↑ comment by TylerJay ·
2015-05-03T21:50:19.278Z · LW(p) · GW(p)
The risks of one-time MDMA use can be roughly sorted into two categories: "Normal Risks" which apply to everyone and "Edge-Case Risks" which only apply to certain people (though it may not always be clear, as we will see, if you are at risk for one of the edge-cases). I will give a very brief and oversimplified description of how MDMA is processed by the body and the effects it has, and then I will describe some of these risks. I didn't have time to put together sources and citations (especially as this was written from memory + fact checking), but my hope is that this will help people understand what the risks are and some of the mechanisms of action so that they can do more informed research into the topic.
Basic Neuroscience Background Information
In the human brain, where two neurons meet is called the Synapse. In reality, there is actually a small gap at the synapse between neurons called the synaptic cleft. When a signal traveling down a neuron reaches the end, it causes a release of neurotransmitters into the synaptic cleft. These neurotransmitters fit like keys into keyholes called receptors on the second neuron. Depending on which keyholes/receptors are activated/filled, the second neuron takes some action like firing or not.
You can visualize this by holding your right fist up and then making a "C" shape around it with your left hand (they should be close, but not touching. While maintaining this, hold your elbows out to the sides. Each of your arms is a neuron. Your forearms are the "Axon" which is the path the signals travel down and the space between your hands is the synaptic cleft. A signal travels from your left elbow to your left fingers which causes them to release neurotransmitters into the space between your left hand and your right fist. All over your right fist are small keyholes called receptors that are shaped to specifically fit certain neurotransmitters. The neurotransmitters float around in the gap for a while, some of them fitting into the keyholes, and some of them being reabsorbed by your left hand to be used later. (This reabsorption process is called "reuptake" by the way) If enough of the keyholes on your right fist are filled, then a signal travels from your right fist down to your right elbow, at which there is another synapse and the same thing happens.
Now, on your fist (or the "receiving" end of a synapse) you have a lot of receptors, but not all of these receptors are "on" or "active" at any given time. Your body maintains homeostasis by regulating the amount of active receptors for a certain neurotransmitter in response to the amount of that neurotransmitter that is typically produced. For example, I might produce (or rather, release) slightly less serotonin than you on average, but my body will deal with that by activating more serotonin receptors. In that case, our expected number of serotonin receptors that are filled with serotonin molecules at any given time would be roughly the same, so there would be no difference between us in that respect.
The last piece of background information we'll need is to explain "free radicals". You learned in high-school chemistry how atoms have electron shells/orbitals that "want" to have a specific number of electrons in them. This applies to molecules as well. When a molecule is missing an electron, it goes crazy and tries to steal one from its neighbors. A molecule in this state is called a "free radical". If it's pull is stronger than a neighbor's, then it takes one of the neighbor's electrons and calms down while the neighbor then goes crazy and becomes a free radical itself, looking to steal an electron from another molecule. This causes a chain reaction and can be very damaging to sensitive structures in your body like DNA or receptors in the brain.
The definition of an "antioxidant" is a molecule that can give up at least one of its electrons to a free radical without becoming a free radical itself, thereby ending the chain reaction. Free radicals are produced by pretty much all metabolic functions, so they are unavoidable to a certain extent. Your body uses antioxidants from your diet and endogenous antioxidants to counter this process every second of every day. Typically, it does a pretty good job and your body maintains homeostasis.
MDMA Mechanism of Action and Pharmacokinetics
MDMA causes excess release of Serotonin, Dopamine, and Norepinephrine into the synaptic cleft, though its action is primarily on Serotonin, so that's what I'll mostly focus on here.
So when you take MDMA, your neurons release excess serotonin into the synaptic cleft. This causes more binding to serotonin receptors which causes more firing of those neurons. This leads to the euphoria associated with MDMA use. However, your body wants to maintain homeostasis, so it starts turning off serotonin receptors. That way, even though there's more Serotonin, there are less places for it to bind, which reduces activity. Then your MDMA wears off and your neurons are actually releasing less serotonin than before. This, coupled with less active serotonin receptors leads to considerably lower serotonin activity. This is associated with the anhedonia, anxiety, and depression that sometimes follow MDMA usage for a few days. However, nothing I've just described is permanent, so your body will eventually up-regulate your serotonin receptors again, your serotonin stores will replenish, and you'll be back to normal.
