNET project.
https://www.sciencedaily.com/releases/2018/07/180723132251.htm
Risk of psychosis from cannabis use lower than originally thought
April 20, 2017
Science Daily/University of York
The research, published in the journal, Addiction, also showed for the first time that there is sufficient evidence to demonstrate that for patients who already have schizophrenia, cannabis makes their symptoms worse.
More than two million people in England and Wales used cannabis in the past 12 months, but the latest research shows that banning the drug would have low impact on mental health.
In order to prevent just one case of psychosis, more than 20,000 people would have to stop using cannabis, as shown by a previous study led by the University of Bristol.
This means that at a population level, an increased risk of psychosis from cannabis use is low, and those vulnerable to developing serious mental health problems is relatively rare. The research highlights, however, that more reviews on the impact of high potency cannabis is needed in order to make a full assessment of the risks.
Ian Hamilton, lecturer in mental health at the University of York, said: "The link between cannabis and psychosis has been an ongoing research topic since the drug became popular in the 1960s. Most of the high profile studies that we have access to, however, are from a time when low potency cannabis was the norm, but today high potency is more common.
"High potency cannabis contains less of a chemical that is believed to protect against negative side-effects, such as psychosis, and a higher level of a chemical that can trigger psychosis. In this new study, we looked at both low and high potency, but it is clear that we need more evidence from high potency-related health cases to further investigate this link in modern-day users."
Despite this, the research was clear that the more high potency cannabis used, the higher the risk of developing mental health problems, even if they are relatively low in number. For those who already had schizophrenia cannabis exacerbated the symptoms.
The greatest risk to health, however, comes from cannabis users who combine the drug with tobacco. This exposes young people in particular to tobacco dependency at an early age, increasing the chances of cancers, infections, and other health-related issues.
Previous research at York showed that regulating cannabis use could result in more effective strategies aimed at helping drug users to access the right support and guidance. The policy report illustrated, however, that there is too much uncertainly around treatment regimes in an unregulated market to target the appropriate level of care.
Mr Hamilton said: "Regulation could help reduce the risks to health that cannabis use poses, as a regulated cannabis market would introduce some quality control.
"This would provide users with information about the strength of cannabis on offer, something they usually only discover after exposure in the current unregulated market.
"The public health message about the link between cannabis and psychosis has been a difficult one to communicate, but the evidence still points to the benefits of regulations that seek to advise on the greatest potential health risks, which currently arise due to tobacco use."
https://www.sciencedaily.com/releases/2017/04/170420132334.htm
How cannabis use during adolescence affects brain regions associated with schizophrenia
May 8, 2012
Science Daily/Royal College of Surgeons in Ireland (RCSI)
New research from the Royal College of Surgeons in Ireland (RCSI) published in Nature's Neuropsychopharmacology has shown physical changes to exist in specific brain areas implicated in schizophrenia following the use of cannabis during adolescence. The research has shown how cannabis use during adolescence can interact with a gene, called the COMT gene, to cause physical changes in the brain.
The COMT gene provides instructions for making enzymes which breakdown a specific chemical messenger called dopamine. Dopamine is a neurotransmitter that helps conduct signals from one nerve cell to another, particularly in the brains reward and pleasure centres. Adolescent cannabis use and its interaction with particular forms of the COMT gene have been shown to cause physical changes in the brain as well as increasing the risk of developing schizophrenia.
Dr Áine Behan, Department of Physiology, RCSI and lead author on the study said 'This is the first study to show that the combined effects of the COMT gene with adolescent cannabis use cause physical changes in the brain regions associated with schizophrenia. It demonstrates how genetic, developmental and environmental factors interact to modulate brain function in schizophrenia and supports previous behavioural research which has shown the COMT gene to influence the effects of adolescent cannabis use on schizophrenia-related behaviours.
The three areas of the brain assessed in this study were found to show changes in cell size, density and protein levels.
'Increased knowledge on the effects of cannabis on the brain is critical to understanding youth mental health both in terms of psychological and psychiatric well-being,' Dr Behan continued.
The research was funded by the Health Research Board and Science Foundation Ireland.
