Sensitivity

Sensitivity describes how strongly a person responds to a substance relative to a typical expectation — an outcome shaped by genetics, enzyme activity, age, liver function, body composition, and the presence of other substances in the body.

In research and testing contexts, the word carries a second meaning: the sensitivity of a test or assay is how reliably it detects a compound that is genuinely present. Both senses are consequential for harm reduction, and confusing them is a common source of misplaced confidence.

How it is done

Accounting for individual sensitivity in practice usually begins with taking a smaller quantity than intended and observing the response before proceeding further. The underlying recognition is that no one can know in advance exactly where they fall on the distribution of responses to a given substance.

Factors that bear on individual sensitivity include which enzyme pathways metabolise the substance (cytochrome P450 enzymes such as CYP2D6 and CYP3A4 are particularly relevant for many psychoactive substances), genetic variation in those enzymes that determines whether a person metabolises a compound quickly or slowly, age, body composition, and the presence of medications or other substances that share or inhibit the same metabolic routes.

For assay sensitivity, the relevant question is whether a reagent test or detection strip reliably identifies the compound of interest — at the concentrations typically encountered, and in the presence of other substances in the sample.

What it cannot tell you

Individual sensitivity cannot be reliably predicted from prior experience with the same substance. Enzyme activity, receptor density, and body composition all shift over time with age, illness, and medication changes — a response that was unremarkable in the past may not be representative now.

Experience with one substance does not transfer as a prediction of sensitivity to another, even within the same pharmacological class. Tolerance to the subjective effects of a substance does not equal tolerance to its toxic effects; those two thresholds can diverge considerably.

For testing, low assay sensitivity means a negative result cannot confirm that a compound is absent — only that it was not detected at the concentration the test can reliably find. A strip or reagent with poor sensitivity for a particular compound can return a negative in a sample that nonetheless contains it. A reassuring negative should be read as not detected, not as not present.