What is pH?

pH simply describes the concentration of hydrogen ions (H+) in a solution. It is a log scale, so for every 1 unit decrease in pH, the concentration of H+ goes up 10 times.

The importance of pH is that it can change the ionization state of many molecules. Ionization will give the molecule a positive or negative charge:

• If a molecule is a base, it can be neutral at higher pH values and positively charged at lower pH values.
• If a molecule is an acid, it can be neutral at lower pH values and negatively charged at higher pH values.

Every molecule has a property called its pKa – this is the pH at which 50% of the molecules are ionized and 50% are un-ionized.

Changing the ionization state can make big changes in the solubility of the molecule, but also in its ability to cross cell membranes. An ionized molecule is typically too highly charged to be able to cross membranes. As you will see in the next section, this is very important for how fast your body can excrete some drug molecules into the urine!

Urine pH and Ion Trapping

Consuming very acidic and basic foods doesn’t do much to the pH of your blood because it is highly buffered. However, your body will excrete the excess acid or base into your urine, which can significantly change its pH. The normal urine pH range is between 4.6 and 8 and can fluctuate throughout the day depending on what you eat.

Urine pH can affect drug elimination through a process called ion trapping, which I will briefly explain:

Your kidney starts to form urine by filtering your plasma (the aqueous part of your blood). The plasma that has been filtered is on the path to becoming urine, but first it has to travel through a tube (technically called a “tubule”). Some molecules can diffuse through the cell membranes that form the walls of these tubes and be reabsorbed into the blood. But remember that molecules cannot cross membranes while in their ionized form. So the ionized molecules are stuck in the tubes and are excreted into the urine.

[Here are more details on how ion trapping works.]

Note that (despite some people saying otherwise) solubility is NOT a limiting factor in excretion of THC or any of its metabolites into the urine. Yes, the water solubility of THC and some metabolites is low, but free concentrations in your plasma and concentrations in your urine never approach anywhere near the solubility limit.

An Example of Ion Trapping with Methamphetamine

I’ll give a concrete example so that you can understand ion trapping better. Methamphetamine is the classic case of where it can have a dramatic effect on drug elimination.

Unlike THC metabolites, meth is a base instead of an acid (meaning that it is more ionized at lower pH instead of higher pH). But the principle is still the same. With a pKa of 9.87, meth is 98.7% ionized at pH 8, but virtually 100% ionized at pH 5.

This small difference in ionization was enough to drastically affect renal elimination of meth. When urine was alkalinized, virtually none was excreted into the urine. But when urine was acidified, over half of the dose was excreted into the urine:

Urine pH Does Not Affect THC and 2 Metabolites

Besides THC itself, there are 3 important metabolites in the pathway that leads to elimination in the urine. These are 11-OH-THC, THC-COOH, and THC-COO-glucuronide. I will examine each one for whether it is possible to increase elimination by altering urine pH. I will assume 6 to be a normal urine pH and that you could achieve a pH of 8 with ingestion of sodium bicarbonate.

THC has a high pKa of 10.6. Raising urine pH from 6 to 8 only increases the ionization from 0% to 0.3%. This is not enough to have any ion trapping effect.

11-OH-THC is similar – with a predicted pKa 9.3, ionization will go from 0.1% to only 4.8%. There is no reason to think that ion trapping can happen.

THC-COO-glucuronide has a predicted pKa of 3.2. Ionization will go from 99.8% at pH 6 to virtually 100% at pH 8. However, it is a relatively large molecule (molecular weight of around 565 g/mol) that would not easily cross membranes, even in an unionized state. So it is not likely to be reabsorbed either way.

There is also clinical evidence that THC-COO-glucuronide is not reabsorbed. The observed renal clearance matched perfectly with the calculated glomerular filtration rate (GFR x free drug fraction). While you don’t have to understand exactly what this means, it is further evidence that no significant reabsorption is occurring and therefore increasing urine pH will not have any effect.

Urine Alkalinization May Slightly Increase Excretion of THC-COOH

THC-COOH is the most interesting metabolite, because it is a good candidate for ion trapping! With a predicted pKa of 4.2, ionization will go from 98.4% at pH 6 to nearly 100% at pH 8. Looks good from a theoretical perspective, but lets dig deeper.

We have clinical evidence that nearly 100% of this metabolite is in fact reabsorbed into the blood after being filtered. We can determine this by comparing its calculated filtration rate (0.58 L/h) to its observed renal clearance (0.0084 L/h) measured by how much metabolite actually makes it to the urine. The actual excretion rate is about 70-fold below the calculated filtration rate, which means that almost all of what is filtered is reabsorbed.

This doesn’t entirely prove that passive reabsorption of THC-COOH is occurring, because it could be that your kidney is actively pumping it back into your blood via transporter proteins. If this is the case, alkalinizing your urine may do nothing. Unfortunately, we don’t know if this is the case or not.

Let’s assume for a moment that alkalinizing the urine would completely block reabsorption. Could this really be an effective strategy for THC detox? The maximum possible renal elimination would be equal to the filtration rate of 0.58 L/h (technical note: I’m assuming no active tubular secretion). This is a nearly 70-fold increase in urine elimination! Although it may seem incredible, it is not out of line with what was observed with methamphetamine.

But before you get too excited, I have to tell you of a major limitation – even this higher kidney clearance is only a fraction of the clearance by your liver. Hepatic (liver) clearance is 5.8 L/h (if you use activated charcoal, which you should!). This means that we are only talking about increasing overall clearance of THC-COOH by 10%. This is not that dramatic compared to some other techniques.

Another issue is whether the detox effect is permanent. My opinion is that it the effect is only temporary. Once urine alkalinization is stopped, fat-stored THC and 11-OH-THC will replenish levels of THC-COOH to what they would have been if you had never changed the urine pH. For this reason, I will give the same recommendation that I do for activated charcoal: only bother using it in the 48 hours before a test.

Don’t forget that increased urine elimination becomes a liability on test day. You want urine THC-COOH levels to be as low as possible, so obviously increasing THC-COOH excretion into the urine is a bad thing. You should STOP urinary alkalinization at least a few hours before the test and make sure that your urine pH returns to the normal acidic range. You can monitor this with urine pH test strips.