• Vaccinations may not produce antibodies in a timely fashion for proper integration with other medical interventions (e.g., drug overdose).

• The beneficial effects of the therapy could be overcome by large amounts of drug.

• The immunotherapy could lead to allergic reactions.

There are other potential problems with the use of antidrug antibodies for the treatment of drug abuse. Because in some cases the drugs of abuse are closely related in structure to either neurochemicals or approved medications (e.g., nicotine replacement therapy for cigarette smoking), it is possible that the therapies could lead to unexpected adverse reactions or reduced effectiveness of other medications. Some of these possible outcomes can be avoided or anticipated by careful screening of the antibodies for cross reactivity against known drugs and neurochemicals before they are used in humans. It is also possible that immunological responses against an antidrug of abuse antibody binding site (called an anti-paratype response) could lead to a second generation of antibodies, which are complementary to the antibody binding site and are capable of being druglike, thus, able to activate receptor systems just like the drug of abuse. It is known that monoclonal antibodies and other protein therapeutics do stimulate an immune response to the product in some individuals; therefore, they may not be suitable for life-long or even extended use in all individuals. Vaccines comprised of the drug-protein conjugate might also lead to entirely unexpected allergic reactions. However, it is expected that most of these potential problems would be anticipated, tested for, and dealt with during the clinical trails of new medications and the FDA approval process.

Finally, there are ethical considerations, however remote, for the use of vaccines. Active vaccination can stimulate long-lasting immunologic memory that could serve as a marker of past immunization and could stigmatize an individual for extended periods of time, or even over their entire life if tests were available for detecting memory immune cells. Monoclonal antibodies, however, have a finite life span, and after some period of time following treatment would no longer be detectable. Depot medications would similarly be undetectable following treatment because of their finite life span.

Depot therapies for opioid addiction pose a different set of advantages and challenges. A great deal is already known about the therapeutic agent (naltrexone) that is being developed for depot use because it has been used in non-depot form for more than 20 years. Naltrexone is known to be very effective as well as safe when patients adhere to the medication. For the depot versions, extensive work has been done by companies seek-