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Marijuana exposure in utero has lifelong consequences in mice (arstechnica.com)
19 points by shawndumas on Oct 20, 2015 | hide | past | favorite | 45 comments



Shame on Ars for this clickbait trash- with "In mice at least, although humans might want to be cautious." as a subtitle it is hard to take the rest of the article seriously. Then you find out they were injecting mice with some unspecified amount of THC within Saline solution (please correct me if there is a specified amount, but I had to dig to find this at http://www.pnas.org/content/suppl/2015/10/09/1514962112.DCSu...)

"THC (THC Pharm) was diluted in 0.9% NaCl (saline) solution containing 3% (vol/vol) DMSO and 2% (vol/vol) Tween-80 and administered intraperitoneally (i.p.) at a final dose of 3 mg/kg to pregnant females for 5 consecutive days, from E12.5 to E16.5. Control mice were injected with vehicle solution."

This will be on Fox news within a week, and when it is- they will monger fear in older generations (those who typically control laws by either voting or creating bills) that are too lazy to research and come to their own conclusions.


A few of the comments on the Ars article are stating the dosage of the THC was given at 3mg/kg- but the word "dilution" along with "intraperitoneally" lets us know it was delivered via liquid injection into the gut directly. Are we sure the amount of THC injected was 3mg per kg of body weight, or was that the diluted solution (of which there was no total liquid measurement for).

This decent question asked within comments:

"Jesus, that dose. 3 mg/kg, An average mouse is 0.0192~ kg if the googles are right. A dose of edibles around 10mg for a 68kg~ (150lb) human will result in a pretty faded human, so that works out to... mm.. 0.147mg/kg if I did the math right.

So the dose being tested here is literally 20 times higher than the average dose a human will ingest. I don't know a single person who could eat 3 pot brownies a day, let alone 20. I'd be willing to wager a lot of money on 20 pot brownies a day, every day, for any length of time would be enough to cause negative health effects!

Silly question - why don't they titrate up? The amount used in this study is a massive, massive dose beyond what even a hardcore recreational user would smoke on a daily basis."-TK


Biologists routinely test with larger concentrations in order to make the effect more visible. Sometimes this creates a new effect where you overwhelm a process. Sometimes it just shortens the test and saves the lives of a lot of mice.

If you are a programmer, think of it as stress testing. I'm testing a concurrent memory allocator right now that I suspect sometimes corrupts itself. I'm hitting with an insane barrage of allocation and deallocation calls, way more than any recreational software user would ever do, trying to provoke it into failing. So far, no luck, but if I can get a failure I will have saved a great deal of time over testing it with normal call rates. On the other hand, if I tested it by just doing an insane number of allocations, I would provoke a failure completely unrelated to normal use (out of memory).


Sure ... if I found eating 60 apples per day for 2 weeks isn't a good idea, I'm not in the right to declare apples as a terrible food to avoid.


It depends, did your stomach rupture in an Alienesque scene? If so it might be specifically related to the quantity.

Did you see increased cancer incidence (granted that would be a longer study)? You might have been eating apples treated with daminozide (aka Alar, out of use in the US since 1989 but likely caused a number of cancers before then). Your larger doses exposed a rare but real effect.

The "Alar Scare" is a good example of elevated dose testing. It possibly does cause cancer, but the extreme elevated doses at which it was tested in the '80s probably exaggerated the effect.


provoke a failure completely unrelated to normal use

and so ... why bother? (wrt biology, not your programming equivalent)


You have to study the failure and the mechanism that leads to it. Then hopefully you can tell which sort you have.


The difference is your test case scenarios will not result in any policy change that could potentially lead to throwing a person in prison for an unspecified duration.

The irresponsibility shown by this, and other news outlets, allows for (potentially willfully) ignorant candidates and uninformed individuals who want to perpetuate the narrative of "Reefer madness" to do so.

The results are not conclusive regarding any human interaction, but the article states "But at a bare minimum, these findings suggest we should be avoiding recreational cannabis use during pregnancy. ". This was a clinical trial with mice, dealing with a sensitive public issue. Ars fueling the media fire by not underlining the usage of an extreme amount of the underlying chemical does nothing for our overall public health and wellness, but does (possibly unintentionally) exacerbate the drug legality discussion around the world.


A similar study was done on chimps in the late 50's. Chimps were setup with a "oxygen mask" where, instead of oxygen, marijuana smoke was present. Ultimately they reported that the marijuana smoke killed the chimps rather than asphyxiation.


Thank you for posting context where it lacks. I've thought that site has had some, well, issues for a while. Mostly when they decided it'd be a great "scoop" to go deep into their forum archives for anything and everything Snowden had said there. While it was within their rights, and an interesting story as a concpet, the execution was so tabloid and tone-deaf to criticism I figured there weren't the type of site for me.


