A major concern about the recreational use of cannabis has been whether it may lead to functional or structural neurotoxicity or “brain damage” in ordinary language. Fehr & Kalant (1983a) defined neurotoxicity as “functional aberrations qualitatively distinct from the characteristic usual pattern of reversible acute and chronic effects, and that may be caused by identified or identifiable neuronal damage”. On this definition an enduring impairment of cognitive functioning could be interpreted as a manifestation of neurotoxicity if neuronal damage were also demonstrated. Cognitive deficits may be the end result of secondary changes associated with drug use, as opposed to a direct toxic effect on neurons. A thorough review of the cognitive literature in relation to long-term cannabis use is presented in Chapter 5. This chapter will concentrate on the direct investigations of neurological function and toxicity arising from exposure to cannabinoids.

The review begins with an examination of the evidence for functional neurotoxicity from animal behavioural studies. Neurochemical, electrophysiological and brain substrate investigations of functionality follow, and the chapter concludes with the findings of more invasive examinations of brain structure and morphology in animals, and of less invasive techniques for imaging the human brain.

Animal behavioural studies

Animal research provides the ultimate degree of control over extraneous variables; it is possible to eliminate factors known to influence research findings in humans, such as nutritional status, age, sex, previous drug history and concurrent drug use. The results, however, are often difficult to extrapolate to humans because of between species differences in brain and behaviour and in drug dose, patterns of use, routes of administration and methods of assessment.