How to Be a Drug Nerd: A Chemist's Guide to Volumetric Dosing, Standard Uncertainty, and Harm Reduction

How to Be a Drug Nerd: A Chemist's Guide to Volumetric Dosing, Standard Uncertainty, and Harm Reduction

A couple edits have been made to reflect suggestions in the comments. Thank you guys!

Introduction

I’m a Chemical Biology major. I’m a total nerd, I love chemistry, I love biology, and I’m kind of a filthy degenerate. That makes me a perfect candidate for the research chemical community, wouldn’t you say?

In spending time here and in related communities, I’ve heard far too many stories about people overdosing, underdosing, or just straight up not knowing how much they took at all (fucking eyeballers). Most of you probably know about volumetric dosing, but I’ve talked to far too many people who think it’s difficult and overwhelming. Let me make this very clear: volumetric dosing is not hard, and it could save your life.

The goal of this guide is to teach you how to to prepare volumetric solutions in a comically rigorous way. But hopefully, by the end of this guide, you should be an expert on how to make doses that are accurate down to the tenths of a milligram, and you will know exactly how confident you can be in your doses.

If I wanted to dose 25mg of chemicals right now, I know that I could measure out a dose that is 95% certain of being between 24.6mg and 25.4mg, and nearly 100% certain of being between 24.0mg and 26.0mg. That confidence is not just anxiety-reducing, it’s also life-saving. And the best part is that you can do it, too.

TL;DR

Yeah, this guide is long. It goes into far more detail than is probably necessary. But let me provide a quick rundown for the lazy (because even the lazy have a right to not kill themselves by overdose!)

  1. Calibrate your scale

  2. Weigh your drugs using a milligram scale

  3. Measure your solvent using a pipette

  4. Divide weight of drug by volume of liquid to determine your concentration

  5. When dosing, divide your desired dose by your concentration to determine the volume of liquid you need to measure

  6. Measure liquid using a pipette

  7. Drink liquid

EDIT: A simple, easier to follow guide is available on psychonaut wiki for those of you who just want to get the steps.

In this guide, I’ll go into detail about how to do each of these steps the right way and how to perform these calculations.

Why?

In short, volumetric dosing reduces your error by a huge amount. A dose of DOM, for example, is about 4mg. Your milligram scale likely has an error of about 3mg. So measuring this directly on your scale, your dose could be anywhere between 1mg (a very light dose) and 7mg (a very strong dose). That’s scary!

Using volumetric dosing, we could very easily get this error down to 0.1mg or less. It would take you about 10 minutes of your time, $50-70 worth of equipment, and it could easily save your life.

Tools of the Trade

You’re going to need some tools to volumetrically dose accurately. I don’t want to read any complaints about this. If you’re putting novel research chemicals in your body to get high, you can afford $50-70 worth of tools that can be life saving. If you can’t, then you shouldn’t be wasting your money on drugs in the first place.

So let’s get down to it. You will need:

  • A milligram (0.001g) scale. This is how you’re going to weigh your chemicals out. I find the AWS Gemini-20 to be very precise for the money. Right now it’s about $47, but it’s typically around $30 and I don’t doubt that the price will drop soon. A 0.001g scale does not mean you’re precise down to 1mg! This only refers to how many digits your scale can read out. I find that a properly calibrated Gemini-20 can be precise to within about 2-3mg when calibrated properly, but when uncalibrated can be off by as much as 20mg. Which brings me to this:

  • Calibration weight set. The gemini-20 comes with two 10g calibration weights. That’s ok. But if you want to be absolutely certain, this extremely cheap ($15) calibration set comes with weights of 1mg, 10mg, 20mg, 50mg, 100mg, 200mg, 500mg, 1g, 2g, 5g, 10g, 20g, and 50g. That’s a lot of weights! Using this, you can test your scale using a weight close to the weight of the chemicals you’re weighing just prior to weighing to make sure everything looks good. An essential, I would say.

  • Graduated pipette set. All the accuracy in the world when weighing your powders doesn’t matter if you can’t accurately measure the liquid. This set is only $15 and comes with 1mL, 2mL, 3mL, 5mL, and 10mL pipettes that are class A. The 10mL pipette, for example, has a precision of 0.05mL, and the 1mL pipette is 0.01mL. Wow!

  • Vials to store your solution in. I use these cute little vials from the container store. They’re extraordinarily cheap and just straight up adorable. You can use whatever you want. You want the size of your vial to match the amount of dose you’re making. The 10 dram vials work well for 30mL of solution. Don’t store your 30mL of solution in a mason jar — you’ll lose a ton of it due to mechanical loss!