It looks like the paper says they were given 3mg/kg THC per day for 5 consecutive days. So it does seem the dose is specified.

It's pre clinical and far from surprising but 3mg/kg is a lot of THC, the equivalent of using ~1g of strong stuff by yourself (assuming no THC is lost during consumption).


After looking up the potency of currently popular edibles, the highest dosage I could find per item was the Cheeba Chew Deca Dose(http://www.cheebachews.com/wp-content/uploads/2015/02/deca_1...) @ claimed 175mg of THC per piece (actual was 162.1). As far as I know, this is a heroic dose of THC of which the typical user would not frequent. In order to match the dosage within the mice, I'd have to eat just over 6 of these per days for a working week to produce the same results (obviously without comparing intake medium).

I understand this was to attempt to see if there were any issues that should be researched further, but the Ars article took it at face value and claimed we should (as humans) avoid during pregnancy.


Yeah I found that- but they never stated dilution amounts or total fluids given to the mice on those days, unless they mentioned it elsewhere.


I don't see why they didn't just have them consume food with oil in it, this seems like a highly unnatural delivery mechanism.

Relevant comment from Ars:

> Interesting to note... If you look at the study

> "THC (THC Pharm) was diluted in 0.9% NaCl (saline) solution containing 3% (vol/vol) DMSO and 2% (vol/vol) Tween-80 and administered intraperitoneally (i.p.) at a final dose of 3 mg/kg to pregnant females for 5 consecutive days, from E12.5 to E16.5. Control mice were injected with vehicle solution."

> DMSO is TOXIC to developing brains. Its actually recommended not to use it in studies because it causes too much damage.

> "The in vitro results suggest avoiding the use of BeOH (which also is more toxic than the other solvents in the in vivo test) and DMSO and using PEG400, EtOH and DMF even though the latter induced a body weight decrease in the B6D2F1 mouse strain. "

> http://www.ncbi.nlm.nih.gov/pubmed/8011014

> It would seem as though they purposefully paired the THC with a solvent that would cause the relevant brain abnormalities.


"So, like alcohol, another recreational drug that is legal in the US, marijuana is likely best avoided by pregnant women."

This is so refreshing to see articles made with a neutral tone about marijuana and not the usual "IT'S EVIL" talk. It's a recreational drug like any other. You wouldn't drink when pregnant, you shouldn't smoke either. Those fact shouldn't be related at all about whether the substance is legal or not.


Why shouldn't women have some alcohol when pregnant? Where's the evidence that small amounts of alcohol are harmful?

The total ban on alcohol during pregnancy is based on the precautionary principle - we know alcohol is harmful, but we don't know what a safe limit is, so we set a limit of zero.

This causes guilt and stress in mothers, and that is probably more harmful than letting pregnant women have a small glass of wine every so often.


> Where's the evidence that small amounts of alcohol are harmful?

>we know alcohol is harmful, but we don't know what a safe limit is, so we set a limit of zero.

Literally that right there. It's not like we can test on humans to find what the safe amount is, that's highly unethical, highly illegal, and will never be done. The safe amount is zero, or as close to zero as you can get. It shouldn't cause any guilt or stress on the mother: it's not impossible or even difficult to completely abstain from alcohol for nine months unless you're an alcoholic, and if you're an alcoholic, you're not going to have "a small glass of wine every so often". There's actually negative societal pressure for pregnant women drinking.

What would cause more stress and guilt? Not drinking while pregnant, or drinking some amount and then wondering if your child will be born with some birth defect because of it? Or wondering if your child's birth defect was caused by your drinking? The safe bet is just to not drink, to not smoke, to not abuse drugs.

I honestly never thought I would be seeing a discussion about how it's not fair to ask pregnant women to abstain from alcohol.


> What would cause more stress and guilt? Not drinking while pregnant, or drinking some amount and then wondering if your child will be born with some birth defect because of it? Or wondering if your child's birth defect was caused by your drinking? The safe bet is just to not drink, to not smoke, to not abuse drugs.

Just for clarity: I mean a small glass per week. I said "a small glass every so often".

There's zero chance of a birth defect from one small glass of wine a week. But women doing that will, as you say, face fierce societal condemnation whenever they drink.

> I honestly never thought I would be seeing a discussion about how it's not fair to ask pregnant women to abstain from alcohol.

It's not about whether it's fair or not. It's about whether the risks from small amounts of alcohol are greater than the risks of stress and anxiety women experience when guilt-tripped by other people.

Society has some really unpleasant judgemental attitudes about pregnant women. They're already under a load of self-imposed pressure. They don't need it from other people.


