Psychedelics

How marijuana can harm teenage brains, and what may be done to prevent the damage

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It was discovered in mouse experiments that anti-inflammatory drugs could protect against any potential cognitive damage from THC administered at a young age
Neurons (red) in the brain's hippocampus. Inhibitory signals (green) that suppress the neurons from firing are located in the synapses – the junctions where the neurons connect and communicate with each other. On the left is a healthy brain and on the right is a brain treated with THC showing fewer inhibitory signals
Pletnikov lab
It was discovered in mouse experiments that anti-inflammatory drugs could protect against any potential cognitive damage from THC administered at a young age

In a compelling new study, researchers at Johns Hopkins Medicine have established a fascinating hypothesis attempting to explain how marijuana use in some teenagers can result in cognitive impairment in adulthood. The research also suggests anti-inflammatory therapies may be able to prevent the marijuana-induced brain damage.

"Now that marijuana is moving toward widespread legalization and recreational use, it's important to learn more about why it's not harmless to everyone," says co-senior author of the new research, Atsushi Kamiya. "There's still a lot that we don't know about how pot specifically affects the brain."

Several studies have confidently linked adolescent marijuana use to certain cognitive impairments in later life. However, the connection has not been consistent across all research leading many scientists to suspect there must be an underlying genetic component that amplifies the adverse effects of the drug. This would explain why some people can smoke marijuana as a teenager with no adverse effects in later life while others may develop memory impairments or suffer from metal health issues.

To try and better understand how marijuana can trigger cognitive problems the researchers began by focusing on a specific mouse model genetically engineered to have a mutation in a gene called DISC1. The effects of a mutation in DISC1 were first discovered in a family found to have a major heritable history of schizophrenia, bipolar disorder and major depression. So, for this new research the mutated gene acts as a good bellwether for studying whether THC amplifies its effects.

The first stage of the research revealed that when the DISC1 mice were administered THC in their adolescent stages, they went on to display enhanced cognitive deficits in later life, compared to animals not administered THC. The next step was to home in on what specific brain cells and genes were activated after THC exposure that could be associated with the worsened cognitive effects.

It was discovered that cognitive problems in the mice only developed when THC exposure triggered the mutated DISC1 gene in astrocyte cells in the brain. Astrocytes are important star-shaped glial cells that surround, and protect, neurons in the brain. Alongside this revelation the researchers discovered that 56 genes specifically related to inflammation were seemingly catalyzing the cognitive problems in relation to THC exposure.

Neurons (red) in the brain's hippocampus. Inhibitory signals (green) that suppress the neurons from firing are located in the synapses – the junctions where the neurons connect and communicate with each other. On the left is a healthy brain and on the right is a brain treated with THC showing fewer inhibitory signals
Pletnikov lab

What all this fundamentally means is that exposure to THC seems to be increasing inflammation in astrocyte brain cells, and in the presence of a specific genetic mutation, this ultimately results in brain damage and cognitive dysfunction.

"The inflammation we saw in our mice is probably activated in many people who smoke marijuana, but our results may help explain why and how some mice – and some people – are genetically predisposed to experience an enhanced inflammatory response and brain damage," says Mikhail Pletnikov, a researcher working on the project.

To test this hypothesis further the researchers restaged their experiment, but this time administered the DISC1 mice with an anti-inflammatory drug before the animals were treated with THC. The results were incredibly compelling, with the mice tested for memory or cognitive impairments later in life and displaying absolutely no signs of brain damage. The anti-inflammatory agent essentially protected the animal's brain from THC-mediated damage in adolescence.

"If our results turn out to be applicable to people, they suggest we could develop safer anti-inflammatory treatments to prevent long-term consequences of marijuana use," notes Pletnikov.

