Drug abuse/addiction tolerance

Drug abuse and dependence Prolonged abuse of ephedrine can lead to symptoms of paranoid schizophrenia. Patients exhibit such signs as tachycardia, poor nutrition and hygiene, fever, cold sweat, and dilated pupils. Some measure of tolerance develops, but addiction does not occur. 

Amphetamines are definitely drugs which have been and are abused. Notice that the organic modifications in the fundamental amphetamine structure are to make the compound more lipophilic and so speed its delivery to the CNS as well as heighten the stimulant and euphoric effect. Therapeutic doses of amphetamines range from 5 to 10 mg for a maximum of 60 mg per day while abusive doses may be as high as 500-1000 mg every 2-3 hours. The side effects of abuse include tolerance, addiction, malnutrition, heart arrthymias, and... 

In this chapter we have attempted to emphasize the psychopharmacological mechanisms of the actions of dmgs of abuse and have used these mechanisms to describe dmg dependence as well. We have attempted to define the terms frequently used in describing drug abuse and dependence, including abuse, addiction, dependence, reinforcement, tolerance, cross-tolerance and cross-dependence, withdrawal, relapse, and rebound. 

Sympathomimetics can be physically addictive and should not be prescribed to people with a history of drug abuse. A person may develop a tolerance to the drug and attempt to increase the dosage. The person may develop intoxication symptoms such as insomnia and severe skin diseases. 

Narcotics addiction provides the classic model of drug dependence, and many of our current notions of drug abuse are based on it. For example, the fundamental principle that addiction con= sists of three features — craving for the drug, tolerance, and withdrawal — developed from observations of opiate addicts. Many popular beliefs about narcotics are untrue, however, and the whole subject is highly contaminated by prejudice and emotion. 

The amphetaminesand anorexiants have abuse and addiction potential. Long-term use of amphetaminesfor obesity may result in tolerance to the drug and a tendency to increase the dose. Extreme psychological dependency may also occur. 

Given the low incidence of severe withdrawal symptoms and the modest effects on the mesolimbic dopamine (reward) system, most investigators have found that cannabis has a low abuse or addiction potential. However, it has been argued that if cannabis is a non-addictive substance, why is its use so widespread and why are there so many longterm and heavy users Finally, contrary to the evidence that cannabis can produce chronic tolerance, some regular users report that they require less drug to achieve the same high, or sensitisation (Chapter 3). Three possible explanations may account for this. First, chronic users may focus on the effects that they wish to achieve. Second, the... 

Upregulation of the cAMP pathway may be a common mechanism by which a number of neuronal cell types respond to chronic opiates and develop tolerance and dependence (see Ch. 56). There is also evidence that similar mechanisms involving alterations in the cAMP second-messenger and protein phosphorylation pathway may mediate aspects of addiction to other types of drugs of abuse, for example, cocaine and alcohol [66],... 

Use opioids with caution in patients with alcoholism or other drug dependencies because of the increased frequency of opioid tolerance, dependence, and the risk of addiction observed in these patient populations. Abuse of opioids in combination with other CNS depressants can result in serious risk to the patient. 

Tolerance, sensitisation, craving, withdrawal and relapse may actually be more complicated than indicated above and may involve separate mechanisms which are too complex to summarise here (See Altman et al., 1996). Recent research on specific drugs of abuse is reviewed by several authors in a special issue of Trends in Pharmacological Sciences 13 169-219 (1992). However, the concept of addiction as "an emotional fixation. .. acquired through learning, which intermittently or continually expresses itself in a purposeful stereotyped behaviour with the character and force of a natural drive, aiming at a specific pleasure or the avoidance of specific discomfort (Bejerot, 1980) still broadly applies. 

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