However, this excess activity at the Serotonin receptors also creates excess free radicals. These free radicals can actually damage serotonin receptors (break them permanently) so that they can never be reactivated. In a single, modest dose, this is likely negligible, though with a single super-dose, it is significant. This highlights the important of having antioxidants available to your brain throughout the MDMA trip. A study was done on monkeys where they gave them super-does of MDMA, some with a Vitamin C injection and some without, and found significant brain-damage reduction (as in, blocked the vast majority of brain damage) in the Vitamin C group. (sorry, I can't find the study right now.)
So, with chronic use or higher doses, this kind of damage becomes more and more of a problem and leads to brain lesions in the serotonergic neural pathways, and is Normal Risk #1
When your neurons absorb MDMA, it has effects on the Monoamine Oxidase system. Therefore, taking MDMA with Monoamine Oxidase Inhibitors (MAOIs) is extremely dangerous and can be life-threatening. Do not take MDMA if you are on MAOIs (and make damn sure you check if any meds you are on or recreation drugs you take are MAOIs). This is Edge-Case Risk #1
Your body breaks down MDMA largely through the CYP450 family of liver enzymes—primarily CYP2D6, but also CYP3A4 and possibly some others to minor extents. Therefore, if these enzymes are inhibited or otherwise not fully functional, your body will not be able to eliminate MDMA (or will do so much more slowly) which can lead to overdose and amplification of the detrimental effects on your brain, cardiovascular system, and more. Inhibition of CYP450 enzymes can be caused by certain medications (like Tagamet/Cimetidine or Ritonavir) or foods like grapefruit and grapefruit juice. This is Edge-Case Risk #2a. Certain people may also have genetically-impaired CYP2D6 activity which can lead to similar complications. This is Edge-Case Risk #2b
Replies from: TylerJay
↑ comment by TylerJay ·
2015-05-03T21:50:43.275Z · LW(p) · GW(p)
Macro-Level Physiological Effects
The increase in Dopamine, Norepinephrine, and Serotonin caused by MDMA causes Central Nervous System (CNS) stimulation that can raise body temperature, heart rate, and blood pressure. It can also cause increased sweating and perspiration, insomnia, nausea, and diarrhea, all of which contribute to dehydration. These comprise Normal Risk #2 family. The fact that MDMA use is often associated with excessive dancing, hot environments, and limited access to water and electrolytes (such as at raves, music festivals, concerts, etc.) compounds these risks. So, if a person has no cardiovascular issues, is mindful of these risks, stays hydrated, ensures not to drink too much water without electrolytes, and keeps their heart rate and body temperature in check, most of these risks can be avoided. However, for anyone with cardiovascular issues (even ones they don't know about) this becomes Edge-Case Risk #3
Other/Unknown-Mechanism Psychological Effects
MDMA is a psychotropic drug. As such, it has the possibility of triggering latent psychological disorders such as Bipolar Disorder, Depression, epilepsy, and Schizophrenia just the same way that LSD, emotional stress, and head trauma do. The mechanism behind this phenomenon is still unknown. This is Edge-Case Risk #4 (I am also not as familiar with this area as most of the others, so I encourage you do to some independent research here.)
MDMA has also been documented to cause acute psychosis. The authors of the case-studies I have read dismissed the idea of there being a latent psychological disorder that was simply triggered because none of the typical milder early symptoms were present before ingestion of MDMA. A clinical psychiatrist that I know also confirmed to me that sometimes these psychotic episodes just happen in conjunction with psychotropic drugs. This is Edge-Case Risk #5 It should be noted that this is considered a rare event.
