Therapeutic margin is the ratio between the therapeutic dose of a medicine and the lethal dose of a medicine. For example, if Substance A has an effective dose of around 500 milligrams and a lethal dose of 50 grams, it has a therapeutic margin of 1:100, which is fairly good. Accidentally overdosing on such a substance is unlikely. On the other hand, if Substance B has an effective dose of 3 grams and a lethal dose of 8 grams, then it has a therapeutic margin of 1:2.6, which means someone could quite possible accidentally die from taking the medication.
As with most medical concepts, therapeutic margin can shift quite a bit depending on a persons metabolism, other medications or drugs they may be taking, and the phase of the moon. That is one reason why drugs with small margins are so dangerous, a person may die from a dose that previously did not harm them.
From comparing the margins of various substances, I have discovered that their is a surprisingly low correaltion between how mentally unbalancing a drug is and what its margin is. Acetameniphen, the main ingredient in tylenol for example, has a therapetutic margin of around 5-10. LSD, on the other hand, has a margin of around 10,000.
Which brings us to one possible problem with this term: as we all know, not everyone who uses a drug uses it for therapeutic purposes. The concept of therapeutic margin still applies when a drug is being used for recreational purposes.