The war on drugs killed my daughter

[zimmah]

The war on drugs killed my daughter

http://www.theguardian.com/society/2014/jun/22/mother-fights-against-war-on-drugs-anne-marie-cockburn-martha-fernback

<< Martha Fernback, 15. died from taking 91% pure ecstasy. Anne-Marie Cockburn is campaigning for drug legalisation to spare others her ordeal. >>

i'm sorry for your loss, or whoevers daughter that was, but why was a 15 year old taking drugs in the first place?

[Marlo Stanfield]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

[DannyElfman]

The war on drugs killed my daughter

http://www.theguardian.com/society/2014/jun/22/mother-fights-against-war-on-drugs-anne-marie-cockburn-martha-fernback

<< Martha Fernback, 15. died from taking 91% pure ecstasy. Anne-Marie Cockburn is campaigning for drug legalisation to spare others her ordeal. >>

So the war on drugs is to blame how? Newsflash, drugs are dangerous and can kill you.  That's the risk you take, that's why they are illegal in the first place.  I used to do cocaine from time to time, I knew the risk I was taking.  Now they are apparently cutting it with fentanyl.  No more cocaine for me, not worth the risk.

Even if legalized and regulated, there is no way to know how it would affect her.

I don't see how the war on drugs is to blame on this one.  Sounds like the same type of people that blame McDonald's for making them fat.

I agree, I think the mother is placing the blame on the wrong person. The article says that her daughter was researching the drug online prior to buying, so she should have been well informed that the more pure the drug was the stronger and more dangerous it is.

If we stopped the war on drugs then many more people would die from overdosing and even more people's lives would be ruined by drugs

[IamCANADIAN013]

I used to do cocaine from time to time, I knew the risk I was taking.  

No you didn't. You probably 'knew' the basic assumptions that most people tended to know as a result of hearsay and anecdote, but did you know at the time that consuming cocaine and alcohol creates the cardiotoxic substance cocaethylene in-vivo? Cocaine is rarely consumed without alcohol, but most people assume the risk is in the cocaine, when it is far more harmful when used in conjunction with alcohol.

Now they are apparently cutting it with fentanyl.  No more cocaine for me, not worth the risk.

Yeah, I'm going to go ahead and call bullshit on this claim. That's like the absurd claim that marijuana is sprinkled with [insert far more expensive drug here] in order to increase it's weight and potency.

There are those that will take cocaine with an opiate, commonly known as a speedball, which can lead to the longer-lasting effects of the opiate, at a dose that was previously tolerable while the short-acting cocaine was stimulating the central nervous system, becoming one that is fatal. But no dealer would ever simply cut cocaine with a powerful and expensive opiate drug.

I don't see how the war on drugs is to blame on this one.

Because it is just as equally a war on knowledge and information about drugs. Objective, unbiased and educational information, not ignorant indoctrination.

You demonise drugs equally, telling children the usual misinformation and lies, you end up with them trying something relatively benign (not entirely harmless but, certainly, proven to be less harmful than alcohol or tobacco), such as marijuana and, when their world doesn't fall apart and they have a giggly time being stoned, they believe they are being lied to about all drugs.

So how do you expect them to then listen to valid warnings about opiate or stimulant drugs if they know they have already been lied to about cannabis?

The girl in this tragic case died, not because she intentionally wanted to take a dangerously high amount of MDMA, but because she couldn't easily gain access to an information resource that would have informed her doses in excess of 120mg were too large and why.

Young people aren't generally stupid and they tend not to want to actually do things which might kill them, so if you let them be educated about the neurochemistry and physiological aspects of drug use, they will be able to see the realities of the situation and judge it for the facts, not the useless scaremongering.

LOL! Yeah I know all about how mixing cocaine and alcohol creates a third chemical.  I've read up a lot about cocaine over the years. So yeah, I knew the risks.

As for calling bullshit on the cocaine and fentanyl, there was a recent spike of cocaine overdoses in a city close to where I live.  They apparently tested it, and they found that it was mixed with fentanyl. Same with heroin, spike in overdoses and found it was mixed with fentanyl.

