By Mark Gold, MD
Preliminary 2018 data from the Centers for Disease Control show a slight decline in drug overdose deaths.1 In the view of many experts, increased availability and use of Naloxone, education, and also increased access to Medication for Addiction Treatments (MAT) contributed to this decline.2 However, opioid use disorders and drug overdose rates remain extremely high nationally. Moreover, decreasing overdoses from prescription misuse and heroin should not distract from rising importation, misuse, and overdoses due to fentanyl, methamphetamine, and cocaine.3 With limited treatment options available for these substance use disorders, researchers are working to create novel approaches, using all technologies available, to prevent, treat, and improve the lives of patients and families. In a number of studies and trials, Tom Kosten and his colleagues at Baylor have looked at cocaine, methamphetamine, opioid and even fentanyl vaccines, showing promising results in reducing overdose, misuse, and treating substance use disorders.4
What did this review find about vaccines and SUD?
A 1974 study showed that vaccines decreased heroin use in monkeys.5 Since then, the field of research on vaccines targeting substance use disorders has expanded, offering a number of encouraging results. A recent review, written by Marco Pravetoni and Sandra D. Comer in Neuropharmacology, outlines these potential benefits with a particular focus on opioid use disorder (OUD). The authors explain that a group of these vaccines work through the stimulation of antibodies in the immune system. The antibodies bind substances of use and stop them from crossing the blood-brain barrier. In essence, vaccines curtail substance distribution to the brain.
Vaccines have shown particular capability in curtailing the distribution of substances such as nicotine and cocaine to the brain in humans, even in Phase 3 clinical trials, which examine risks and benefits while comparing one medication to other alternatives. Pravetoni and Comer also observe that vaccines may be a better alternative for treating OUD than current options. They note, for example, that methadone is stigmatized and accessing it daily can be inconvenient for patients. Buprenorphine requires physicians receive federal waivers before prescribing to patients, and it can also initiate withdrawal symptoms. Both are opioids themselves and it is not clear whether replacement does more, including the promotion of neurobiological recovery and the return to pre-abuse brain function. Pravetoni and Comer’s review suggests that vaccines for OUD may meet a number of different “desirable characteristics” for an alternative treatment course. Among these are low misuse potential, long duration, safety, compatibility with opioid agonists or antagonists, and not requiring detox. OUD vaccines have a long half-life, which means they will last longer. Because they selectively target the substance, the authors say, OUD vaccines are not expected to interfere with other medications. In fact, they may well be able to work with methadone, buprenorphine, naltrexone, and naloxone.
Pravetoni and Comer point to a key issue: how will OUD vaccines perform in human studies? So far, there is preclinical evidence that vaccines are effective against opioids, methamphetamine, and designer drugs in animal studies. There are additional complications. Experts’ foundational understanding of why vaccines targeting substance use disorders work in the immune system is still limited. For fentanyl and its variants, researchers must also attempt to determine whether one vaccine is most appropriate, or whether multiple ones targeting different components of the substance would work best. Relatedly, experts question why vaccines may affect different individuals in different ways. Pravetoni and Comer suggest that the design, composition, and regimen of the vaccine likely play a role. The host’s immune system function and genetics, age and sex, and substance use history could also factor into the equation. Their review reports that OUD patients may use combinations of opioids, alternating the delivery mechanism and amount of the substance, possibly changing the effect of a vaccine in the process. Because of these and other variables, the report indicates that for heroin and prescription misuse, vaccines may work best for patients at risk of relapse or in earlier stages of substance use disorder, and in conjunction with existing MAT. The dosage levels of patients’ substance use may also alter the effectiveness of a vaccine. Addressing these questions and variables is crucial for those fighting our substance use epidemics, and additional research and vaccine development is the best way to do so.
Why is this important?
Pravetoni and Comer conclude their review by listing some hurdles for progress in developing vaccines against substance use disorders. Funding, regulation, and licensing can prove burdensome. I asked Baylor College of Medicine’s Dr. Thomas Kosten, a pioneering expert working in the vaccines and substance use field, about approval for these treatments.6 Dr. Kosten and his team are collaborating with Teva on a cocaine vaccine. He identified funding and stigma as barriers to vaccine projects. A cocaine vaccine is particularly promising, as is a methamphetamine vaccine. More recently, Pravetoni and a number of other partners have received NIH funding to create an OUD vaccine.7 This is good news because research and advancement in development can unlock another means of fighting substance use disorder. Those working for fewer overdose deaths should support efforts at vaccine progress and help push back against stigma, pointing to this valuable research as a sign of how better science can improve lives.
Ahmad, F.B., Escobedo, L.A,. Rossen, L.M., Spencer, M.R., Warner, M., Sutton, P. (2019) Provisional drug overdose death counts. National Center for Health StatisticsCollins, F. (2019) Easier Access to Naloxone Linked to Fewer Opioid Deaths. NIH.Gov
Nolan, M.L., Shamasunder, S., Colon-Berezin, C., Kunins, H.V., Paone, D. (2019) Increased Presence of Fentanyl in Cocaine-Involved Fatal Overdoses: Implications for Prevention. Urban HealthYang, F., Kosten, T.R. (2019) Psychopharmacology: neuroimmune signaling in psychiatric disease-developing vaccines against abused drugs using toll-like receptor agonists. Psychopharmacology Bonese, K.F., et al. (1974) Changes in heroin self-administration by a rhesus monkey after morphine 599 immunisation. NatureKosten, T. interviewed by Gold, M. (January 3, 2018) Antidrug Vaccines to Treat Substance Use and Addiction. RiverMend Health, Ask the ExpertUM News Service. (July 22, 2019) UM researchers land NIH contract for opioid addiction vaccine. Missoula Current
Citation: Pravetoni, M., Comer, S.D. (June 4, 2019). Development of vaccines to treat opioid use disorders and reduce incidence of overdose. Neuropharmacology
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.