How Cannabis Use During Adolescence Affects Brain Regions Associated With Schizophrenia

[nabraxas]

ScienceDaily (May 8, 2012) — 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 regionsassociated 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.

 

www.sciencedaily.com/releases/2012/05/120508112748.htm

[shruman]

Surely they could have somehow worked the word 'mice' into the article if not the title but it probly would not have given them the sensationalist effect they were looking for.

"Chronic Adolescent Exposure to Delta-9-Tetrahydrocannabinol in COMT Mutant Mice: Impact on Indices of Dopaminergic, Endocannabinoid and GABAergic Pathways

Áine T Behan, Magdalena Hryniewiecka, Colm M P O'Tuathaigh, Anthony Kinsella, Mary Cannon, Maria Karayiorgou, Joseph A Gogos, John L Waddington and David R Cotter

Abstract

Cannabis use confers a two-fold increase in risk for psychosis, with adolescent use conferring an even greater risk. A high-low activity polymorphism in catechol-O-methyltransferase (COMT), a gene encoding the COMT enzyme involved in dopamine clearance in the brain, may interact with adolescent cannabis exposure to increase risk for schizophrenia. The impact of such an interaction on central neurotransmitter pathways implicated in schizophrenia is unknown. Male mice with knockout of the COMT gene were treated chronically with delta-9-tetrahydrocannabinol (THC) during adolescence (postnatal day 32–52). We measured the size and density of GABAergic cells and the protein expression of cannabinoid receptor 1 (CB1R) in the prefrontal cortex (PFC) and hippocampus (HPC) in knockout mice relative to heterozygous mutants and wild-type controls. Size and density of dopaminergic neurons was also assessed in the ventral tegmental area (VTA) across the genotypes. COMT genotype × THC treatment interactions were observed for: (1) dopaminergic cell size in the VTA, (2) CB1R protein expression in the HPC, and (3) parvalbumin (PV) cell size in the PFC. No effects of adolescent THC treatment were observed for PV and dopaminergic cell density across the COMT genotypes. COMT genotype modulates the effects of chronic THC administration during adolescence on indices of neurotransmitter function in the brain. These findings illuminate how COMT deletion and adolescent cannabis use can interact to modulate the function of neurotransmitters systems implicated in schizophrenia."

http://www.nature.com/npp/journal/vaop/ncurrent/full/npp201224a.html

[∂an]

maybe it is a bit sensationalist, but cannabis use during adolescence does seem risky for some individuals. There are more than a few stories of teenagers developing schizophrenia who also used/abused cannabis. I certainly would encourage my kids to wait until they are 18 at least before indulging.

[shruman]

I think they could have also worked the word 'chronic' in there aswell.

Anybody have acces to the article?, could you let us know just how chronic the levels of THC administered were?

Also THC is a long way from Cannabis which contains a large array of cannabinoids not just THC.

Fair enough kalika, I think its tricky, waiting until kids are 18 before they use alcohol does not seem to have a positive effect in our society, as once kids turn 18 it seems to be a mad rush to make up for lost time or something. I think educating & maybe even some level of exposure done in the correct way with the emphasis on use not abuse to children might lessen some of the adverse effects of drugs. It seems to work much better in france with alcohol for instance.

Edited May 9, 2012 by shruman

[∂an]

yeah it is tricky, if we say no weed until your 18 then kids will drink instead. i agree the attitude to substances, both legal and illegal, does seem better in europe where alcohol is much more casually policed. seems to say that if you treat young people with respect, they respond with better choices. i guess really any chronic drug use in adolescence is a bad thing, whether it be weed, alcohol or psychedelics. the current prohibitionist model seems to encourage abuse of all drugs from an early age. maybe our modern society lacks an authentic initiation tradition that teaches the true power of these substances from an early age?

[∂an]

bring back the iboga banana!

[nabraxas]

It does seem to be a complicated issue.

contrary to some beliefs, the stricter control of consumption of alcohol in teens in America has not translated into a "forbidden fruit" type mentality where American teens drink more and experience more problems than other countries that have a weaker control on alcohol sales and consumption.

Alcohol statistics in Europe say that teens coming from homes that had no alcohol and were not taught how to drink responsibly had more issues with alcohol. Also, 33% of the teens who said that they bought their own alcohol, were six times more likely to drink in a public space, 3 times more likely to drink frequently and twice as likely to overindulge on alcohol. The behavior in these teens was less risky if parents allowed them to drink in the home.

