Antidrug Vaccines

Substance use disorders (SUD) are recognized worldwide as causes of negative medical, psychological, and social outcomes, and they result in significant personal consequences for affected persons, their families, and society at large. Treatment of SUD has focused on a combination of pharmacotherapy and behavioral therapies in an effort to improve patients’ chances of successfully entering and maintaining recovery. Antidrug vaccines are a potentially important class of medications currently under investigation. They represent yet another frontier in the ongoing quest for novel pharmacological strategies that could be easily integrated into treatment plans to reduce substance use and establish abstinence. Ultimately, these vaccines reflect an important shift in our conceptualization of drugs of abuse, ie, that these substances are “foreign” and that the body’s own defenses can be used against them. Mechanisms of action Drugs of abuse act centrally on the reward and reinforcement pathways of the brain. After introduction into the body, via oral, intranasal, inhalation, or intravenous route, these substances rapidly enter the brain to activate target neurotransmitter systems. One factor of particular importance in addiction pharmacology relates to the size of the molecule, because substances of abuse must be small enough to traverse the blood-brain barrier. Once in the brain, the initial common pathway of the addictive process is through stimulation of dopamine release from the ventral tegmental area to the nucleus accumbens; this, in part, determines the addictive liability of a substance. Although the use of a vaccine to treat chemical dependency—an illness characterized by its multifactorial etiology and biopsychosocial underpinnings—sounds like a concept from the pages of a science fiction novel, the field of addictions treatment is much closer than many may realize. Interestingly, the idea of treating SUD using immunological means was introduced almost 40 years ago. In 1972, based on an animal study, Berkowitz and Spector1 published their findings on the creation of a morphine vaccine. In rats, administration of a morphine hapten–bovine serum albumin (a carrier protein) was found to result in the creation of antimorphine antibodies. These antibodies were