  • Spatula or Scoop. This is for transferring your powders. These work really great.

  • Clean solvent. This will depend on what chemical you’re using. This can be distilled water ($1.50 per gallon at a grocery store) for things like amphetamine derivatives, etc, or Propylene Glycol for things like tryptamines ($15 per quart on amazon), or ethanol (Everclear works well if you’re in a state that has 95%).

  • Optional: Beaker. This is just a convenient way to hold your solvent while you’re measuring things. You can use just a small glass or whatever if you want.

  • Optional: Latex gloves and a mask. I don’t see this recommended enough. While not strictly necessary, it’s a good safety AND precision precaution. Your hands and fingers are oily, and a lot of powder can stick to them. Much more than on gloves. A mask also helps — not only will it help you not breathe in chemicals, it can also help make sure you don’t blow your chemicals off your scale while you’re breathing! Plus if you breath too hard, you can actually throw off the scale. So it’s good to wear one.

  • Paper, pencil, and calculator. Get ready to do some very basic math. Don’t worry, it’s easy! I’ll guide you through it.

Preparation

In this example, I will make a 5mg/mL solution of 2-FMA in distilled water. This is applicable to anything. I’m just giving an example, and I think using concrete numbers and names will help with your understanding as you read this guide. If you’re making, for example, a 2mg/mL solution of 4-HO-MET in propylene glycol instead, replace the words and numbers in your head as you read on.

Get in a room with little airflow. Close your windows, your doors, etc. This will prevent wind from blowing chemicals away. Wash your hands, then put on your mask and gloves. Bust out your equipment. You don’t want to be getting up and searching for your stuff in the middle of this procedure.

Wash your glassware using your solvent. We will wash our 10mL pipette and our beaker using distilled water.

Determine how much solution you will make, and at what concentration. We will make 30mL of a 5mg/mL solution of 2-FMA. To calculate how much 2-FMA we will need, we can multiply those two numbers: 30mL * 5mg/mL = 150mg of 2-FMA.

Pour enough distilled water in your beaker to make the solution, and a bit extra. I just poured like 100mL into my beaker.

Calibrate and Estimate Uncertainty

Calibrate your scale frequently. This part only has to be done sometimes — not every time you want to weigh something. But you should always check before each weighing if your scale needs recalibration by weighing the 10g calibration weight. Toss your 10g weight on the scale — if it reads between 9.997 and 10.003, you’re golden. If not, you need to recalibrate your scale.

To recalibrate on the gemini-20, turn on your scale, then hold the on button until it says “CAL”. Take everything off the scale (no weigh boat). It will ask you to place your 10.000g weight on the scale, then the 20.000g weight. Then it will say “PASS” and you’re good to go.

Estimate your scale uncertainty. We’re going to get a gauge of how accurate our scale is. I place the 10g weight, 5g weight, and 1g weight on there and write down the measurements.

Because the gemini-20 is a 20g scale, and it’s probably most accurate around the midpoint (10g), I’m going to toss the 10g weight on there to measure smaller weights. So with the 10g weight on the scale, I will measure the 500mg, 200mg, 100mg, 50mg, and 10mg weights and write down the measurements.

This next part is sort of just intuition. Look at your numbers. For me, all of these weighs were less than 2mg off. Most of them were 1mg off, and some were not off at all. Therefore, I’m going to guess my scale is accurate to about ±2mg.

Optional: there is a more scientifically rigorous way to do this if you were so inclined. The next step up would be to actually calculate the uncertainty of your scale mathematically. I’m not going to go into this. To do this, you would need more accurate calibration weights. These cheap weights can be off by 1-3mg, so it’s a little bit extra to do that. It’s my opinion that an estimation is enough.

The nerdiest possible thing you could do at this point would be to also make a calibration curve for your scale. This would mean weighing a bunch of really accurate weights, graphing the result, and finding a line (or polynomial) of best fit. Not necessary at all. But it can be fun!

Weigh

Now let’s actually weigh our 2-FMA! I’m going to place the weigh boat on the scale, and additionally place the 10.000g calibration weight. This will bring our load closer to the midpoint of the scale, which should theoretically increase precision.

Wait until the weight stops changing, then press the tare button. Now use your spatula to slowly transfer 2-FMA to the scale until it weighs 150mg. If you go slightly over or slightly under, don’t worry. Just write down exactly what it says. We got 149mg of 2-FMA.

