Abuse liability
From Drug Rehab Wiki
Abuse liability is the potential that a drug has for addiction. The term is used interchangeably with potential for addiction, and addiction-sustaining properties.
In the United States, scientists employed by drug companies must determine the abuse liability of any new drug that the company wants to manufacture and sell. The process is as follows. Drug company officials fill out either a New Drug Application or a Biologics License Application (if the medicine is biologic) and then submit it to the U.S. Food and Drug Administration (FDA). Next the company must conduct extensive tests on laboratory animals and humans to determine if the drug is addictive or harmful, how quickly it is absorbed into the body, how effective it is at treating a condition or illness, and so forth. Scientists at the FDA Center for Drug Evaluation and Research go over the tests and evaluate them in terms of whether the testing was properly done and if the results are scientifically valid. If a drug has a great deal of abuse liability and only a small medical benefit, the FDA may not allow it to be sold because of the potential danger to public health.
If the new drug has a potential for abuse, the FDA may approve it as a governmentally "controlled substance." Controlled substances are drugs that may or may not have medical uses, but are regulated by the government because they are addictive. The government currently has five levels of abuse potential, with Schedule I drugs being the most highly regulated, and Schedule 5 drugs having less potential for abuse and therefore needing fewer restrictions.
Drug companies must go through an arduous process to determine if a new drug is addictive. Their scientists first study its chemical composition and relationship to other addictive drugs already on the market, and determine the drug's pharmacological effects. The drug is first tested on animals, most often rodents and primates. In order to test for abuse liability, animals are sometimes given a task to do before they can have the drug, such as working their way through a maze. If the drug has a potential for addiction, animals work harder to get it. Another test is to set up two bars. If the animal presses the first bar, it will receive a placebo. If he presses the second, he obtains the drug. If the drug has a potential for abuse, the animal will keep pressing the second bar. Another way of testing for abuse liability is called "conditioned place preference." In this test, an animal can choose between spending time in a neutral place or in an environment where it can get the drug. Conditioned place preference testing is not as reliable as the others.
Animal tests of new drugs will most often include three groups, in which one group of animals receives a placebo, another group gets a different drug, and just one group actually gets the new drug. This way scientists can determine the physiological effects of the drug, and if stopping its use produces withdrawal symptoms.
Next the drug must be tested on human beings. Usually, participants in abuse liability tests are abusers of drugs similar to the one being tested. These subjects tell scientists if they "like" the new drug and how it compares with the ones they have used before, in terms of producing feelings of pleasure and relaxation. Human abuse liability tests are most often double blind, double dummy, placebo-and positive comparator controlled.
In a double blind study, participants do not know if they are being given the real drug or a placebo, or even if every group in the study is getting a placebo. In a double dummy study, all participants take both the placebo and the real drug on an alternate basis. "Active comparator" studies compare the new drug against therapies that are standard care.
Abuse liability tests also determine if certain ways of administering the drug make it more addictive. For example, does taking it by injection produce a "rush" of pleasure that is different from taking it in a time-released form?
Abuse liability testing should also determine whether a patient can build up a tolerance to the drug -- that is, if he needs more to produce the same effects, and if the drug produces withdrawal symptoms when he stops using it.
The final step is for statisticians at the FDA Center for Drug Evaluation and Research to go over the drug company's test process and determine if the tests did indeed follow rigorous protocol. If this is so, they will approve the drug for sale.