Developing a drug that protects against the potential negative effects of adolescent marijuana use isn't the primary goal of this research, though, the more pressing outcome is to better understand and identify those young people that are most at risk from the harmful effects of marijuana. The next step for this research is to further investigate the different genetic vulnerabilities that amplify marijuana's harmful cognitive effects, and hopefully be able to better target the teenagers that are most susceptible to these effects.

The new study was published in the journal Biological Psychiatry.

Source: Johns Hopkins Medicine

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9 comments
Kolja Lehmann-Muriithi
Hmm, curious that anti-inflammatory drugs prevented cognitive impairment by THC, since THC is itself an anti-inflammatory drug. Surely this is not a satisfying explanation. But then it is only in genetically modified mice after all. Cannabis users should be safe anyway, as long as there is also a sizeable portion of CBD in their grass, since this is also a powerful anti-inflammatory drug, as can be seen from various scientific reports, e.g. here: https://www.ncbi.nlm.nih.gov/pubmed/23851307 So, Mr Pletnikov, there is really no need to develop a solution to this fabricated problem, since nature provides it all in one package, when you use the whole plant instead of isolated or chemically synthesized compounds. There is not much of a profit to be made from these compounds for the drug companies wanting to cash in on Marihuana use then, of course...
Aross
As we have all known for years this stuff will fry your brain. Now our government has made it legal and caused the creation huge business opportunities including the conversion of many food producing green houses to the more lucrative drug producing business. and now to prevent some of the damage we have added new business for the drug giants. All of this wonderful new stuff for the benefit of business in profits, the government in taxes and all at the cost of a few young unsuspecting brains of our youth who are only looking for a few moments of happiness.
DasFluchen
Thumbs Up to Kolja Lehmann-Muriithi. I was going to comment the same but you beat me to it.
With 12 years of data warehousing experience in clinical trials, I always have a hard time "buying" into some of these studies. Were they using pure THC w/out CBD? What was the (Not So) randomization criteria of the mice? What factors/sign & symptoms that were NOT recorded/used when considering the outcomes?
That's way lots of studies are debunked or overturned because it's hard to know before ... Like coffee is good to drink one month and bad the next. It's not that's it's an all or nothing but the studies are for 2 very different things. Good for one thing and bad for another.
Or the study could just be complete garbage with fake data. Like the vaccine-autism studies by Mister Andrew Wakefield. Yes, it was Dr Wakefield but he made it all up, more or less. The UK pulled his medical license. Yes same fraud that has a following of anti-vaxers like Jenny McCarthy!!!
Douglas Bennett Rogers
Cigarette smoking is almost passe but marijuana smoking is taking off. The only difference is THC vs. nicotine. Both of these have their problems but the big culprit is the smoke. Highly carcinogenic smoke from cigarettes is bad but the same, or worse from marijuana cigarettes is good!
Captain Danger
I have a novel way of preventing brain damage from drug use. Just say No!
ljaques
Kolja seems to be on the right track here. I wonder if the scientists are trying to come up with a reason for the cognitive lapse which doesn't somehow point to the lame indoctrination kids are getting in school nowadays. They are being taught to =avoid= life experiences which would otherwise expand their awareness and curiosity; being taught to avoid debate which would create those extra pathways in their brains which lead to greater insight. The current curriculum is creating these problems, not the pot, although too much smoke for too long has always created a few of these dimbulbs. Just ask Mr. Orwell.
Wolf0579
It sure is easy to spot the people who have been through the US brainwashing program. I've been using marijuana for approx. 45 years. Started smoking pot when I was 12. I am now 61, and I'm just starting to have memory lapses commonly associated with aging. In other news, I'm still waiting for one of those free "trips" the government was always promising me from LSD... I feel cheated somehow.
Robert in Vancouver
Wolf0579, you say you don't have any brain damage even though you smoked pot since 12 years old? I'll bet anything that if you had a proper medical review of your brain you would find significant damage.
warren52nz
@Captain Danger. "Just say No!" That's like telling women that just saying no prevents pregnancy. The "Just say No" approach isn't that useful in the real world.