I then transferred this to the vial. To do this, I got a piece of plastic transparency sheet about 1.5” x 1.5”. I creased the plastic in half in both directions to make sort of a plus sign, which made a little divot in the middle to hold the powder better. Then I dumped the powder on this plastic, using my spatula to try to scrape every last little bit from the weigh boat onto the plastic. Then I picked up the plastic, and folded it in half along the crease I had made earlier, to make a little track along which the 2-FMA could slide down into the vial. I scraped the plastic with my spatula to get off all the last little bits.

I now have 149mg of 2-FMA in the vial.

Measure Solvent

I’m going to dissolve the 149mg in 30mL of water. My plan is to pipette three times 10mL using the 10mL pipette.

Watch this video! This is very important! Originally, I wrote out a whole 3 paragraphs describing how to properly use a pipette. But honestly, it’s much easier to see this in action. Here’s a 2 minute video showing how to pipette properly. In this video, they use a volumetric pipette rather than a graduated pipette, but it’s the same idea.

Now you might notice that the pipettes which I linked don’t have bulbs that fit onto the tip and come off easily like the bulb in the video. This is because I just couldn’t find the right type of pipette on Amazon. But you can do the same thing using the pipettes I linked, it just takes a little bit of practice.

Please don’t kill me: you can also use the mouth pipetting technique with food grade solvents. This is kind of a meme in the chemistry community because it’s a fucking terrible idea in most cases. But since we’re using food grade stuff here, I think it’s okay. If you’re having trouble using the pipette bulb as described in the video, you can put your mouth on the end of the pipette and suck just enough to get the water a couple centimeters above the 10mL graduation mark. MAKE SURE THE SOLVENT DOESN’T TOUCH YOUR MOUTH! Otherwise you’ll have contaminated it. You do NOT want saliva in your volumetric solution, as it can degrade your chemicals!

EDIT: When actually dosing, avoid using the mouth pipetting technique. It can be very easy to estimate wrong how hard to suck, and end up with a mouthful of potentially orally active drugs. That's a big danger!

This pipetting technique will take a bit of practice to get right. I recommend you just sit there and practice doing this a few times.

Pipette 3x 10mL of distilled water into your vial with the 2-FMA.

Write down exactly how much solvent you used. Each time you pipette, write down exactly how much solvent you used. To do this, you always estimate one more digit than your pipette shows. The 10mL pipette I linked has graduations for 0.1mL, so we can estimate one digit more than that. For example, if the bottom of your meniscus is a little bit under halfway between 9.9 and 10.0, you should write down 9.94mL.

EDIT: A more accurate way would be to actually mix your drugs with the ~30mL first, and then measure how much total solution there is. This is because, as a commenter pointed out, the drugs can actually increase the volume of solution. 150mg in 30mL isn't going to make an appreciable difference, but technically the right way to do it would be to make a concentrated solution first (using, say, 10mL), and then top up the volume until it's exactly 30.00mL. Alternatively, you can make your mixture in one vial, then use the pipette to transfer to a second vial, writing down exactly how much total liquid was pipetted to the second vial.

Because I have a lot of practice at pipetting, I was able to get 10.00mL exactly three times for a total of 30.00mL. Don’t worry if you get 9.94, then 9.67, then 9.81. It doesn’t matter, as long as you have written down exactly how much you used. In order to show better examples of calculations, I’m going to pretend that I got just that; so lets say I got 9.94, 9.67, and 9.81 for a total of 29.42mL.

When pouring your water into your vial, you can use this as an opportunity to rinse off the weigh boat and the piece of transfer plastic we used. Because they both had a tiny bit of powder left over on them, I simply held them over the vial and allowed the water from the pipette to run over them and into the vial. Be very careful not to allow any water to spill out.

Make sure you record the standard uncertainty of the pipette. On a trustworthy pipette, this will be written on the glass. In the 10mL pipette I linked, you can see at the top it says 10, and then under that it says 0.05 A. This means that this is a 10.00mL pipette, with a 0.05mL standard uncertainty (class A). You can also see a marking that says ±0.05 on there.

Exactly what this means is somewhat difficult to grasp. But I can ELI5 like this: (10.00±0.05)mL means that 95% of the time, your 10.00mL marking will actually be between 9.95mL and 10.05mL. There’s a bit of nuance to this, but I won’t go into that right now.