You bring up speedballs like I'm some kind of clueless idiot about drugs.  I lost a friend some years ago from overdosing on a speedball combo.  I live near the city of Vancouver, which has the poorest postal code in Canada.  Drug use is rampant.  Was at The Queen concert last night.  Got to watch a guy shoot up in his neck down a back alley, good times.  Been down around there on and off for 18 years.  My sister was a heroin addict and lived on those streets for years. Seen and learned a lot down there over the years.

Yes, young people generally are stupid.  This had nothing to do with not having access to information.  Basic rule of thumb.  You risk taking harder drugs, there is a chance it can kill you.

[IamCANADIAN013]

The war on drugs killed my daughter

http://www.theguardian.com/society/2014/jun/22/mother-fights-against-war-on-drugs-anne-marie-cockburn-martha-fernback

<< Martha Fernback, 15. died from taking 91% pure ecstasy. Anne-Marie Cockburn is campaigning for drug legalisation to spare others her ordeal. >>

So the war on drugs is to blame how? Newsflash, drugs are dangerous and can kill you.  That's the risk you take, that's why they are illegal in the first place.  I used to do cocaine from time to time, I knew the risk I was taking.  Now they are apparently cutting it with fentanyl.  No more cocaine for me, not worth the risk.

Even if legalized and regulated, there is no way to know how it would affect her.

I don't see how the war on drugs is to blame on this one.  Sounds like the same type of people that blame McDonald's for making them fat.

I agree, I think the mother is placing the blame on the wrong person. The article says that her daughter was researching the drug online prior to buying, so she should have been well informed that the more pure the drug was the stronger and more dangerous it is.

If we stopped the war on drugs then many more people would die from overdosing and even more people's lives would be ruined by drugs

Yep, and in reality, the problem would sort itself out.  Darwin would win many rounds.  I don't have much sympathy for people who become addicts.  I've seen first hand how it can ruin lives and the lives of the people around them.

People want them legalized, fine.  But if thats what they want, then I don't want my tax dollars to fund their medical care or their social assistance checks.  i also want the firearms laws changed so I can take out a drugged out idiot on my property if they're trying to break into a vehicle, out build, and/or my house.

Down in Vancouver they have a safe injection site, needle exchange, crack pipe vending machine, etc. It's become a drug haven for addicts.  They claimed it would create less drug addicts. Quick walk down a few streets in the Down town east side proves the opposite.

[Mike Christ]

If we stopped the war on drugs then many more people would die from overdosing and even more people's lives would be ruined by drugs

No; what's more likely to happen is that businesses would begin to sell these drugs in manageable doses (i.e. not at 91% purity, but something marketed as the perfect dose for an enjoyable night for example) whilst street dealers lose their jobs, assuming the government doesn't put some stupid restriction on who can buy what such as a license.  Or perhaps something else would happen; I can't predict the future.  What we do know is that the War on Drugs is not actually stopping anyone from taking drugs, or taking them inappropriately; at best it can scare people into not doing them, which has not proven effective, and at worst it limits a person's knowledge of how to actually take a drug thus leading to more overdosing, not less (which was the argument presented by the mother in this article), due to what is known as the chilling effect (e.g., nobody wants to talk about it because they're afraid they'll become noticed by an unfavorable party, such as the DEAs.)

The fallacy you've committed is known as a false dilemma, where you present a limited amount of choices--either imprison a huge chunk of the population in the name of protecting our children, or letting people overdose because everyone is, by and large, too incompetent to take a drug properly--as the only two possible options that we must decide between, when there is in fact more options; you can read more about it here: False dilemma

[vokain]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

[koshgel]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

What destabilization of neural pathway equilibrium do you mean specifically? Neuroreceptors?

Also, every single drug, prescription or not has been synthesized in a lab.

Take an Organic Chemistry course and learn about the ways molecules interact

[vokain]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

What destabilization of neural pathway equilibrium do you mean specifically? Neuroreceptors?

Also, every single drug, prescription or not has been synthesized in a lab.

Take an Organic Chemistry course and learn about the ways molecules interact

Don't condescend me please. If you any sense of reading comprehension, I refer to molecules that are only synthesized in labs and not synthesized in nature. The example I used, D-ascorbate, is not synthesized in nature. I understand that we can mimic natural chemical processes to synthesize the L- enantiomer configuration of Vitamin C and other naturally synthesized chemicals, but we don't always do this.

