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Jordan Gaines
Neuroscience
Pennsylvania State University USA

A blog on biology, psychology, cognition, learning, memory, aging, and everything in between. Explaining recent discoveries in neuroscience, translated to language we can all understand!

My posts are presented as opinion and commentary and do not represent the views of LabSpaces Productions, LLC, my employer, or my educational institution.

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Friday, June 15, 2012

Call me a prude, but I'm not so thrilled about the announcement made yesterday by British Columbia's top health official that ecstasy is "safe."

Dr. Perry Kendall asserted yesterday that the health risks of 3,4-methylenedioxymethamphetamine—or MDMA, the active ingredient in the drug ecstasy—are exaggerated, and that pure ecstasy is not dangerous when consumed responsibly by adults.

Its lethal dangers arise, he says, when gangs pollute the drug with other chemicals.

I'm not sure when the notion came into play that anything which doesn't kill you automatically means its "safe," but I would like to respectfully debunk Dr. Kendall's remarks with a very powerful and striking study published 13 years ago.

 
 Ecstasy, best known for its recreational use among the "rave" scene, can induce euphoria, diminished anxiety, and a sense of intimacy with others.

Specifically, MDMA induces release of the neurotransmitter serotonin by causing serotonin-containing vesicles to dock and enter the synapse. Higher-than-normal serotonin levels can result in neurotoxicity in the brain.

What, exactly, causes the euphoria from MDMA is not entirely clear; other drugs that release serotonin, such as fenfluramine, do not have this effect.

Remember those old "Just Say No" PSAs from the late '80s championed by First Lady Nancy Reagan? "This is drugs." An egg cracks into a sizzling skillet. "This is your brain on drugs. Any questions?" The commercials were short, memorable, and got the point across, albeit lacking scientific support. Who cares about the science with such a powerful visual, anyway?

 
How's this for a scientific visual: in 1999, the Journal of Neuroscience published a study by Johns Hopkins researchers examining the effects of short-term MDMA use on the brain over the long-term. In other words, can a single weekend of hard partying result in deficits years down the road?

Hatzidimitriou and colleagues injected 5 mg/kg MDMA (pure MDMA—just as Dr. Kendall assures is "safe") in squirrel monkeys subcutaneously twice a day for four days. That's about the equivalent of an average 150 lb. person consuming 3 ecstasy tablets per day.

The researchers then examined serotonergic neurons (neurons that release serotonin) in the cortex of the brain over time by staining the cells with an antibody for visualization. The results were astounding:

Two weeks after just four days of ecstasy use, there is a highly significant reduction of serotonergic neurons in the cortex (middle panel) compared to control. Terrifying, right? It gets worse. Just look at the effects after seven years of recovery (right panel)—still a marked reduction in neurons.

Short-term physiological effects of MDMA include increased heart rate, blood pressure, and body temperature; blurred vision; sweating; loss of appetite; nausea; and jaw-clenching. Overdose can cause paranoia, hallucinations, hemorrhage, fainting, and organ failure.

Sure sounds like "ecstasy" lives up to its name, right?

Currently, clinical trials are testing the therapeutic potential for controlled MDMA in anxiety disorders such as post-traumatic stress disorder (PTSD) and the anxiety associated with terminal cancer.

Dr. Kendall's statement comes after a string of 16 death in British Columbia since last July associated with a tainted batch of ecstasy containing the toxin PMMA. The health official wants to explore legalization of the drug, asserting that he is "quite a strong critic of prohibition" in that it doesn't do "much to reduce harmful use" or put "billions of dollars into the hands of criminal enterprises."

On a socio-economic level, he has a point. But...safe? Ecstasy is safe?

Let's make sure citizens are getting the facts before we tell them what they want to hear.

Photos courtesy Bassam Loucas, Wikipedia, Drugs Forum, and CBC. Video courtesy pushthefire (YouTube). 

Hatzidimitriou G, McCann UD, & Ricaurte GA (1999). Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. The Journal of neuroscience : the official journal of the Society for Neuroscience, 19 (12), 5096-107 PMID: 10366642

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Daniel

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Study Questions Toxic Effects of MDMA in Monkeys

New findings suggest that when use patterns are more similar to humans, brain toxicity no longer detectable

http://www.maps.org/sys/w3pb.pl?mode=show&type=review&r_id=1


Cynthia McKelvey
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Great article, Jordan! I think you raised a really good point. Simply declaring any drug "safe [in moderation]" isn't very helpful to the public. Knowledge is power, and you really put the facts out there. On the other hand, I do raise issue with the study's definition of "moderation." I don't believe most people would consider a three doses of ecstasy within a weekend to be moderation. It sounds more like a bender to me. But perhaps I'm giving most people too much credit for understanding the idea of moderation.

