Tolerance & Dependence

When drugs such as heroin, morphine, nicotine are used repeatedly over time, TOLERANCE may develop.

Tolerance occurs when the person no longer responds to the drug in the way that person initially responded.                                                                                       

It takes a higher dose of the drug to achieve the same level of response achieved initially.

For example, in the case of heroin or morphine, tolerance develops rapidly to the analgesic effects of the drug.

The development of tolerance is not addiction, although many drugs that produce tolerance also have addictive potential.

Tolerance to drugs can be produced by several different mechanisms, but in the case of morphine or heroin, tolerance develops at the level of the cellular targets.

For example, when morphine binds to opiate receptors, it triggers the inhibition of an enzyme (adenylate cyclase) that coordinates several chemicals in the cell to maintain the firing of impulses.  

                                               

After repeated activation of the opiate receptor by morphine, the enzyme adapts so that the morphine can no longer cause changes in cell firing.

Thus, the effect of a given dose of morphine or heroin is diminished.

The development of tolerance to the analgesic effects of morphine involves different areas of the brain separate from those in the reward pathway.

The areas involved in tolerance are the thalamus and the spinal cord.

Both of these areas are important in sending pain messages and are responsible for the analgesic effects of morphine.

 With repeated use of heroin, morphine and nicotine Dependence also occurs.

Dependence develops when the neurons adapt to the repeated drug exposure and only function normally in the presence of the drug.

When the drug is withdrawn, several physiologic reactions occur. These can be mild (e.g., for caffeine) or even life threatening (e.g., for alcohol).

This is known as the withdrawal syndrome.

In the case of heroin, withdrawal can be very serious and the abuser will use the drug again to avoid the withdrawal syndrome.

The development of dependence to morphine also involves specific areas of the brain, separate from the reward pathway.

The area involved in the dependence are thalamus and brain stem.

Many of the withdrawal symptoms from heroin or morphine are generated when the opiate receptors in the thalamus and brainstem are deprived of morphine.

Different parts of the brain are responsible for the addiction and dependence to heroin and opiates.

Thus, it is possible to be dependent on morphine, without being addicted to morphine. (Although, if one is addicted, they are most likely dependent as well.)

This is especially true for people being treated chronically with morphine, for example, pain associated with terminal cancer.

They may be dependent - if the drug is stopped, they suffer a withdrawal syndrome.

But, they are not compulsive users of the morphine, and they are not addicted.

Finally, people treated with morphine in the hospital for pain control after surgery are unlikely to become addicted; although they may feel some of the euphoria, the analgesic and sedating effects predominate.