MDMA has also been observed to cause seizures, though this is rare. It is unknown whether this can be fully-attributed to dehydration, drug interactions, drug adulterants, or undiagnosed epilepsy. However, I have personally seen two people have seizures while on MDMA, so take from that what you will. This is Edge-Case Risk #6
And finally, long-term psychological side-effects such as insomnia and sleep disturbances, anxiety, depression, anhedonia, irritability, and memory-impairment have been found in epidemiological studies (and reviews of such studies) of MDMA users. Unfortunately, epidemiological studies only show correlation, not causation, and many of the results could be attributed to self-medication. Human prospective studies and clinical trials are extremely limited with MDMA due to its legal status and ethics constraints, meaning that the majority of the published information on effects of MDMA is either animal studies, or is epidemiological and typically skewed toward chronic MDMA users. However, that correlation does exist which is at least weak evidence that MDMA use can cause these long-term effects. This is Normal Risk #3
Disclaimer: I am not a doctor. This is not medical advice. This is not intended to encourage or enable any illegal activity. I have posted this information in the interest of harm reduction and scholarly interest alone. If you do anything stupid or if any harm comes to you based on this advice, it's not my fault.
If you found this valuable, leave me a comment. I'd appreciate it. And if you have any followup questions, feel free to ask. Cheers all.
Replies from: drethelin
↑ comment by drethelin ·
2015-05-03T22:54:05.799Z · LW(p) · GW(p)
How high is the risk of adulterants with unexpected effects?
Replies from: TylerJay
↑ comment by TylerJay ·
2015-05-04T23:02:34.151Z · LW(p) · GW(p)
There's no way to give a broad estimate on that. It's going to vary widely based on source, geographic location, and form (pressed pills vs powder/crystals/rocks).
Pressed pills or "Ecstasy" pills are more likely to have Amphetamine and/or other stimulants like caffeine and piperazines in addition to the MDMA, as they are intended as "rave drugs" for clubbing and dance parties. (Many users actually prefer amphetamine/caffeine in their pills because MDMA alone is more of a psychedelic than an "upper" and can make people want to sit down, look at the pretty colors, and rub each other instead of dance. Piperazines are typically considered "bad" adulterants, even by the crowd who likes amphetamine, and can be very dangerous, especially when combined with other drugs.)
Sometimes, product sold as MDMA (or Ecstasy) will not contain MDMA at all. Common drugs sold as MDMA are MDA (a metabolite of MDMA with similar effects), Methylone, and BZP (a piperazine), though there are many others depending on your geographic location and source.
Regarding geographic location, you can often find reports on government websites. For example, in the USA, I believe the DEA publishes the percentage of seized drugs that are adulterated (or are another drug altogether) by area (I have seen published numbers on their site for certain areas before, but I don't know if it's done regularly and I wouldn't expect out-of-date reports to still be accurate).
However, your estimate of the likelihood of having dangerous adulterants in your MDMA will likely be dominated by your ability to get trustworthy reports of other people who have taken the same "batch". (Note there are multiple areas for uncertainty here to account for. Honesty/motives of the people reporting + number of reports, ability of the people reporting to tell the difference, is it actually the same batch, and heterogeneity of the batch, to name a few.)
A few sources of this kind of information are:
- Seller reviews and track record if you're buying online
- Other people you know personally who have taken the same batch if you're buying in person
- pillreports dot com (website. do NOT use this as your only source of information, as you never know if your pill is actually the one you see reviewed or an imitation)
- Chemical reagent tests
If you are buying online, here is a harm reduction strategy: Select a seller with a perfect track record with regard to quality and a large number of reviews. Once you've received it, wait until you've seen a significant number of reviews from orders placed around the same time as and after you placed yours that are all still positive with respect to quality. This will help protect you from bait-and-switch tactics and should increase your confidence that the reviews you've read are of the same batch/product as you've received.
A chemical reagent test is a good risk- and harm-reduction measure that can be used in conjunction with any of the other measures. They change color based on the presence of MDMA and common adulterants (obviously sacrificing some of the stuff you're testing in the process). The most popular test is the Marquis Test. Other common tests include the Mecke Test and the Simons test. (Make sure to check the legality of these "test kits" in your area before ordering/purchasing one.)
Disclaimer (again): Do not do any of these things if it is illegal for you to do so. This is not intended to encourage or enable any illegal activity. I have posted this information in the interest of harm reduction and scholarly interest alone. If you do anything stupid or if any harm comes to you based on this information, it's not my fault. If you do anything illegal based on this information, I am not in any way responsible and I told you not to do it.