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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

The third major mechanism by which psychoactive substances may have
adverse effects is through dependence. As technically defined, the concept of
dependence includes elements which are directly biologically measurable, such
as tolerance and withdrawal and those which are cognitive and experiential,
such as craving and impairment or loss of control. These latter elements can
be modelled in or inferred from biological measurements, but cannot yet be
directly measured. Thus, while neuroscience research can directly measure
states and effects which are relevant to concepts of dependence it cannot
measure dependence itself. Dependence is seen as a major contributor to the
health and social harm from psychoactive substance use according to its
definition as the motor of continuing use. In fact, one element of the definition
of dependence is by imputation back from the occurrence of harm: that use
has continued despite knowledge of the harm (Chapter 1, Box 1.2, Criterion 3).
The strength of effect on the various components of dependence differs
between different psychoactive substances, and according to the dosage and
dosage schedule. The potential of a given substance to produce various aspects
of dependence is also affected by the sociocultural circumstances in which it
is used and by individual genetic inheritance.
Dependence is a complex disorder; how an individual becomes dependent
on drugs is probably as complex as the brain itself. Some aspects of the
syndrome are clear, but much remains to be learned, for instance in the areas
of craving and loss of control. There is no linear relationship between the
amount of a substance used and the severity of dependence, no single
relationship between pattern of use and onset of dependence, and no fixed
relationship between experimentation and dependence. Thus, despite our
knowledge about such matters as vulnerability, mechanisms of tolerance,
withdrawal and craving, we presently cannot predict who will lose control
over use and become dependent. A lot thus remains to be learned about these
processes when studying the neuroscience and social science of dependence-
related behaviours.
Thus far, one side of the findings from neuroscience has been emphasized:
how psychoactive substances act in terms of the common biological
inheritance shared by all humans. The other side of the neuroscience research,
reflected in Chapter 5 and partly in Chapter 6, is to some extent a counterpoint
to this. The genetic research focuses on the differences in action of the
substances between one human and another which are attributable to
different genetic inheritances. The findings from this literature suggest that
genetics modulates many aspects of the actions of psychoactive substances
in humans. Thus genetic differences can make the use of the substance more
or less pleasurable or aversive to a particular individual and can affect the
toxicity of the substance, both in terms of overdose and of chronic health
effects. Genetics can also affect the intensity of psychoactive effects of a given
formulation and dose of a substance, as well as the likelihood of the
occurrence of different aspects of dependence, i.e. tolerance and withdrawal,
and those aspects which are not directly biologically measurable.

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