And yes, neuroreceptors, but that refers to drugs' mechanism of action upon receptors. I was talking about the byproducts of breaking down synthetic unnatural drugs and the chemical effects from said reactions and the oxidative stress they can induce. I understand that metabolism of natural foods cause oxidative stress too, but the interactions of molecules the body didn't evolve to interact with under optimal living conditions are arguably harder on the body, as resilient as the body is.

Destabilization of neural pathways can be inherent in any addictive drug, synthetic or not. For those not familiar, uppers like caffeine, MDMA, cocaine, and amphetamines increase the release of the amine transmitters of serotonin and dopamine (and norepinephrine, but that is not so much a learning neurotransmitter). Our brains have an equilibrium that uses these neurotransmitters for signaling pathways. When uppers are introduced to a delicate equilibriated system, the novel experience, the resulting flood of serotonin and dopamine, disturbs the brain's learned sense of baseline. Afterwards, under normal conditions (without the drug), the brain would never release the same amount of neurotransmitters without these agonists acting upon the receptors to heavily induce signal cascades of said neurotransmitters.  As such, people feel different, or "off" in some sort, after the comedown of drugs . That's why you see people grow to believe they cannot function as well without caffeine or amphetamines (in addition to the reward learning mechanism that comes from dopamine release). That's why people that go to bad concerts chase that good roll but never are able to again without taking higher doses (excitotoxicity, over excitation of receptors and their subsequent destruction also plays a, probably compounding, role). That's why people don't enjoy parties as much without cocaine if they've had a blast doing cocaine before. I've seen it all before, I'm in a frat. It is reversible.

it's the same thing with opiate abuse. Our body has a learned sense of equilibrium of pain. We sit here and we're healthy and nothing is causing us pain, it is because opiate system is in equilibrium. When you flood your opiate receptors with heroin, your brain feels a rush of pleasure and your learned baseline ticks up a bit towards a higher level of opiates for what it considers should be normal. When the opiate leaves the system, since the baseline is adjusted, people feel a bit off because their bodies do not naturally release as many opioid neurotransmitters as compared to when induced by an opiate. If a cycle of abuse is established, the baseline ticks up higher and higher. In the event an addict cannot get more, the pain baseline is so high that without an external agent inducing more opiate release, the normal trickle of opioid neurotransmitters from the brain will not enough for normalcy and addicts actually start feeling pain. Again, reversible, but not easy.

Anyway, what I was trying to say with synthetic psychoactive drugs is that they attempt to specifically target these receptors and as such destabilize the equilibrium and in addition to their possibly unnatural synthesis, the resulting decomposition might have adverse effects on the body as well, perhaps moreso than naturally synthesized analogs.

[koshgel]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

What destabilization of neural pathway equilibrium do you mean specifically? Neuroreceptors?

Also, every single drug, prescription or not has been synthesized in a lab.

Take an Organic Chemistry course and learn about the ways molecules interact

Don't condescend me please. If you any sense of reading comprehension, I refer to molecules that are only synthesized in labs and not synthesized in nature. The example I used, D-ascorbate, is not synthesized in nature. I understand that we can mimic natural chemical processes to synthesize the L- enantiomer configuration of Vitamin C and other naturally synthesized chemicals, but we don't always do this.

And yes, neuroreceptors, but that refers to drugs' mechanism of action upon receptors. I was talking about the byproducts of breaking down synthetic unnatural drugs and the chemical effects from said reactions and the oxidative stress they can induce. I understand that metabolism of natural foods cause oxidative stress too, but the interactions of molecules the body didn't evolve to interact with under optimal living conditions are arguably harder on the body, as resilient as the body is.

Destabilization of neural pathways can be inherent in any addictive drug, synthetic or not. For those not familiar, uppers like caffeine, MDMA, cocaine, and amphetamines increase the release of the amine transmitters of serotonin and dopamine (and norepinephrine, but that is not so much a learning neurotransmitter). Our brains have an equilibrium that uses these neurotransmitters for signaling pathways. When uppers are introduced to a delicate equilibriated system, the novel experience, the resulting flood of serotonin and dopamine, disturbs the brain's learned sense of baseline. Afterwards, under normal conditions (without the drug), the brain would never release the same amount of neurotransmitters without these agonists acting upon the receptors to heavily induce signal cascades of said neurotransmitters.  As such, people feel different, or "off" in some sort, after the comedown of drugs . That's why you see people grow to believe they cannot function as well without caffeine or amphetamines (in addition to the reward learning mechanism that comes from dopamine release). That's why people that go to bad concerts chase that good roll but never are able to again without taking higher doses (excitotoxicity, over excitation of receptors and their subsequent destruction also plays a, probably compounding, role). That's why people don't enjoy parties as much without cocaine if they've had a blast doing cocaine before. I've seen it all before, I'm in a frat. It is reversible.