Amongst the imposed measures that had an effect is a legal drinking age which has substantially reduced drinking by teens. As a direct result, it reduces drinking-related injuries amongst teens, but also the risk of alcohol abuse and dependence later in life. Thus, having a legal drinking age has greatly reduced consumption of alcohol in teens.

Another alcohol related problem in Europe is binge drinking. Alcohol statistics in Europe did recently reveal that binge drinking is a current problem among teens. This is because legal drinking age in Europe is mostly 18. A possible solution is to extend the teen alcohol drinking limit until they are 21 years of age.

Recent alcohol statistics have shown that binge drinking has decreased by 12 percent when 21 was adopted as the legal drinking age in some countries.

The United States Department of Transportation also concluded that imposing a minimum drinking age law, by itself, has played an important role in reducing both teen drinking and driving after drinking.

A member of the European Health Department said that they are currently working with the alcohol industry to persuade the responsible production and sale of alcohol in teens

 

http://alcohol-statistics-in-europe.own69.com/alcohol_in_teens/

[chilli]

Cannabis use at any age causes changes in brain chemistry, and heavy use during adolescence is almost certainly not a good idea.

But correlation does not equal causation. One issue to consider is that adolescents who are using Cannabis at a young age are more than likely to come from a situation that predisposed them to mental health issues later in life anyway.

But the strongest evidence against any causative link is the simple fact that if Cannabis use caused schizophrenia, there should be an increase in the incidence of schizophrenia in times/places where there is an increase in the use of Cannabis, but statistics show there is not. The incidence of schizophrenia remains stable at roughly 1% percent of the population between cultures and throughout history, regardless of differences in Cannabis use.

For example:

Frisher and colleagues compared the trends of cannabis use with general practitioner records of schizophrenia.

They argue if cannabis use does cause schizophrenia, then an increase in cannabis use should be followed by an increase in the incidence of schizophrenia.

According to the study, cannabis use in the UK between 1972 and 2002 has increased four-fold in the general population, and 18-fold among under-18s.

Based on the literature supporting the link, the authors argue that this should be followed by an increase in schizophrenia incidence of 29% between 1990 and 2010.

But the researchers found no increase in the diagnosis of schizophrenia or other psychotic disorders during that period. In fact some of the data suggested the incidence of these conditions had decreased.

"This study does not therefore support the specific causal link between cannabis use and the incidence of psychotic disorders," the authors say. "This concurs with other reports indicating that increases in population cannabis use have not been followed by increases in psychotic incidence."

 

Source: http://www.abc.net.au/science/articles/2009/09/01/2673334.htm

No doubt, Cannabis can trigger an early psychotic episode in those who already have a genetic predisposition to schizophrenia, but this is not causation, but uncovering of a latent mental illness that almost certainly would have occurred at some point regardless of Cannabis use.

[Zen Peddler]

COMT seems like a pretty random target. is the gene epigeneticaly altered or how is it 'activated'. Why do they think that it relates to changes in dopamine specifically when COMT has pretty wide ranging catabolic actions - including in the peripheral ANS.

I dont know about weed. I know heaps that have smoked it heavbily for years without any ill effects and others that have either lost it almost instantly (well one kid) and about four that over longterm lost it (one dude bashed his wife and went to jail, another eventually developed psychosis with no known family history, etc)

Maybe they were predisposed, maybe it brought it out in them. hard to say, but its sad what happened to at least two of these guys. Lots of potential lost.

that being said the stuff is quite amazing in some ways.

Edited May 9, 2012 by Zen Peddler BlueGreenie

[SunChaser]

When my grandparents were adolescents, using cannabis recreationally was unheard of in Australia, but now it’s like a right of passage, Australia now has one of the highest rates of cannabis use in the world.

So if there were any truth to these claims, we would have seen a major rise in permanent psychosis within the Australian population over the last 50 years. Obviously no such rise has occurred, in fact the rate of schizophrenia in Australia is about the same as countries who have a very low rate of cannabis use.

I don’t think anyone would argue that adolesants abusing cannabis is a good thing, but the same could be said about any drug.