>There's zero chance of a birth defect from one small glass of wine a week.

Where's the evidence to back this up?

Here are the facts:

1. Alcohol is harmful.

2. We don't know exactly how harmful.

3. We can't test to see exactly how harmful.

The output of that is, the recommendation is zero. The recommendation is zero because any other recommendation would be arbitrary at best, harmful on average, and debilitating at worst when people realize "one drink a week" isn't backed up by any science. And the social pressure will never let up, because who knows if that is the woman's first drink of the week or her fourth drink of the day?

Yes of course people need pressure to not drink while pregnant! And even with that pressure, people still smoke and drink and do drugs while pregnant. Just like they need pressure not to speed, not to shoot up heroin, not to kill other people! That's the entire point of societal pressure, is to make people conform to activities that aren't actively harmful to society.

If you tell women "don't drink", that's a very clear statement. Easy to follow. If you say "only drink one drink per week, maybe, we don't really know", there's a non-zero chance that more women will drink more than they should than we have today. But how much is too much? No one knows. So in effect, how much is too much? Any amount.


Where's the evidence that zero os risk free? Obviously you avoid the minimal risk from tiny amounts of alcohol, but you've created other risks - you just aren't aware of them.


I replaced "alcohol" with "sex", and "drink" with "lay", and it worked out remarkably well, with appropriately humorous results.

I invite the reader to do the same.


Now try replacing "alcohol" with "a bullet through the head" and see if it's still funny. Or try doing a Google image search of "fetal alcohol syndrome". Smart asshole.


But it's ridiculous to suggest that fetal alcohol syndrome is a risk for someone having one small glass of wine per week.


Please don't do this on HN. personal attacks are not welcomed on this website.


Calling someone an asshole is not a personal attack. A personal attack is attacking someone's character instead of their argument. I'm not saying he's wrong because he's an asshole, I'm saying he's wrong and he's an asshole.


In my view - which I expect is shared by at least some others - saying that another poster is an asshole is a personal attack whether or not it has anything to do with their argument.


A personal attack is not justified because you disagree with someone. Again, please stop doing this on HN.


> it's not impossible or even difficult to completely abstain from alcohol for nine months unless you're an alcoholic

Its perhaps fairly simply to abstain from things that are legally-mandated to be labeled as alcoholic beverages.

It is not simple to completely abstain from alcohol, because alcohol is present at lower levels in things that don't meet the standards that make them legally regulated.

Without knowing the actual relation between alcohol consumption and effects on fetal development, its true you don't know whether abstaining from occasional, small quantities of things legally labeled as alcoholic is necessary -- but you also don't know if complete abstention from things legally labeled as alcoholic is a sufficient degree of abstention from alcohol, or whether it is worthwhile (in cost/benefit terms) to exercise additional vigilance in terms of other products which contain alcohol but at lower levels than meet the legal standard for labeling.


"Alcoholic beverages" are not the only things a doctor tells a pregnant woman to abstain from. There is a huge list of things that are much harder to avoid, like soft cheeses or a cat's litter box.


> "Alcoholic beverages" are not the only things a doctor tells a pregnant woman to abstain from.

I am quite acutely aware of that, but what's your point?


If you're pregnant, do the things your doctor advises you to do. Don't try to make up the rules as you go along. Just because vanilla extract contains a negligible amount of alcohol doesn't mean a six pack of Natty Ice is okay.

That's my point. I'm still not 100% sure what yours was.


> If you're pregnant, do the things your doctor advises you to do. Don't try to make up the rules as you go along.

The issue of absence of science on which to base certain recommendations affects doctors providing advice as much as pregnant women making up their own rules as they go along.

> Just because vanilla extract contains a negligible amount of alcohol doesn't mean a six pack of Natty Ice is okay.

Vanilla extract doesn't contain a negligible amount of alcohol (its typically 35% ABV, Vodka is 35-50% ABV -- homemade vanilla extract is typically vodka in which vanilla beans have been soaked for an extend period of time, and then removed); its just typically used in small quantities.

> doesn't mean a six pack of Natty Ice is okay.

No one in this thread has suggested that. What has been suggested is that:

(1) Science making clear the impact of different levels of alcohol consumption in pregnancy isn't clear (and guidance from medical sources based on that lack of science is, unsurprisingly, mixed, though government guidance in the US and most other countries is fairly consistently for complete abstinence.) [0]

(2) Complete abstention from alcohol (vs. complete abstention from things labelled as alcoholic beverages) isn't easy.

