Ecstasy: "safe"?

Jun 26 2012 Published by under Uncategorized

The following is a post I had written last week in response to British Columbia's top health official announcing that pure ecstasy (MDMA) is "safe."

Call me a prude, but I'm not so thrilled about the announcement made on June 14 by British Columbia's top health official that ecstasy is "safe."

Dr. Perry Kendall asserted 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 thescience 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.

* Note: Ricaurte's research has received criticism for his methodologies. In 2003, four of his studies were revealed to have administered methamphetamine instead of MDMA due to a mislabeled purchase, but the particular experiment I presented here was not among them. I welcome any other comments and insight regarding Ricuarte's MDMA studies.

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

16 responses so far

  • DrugMonkey says:

    Wrt Ricaurte- it is also the case that this basic finding has been replicated by many other laboratories in multiple species (mouse is the weird one because there is a dopamine hit as well).

  • Rob Knop says:

    Does alcohol abuse have any long-lasting detrimental effects on the brain? If so, how do they compare? I'd also be curious if there were similar studies about marajuna.

    -Rob

    • scicurious says:

      Yes it does, but the effects are different because the drugs are drastically different (MDMA is neurotransmitter increases in serotonin, dopamine, etc. Ethanol is a GABA potentiator among other things). Marijuana there are various studies on acute and long term effects as well, but again, different because the drug itself is a very different mechanism of action (CB1 agonist).

  • DrugMonkey says:

    It does, it's different, there are.

    What's your question?

  • Horrible Clarity says:

    Not sure I agree with the argument that a 5mg/kg injection twice daily for four days is equivalent to three pills a day in a human, even if we ignore all the issues of inter-species drug dosing, the different methods of administration (humans very rarely inject MDMA) make this a rather extreme dosing regimen.

    I don't disagree that MDMA can potentially cause damage to 5-HT neurons, but a more appropriate comparison would be with a single oral dose (to be fair it should be in combination with alcohol, marijuana and maybe some ketamine too).

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  • Grumble says:

    I'd like to know what happens to human MDMA users after a few years of use. If they have only minor health and psychiatric issues, I'd say that result trumps the effects of high doses of MDMA on 5HT neurons in animals. And then the arguments for having a legal and regulated (i.e., uncontaminated) supply become much stronger.

  • drugmonkey says:

    As you would suspect Grumble the human effects range from death, to lasting severe morbidity to severe affective disorders to the minor , undetectable and, likely, absent.

    So let's not be naively binary about this.

    Now where do you come down on the "arguments"?

  • Grumble says:

    It depends on the relative frequency of the severe vs minor consequences. Given that people are still taking MDMA even though it's illegal, the question is whether legalizing it would result in a net increase in negative effects (due to increased usage) or a decrease (due to decreased contamination and/or more responsible usage due educational campaigns that could be funded by a tax on it).

    Sometimes I wonder whether we would benefit if pharma companies were allowed to sell drugs that are consumed purely for recreation, without any medical need. They might then be motivated to develop a drug like MDMA that doesn't kill 5HT neurons or people. But since they aren't allowed to even think about it, we'll never know what we might be missing.

    • DrugMonkey says:

      The legal substances alcohols and tobacco and the quasi-legal pot tell us that use would expand quite a bit. The harms would scale up accordingly.

      Education campaigns? Yeah, again, see tobacco, see alcohol. They help some but are hardly a silver bullet.

      What rate of acute death or lasting anxiety is acceptable for you? Remember when prescription meds are pulled for a handful of deaths or even "suicidal ideation"? And that is for compounds with medical benefit, not mere recreational purpose. So how do you draw your line?

      • Grumble says:

        "What rate of acute death or lasting anxiety is acceptable for you? "

        I don't know. I do know that it's not zero. There are risks in everything, and the reason why prescription meds get pulled is because their benefits weren't seen as justifying the costs of even a few deaths. Part of that is because (1) the drugs weren't all that effective to begin with; if they were "magic bullets" they wouldn't have been pulled, in the same way that we tolerate some morbidity and even mortality from vaccines because they are otherwise extremely effective. And (2) often there are other drugs on the market that serve similar purposes. Of course none of this applies to a recreational drug. The question is similar, though: what is the harm from keeping the drug illegal vs the harm from legalizing it?

        And that's how to draw the line. What would help is hard data that gives good estimates of the risks of either course. I'm not arguing that MDMA should be legalized, but that the decision should be based on epidemiological and other evidence.

      • Isabel says:

        "The legal substances alcohols and tobacco and the quasi-legal pot tell us that use would expand quite a bit. The harms would scale up accordingly."

        Was tobacco ever prohibited?

        Tobacco use has deceased dramatically while remaining legal mostly due to educational campaigns.

        http://www.washingtonpost.com/wp-dyn/content/article/2007/11/08/AR2007110801094.html

        Good 'ol Drugmonkey, turning a blind eye to the harms of prohibition as usual.

  • Rob says:

    Thanks for your insight. Based on your article thought, I assume you have never taken it. Millions of people have been taking MDMA for decades and still take it every weekend at clubs, parties and events across the world. I personally know many, many MANY who have taken it for years!..they have never had any issues. These are professional, responsible people, not street junkies. If there are long term affects, you will have a whole generation of them. It is one of the most amazing experiences you can have, while still being in total control. Ecstasy at a club is like popcorn at a movie. Overdoses are VERY rare. Believe me I have been at events where EVERYONE is on it. The majority of people who take it, do it responsibly. They know the golden rule.. keep hydrated. The crash you mention is also over hyped and only certain people experience it. Its actually a very relaxing and peaceful comedown. Unlike a speed or coke crash. You may feel a bit cranky 2 days later. The point is, right now the pills being sold on the street are getting more and more dangerous and are containing less and less actual MDMA, but are sold as ecstasy. Now they are even containing bath salts. Responsible users know to test their pills before consuming. (Test kits can be easily bought online.)But the average person does not test. The reality is people will always be looking for it. I would rather it be legal and "real" or "safer" then something harmful with God knows what. In close, I know what you are trying to say, but just say no, has not and will never work. People overdose on prescription drugs everyday. And I would rather be around a person on x any day than someone who is drunk. Lots of love in the room.

    • DrugMonkey says:

      The fact that adverse effects are rare doesn't mean public policy should be unconcerned. Alcoholism is maybe 4% of users and yet it is a huge problem.

    • jordangaines says:

      I appreciate the insight. Your physical descriptions of the drug's effect don't describe the neurobiological changes occurring, which is what I aimed to do in sharing this admittedly extreme study.

      It's a tricky issue of legalize versus don't legalize. I'm not well-informed in drug policy nor have any relevant social statistics up my sleeve, so I'm the last person to make an unbiased judgment. I can just read the papers and report the data.

      When drug users hear what they want to hear ("it's safe!" "legalize it!"), and especially from a health official, they latch onto it, which is what worried me most about Dr. Kendall's announcement. Like you alluded to, the average person is probably not considered "responsible." Accordingly, they may also not understand or care about its biological effects. People take the drug because it feels good, so whether or not it's biologically addictive (still up for debate), there are certainly grounds for psychological dependence. Like DrugMonkey alluded to in a prior comment, legalization would expand usage, as well as the incidence of harm. And toxic or not, people will still overdose on the stuff.

      Certainly a good topic for debate!

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