Also, maybe the people who abused cannabis as teenagers and now just sit around in a cloud of smoke all day as adults, would have been doing the same thing with alcohol 50 years ago?

I personally believe the abuse of any substance is a symptom of mental illness, rather than a cause. I think its incrediblly ignorant to think a completely healthy person would decide to spend there days constantly being pissed or high.

[Pat Uri]

Agreed - funny how the majority of these adolescent paranoid schizophrenic adverse reactions only seem to occur in countries where cannabis is illegal.

Compare to Hindu Holi festival - where everyone, young and old, drink bhang and feel the embrace of Krishna - it doesn't 'fill the psych ward' when they celebrate it.

In the West there's less freak outs now there is not so much meth - that converts to some para-methoxyamphetamine, that takes months to leave, causes much of the amphetamine toxic psychosis and I suspect is amplified by strong weed.

Please to read http://www.ndsn.org/jan96/lancet.html The famous Lancet Editorial Advocate the Decriminalisation of Cannabis - well worth printing, framing and hanging on the wall.

But to smoking weed per se:-

I've known tradespeople (chronic smokers since teens) who excel at their craft - their craft yes, algebra no.

Forced to give up months for employment testing, and not a second more (bhongs packed in cars outside the pathologist), they complain there is no improvement in memory, concentration or motivation at all to suggest their years of devotion to the Good God Jai have much affected them.

Sure they go without - drink more - but the whole time stare at your consumption while licking their lips eerily with the strange haunted look of a pedophile at a Wiggles concert.

Edited May 10, 2012 by Pat Uri

[Zen Peddler]

In the West there's less freak outs now there is not so much meth - that converts to some para-methoxyamphetamine, that takes months to leave, causes much of the amphetamine toxic psychosis and I suspect is amplified by strong weed.

 

It also downregulates D2 receptors in some regions of the brain that do not seem to upregulate when the drug is removed...

[CβL]

Well, it's too late for me...

But I would also like to know what the dosages were, and how often they were administered.

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 regionsassociated 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.

I acknowledge that these quotes come from the abstract of the report, but where do these two statements come together? Is the latter true, and the former a possible implication of the latter?

Edit:

but the whole time stare at your consumption while licking their lips eerily with the strange haunted look of a pedophile at a Wiggles concert.

BAHAHAHA!!

Edited May 10, 2012 by βluntmuffin

[Shamanistic]

A small group of friends indulge in a toke or two a day and I have to say that the majority of them I've not noticed any negative changes to their personality. However I do know two people who were a little 'unstable' before using cannabis and since they've started smoking their periods of instability are worse. Both of these people I would say were going to have problems down the line anyway, so you couldn't blame marijuana. It's also a little difficult to judge if it's marijuana which has made their problem worse because they've both gone through periods of fairly heavy amphetamine use which I'd say would be much worse long term than Mary Jane.

Pat,

I would actually have to disagree with you saying that methamps aren't as prevalent because it seems to be the main party drug going around my area these days. Ecstacy used to be everywhere but not anymore it's all meth based. One day a friend was talking about eating mescaline cactus and one friend said that they'd never do that because they don't know what's in it and continued to dip his finger into his bag of pale blue powder..oh the irony.

[nabraxas]

Ecstacy used to be everywhere but not anymore it's all meth based.

used to be the same for me.

when MDMA first burst onto the scene, other amphetamine use dropped.

Consequently speed prices dropped & it started to become stronger, morphing into crystal meth.

I wonder if it's renewed popularity will cause a price increase & drop in purity/strength?

Edited May 17, 2012 by nabraxas

[ThunderIdeal]

it's like this, IMHO. often people that sell speed are in the habit of using it more than a couple of times a week (which is just ridiculous on several levels). they have a dance with their customers, the goal is to extract maximum payment from their customers while handing over minimum purity.

prices with everything seem to fall within an accepted maximum and minimum. in the case of ice, if you show that you will hand over money for crud, then crud is what you'll get.

buyer beware.

what i'm saying is that it's a market at work, only this end of the market is about as conniving as it gets owing to certain factors eg ethics fade further into the background. yeah things like mdma and heroin availability have an effect, but if you don't hand over money for crud then how can purity possibly drop?

Edited May 18, 2012 by ThunderIdeal

[ThunderIdeal]

upsy daisy

Edited May 18, 2012 by ThunderIdeal