  It is well known that individuals who abuse drugs usually use more than one
substance. Toxic consequences of single and multiple drug use are well
documented in the Treatment Episodes Data Set that lists combinations that
result in hospital admissions. Using this list as a guide, we focused our
attention on combinations that result in the most hospital admissions and
searched the PubMed database to determine the number of publications dealing
with these toxic combinations. Of special interest were those publications that
looked for or used the term synergism in their titles or abstracts, a search
that produced an extensive list of published articles. However, a further
intersection of these with the term isobole revealed a surprisingly small
number of literature reports. Because the method of isoboles is the most common
quantitative method for distinguishing between drug synergism and simple
additivity, the small number of investigations that actually employed this
quantitation suggests that the term synergism is not properly documented in
describing the toxicity among these abused substances. The possible reasons for
this lack of quantitation may be related to a misunderstanding of the modeling
equations. The theory and modeling are discussed here.
