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InvisibleMostly_HarmlessM
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Using marijuana as a teen could make another drug even more intense * 1
    #26638336 - 04/30/20 08:08 AM (28 days, 13 hours ago)

https://www.inverse.com/mind-body/cocaine-cannabis-study

Quote:

4.20.2020

There's extra time to reminisce about teenage 4/20s while in quarantine. But a new study may make you view those early weed experiences in a new way: Being exposed to marijuana during teen years can cause fundamental changes in the brain that make other drugs hit different, according to research conducted on rats.

This study suggests that exposure to a synthetic THC-lookalike during adolescence can reprogram key areas of the brain.

Specifically, the scientists found that exposure to a synthetic cannabinoid made adolescent rats more sensitive to the effects of cocaine, and changed gene expression in the pre-frontal cortex, an area of the brain involved in planning and complex behavior.

The prefrontal cortex is already a messy environment for teens. As some connections are strengthened and others are pruned, our executive functions (circuits in the brain that make you think twice before being foolish) are offline. Adding marijuana to the mix makes things more chaotic: Weed can negatively affect working memory and change the brain's normal development pattern in teens, previous studies suggest.

Now, researchers suggest that the effects of a synthetic cannabinoid can cause changes in the brain that ultimately makes cocaine an even more intense experience than it already is. This finding was published Wednesday in the journal Proceedings of the National Academy of Sciences.

While most studies on rats and marijuana focus on THC, this study used a synthetic cannabinoid called WIN 55,212-2 (WIN), which has similar effects to THC but has a different chemical structure.

Philippe Melas is the study's last author and a postdoctoral researcher at the Karolinska Institutet in Sweden. He tells Inverse that past studies suggest that WIN and THC have similar neurochemical changes in the brain. However, WIN does bind more strongly to cannabinoid receptors in the brain than natural THC does.

One group of pubescent rats and another group of adult rats received increasing doses of WIN for 11 days. The researchers intentionally increased the doses of the drug to replicate "heavy" cannabis use during adolescence (they describe this intent in their supplemental material).

Because of that these findings "may not apply to single or occasional cannabis use of low THC doses," Melas adds.

For these rats, the highest dose was two WIN doses of 8mg/kg per day. Then, after letting the rats dry out for a week, they gave them their first taste of cocaine.

Ultimately, the team found that the adolescent rats were "cross-sensitized" to that first cocaine dose, which means that they were hypersensitive to the effects of the drug and wild out — aka, moved around a ton in their cage.

The team doesn't go into detail about what that "cross-sensitization entails." But previous studies have shown that THC exposure during adolescence can cause rats to pick up a cocaine habit more quickly. Other studies have shown that rats become more hyperactive when they take cocaine if they've been exposed to THC first.

However, the adult rats didn’t appear hypersensitive to cocaine — even though they were exposed to synthetic THC too. This suggests that there's something unique happening when cocaine meets a teenage brain with prior exposure to THC.

The rats were sacrificed soon after their drug experiences, which allowed the researchers to look for changes in their brains that might explain their intense reactions.

While they found numerous small changes in gene expression, one of their most powerful findings was an attachment of additional chemical groups to histones (histones are collections of proteins that DNA is wrapped around).

Scientists have already proposed that cocaine use can add tiny chemical tails to these spools of proteins, which change the way genes are expressed. Those histone-related changes spike when cocaine-addicted mice are deprived of cocaine, which scientists believe may be the precursor to a drug relapse.

In this study, they saw the bulk of these changes in the prefrontal cortex (dysfunction in that area of the brain is linked to compulsive drug use).

Their results suggest that in, taken in tandem with other changes in gene expression, these changes contribute to the rats' hyperactive reactions to cocaine.

If the results hold up in humans, Melas adds that they could underpin a "favorable" reaction to cocaine for teens that use a lot of marijuana. However, this study can't prove this connection exists on its own.

Is marijuana actually a gateway drug?

It might be easy to paint these results as further evidence of a "gateway drug hypothesis" or the idea that marijuana use can cause the use of harder drugs later on. While there is evidence that some marijuana users do go on to use other drugs later on, that's not enough evidence to say marijuana use drives that decision.

"Although favorable first encounters with a drug of abuse are known to predict repeated use of that drug in the future, we need to remember that additional environmental, social or genetic vulnerabilities are also needed for an addiction to develop," Melas says.

For instance, one 2015 study found that 44.7 percent of 6,624 marijuana users went on to use other drugs. But that progression was influenced by socioeconomic demographics and psychiatric disorders. Other research suggests there are lots of reasons that people might choose to use drugs in the first place. And as other drugs come onto the radar, like cocaine, those same social or environmental factors may make using those drugs more likely too.