[0] And, while it hasn't been discussed previously, in the thread, there's even some controversy over whether the research establishing the correlation between "Fetal Alcohol Syndrome" (which is relatively rare even among children of women who drink heavily in pregnancy) and alcohol consumption actually establishes causality (there are strong reasons to think that,at a minimum, there are other factors at play, and its not impossible that alcohol may not be a cause at all -- the much higher rates some studies have shown in FAS among children of heavy-drinking low-income mothers vs. heavy-drinking high-income mothers, along with the fact that FAS symptoms are sometimes seen in children of women who completely abstain are suggestive that alcohol consumption is neither a necessary nor sufficient cause of FAS, and may even just be something that happens to frequently happen alongside the things that are the actual risk factors, such that controlling alcohol consumption isn't actually useful in preventing FAS.)


And literally my last word is:

"If you tell women "don't drink", that's a very clear statement. Easy to follow. If you say "only drink one drink per week, maybe, we don't really know", there's a non-zero chance that more women will drink more than they should than we have today. But how much is too much? No one knows. So in effect, how much is too much? Any amount."


Why would you risk it? You're talking about risking lifelong diminished brain function (and more) in an innocent human being just because you can't resist getting high off drugs (which is exactly what drinking is) for 9 months.

We know at the micro level that alcohol is damaging to fetuses. The failure of survey studies to find that effect across a population for very moderate amounts of alcohol could speak more to the limitations of those kinds of studies than to the lack of risk. Like a lot of things involving pregnancy, we don't know and we encourage people to err on the side of caution because the person who stands to suffer greatly is someone else, someone else who can't stand up for themselves.

I don't buy the guilt and stress argument. Parenthood is a very serious responsibility that requires making tough choices. Abstaining from toxins that could be damaging to the child during pregnancy is just one of the first. Women are fully capable of accepting this responsibility. To claim otherwise is to not treat them as fully responsible adults.


There are some recent articles going around the web about alcohol during pregnancy. Paediatricians say not to drink.

http://www.npr.org/sections/health-shots/2015/10/19/44993131...


Everyone says not to drink. But show me the evidence. That article, like I said in my post, talks about precautionary principle.

The evidence around mild drinking - one small glass once a week - is weak at best.


Agreed. My first thought when I saw the article was: "Yay, scientists are finally able to do some legitimate research on marijuana"


except you can second hand inhale it, so there is an additional concern. That same concern occurs when you have children around. How much THC is in second hand smoke, let alone carcinogens and pollutants?


I haven't seen data for THC, but for regular smoking: after smoking inside restaurants and bars was banned in Norway, the frequency of waitresses giving birth prematurely or giving birth to babies weighing less than 1500g was significantly reduced [1].

[1] http://www.econstor.eu/bitstream/10419/67237/1/730406490.pdf


It's pretty intellectually difficult to extrapolate effects from heavily dosing pregnant mice into effects from microdosing pregnant humans.

By which I mean your comment has no logical basis, only an emotional one.

I explain this only so you understand the downvotes.


Is it? When I was a kid second hand cigarette smoke was considered harmless. It certainly isn't today. We just don't the research because of restrictive laws banning it for the most part and the pro-pot acitvists disingenuous commentary about how "safe" it is.

I feel like any politicized recreation substance will go down the path of cigarettes. Fanboys will claim its neutral, if not good for you, and then eventually the science and bias will shake out about its dangers. For example, we do know there's an increase for mental illness an decrease in IQ in kids who habitually smoke pot:

https://today.duke.edu/2012/08/potiq

Among a long-range study cohort of more than 1,000 New Zealanders, individuals who started using cannabis in adolescence and used it for years afterward showed an average decline in IQ of 8 points when their age 13 and age 38 IQ tests were compared. Quitting pot did not appear to reverse the loss either, said lead researcher Madeline Meier, a post-doctoral researcher at Duke University. The results appear online Aug. 27 in PNAS.

The key variable in this is the age of onset for marijuana use and the brain's development, Meier said. Study subjects who didn't take up pot until they were adults with fully-formed brains did not show similar mental declines.

---

So yes, pot can be harmless for a 21 year old, but not for a 15 year old. I'm all for legal pot, but only at age 21 or higher. I don't think the especially libertine attitudes we're seeing via web culture are helping. Its not harmless for certain age groups. We don't know enough about the brain and pot to make these types of assessments. Erring on the side of caution is the only rational path here and that includes making sure pregnant women aren't exposed to pot smoke.


Where I am from, people will not smoke tobacco when there are pregnant women or children in the room. Surely people won't be smoking marijuana either in those situation.


I'd highly recommend listening to this experiment on how this truly works when considering epigentics:

https://youtu.be/9DAcJSAM_BA?t=1764


Fantastic suggestion- I enjoyed this immensely. Thank you.


Your welcome. The whole field of epigentics is turning everything we know about biology on its side. It's amazing.




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