Psychostimulant drugs subjective effects

Table 3.8 Effects of psychostimulant drugs in healthy subjects...

The subjective effects of all the psychostimulants depend on personality, the environment in which it is administered, the dose of the drug, and the route of administration. For example, moderate doses of D-amphetamine (10-20 mg) in a normal person will produce euphoria, a sense of increased energy and alertness, anorexia, insomnia, and an improvement in the conduct of repetitive tasks. Some people become anxious, irritable and talkative. As the dose of amphetamine is increased, the symptoms become more marked and the influence of the environment less pronounced. 

A Rde for Norepinephrine. Although the vast majority of studies of psychostimulants have focused on the role of dopamine and/or serotonin, the importance of norepinephrine (thought to be paramount 30 years ago) is generally now overlooked. Details of the mechanism of action of psychostimulants have been developed primarily through the use of animal models, in which dopamine seems to be the key player, and these results then have been extrapolated to humans. Yet, cocaine also is a potent NE uptake inhibitor, and the potency of amphetamine for norepinephrine release is similar to that for dopamine release. Indeed, in the rat prefrontal cortex, amphetamine and cocaine increased extracellularnorepinephrine to an extent that was quantitatively similar to that of dopamine (116).Further, it appeared that the increase in prefrontal cortical norepinephrine was actually attributable to the blockade of the norepinephrine transporter by both drugs. Recently, Rothman et al. (117) reported that the oral doses of several stimulants required to produce amphetamine-like subjective effects in humans were most closely correlated with... 

Loeomotor aetivity has historically been used as an index of psychostimulant effects. Simple assessment of amount of loeomotor activity can provide the basis for anatomical as well as pharmaeologieal analysis of the neural substrates that mediate the behavioral expression of stimulant action. More sophisticated behavioral measurement systems ean reeord multiple measures of activity and describe spatial and temporal patterning of loeomo-tion. In such systems, qualitative aspects of behavioral activation can be evaluated by examining the entire activity profile. A comparison of the effects of novel drugs with those produced by well-characterized substanees may lead to a better understanding of their mechanisms of action and subjective properties. 

The psychomotor stimulants, cocaine and D-amphetamine, are considered together because they share a similar psychopharmacological profile.19 20 Low to moderate doses of both drugs given acutely to nontolerant, nonanxious subjects produce increases in positive mood (euphoria), energy, and alertness. Experienced cocaine users were unable to distinguish between intravenous (IV) cocaine and D-amphetamine,21 and cross-tolerance between cocaine and D-amphetamine with respect to their anorectic effect has been demonstrated.22 Additionally, the toxic psychosis observed after days or weeks of continued use of both psychostimulants is very similar. The fully developed toxic syndrome, characterized by vivid auditory and visual hallucinations, paranoid delusions, and... 

In addition to acute effects, however, prolonged usage of amphetamines (and other psychostimulants) can produce an "amphetamine psychosis." This syndrome was first clearly documented by Connell (25) and is regarded as very similar to paranoid schizophrenia, characterized by "paranoid psychosis with ideas of reference, delusions of persecution, auditory and visual hallucinations in a setting of clear consciousness" (25). The psychosis clears quickly after the drug is withdrawn. Psychosis has been induced experimentally in normal subjects by continuous amphetamine administration (26). Amphetamine psychosis has... 

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