Marijuana may not be a gateway drug in that there's some nefarious characteristic that guides someone down the path to other drugs. Rather, it might just be more readily available, as the NIH notes.

That said, research like this study does show that weed can reshape the brain, especially during adolescence, suggesting that there is some biology to consider as well. Using a drug may not drive you to use another, but it could change the way that your brain responds to further substances.

Quote:

Abstract: The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain’s initial molecular and epigenetic response to cocaine. Here, we utilized a multiomics approach (epigenomics, transcriptomics, proteomics, and phos- phoproteomics) to characterize how the rat brain responds to its first encounter with cocaine, with or without preexposure to the synthetic cannabinoid WIN 55,212-2 (WIN). We find that in adolescent (but not in adult) rats, preexposure to WIN results in cross- sensitization to cocaine, which correlates with histone hyperacetylation and decreased levels of HDAC6 in the prefrontal cortex (PFC). In the PFC, we also find that WIN preexposure blunts the typical mRNA response to cocaine and instead results in alternative splicing and chromatin accessibility events, involving genes such as Npas2. Moreover, preexposure to WIN enhances the effects of cocaine on protein phosphorylation, including ERK/MAPK- targets like gephyrin, and modulates the synaptic AMPAR/GluR composition both in the PFC and the nucleus accumbens (NAcc). PFC–NAcc gene network topological analyses, following cocaine exposure, reveal distinct top nodes in the WIN pre-exposed group, which include PACAP/ADCYAP1. These preclinical data demonstrate that adolescent cannabinoid exposure reprograms the initial behavioral, molecular, and epigenetic response to cocaine.







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Invisiblesplit_by_nine
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Re: Using marijuana as a teen could make another drug even more intense [Re: Mostly_Harmless]
    #26638434 - 04/30/20 09:26 AM (28 days, 11 hours ago)

Quote:

Ultimately, the team found that the adolescent rats were "cross-sensitized" to that first cocaine dose, which means that they were hypersensitive to the effects of the drug and wild out — aka, moved around a ton in their cage.




:mel:


interesting study. i wouldnt mind doing a little wild'n out myself.


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OfflineHamHeadS
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Re: Using marijuana as a teen could make another drug even more intense [Re: split_by_nine] * 1
    #26640500 - 05/01/20 07:04 AM (27 days, 14 hours ago)

"This study suggests that exposure to a synthetic THC-lookalike during adolescence can reprogram key areas of the brain."

Invalid studies IMO.

Why are we working with look-a-likes?

Of course a synthetic is going to have an impact. Much more than the real thing.


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The mushroom skull fuck you or what bro :lol: don't worry in a month you'll be posting another thread just like this

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OfflineHolybullshit
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Re: Using marijuana as a teen could make another drug even more intense [Re: HamHead]
    #26640545 - 05/01/20 07:42 AM (27 days, 13 hours ago)

There is nothing invalid about the study(at least not for that reason)...upon a cursory reading I didn't see the study actually claim cannabis as having the same effect, and didn't talk about THC much at all other thank talking about the effects cannibinoids posses, thats not quite the same as claiming THC would produce the same result seen in this study...but even the title used in the article says "could".

It's a hypothesis, or a theory, it hasn't been proven but it is logical and supported by the study.

Your hypothesis is that THC won't have the same effect as the substance used in the study...I don't think it being synthetic has anything to do with it one way or the other, your body doesn't know the difference between synthetic and natural. But, THC is a partial agonist, now I don't know much about WIN 55,212-2 but if it is a full agonist or has a higher intrinsic activity or if its binding affinity is significantly higher then that "could" make a difference, especially if not accounted for when dosing the rats.

I understand the urge to defend cannabis, but its no surprise that an otherwise harmless(for adults) substance can have all sorts of deleterious effects on a still developing brain.


Edited by Holybullshit (05/01/20 09:26 AM)


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Onlinelifeiswhatyoumake
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Re: Using marijuana as a teen could make another drug even more intense [Re: HamHead]
    #26641031 - 05/01/20 12:55 PM (27 days, 8 hours ago)

Quote:

HamHead said:
"This study suggests that exposure to a synthetic THC-lookalike during adolescence can reprogram key areas of the brain."

Invalid studies IMO.

Why are we working with look-a-likes?

Of course a synthetic is going to have an impact. Much more than the real thing.





I wouldn't say the study is invalid, but I would say the conclusion of "Using marijuana as a teen could make another drug even more intense" based on this study is invalid.


