Introduction
Few words in the English language are more polarizing than “drug” but what exactly is a drug? As Dr. Andrew Weill states, the common definition of a drug is “any substance that in small amounts produces significant changes in the body, mind, or both.” Are all drugs medicine, and are all medicines drugs? The answer is subjective and unclear.
Most people would consider an antidepressant like a benzodiazepine or a narcotic like heroin to be a drug. What about caffeine and nicotine, which are habit-forming stimulants; salt, which can also be addictive and affects the body’s physiological function; or sugar, which is highly addictive, and affects mental and physiological function and mood? Are these substances also medicines?
The U.S. Food and Drug Administration goes a step further to include in the definition of a drug as “a substance (other than food) intended to affect the structure or any function of the body” [1] which would exclude sugar. Is salt considered a food? (Maybe) Could it be used medicinally? (In some cases, yes) Is alcohol a food, given that it can be used as an energy source for the body similar to a carbohydrate, or a drug considering its intoxicating and even poisonous properties? (Perhaps both)
The definition of what constitutes a drug is subjective. Even more subjective is how a society judges a substance, whether a drug or a food. While Sufi Muslims and Buddhists originally encouraged the use of caffeine for alertness during prayer/meditation and shunned the use of alcohol, the Catholic Church originally viewed wine as sacred but saw caffeine as a threat to social order [2]. As Dr. Weill states: “Everybody is willing to call certain drugs bad, but there is little agreement from one culture to the next as to which these are.” [3]
Food as nutrition, medicine, and poison
The history of medicine is inextricably tied to plants, as food was seen by early societies as a source of nutrition as well as a source of healing. The world’s earliest pharmacopeia dates back to 3rd century China, and is attributed to Shennong, the “Divine Farmer” who discovered tea, the use of the cart and plow, and the planting of staple crops to fight repeated famine. While it’s unknown when Shennong lived (believed to be 2737 BCE), it’s notable that the first medicinal catalog is attributed to the legendary father of Chinese agriculture, indicating an early understanding of the healing power of food. As the Greek physician Hippocrates stated in 440 BCE, “Let food be thy medicine and let thy medicine be food.”
Early Chinese alchemists and physicians understood that there is a fine line between a medicine and a poison; the Chinese word du (毒) even holds a dual meaning that can be interpreted as either a poison or a potent cure. This belief is reflected in the 2nd century Daoist text Huainanzi, describing the anesthetic / analgesic derived from wolfsbane roots (Aconitum Fischeri): “For all things under heaven, nothing is more vicious than the poison of aconite. Yet a good doctor packs and stores it, because it is useful.”
As Paracelsus famously stated 1600 years later: “the dose makes the poison”, reflecting that every substance, including vitamin D, water, and oxygen, can be toxic if consumed in excess [4]. What makes one drug more poisonous than another is the pharmacology of how much of a dose is too much.
Role of Regulatory Agencies
How do we know which drugs are approved to treat which indications (signs, symptoms, or medical conditions), and within what dosing range? All drugs must go through a rigorous clinical evaluation and approval process overseen by a regulatory body like the Food and Drug Administration (FDA) in the U.S. or the European Medical Agency (EMA) in Europe. The New Drug Application (NDA) process is costly and lengthy, requiring nearly 8 years and $1.4 Billion on average (not including R&D) [5].
The mission of agencies like the FDA and EMA is to protect and promote public health, which extends their jurisdiction beyond drugs and medicines to food, supplements, bottled water, tobacco, and even cosmetics.
Supplement vs. Drug
Given the fluid definition of “drug”, how do regulatory bodies like the FDA distinguish a caffeine pill from a painkiller like ibuprofen? While there may not be a scientific distinction between a drug and a supplement, there is a clear regulatory definition: drugs are intended for use in the diagnosis, cure mitigation, treatment, or prevention of disease whereas supplements are intended to supplement the diet and cannot be represented for treatment, prevention, or cure of a disease [6].
While caffeine and ibuprofen are both drugs (by our scientific definition), only ibuprofen is considered by the FDA to be a drug as it has been approved for treatment, prevention, or cure of a disease. For caffeine to be considered as a drug by the FDA, it would have to have undergone the lengthy and costly process of clinical evaluation in a New Drug Application for treatment, prevention, or cure of an indication.
This does not mean that a supplement like caffeine could not be an effective drug for treatment of a disease (as of September 2022, 1,246 clinical research studies involving caffeine have been completed or are in process [7]). It simply means that caffeine has not been approved for treatment of a disease and cannot be represented as such.
“A rose by any other name would smell as sweet.”
– William Shakespeare, from Romeo and Juliet
The designation of a caffeine pill as a supplement rather than a drug does not change what caffeine is or does – it is a substance that affects the mind, body, and mood; has been used therapeutically; and is poisonous at high doses. Why would anyone choose to develop a supplement vs. a drug? This will be the topic of a future post.
References
- [1] Drugs@FDA Glossary of Terms. https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-terms#D, Sep 27, 2022.
- [2] Pollan, Michael. This is Your Mind on Plants. New York, Penguin Press, 2021, pp. 105.
- [3] Weill, Andrew, and Winifred Rosen. From Chocolate to Morphine. New York, Houghton Mifflin Company, 2004, pp. 10-14.
- [4] Trautmann, Nancy M., et al. Assessing Toxic Risk. Harrisonburg, NSTA Press, 2001.
- [5] Congressional Budget Office. Research and Development in the Pharmaceutical Industry. April 2021.
- [6] Questions and Answers on Dietary Supplements. https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements May 6, 2022.
- [7] https://clinicaltrials.gov/ct2/results?cond=&term=caffeine&cntry=&state=&city=&dist=. Sep 27, 2022.