Senior authors include Professor David Cotter and Professor Mary Cannon, Department of Psychiatry and Professor John Waddington, Department of Molecular and Cellular Therapeutics, RCSI. Additional authors in the study included Magdalena Hryniewiecka,
Department of Psychiatry, RCSI, Dr Colm O'Tuathaigh and Dr Anthony Kinsella, Department of Molecular and Cellular Therapeutics, RCSI as well as collaborators Professor Maria Karayiorgou and Professor Joseph Gogos from the Department of Neuroscience, Columbia University, New York.
https://www.sciencedaily.com/releases/2012/05/120508112748.htm
How cannabis causes 'cognitive chaos' in the brain
October 28, 2011
Science Daily/University of Bristol
Cannabis use is associated with disturbances in concentration and memory. New research by neuroscientists at the University of Bristol, published in the Journal of Neuroscience, has found that brain activity becomes uncoordinated and inaccurate during these altered states of mind, leading to neurophysiological and behavioural impairments reminiscent of those seen in schizophrenia.
The collaborative study, led by Dr Matt Jones from the University's School of Physiology and Pharmacology, tested whether the detrimental effects of cannabis on memory and cognition could be the result of 'disorchestrated' brain networks.
Brain activity can be compared to performance of a philharmonic orchestra in which string, brass, woodwind and percussion sections are coupled together in rhythms dictated by the conductor. Similarly, specific structures in the brain tune in to one another at defined frequencies: their rhythmic activity gives rise to brain waves, and the tuning of these brain waves normally allows processing of information used to guide our behaviour.
Using state-of-the-art technology, the researchers measured electrical activity from hundreds of neurons in rats that were given a drug that mimics the psychoactive ingredient of marijuana. While the effects of the drug on individual brain regions were subtle, the drug completely disrupted co-ordinated brain waves across the hippocampus and prefrontal cortex, as though two sections of the orchestra were playing out of synch. Both these brain structures are essential for memory and decision-making and heavily implicated in the pathology of schizophrenia.
The results from the study show that as a consequence of this decoupling of hippocampus and prefrontal cortex, the rats became unable to make accurate decisions when navigating around a maze.
Dr Jones, lead author and MRC Senior Non-clinical Fellow at the University, said: "Marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers. These findings are therefore important for our understanding of psychiatric diseases, which may arise as a consequence of 'disorchestrated brains' and could be treated by re-tuning brain activity."
Michal Kucewicz, first author on the study, added: "These results are an important step forward in our understanding of how rhythmic activity in the brain underlies thought processes in health and disease."
The research is part of a Medical Research Council (MRC)-supported collaboration between the University and the Eli Lilly & Co. Centre for Cognitive Neuroscience that aims to develop new tools and targets for treatment of brain diseases like schizophrenia and Alzheimer's disease.
https://www.sciencedaily.com/releases/2011/10/111025172633.htm
How marijuana affects the way the brain processes emotional information
April 11, 2011
Science Daily/University of Western Ontario
Drugs like marijuana act on naturally occurring receptors in the brain called cannabinoid receptors. However, the mechanisms by which these drugs produce their sensory and mood altering effects within the brain are largely unknown. Research led by Steven Laviolette at The University of Western Ontario has now identified a critical brain pathway responsible for the effects of cannabinoid drugs on how the brain processes emotional information.
The findings, published in The Journal of Neuroscience, also help to explain the possible link between marijuana use and schizophrenia.
Laviolette and his team at the Schulich School of Medicine & Dentistry discovered that activating cannabinoid receptors directly in a region of the brain called the amygdala, can strongly influence the significance of emotional information and memory processes. It also dramatically increased the activity patterns of neurons in a connected region of the brain called the prefrontal cortex, controlling both how the brain perceived the emotional significance of incoming sensory information, and the strength of memories associated with these emotional experiences.
"These findings are of great clinical relevance given recent evidence suggesting that exposure to marijuana during adolescence can increase the likelihood of developing schizophrenia later in life," says Laviolette, an associate professor in the Department of Anatomy and Cell Biology. "We know there are abnormalities in both the amygdala and prefrontal cortex in patients who have schizophrenia, and we now know these same brain areas are critical to the effects of marijuana and other cannabinoid drugs on emotional processing."
Furthermore, the findings by Laviolette's laboratory identify a novel new brain pathway by which drugs acting on the cannabinoid system can distort the emotional relevance of incoming sensory information which in turn may lead to psychotic side-effects, such as paranoia, associated with heavy marijuana use. Developing pharmacological compounds, and there already are some, that block or modify this pathway could help control psychotic episodes. It could also be used to help patients with Post Traumatic Stress Disorder who have difficulty controlling the resurgence of highly emotional events into their memory.
Laviolette's research was funded by the Ontario Mental Health Foundation and the Natural Sciences and Engineering Research Council of Canada (NSERC).
https://www.sciencedaily.com/releases/2011/04/110405174833.htm
Cannabis-related schizophrenia set to rise
March 26, 2007
Science Daily/Bristol University
If cannabis causes schizophrenia - and that remains in question - then by 2010 up to 25 per cent of new cases of schizophrenia in the UK may be due to cannabis, according to a new study by Dr Matthew Hickman of the University of Bristol and colleagues, published in Addiction journal.