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Offlinesk8fast
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Re: Using marijuana as a teen could make another drug even more intense [Re: Holybullshit]
    #26642092 - 05/01/20 09:57 PM (26 days, 23 hours ago)

Quote:

Holybullshit said:
There is nothing invalid about the study(at least not for that reason)...upon a cursory reading I didn't see the study actually claim cannabis as having the same effect, and didn't talk about THC much at all other thank talking about the effects cannibinoids posses, thats not quite the same as claiming THC would produce the same result seen in this study...but even the title used in the article says "could".

It's a hypothesis, or a theory, it hasn't been proven but it is logical and supported by the study.

Your hypothesis is that THC won't have the same effect as the substance used in the study...I don't think it being synthetic has anything to do with it one way or the other, your body doesn't know the difference between synthetic and natural. But, THC is a partial agonist, now I don't know much about WIN 55,212-2 but if it is a full agonist or has a higher intrinsic activity or if its binding affinity is significantly higher then that "could" make a difference, especially if not accounted for when dosing the rats.

I understand the urge to defend cannabis, but its no surprise that an otherwise harmless(for adults) substance can have all sorts of deleterious effects on a still developing brain.



The study used WIN55,212-2 but the article mentioned it as a THC look-alike. It might look kind of similar to THC in its chemical structure but it has a much higher binding affinity and is much different in effects compared to smoking cannabis flower as I'm sure people other than me who were in the RC community in the 00's and tried it can corroborate.


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OfflineHolybullshit
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Re: Using marijuana as a teen could make another drug even more intense [Re: sk8fast]
    #26643134 - 05/02/20 10:21 AM (26 days, 10 hours ago)

First off, I don't remember them quite saying it was a THC "look-alike"...they mostly just pointed out that they were in the same class and had similar methods of action, which is true.

But what you are saying about BA and IA "could" make a difference(as I already stated in my first post)...it also might not. Relatively low potency variations of any class of drugs generally still come with most/all the negative long term effects, caused by chronic use, of high potency agents in the same class if given enough time and high enough dosage.

If anything, it's more likely that this just means that it will take THC longer to produce the same outcomes, not that it can't happen at all.

It isn't like there hasn't already been a plethora of experiments which indicate cannabis use can have negative consequences on a still developing adolescent mind.

I get the hesitance to definitively say these results would be replicated with cannabis/THC(but that's not what either the study, or the author of the article, said)...but if we are being honest, not biased, there is much more reason/evidence to suspect that it would than it wouldn't.


Edited by Holybullshit (05/02/20 10:33 AM)


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Invisiblenooneman
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Re: Using marijuana as a teen could make another drug even more intense [Re: Mostly_Harmless]
    #26643611 - 05/02/20 02:35 PM (26 days, 6 hours ago)

So, what this article is saying is: I should have used pot as a teenager. :cookiemonster:


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OfflineFractal420
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Re: Using marijuana as a teen could make another drug even more intense [Re: nooneman]
    #26644912 - 05/03/20 02:07 AM (25 days, 19 hours ago)

You don't have to be a teen. Drop a tab and smoke, pot intensifies everything

Seriously everything but maybe K and ironically COKE lol. I dont like smoking with that stuff. I dont even like it period

But with MDMA- wow

Also synth cannabinoids like WIN aren't pot. Dont extrapolate from that and animal studies

But cannabis with esp lower doses of things makes them Much more noticeable for me. I had an acid trip I barely felt. Had one bowl. Boom


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OfflineHolybullshit
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Re: Using marijuana as a teen could make another drug even more intense [Re: Fractal420] * 1
    #26645385 - 05/03/20 09:43 AM (25 days, 11 hours ago)

They don't mean it intensifies everything while high...they mean coke will be intensified sans cannabinoid due to neuronal changes that occurred from past cannibinoid use. That's a big reason to suspect why its more likely that you would see the same thing from THC as from the synthetic used in the study...its not that getting high on WIN intensifies coke, its neuronal changes that resulted from using a CB receptor agonist...any agonism(of sufficient levels) would likely do. Although it's possible THC use would stay below the "threshold" needed to reproduce this effect, or that it would require higher doses/longer pattern of use.

But yeah, its effect on MDMA is crazy...I remember one time me and a group of friends got some pressed pills, not as many as we would have liked, and dosed but while we felt it we weren't really rolling and we didn't have any pot, but we got some like 2 hours after dosing, definitely long enough that we should have peaked but as soon as we smoked it increased the effect far more than taking more mdma would have.