Calculating Your Concentration and Uncertainty

Ok, so we now have a solution of 149mg of 2-FMA in 29.42mL of water. Calculating the concentration is easy: just divide. 149mg / 29.42mL = 5.06mg/mL.

But now we have to calculate uncertainty. We don’t just want to know exactly how much we’re dosing — we also want to know how certain we are of that dose.

Propagating Uncertainty

Let’s recap our measurements, this time including our uncertainties. We had a ±2mg uncertainty from our scale, and a ±0.05mL uncertainty for each of our pipette measurements, so we have:

(149±2)mg 2-FMA

(9.94±0.05)mL + (9.67±0.05)mL + (9.81±0.05)mL water.

Calculating uncertainty isn’t as simple as adding them. The reason is simple: take our water measurements for example. Adding the 0.05mL uncertainties directly would yield a 0.15mL uncertainty. But it’s not likely that all three measurements would have been 0.05mL more or less than measured. It’s more likely that some of these uncertainties would cancel; some measurements will be slightly over, some will be slightly under, and those would cancel. So our uncertainty should be more accurate than 0.15mL.

Let’s add our water uncertainties. The formula for this is the following:

e4 = √(e12 + e22 + e32)

So lets calculate the uncertainty of our 29.42mL of water figure:

e4 = √(0.052 + 0.052 + 0.052)

= √(3 * 0.052)

= 0.087mL

Retain one extra digit than the number of significant figures, unless your first sig fig is 1, in which case retain two extra digits. If you don’t know what that means, it’s not really that important. Just don’t round your numbers off too aggressively. So we have (29.42±0.087)mL of water.

Now we have to deal with the division of the milligrams of 2-FMA by the milliliters of water. The formula for division/multiplication of uncertainty is different than addition/subtraction. Actually, technically the formula is the same, but instead of calculating on the absolute uncertainty (the number of milligrams or milliliters), we calculate on the relative uncertainty (a percentage).

So we have to convert our uncertainties into percentages. This is easy, just divide and multiply by 100:

(29.42±0.087mL)

0.087 / 29.42 * 100 = 0.29%

(29.42±0.29%)mL

And similarly,

(149±2)mg

2 / 149 * 100 = 1.34%

(149±1.34%)mg

Now we use the same formula as above, but with our percentages:

e = √(0.292 + 1.342)

= 1.37%

(5.06±1.37%)mg/mL

Finally, we convert our percent error back into absolute error by multiplying and dividing by 100:

5.06 * 1.37 / 100 = 0.069

(5.06±0.069)mg/mL

Technically your uncertainty should be rounded to 1 significant figure, unless it starts with a 1, in which case 2 sig figs. Then, the last digit of your value should be the first digit of the uncertainty. So in our case, we have, finally:

(5.06±0.07)mg/mL

Yay!

We now know that (basically) we are 95% certain that our solution has a concentration between 4.99mg/mL and 5.13mg/mL.

Dosing

So how do we dose? Let’s say we want to dose 25mg. First, we figure out how many milliliters we need by dividing:

25mg / (5.06mg/mL) = 4.94mL

Then we will use the same pipetting technique to measure that amount of solution. Make sure your liquid is well mixed first! Give ‘er a shake. I like to pour this liquid into a drinking class, and fill up the rest with water, and bottoms up!

EDIT: When actually dosing, avoid using the mouth pipetting technique. It can be very easy to estimate wrong how hard to suck, and end up with a mouthful of potentially orally active drugs. That's a big danger!

So… how certain are we that we have exactly 25mg?

Remember how to calculate uncertainty with multiplication and division? We need to use the percentage uncertainty. We have:

(4.94±0.05)mL * (5.06±0.07)mg/mL

Convert to percentage errors:

(4.94±1.01%)mL * (5.06±1.37%)mg/mL

e = √(1.012 + 1.372)

= 1.70%

(25.0±1.70%)mg

Convert back to absolute error:

25.0 * 1.70 / 100 = 0.43

(25.0±0.4)mg

Excellent! So we are 95% certain that our dosage is between 24.6mg and 25.4mg. How cool is that???

Conclusion

Is most of this necessary? In short, no, not really. I’m just a nerd.

What is necessary is volumetric dosing. If you don’t do this, you’re intentionally gambling with your life out of laziness. No, you don’t need to calculate error and all that shit. But the basic operation of creating a volumetric solution can be done in 5-10 minutes for under $60 and can save your life. So please, please be responsible and do the right thing.

If you have any questions or if there’s anything I can clarify, please post a comment. I’ll be happy to help out any way I can!