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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

corresponded with the initial appearance of a decrease in cocaine self-
administration behaviour in rats (Kantak et al., 2001). The antibody response
was maximal after the third immunization and remained at this level for
4months. As with rats, there was substantial variability between individuals
in the magnitude of the antibody response. By one year after immunization,
antibody levels in all three groups declined to baseline values. Adverse effects
were minor and included small temperature elevations, mild pain and
tenderness at the site of injection, and muscle twitch at the highest dose.
Phase II clinical trials with TA-CD are currently underway; however, press
releases describing preliminary findings are available on the Internet. In the
initial phase II study, an improved dosing regimen was initiated to boost anti-
cocaine antibody levels. The immunotherapy produced high levels of
antibodies against cocaine which approached levels produced in the rodent
self-administration model.
In terms of clinical treatment with the cocaine immunotherapy, it is likely
to work best with individuals who are highly motivated to quit using drugs
altogether, since anti-cocaine antibodies are liable to have pharmacological
specificity in addition to their behavioural specificity. The cocaine
immunotherapy induces antibodies that are highly specific for recognizing
cocaine and its active metabolite norcocaine and active derivative
cocaethylene (Fox et al., 1996), and therefore they would not recognize
structurally dissimilar stimulants.
It is clear from the present series of studies that the anti-cocaine actions
of the cocaine immunotherapy emerge gradually over time once
immunization begins. Therefore, the immunotherapy is not expected to
immediately target craving for cocaine. Craving is significantly more common
among inpatients than outpatients, but cocaine-abstinent individuals report
less craving across outpatient treatment and follow-up compared to moderate
and heavy cocaine users (Bordnick & Schmitz, 1998). On the basis of these
considerations, it is hypothesized that treatment with the cocaine
immunotherapy may eventually help ease craving and prevent relapse if it
extinguishes cocaine use. Adjunct treatment with an anti-craving medication
may help in this regard, particularly during the immunization process. How
anti-cocaine antibodies interact with anti-craving medications deserves
serious attention (e.g. Kuhar et al., 2001) as the development of these
medications continues and the ability of the immunotherapy to block the
reinforcing effects of cocaine in human clinical trials unfolds.
The ethical implications of this new type of therapy are considered in
Chapter 7.

Amphetamines

Introduction
Amphetamines include ∆-amphetamine, L-amphetamine, ephedrine,
methamphetamine, methylphenidate, and pemoline. Another member of this

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