Substantial increases in both prevalence and incidence of the disease are forecast by the end of the decade, with increases in schizophrenia starting earlier among young men in particular.
The research study matches historic trends in cannabis use and exposure from a national population survey against estimates of new occurrences of schizophrenia in three English cities (Nottingham, Bristol and the London Borough of Southwark).
The researchers assess what might happen to schizophrenia cases if we assume a causal link between cannabis use and onset of psychotic symptoms, an association widely recognised by some psychiatrists and researchers and considered recently by the Advisory Council on the Misuse of Drugs.
Exposure to cannabis grew fourfold over the thirty years to 2002, and its use among under-18s by 18-fold, say the researchers. If cannabis use causes schizophrenia, these increases in its use would lead to increases in overall schizophrenia incidence and prevalence of 29 per cent and 12 per cent respectively, between 1990 and 2010. (Incidence is defined as the frequency of new occurrences; and prevalence is the percentage of the population affected by the disease.)
Model projections suggest that if the association is confined to heavy cannabis users only, then approximately 10 per cent of schizophrenia cases may be due to cannabis by 2010. However, assuming an association between onset of the disease and both light and heavy users, then approximately one-quarter of new cases could be due to cannabis.
John Macleod, co-author and academic GP, said: “We need to remember that our study does not address the question whether cannabis causes schizophrenia: this remains unclear.”
Matthew Hickman, lead author of the study, added: “The challenge now is to improve our data on schizophrenia occurrence to see whether the projected increase occurs. This will tell us more about how important cannabis is as a cause of schizophrenia.”
Reference: Matthew Hickman, Peter Vickerman, John Macleod, James Kirkbride, Peter B. Jones. Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales (2007). Addiction 102 (4), 597-606.
https://www.sciencedaily.com/releases/2007/03/070324132832.htm
Long-term cannabis use may blunt the brain's motivation system
July 1, 2013
Science Daily/Imperial College London
Long-term cannabis users tend to produce less dopamine, a chemical in the brain linked to motivation, a study has found.
Researchers found that dopamine levels in a part of the brain called the striatum were lower in people who smoke more cannabis and those who began taking the drug at a younger age.
They suggest this finding could explain why some cannabis users appear to lack motivation to work or pursue their normal interests.
The study, by scientists at Imperial College London, UCL and King's College London, was funded by the Medical Research Council and published in the journal Biological Psychiatry.
The researchers used PET brain imaging to look at dopamine production in the striatum of 19 regular cannabis users and 19 non-users of matching age and sex.
The cannabis users in the study had all experienced psychotic-like symptoms while smoking the drug, such as experiencing strange sensations or having bizarre thoughts like feeling as though they are being threatened by an unknown force.
The researchers expected that dopamine production might be higher in this group, since increased dopamine production has been linked with psychosis. Instead, they found the opposite effect.
The cannabis users in the study had their first experience with the drug between the ages of 12 and 18. There was a trend for lower dopamine levels in those who started earlier, and also in those who smoke more cannabis. The researchers say these findings suggest that cannabis use may be the cause of the difference in dopamine levels.
The lowest dopamine levels were seen in users who meet diagnostic criteria for cannabis abuse or dependence, raising the possibility that this measure could provide a marker of addiction severity.
Previous research has shown that cannabis users have a higher risk of mental illnesses that involve repeated episodes of psychosis, such as schizophrenia.
"It has been assumed that cannabis increases the risk of schizophrenia by inducing the same effects on the dopamine system that we see in schizophrenia, but this hasn't been studied in active cannabis users until now," said Dr Michael Bloomfield, from the Institute of Clinical Sciences at Imperial, who led the study.
"The results weren't what we expected, but they tie in with previous research on addiction, which has found that substance abusers -- people who are dependent on cocaine or amphetamine, for example -- have altered dopamine systems.
"Although we only looked at cannabis users who have had psychotic-like experiences while using the drug, we think the findings would apply to cannabis users in general, since we didn't see a stronger effect in the subjects who have more psychotic-like symptoms. This needs to be tested though.
"It could also explain the 'amotivational syndrome' which has been described in cannabis users, but whether such a syndrome exists is controversial."
Other studies have looked at dopamine release in former cannabis users and not seen differences with people who haven't taken cannabis, suggesting that the effects seen in this study are likely to be reversible.
https://www.sciencedaily.com/releases/2013/07/130701081053.htm