Edited by Holybullshit (05/03/20 09:49 AM)


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OfflineFractal420
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Re: Using marijuana as a teen could make another drug even more intense [Re: Holybullshit]
    #26647485 - 05/04/20 07:10 AM (24 days, 13 hours ago)

Is it a CB1 agonist? I don’t really follow the synth noids, I really only tried JWH073 once, was pretty off the rails in a weird way, runaway thc train. Not 100% comfortable tho

I’m pretty sure that one was a full agonist. But I always thought, by banning them all, as much as I don’t care recreationally, I’m sure some work orally and could be potential cancer meds and such

And yeah that’s the synergy I’m talking about. It’s seemingly with most things serotoninergic, def with mushrooms, acid, all tryptamines (hell i don’t smoke after melatonin) and most things psychoactive

I knew a girl that did a lot of coke, she was born into a rich family, and she’d get NYC delivery quality ($$$) weed all the time. But she was always on coke so it would just make her feel it more. Then one day she quit for a while, smoked without the blow and got much more blazed


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

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Re: Using marijuana as a teen could make another drug even more intense [Re: Fractal420]
    #26649063 - 05/04/20 10:01 PM (23 days, 23 hours ago)

Yea stimulants barely let me feel weed unless I'm on the comedown or after


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Re: Using marijuana as a teen could make another drug even more intense [Re: sk8fast]
    #26650292 - 05/05/20 12:21 PM (23 days, 8 hours ago)

You and Fractal both clearly didn't read the OP at all because y'all are not understanding the point of the study in this thread.
Y'all are thinking too small.
Think big.
This isn't about taking two drugs at the same time.  This is about taking weed as a teen and then months, even years later, taking another drug without mixing weed with it and the effects of that drug are more pronounced than they would have been if you didn't take weed as a teen.

From the article: "For these rats, the highest dose was two WIN [synthetic cannabinoid used in the study] doses of 8mg/kg per day. Then, after letting the rats dry out for a week, they gave them their first taste of cocaine."

As you can see, they didn't mix the drugs at the same time.  They did the cannabinoid first for a week, then took a week off, then did only cocaine.

"Being exposed to marijuana during teen years can cause fundamental changes in the brain that make other drugs hit different."  This means permanent changes, not temporary.


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Invisiblesplit_by_nine
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Re: Using marijuana as a teen could make another drug even more intense [Re: lifeiswhatyoumake]
    #26651261 - 05/05/20 07:04 PM (23 days, 2 hours ago)

permanent changes, yes. but it doesnt equate to negative changes. so some teens who smoked reefer when they were 14 might possibly be more sensitive to the effects of cocaine later in life.. okay, and?

i feel like scientist could be spending their time better than giving some lucky rats synthetic weed and cocaine. its not that i dont appreciate the research, i just feel like there are bigger issues that need attention.


edit: also, two things, 1. how are the rats ingesting the drugs? i dont think they are smoking little bowls, as a teenager would do. these rats are being injected with lab-grade synthetic weed. definitely not the same as the occasional doober you had as a teen. and 2. the rats are "sacrificed" (or murdered) in order to slice the brain up and study it. i know they kill sober rats for control, but i feel like a dead brain is going to have some significant differences than a living one :shrug:


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Edited by split_by_nine (05/05/20 07:12 PM)


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OfflineHolybullshit
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Re: Using marijuana as a teen could make another drug even more intense [Re: split_by_nine] * 1
    #26651746 - 05/05/20 11:22 PM (22 days, 21 hours ago)

Are you really arguing that cannibinoid use during adolescence causes positive changes to the brain, let alone the changes observed here?

The "and", at least obviously, is that said teenagers could be much more susceptible to cocaine(and other drugs) addiction as adults. Less obviously, their executive function could be impaired affecting working memory, flexible thinking, and self-control...not to mention all the mental health issues that involve the same areas of the brain implicated by this experiment.

But, you are right about the differences in route of administration...smoking will increase CNS levels much faster than an intraperitoneal injection.

The rest of your post is pretty ridiculous..."little" bowls? "occasional" doober? Do you even hear yourself? You should at least try to keep up the pretense that you are being objective. And they are comparing they are comparing two dead brains, one from the control and one from the experiment group...I'm really not grasping whatever point you are trying to make.


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Invisiblesplit_by_nine
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Re: Using marijuana as a teen could make another drug even more intense [Re: Holybullshit]
    #26651821 - 05/06/20 12:07 AM (22 days, 21 hours ago)

my point was that main lining synthetic pot into a tiny mouse is not a fair comparison to a 14 year old that smokes weed a few times a year. little bowl or small doob.


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OfflineHolybullshit
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Re: Using marijuana as a teen could make another drug even more intense [Re: split_by_nine]
    #26652304 - 05/06/20 08:30 AM (22 days, 12 hours ago)

I guess your right, whose ever heard of a teenager who doesn't practice moderation? Also, those parts of our brain are still developing into your 20's, so I don' think just 14 year olds could still be at risk.


Edited by Holybullshit (05/07/20 09:57 AM)


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