it's the same thing with opiate abuse. Our body has a learned sense of equilibrium of pain. We sit here and we're healthy and nothing is causing us pain, it is because opiate system is in equilibrium. When you flood your opiate receptors with heroin, your brain feels a rush of pleasure and your learned baseline ticks up a bit towards a higher level of opiates for what it considers should be normal. When the opiate leaves the system, since the baseline is adjusted, people feel a bit off because their bodies do not naturally release as many opioid neurotransmitters as compared to when induced by an opiate. If a cycle of abuse is established, the baseline ticks up higher and higher. In the event an addict cannot get more, the pain baseline is so high that without an external agent inducing more opiate release, the normal trickle of opioid neurotransmitters from the brain will not enough for normalcy and addicts actually start feeling pain. Again, reversible, but not easy.

Anyway, what I was trying to say with synthetic psychoactive drugs is that they attempt to specifically target these receptors and as such destabilize the equilibrium and in addition to their possibly unnatural synthesis, the resulting decomposition might have adverse effects on the body as well, perhaps moreso than naturally synthesized analogs.

You add a lot of fluff by defining terms. Thanks captain wikipedia.

The point is there is no source or proof for what you're proposing. It's just your opinion.

[vokain]

I think there's a George Carlin quote for this

[Marlo Stanfield]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

Oh ok. I misunderstood what you were getting at. I see what you're trying to say but it's just one of those things that people can only speculate on for now. Personally, I think our bodies have evolved to be quite adept at breaking down a wide variety of molecules. But it's not something we're going to really know the answer to for a long time. It's going to take a lot science to begin to answer those type of questions.

[vokain]

I'm of the opinion that most synthetic/unnatural drugs end up destabilizing the equilibrium under which neural feedback pathways work.

Woah, woah, woah. You are barking up the wrong tree here my friend. There is no such thing as "unnatural". That's a complete fallacy. You're claiming that two chemicals that are identical, one derived from an organism, and the other synthesised in a lab, yet functionally equivalent, will have different effects when consumed in identical situations?

Not exactly. I'm claiming that synthetic molecules that would not exist from organically (perhaps co-)evolved processes (i.e. not in a lab from fallible humans playing God) tend to not be meant for our bodies which evolved in for the most part untampered nature for the majority of our timeline. As an example, synthetic Vitamin C (D-ascorbate) is not the full Vitamin C complex (L configuration of ascorbate):
"Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific.

[3]Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37.

So, my supposition is that things like MDMA and amphetamines are typically bad for you because 1) the chemical reaction from breaking these molecules down is not something our bodies evolved to break down and 2) the bioactivity from these reactions taking place in our bodies disturb the sensitive equilibrium they were meant to operate at.

Oh ok. I misunderstood what you were getting at. I see what you're trying to say but it's just one of those things that people can only speculate on for now. Personally, I think our bodies have evolved to be quite adept at breaking down a wide variety of molecules. But it's not something we're going to really know the answer to for a long time. It's going to take a lot science to begin to answer those type of questions.

It is the Golden Age of Neuroscience. The field is learning new things every day.

http://www.ncbi.nlm.nih.gov/pubmed/15228154
Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition.

MDMA metabolism is rather complex and includes 2 main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The fact that the polymorphic enzyme CYP2D6 partially regulates the O-demethylenation pathway prompted some expectations that subjects displaying the poor metabolizer phenotype may be at higher risk of acute toxicity episodes. In this metabolic pathway a mechanism-based inhibition of the enzyme operates because the formation of an enzyme-metabolite complex that renders all subjects, independently of genotype, phenotypically poor metabolizers after the administration of 2 consecutive doses. Therefore, the impact of CYP2D6 pharmacogenetics on acute toxicity is limited. One of the interesting features of MDMA metabolism is its potential involvement in the development of mid- to long-term neurotoxic effects as a result of progressive neurodegeneration of the serotonergic neurotransmission system.