Unlike other drugs, hallucinogens generally do not lead to an increased tolerance to the drug. While other drugs often create a pattern where the user needs to take more and more of the drug to reach a desired effect, this does not happen with most hallucinogens, although PCP may be an exception. While physical dependence does not occur, psychological dependence can result from the use of hallucinogens. This means that a person feels that he or she needs to use the drugs in order to function. This can lead to compulsive behaviors. Some people may be more prone to dependency, including those with a mental illness such as depression or bipolar disorder, a family history of drug abuse, or those who use other drugs as well.

Heavy use of the drugs can lead to a variety of health concerns, including brain damage, memory loss, a shorter attention span, confusing, and difficulty thinking. Some of these symptoms may be permanent; others may disappear after quitting use. Other side effects of the drugs can include damage done oneself while high.

Treatment to hallucinogenic dependence requires the cessation of all drug use. Withdrawal symptoms may be unpleasant, but are not harmful. These can include cravings for the drugs, hallucinations, and panic. Support groups, such as Narcotics Anonymous may be useful as well as counseling. Some medications can also help ease the discomforts of withdrawal symptoms.