When a given drug dose fails to elicit an effect of the expected magnitude after repeated administration, tolerance toward the drug has developed. Tolerance may be physiological or behavioral. There are several potential mechanisms for physiological changes that reduce the potency of a drug. With repeated administration many psychoactive drugs can increase the efficacy of the hepatic enzyme systems that metabolize them. This process, called enzyme induction, can increase the speed of elimination of these drugs. Barbiturates serve as a classic example of this type of tolerance induction.

To overcome tolerance, the dose must be increased or drug administration must be stopped for a period of time. Doctors working with opiate addicts say that occasionally their patients volunteer for treatment not in order to become completely free from their habit, but to reduce the tolerance and the amount of drug they need because the financial burden has become unbearable. Other pharmacokinetic mechanisms for tolerance development include a reduction in absorption of the drug and an increase in the number of drug acceptor sites that bind the physiologically active molecules. From the side of pharmacodynamic mechanisms, tolerance may develop because of a down-regulation of the number of receptors, decrease in efficiency of the intracellular signal transduction, or recruitment of functionally antagonistic physiological mechanisms, which can be a fairly complex phenomenon.

Cross tolerance refers to the fact that tolerance induced by a drug may generalize to the efficacy of other, related drugs. For example, opiates elicit cross tolerance. Cross tolerance can also occur because of the enzyme induction in the liver since the relatively low specificity of the hepatic enzyme systems means that an increase in the catalytic activity or in the expression of a given enzyme caused by a drug will enhance the biotransformation of several drugs that are inactivated via similar chemical reactions. When tolerance develops rapidly—as when a single dose severely weakens any forthcoming drug responses—it is called tachyphylaxia. Tachyphylaxia occurs with such drugs that deplete the endogenous resources recruited in their mechanisms of action, for example, causing an extensive release of a neurotransmitter.

In psychopharmacology, behavioral tolerance plays a role, but remains difficult to explain in physiological terms. It is manifested as a reduction of the potency of the drug in familiar circumstances and can include volitional control that the subject has learned to exert over behavior. For example, a subject may acquire a degree of control over the inebriant effects of alcohol or cannabis, creating the impression of being in a sober state.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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