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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

of repeated use, and will not recur unless a period of several days of abstinence
occurs. There is no evidence of withdrawal occurring to any of the hallucinogens
(Jacobs & Fehr, 1987).

Neurobiological adaptations to prolonged use

Few data are available on the long-term neurological effects of
hallucinogens. “Flashbacks” may occur either shortly after using the drugs,
or up to 5 years later (Jacob & Fehr, 1987). Flashbacks are spontaneous
recurrences of experiences which occurred during a previous LSD episode.
Other effects of long-term use include increased apathy, decreased interest,
passivity, and failure to plan ahead, and there may also be disregard for
social norms. However, it is difficult to ascribe these effects entirely to
hallucinogens, as they are often used with other drugs as well. Finally,
chronic use of hallucinogens can result in acute or long-term psychotic
episodes.

Summary

It is evident that almost all psychoactive substances share the common
property of increasing mesolimbic dopamine function. Not only
psychostimulants such as cocaine (Kuczenski & Segal, 1992) and
amphetamine (Carboni et al., 1989) but also narcotic analgesics (Di Chiara &
Imperato, 1988b), nicotine (Imperato, Mulas & Di Chiara, 1986), ethanol
(Imperato & Di Chiara, 1986) and phencyclidine (Carboni et al., 1989)
stimulate dopamine transmission in the nucleus accumbens (Di Chiara
&Imperato, 1988a), the main area of the ventral striatum. The implications
of this with respect to dependence were discussed in Chapter 3.
The understanding of the acute and chronic effects of psychoactive
substances on the brain has expanded greatly in recent years to begin to
provide a substantial molecular and cellular fingerprint of the extensive
changes in neuronal systems. The major realization has been that the use of
psychoactive substances usurps the normal physiological mechanisms that
mediate reward, learning and memory, and eventually results in remodelling
of neuronal contacts and pathways, producing long-lasting, near-permanent
changes. Furthering our understanding of the mechanisms involved still
requires intensive research effort, and the availability of sophisticated
molecular and biochemical tools should greatly facilitate this process.
Although psychoactive substances have these common effects, there
is still considerable variability between drug classes in terms of primary
physical and psychological effects, mechanisms of action, development of
tolerance and withdrawal, and long-term effects (see Tables 4.1 and 4.2).
Differences in the availability, cost, legality, marketing and cultural attitudes
towards psychoactive substances and their use also affect which substances
are used, and the development of dependence upon them. Thus, the study

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