I would like to maybe re-open and expand this topic in my blog. I'm currently doing the research for it now. But I think MDMA and other psychedelics are really fascinating, and are often misrepresented in the media. This is not to say that MDMA is not a dangerous and a popular club drug with harmful long-term effects, but I'd like to give due process to the potential thereputic benefits of psychedelics that you mentioned in your article, and I'd be interested to hear what you think.


Jordan Gaines
Pennsylvania State University
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Hey Cynthia, I think this would be a great idea and I'd love to hear your perspective!

I'm actually guest-blogging at Scientopia this week. I cross-posted this blog on Tuesday, and it's received some insightful comments. You might find it interesting: http://scientopia.org/blogs/guestblog/2012/06/26/ecstasy-safe/

Sethers McGee

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Ms. Gaines, 

     I like how you simply skipped right over Daniel's comment and link at the top and responded only to Cynthia's comment!  Great dodge there!  Care to be a big girl instead?  Here I'll give you another chance and ask you directly: in light of the fact that the study you cited has been exposed as complete non-sense, is there any evidence at all to suggest that pure ecstacy taken in moderate doses is "terrifying"?

     Of course, I knew that your study was pure comedy before I even saw Daniel's post/link.  Who on God's green earth takes 3 doses a day for 4 days straight?  In fact, what normal ecstacy user takes any dose for 4 days straight?  Of course, everyone knows someone ridiculous but the real life facts are pretty simple: it doesn't work the next day.  If it did, you'd have ecstacy junkies camped out in front of the bus station.... but you don't.  This is why it's non-addictive.  This is part of the reason why it can be safe.

     I get the feeling like you'd have known this if you hadn't already had a formed opinion before starting this blog.  The same research you've quoted hints at what other studies have found time and again: there isn't enough seratonin the next day to do anything for you.

     All of this is completely beside the point anyway.  The only relevant question is whether you want people to have access to actual ecstacy or whether you prefer that they take their chances with the street stuff?


Jordan Gaines
Pennsylvania State University
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Hi Sethers McGee,

Thanks for giving me a chance to be a big girl. I have read what Daniel posted several times now and have talked to a number of drug researchers and drug policy reformers since writing this post. I maintain my "opinion" which is simply: the data are the data.

When you say that Hatzidimitriou's study has been "exposed as complete nonsense," are you referring to the dosage, or something else? Can you clarify?

Four Hatzidimitriou studies were recalled years back due to the use of methamphetamine instead of MDMA (due to a mislabeled commercial purchase, they say), but this was not one of those studies. Not sure if you were alluding to that?

I made no comment regarding whether I believe ecstasy should be legalized. I'm not well-informed in drug policy nor have any relevant social statistics up my sleeve—my aim was to present counter-data and explain the neurobiology of MDMA. Drug users tend to focus on the politics, not what's actually happening to their bodies. When they hear what they want to hear ("it's safe!" "legalize it!"), and especially from a health official, they latch onto it. Responsible drug users can buy test kits online very easily, but the average person does not do this. The point I was trying to make was: whether or not people have access to pure MDMA or the toxic street stuff, we need to re-think the definition and usage of the word "safe," especially when informing the public. 

People have different ideas of the word "safe," which is the issue. You say MDMA is non-addictive, which is still up for debate in both animal and human studies. While perhaps not biologically addictive, it clearly makes people feel good, which is grounds for psychological dependence. Either way, being non-addictive doesn't necessarily make it safer—it may just result in comparatively less usage. If tobacco products didn't contain nicotine, but people used at the same rate, I don't believe cancer (or other illness) rates would drop. The drug effect is the issue, not its addictive properties. And even if one considers adverse effects to be minor, legalizing it versus banning it are both tricky solutions. Legalizing it means use would expand significantly. Alcohol is legal, though while only 4% of alcohol users develop alcoholism, it's still a huge social issue.

Did you read the study Daniel posted? Not just the review he provided, but the actual study. Only seven monkeys were used, and ALL effects were measured two months after the last MDMA dose was given. I don't think a weekend of moderate cigarette smoking or alcohol consumption would show effects two months later, so I wouldn't expect this study to show anything. Most drug studies have flaws or methodologies that can be nitpicked, so the important thing is to be well-read in a wide variety of drug studies to compare methods and effects. The study I presented was an extreme case of MDMA abuse, and I'm glad you recognized it as such. But the sad truth is that people overdose, whether it's three people or millions of people.

