When a patient or test subject is given a placebo, what, specifically, are they given? In college the textbook said “sugar pill,” but I’m unclear on if that’s industry speak or if the placebo is literally made of sugar. Or do they use something else, like cornstarch or something?
If the placebo is injected, what do they get? Water? Saline solution?
There are different types of placebos for different applications.
One commonly accepted definition of a placebo in a drug or vaccine trial is a substance(s) that are identical to the product being tested, with the exception of the active ingredient(s). Sometimes a totally inert placebo like saline or a “sugar pill” will be used.
People sometimes react negatively to inert placebos.
There’s even “sham surgery” in which a procedure is actually performed on the patient; the patient undergoes real surgery and gets a real scar, but the specific therapeutic procedure is skipped.
Yes, but the question is, what are they made of? Is a sugar pill literally made of sugar?
No. The placebo pill is made up of everything else, except the active. If the dosage of a medicine is, say 100 milligrams, and the pill weighs 500 milligrams or half a gram, then its 4/5 excipients. So replace the active with “sugar” and form it into a pill.
You want to know what “excipients” are. They’re things, added to actives, to make them into medicine. Active ingredients aren’t medicine – active ingredients don’t work if you can’t ingest them properly. No one, ever, made medicine that needed a person to swallow 1/10 or 1/50th of a gram. Particularly not if the patient had to measure it accurately. Mixing active with something to get it down has been the doctor’s task since Ancient Greece, and was still done by hand by doctors in the Victorian era and beyond. And yes, manufacturing and dispensing has changed over time to pharmacists and pharmaceutical manufacturing companies. Same job, new name, and yes, much more advanced manufacture.
You can easily read, on the back of a bottle of vitamins, what things are typical excipients:
gum arabic, crystalline cellulose, calcium stearate, silicon dioxide, titanium dioxide, FD&C lake.
So: glue, wood pulp, sand, grease and paint, if you have to make the worst analogies possible.
What is the “sugar” that replaces the active ingredient?
If I interpret Arkcon correctly, a normal pill is 1/5 drug, and 4/5 filler. A placebo is 5/5 filler.
A tablet is made up of the active substance, functional excipients and filler(s) - so well done for either knowing the term or just happening to use the word more or less correctly. Excipient means other stuff in the dosage form. Functional excipients do things like help a tablet disintegrate to release the active, or help form the tablet in the first place, or taste mask (etc). (In a liquid medicine they might adjust pH, flavour the medicine and so on.) Tablets contain fillers in order to produce a dosage form of a convenient physical size.
All of the placebo tablets I have worked on simply replace the active with more filler. As it happens, lactose (milk sugar) just happens to be a very common filler. I think the reference to a “sugar pill” refers to something that was done generations ago but, as it happens, often the thing that replaces the active just happens to be lactose.
j
There are very good reasons why it could not literally be sugar. Studies have shown psychological effects associated with size, shape and color of pills. People might certinainly (say) associate a bitter taste with a medicine being effective. You’d want to make sure that the placebo looks and tastes exactly the same.
I also recall that the "sugar"as lactose. Now, at a few milligrams level, its not likely to trigger the average person who happens to be lactose intolerant, but the risk to someone very sensitive might not be worth the risk. Unless the placebo is just for a study, and people are screened first. But sucrose would work. Its bound in a pill of excipients and coated on the outside with something slippery like all medicine – both for release from the tablet pressing machine and to help it slide down the patient’s throat. There’s no need to suck on it like a lozenge – unless you’re trying to check if you’ve got a placebo or not. Then again, maybe sugar is an excipient – we just have to bulk up the pill, we can use just about anything, so long as its not harmful.
The active ingredient in many pills is measured in milligrams. More like 99.9% filler.
When drugs are tested the placebo should consist of everything normally in the drug except for the active ingredient. When a doctor prescribes a placebo on the basis that the patient does not know what it is then it could be anything, ‘sugar pills’ are likely. I think ‘sugar pills’ are not pure sugar but a sweetened filler, sometimes with artificial sweeteners.
This is absolutely true. In some cases, even an inert ingredient can produce a transient side effect, like a funny taste in your mouth for 10 or 20 minutes, and you want to make sure the placebo group is getting that effect.
The “placebo effect” is actually referred to as the “placebo response” now.
A couple of very interesting studies have shown that response to medication is partly a learned behavior: one was a study that demonstrated a placebo response in non-humans, and the other was a study the demonstrated that memory-impaired people have impaired ability to respond to placebos, and their ability is in direct proportion to their impairment. People with just slight impairment can still respond, albeit, have difficulty learning to respond to new drugs; highly impaired people have no response.
The studies support people who insist that they need a brand name drug, not a generic, or even a particular brand name. That is what they have learned to respond to, and they have trouble transferring their response to a different-looking drug.
It’s particularly true when the generic is a smaller pill.
Drug companies are onto this. Usually the amount of actual medication in a pill is pretty small, and the 5mg and 10mg versions of two pills could be the same size, but drug companies know to make the 10mg pill bigger, because people expect more medicine = bigger pill.
Gum arabic is not so common these days. It’s usual use is in syrups, in my experience those in which the active is suspended rather than dissolved. It makes a liquid thixotropic - so that it’s thick (so that the active doesn’t settle) until you shake it, when it becomes runny (so you can resuspend the active if settled, and pour out a dose); and thereafter it thickens again. More than just glue.
Cellulose (microcrstalline cellulose) is usually used in tablets - it’s compressible, so it helps with tablet formation (it’s occasionally used to thicken liquids).
Silicon dioxide (also with a miniscule particle size) can also be used to produce thixotropy in liquids, but its usual use is in tabletting, where it aids flow in the powder mix during the tabletting process, thus improving consistency of tablet weight.
Titanium dioxide and FD&C lake(s) are colourings - it’s desirable that tablets are not confused with one another, and colour is one of the ways of doing this.
j
My favourite placebo fun fact is that more expensive placebos work more effectively than cheap ones. In answer to the OPs question it could mean mimicking the visual difference between a brand medicine and a store-brand or generic form of the drug and its packaging, and seeing if that has an effect on the outcome.
Correct, and the reason why lactose is less likely to be used today than in earlier decades.
Some pills are big enough to be a bit difficult to swallow, and all for a few milligrams of active ingredient. Calcium/VitaminD supplement pills are a notable case in point. I know they can be made much smaller (because I used to find the “petite” variety in stores) but those have disappeared. Some antibiotic pills I’ve been prescribed also came in unusually large tablets or capsules, all for a few milligrams of medicine.
Some of those antibiotics (erythromycin is an excellent example of this) and other drugs too are enteric-coated because they’re too irritating to the stomach, or may not be useful after exposure to stomach acid, and those coating can be very thick. Hence the big tablets for a seemingly small amount of medication.
I just realised I forgot calcium stearate. That’s a lubricant - it prevents tablets sticking to the punches/dies during compression. Sorry 'bout that.
j
I’m swallowing lube? 