Introduction 5idea. Ultimately some still unknown physical process may explain why people
who take a drug for pleasure develop a tolerance to its effects, while people
who take the same substance for medical purposes never experience a change
in what the drug does.
From a purely physical standpoint, someone who has recreationally abused
a drug for years may indeed be able to tolerate a stronger dose than someone
who takes the same drug for the first time. The abuser’s body may develop
physical adaptations permitting high doses. For instance, body chemistry can
change in ways that counteract a drug, requiring more and more of the sub-
stance to overcome the change. Nonetheless, for many practical purposes we
can say the cause of tolerance is psychological. This was implied in medical
research comparing the amount ofmeperidinerequired to relieve pain in
appendectomy patients.^4 The study was conducted in Beirut and examined
records of patients who underwent surgery before, during, and after a brutal
civil war that destroyed much of that city. For pain relief, prewar patients
needed more of the drug than wartime or postwar patients did. Researchers
concluded that part of the reason was a psychological change in how pain
was evaluated during those years of brutality. The study did not directly in-
vestigate tolerance, but it did demonstrate that a change in attitude can change
the amount of drug effect perceived by users.
Change in attitude illustrates the influence of set and setting on drug effects.
Setdescribes someone’s basic personality and expectations about what a drug
does.Settingis the environment in which drug use occurs. Rat experimenta-
tion^5 demonstrated that the setting in which a drug is administered can alter
the amount of tolerance, with those conditions demonstrating a psychological
component in physical tolerance. Countless human examples demonstrate that
set and setting can determine how much effect a given drug dose produces,
whether it is pleasant or unpleasant, even whether a dose is tolerable or fatal.
Dosage affects a drug’s impact. Overdose of most drugs can produce serious
unwanted effects, including death. In addition to the amount of drug, the
method of dosage (injection, oral, smoking, or other routes) can make a huge
difference in effects. The same amount of drug can have a much different
impact depending on route of administration. A “safe” dose by one route can
be fatal by another. An effect at one dosage level may be the opposite of what
happens at a different dosage level. Sometimes a drug can cause a condition
that it is supposed to prevent. Such paradoxical actions illustrate hazards in-
volved in reckless drug use.
Taking more than one drug of a given type can be expected to increase
effects typical of that type. For example, a person who ingests the depressant
alcoholsimultaneously with an opiate depressant will normally experience
deeper depressant effects than if just one of the drugs was used. Taking a
normal dose of several drugs from one type can be the practical equivalent of
overdosing on any one of them. Taking drugs of different types can also be
hazardous. For example, the stimulantcocaineand the depressantheroindo
not cancel each other’s effects if taken together; instead, the body may be
assaulted from different directions simultaneously and break down under the
attack.