Thanks for your thoughtful comment and I'm sorry I couldn't respond earlier.

Lori

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In context he said "can be safe" not "is safe". I liked your article, but I disagree that his was irresponsible. On the contrary, he raises some good points as well.

FriedZombie

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Hello Ms. Gaines, I read both your and Daniel's link post which pretty much make me think the results still are inconclusive. The biggest hurdle seeming to be the type of MDMA used in previous studies as well as the recommended dosage and periods of time when results were recorded. They really should have tests that can record resusts in multiple timelines that don't harm the animals. The article that Daniel linked to talked about how the monkeys were euthanized and their brains removed for study, they should be able to use CAT scans or something similar to record results rather than this asinine and life wasting ways of the past.


Jordan Gaines
Pennsylvania State University
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FriedZombie,

Thanks for reading. As you say, results are inconclusive. Different dosages, different dosing schedules, and different methods of recording results all certainly turn up with different stories. It's hard to say with certainty which is the "right" method or which is the "right" conclusion.

I was a bit unclear as to why (in the study Daniel posted) their PET analyses were done in harvested brains, given that's a technique that relies on the animal's metabolism, though it's not a methodology I'm personally familiar with. But certain procedures do require sacrifice to examine the system in question—like the figure of serotonin neurons in my post. Research proposals do undergo serious consideration by the Institutional Animal Care and Use Committee (IACUC), so we have to trust that the committee found their procedures within reason. Full brain scans—CAT, fMRI, PET—don't tell the whole biochemical and molecular story.

Sean Garvin

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hi,

i think the point of arguing as to the context of the word "safe" is fairly pointless regarding drugs. there are far more pressing issues that need to be dealt with, rather than focussing on the ethical point of whether an illegal substance should be referred to as safe or not. there are far more damaging substances available that are legal and in everyday use, and are also considered safe when used in moderation. alcohol, and tobacco for example are the most commonly consumed substances and account for a huge number of deaths every year, not to mention the massive costs associated with them from a health care point of view, and social/law enforcement issues. you see my point is, arguing about whether a drug should be referred to as safe is about as practical and useful as arguing whether atomic weapons should be allowed to exist. the facts are, like nuclear weapons, drugs exist, they will always exist, whether they are safe or not, whether people say they are safe or not, and people will always want to take them. this is a fact that we all have to just deal with. 

so whats the real issue. i think that there are many good arguments for and against the legalisation of drugs, however certain facts can not be denied. it would be far more beneficial to everyone if certain drugs were decriminalised. i understand that many people feel that legalisation would enable people to endulge in their curiousities. what most of these people don't seam to realise is how easy it is to obtain drugs these days, legalising drugs will not suddenly make everyone on the planet go out and take drugs. i know many people on both sides of the coin, and not one single person i have ever met that chooses not to take drugs, has ever stated that the legal status of a drug is a determining factor, for all people the main factors are the risk to their health, and the fact that some people just do not enjoy the experience. alcohol and tobacco for many years was considered perfectly safe, did everyone on the planet go out and smoke and drink like it was going out of fasion. NO they didn't. to suggest that implying a drug is safe would make us all do it, would suggest that all people are mindless zombies, we are not, we are intelligent and we all exercise our right to choice all the time.

it would be far better to allow people the choice of taking a drug, whilst providing them with a product that has been rigorously tested, that has proper quality controls in place, and that has proper subjective information provided, so that people may make an informed decision on whether they would like to take the drug. i am sure you would find that the associative deaths related to certain drugs would drop dramatically once a product is available with proper information and free of fillers, which quite often account for the complications usually found with drug overdoses. further more, a product that is correctly produced would more than likely include other products that could be taken if the situation became undesireable.

to my last and probably most important point, i think the greatest benefit to society in legalising certain drugs would come from the reduction of crime. i think you would find that a very large percentage of all crime has associations with drugs. maintaining a prohibition on drugs only enables criminal communities to further their already vast empires. in my opinion, to outlaw a drug is the same things as handing cold hard cash directly to criminal gangs. crime has become a multi-billion dollar indusrty, and in certain parts of the world organised crime related to the drug trade has seized control of parts of countries.

so, my question to all is, what is worse.

that we legalise a substance we are a bit uncomfortable about, and in return get fewer deaths and less crime, not mention the revenue that would benefit our own countries.

OR

we continue to outlaw these substances, the death tolls continue to rise, crime worsens, we lose more control to the cartels and other organise crime, which in quite alot of cases are funding wars and organisations that threaten our societies.

I THINK THE ANSWER IS FAIRLY STRAIGHT FORWARD. 

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