Why Don’t We Have Addiction Vaccines?

vaccinations
After decades of research, those suffering from addiction still have few medication options.

After three decades of research, people with addiction still have few medication options. While there are a handful of modestly effective FDA-approved drugs to treat alcohol, nicotine and opioid-use disorders, there are none at all for cocaine, methamphetamine and other narcotics. And the fact remains that most people with a substance use disorder will relapse – from 40 to 60%, according to the National Institute of Drug Abuse (NIDA).1


You want it to take away withdrawal symptoms, you want it to reduce craving and you want it to block the high.Dr. Kyle Kampman

One problem is that addiction is a complex condition involving the brain, body and psychology. “If you want to treat addiction, you want [the medication] to do three things,” says Dr. Kyle Kampman, a psychiatry professor and medical director of the Charles O’Brien Center for Addiction Treatment at the University of Pennsylvania.2 “You want it to take away withdrawal symptoms, you want it to reduce craving and you want it to block the high.”

No current medication can do all three things. That’s why the idea of vaccines for addiction has long—some critics would say too long—been embraced by researchers. A vaccine could prevent a person from getting high in the first place, which would theoretically moot the issue of cravings and withdrawal symptoms.

According to Kampman, other potential advantages of vaccines are the long duration of action, the certainty of administration and a potential reduction of toxicity to important organs.

No less significant is that patients do not have to detox or go through withdrawal before treatment—as is the case with most currently available medications. “It is not necessary to be abstinent first,” says Dr. Diana Martinez, associate professor of clinical psychiatry at Columbia University.3

How Addiction Vaccines Would Work

An effective addiction vaccine would kill the buzz induced by booze and other substances before a person could feel it. But it also requires the person’s buy-in: Knowing that they could not get high, they would not continue trying to.


The science of vaccines for addiction is like that of other vaccines: They produce antibodies against the virus that target the virus (or molecule), neutralize it and thereby prevent infection. In the case of addiction, the antibodies bind to the cocaine or heroin molecule, bulking it up and making it too big to pass through the barrier between blood and brain. If it doesn’t get to the brain, it doesn’t get a person high.

Addiction vaccines will not prevent addiction, nor will they “cure” someone who is not trying to overcome their condition. Most researchers agree that they would work best as relapse prevention — in combination with another anti-craving medication, an antidepressant, behavioral therapy or a combination of all three. Dr. Kim Janda, a professor of chemistry and immunology at the Scripps Research Institute, says the aim is to use them as an assist once someone is sober since vaccines would not be helpful for those who do not wish to be abstinent.4

They don’t prevent or reduce cravings, however, and that’s one of their main drawbacks. In several of the scant number of clinical trials run on nicotine and cocaine vaccines, patient compliance has been a key issue. If the physical and psychological cravings are not blunted, they can easily override a person’s willpower not to use. “I think that the vaccines aren’t going to take away craving issues,” says Janda. “They’re just going to enforce the inability to receive any benefits from taking the drug.”4

The vaccines aren’t going to take away craving issues. They’re just going to enforce the inability to receive any benefits from taking the drug.Dr. Kim Janda

Current Options Are Few and Faulty

Vaccines may be no magic bullet, but even at partial effectiveness they would improve the current state of the addiction medicine cabinet. Here’s a list:

  • Alcohol: Naltrexone (Vivitrol), acamprosate (Campral) and disulfiram (Antabuse) are FDA-approved, while topiramate is showing good results in trials.5
  • Nicotine: Bupropion (Wellbutrin) and varenicline (Chantix) are FDA-approved medications; replacement therapies include the patch, spray, gum and lozenges.6
  • Opioids: Methadone and buprenorphine (Suboxone) are FDA-approved substitute medications, while naltrexone is approved to treat cravings.7
  • Cocaine: Nothing
  • Methamphetamine: Nothing
  • Cannabis: Nothing

The most innovative of these medications is the anti-smoking treatment Chantix, a nicotinic receptor partial antagonist. A review by the independent Cochrane Collaboration is mixed: Chantix was better than Wellbutrin but not superior to over-the-counter nicotine replacement therapies, which are far cheaper.8

A recent study found that prescribing both Chantix and Wellbutrin may work best (combination treatment is typically more effective than a single drug, but also more toxic).9 Chantix can have severe side effects, too, including depression, bizarre dreams and suicidality; the FDA put a black box warning—the agency’s strongest safety warning—on the drug.10

Naltrexone, an opioid receptor antagonist, can block the intoxicating effects of alcohol and opioids—but again, only for some people and only to some extent.

Naltrexone, an opioid receptor antagonist, can block the intoxicating effects of alcohol and opioids—but again, only for some people and only to some extent. In the case of opioid addiction, it is effective only for people with a specific genetic mutation in an opioid receptor.11 Most clinical trials of naltrexone’s efficacy for alcohol use disorders studied the medication as an assist to behavioral therapy — and that’s how it’s often recommended to be used. “It’s a tool,” says Dr. Larissa Mooney, assistant clinical professor of psychiatry at UCLA’s Integrated Substance Abuse Programs.12

What’s Coming Out of the Pipeline?

Addiction vaccines have been in development since the 1990s—without a single success. The biggest investment of resources has gone to experimental vaccines against nicotine and cocaine, and numerous agents have made it as far as Phase III. But their repeated failures to show efficacy in humans in the clinic (as opposed to animals) may cast doubt on the viability of the vaccine project.

  • Nicotine: After early promise, two 2011 Phase III trials found that NicVax, the leading anti-smoking vaccine candidate, worked no better than a placebo.13 Research continues, however. A small 2013 study showed that NicVax immunization reduced binding of nicotine to its receptor by 12.5% and decreased cigarette use by 40% as well as reduced cravings.14 In 2013, a similar anti-smoking vaccine, Niccine, failed in Phase II trials.15
  • Cocaine: Most of the progress in the development of a cocaine vaccine has come from the labs of Weill Cornell Medical College’s Dr. Ronald Crystal and Baylor College of Medicine’s Dr. Thomas Kosten’s labs. But recent setbacks have frustrated the work. In July 2014, Kosten published the disappointing results of a small Phase III study of an experimental cocaine vaccine showing adequate safety but poor efficacy. “It was not overly successful,” Kampman, a co-author on the study, says. “It is hard to get good levels of antibodies.”16
  • Heroin: An effective vaccine would be a big boost for people with heroin use disorder, who have the lowest rate of recovery. (This is why methadone and Suboxone are essential medicines.) The labs of Dr. Kim Janda and Dr. George Koob at the Scripps Research Institute have made the most progress, using a so-called “dynamic” heroin vaccine. A 2013 study in rats showed that vaccination significantly decreased their relapse rates. “Right now, [the heroin vaccine] is pretty good,” Janda says. “We can give a large overdose, and the animals are still fine. We can’t really do that with the other drugs.”17
  • Methamphetamine: The Scripps group is also moving a methamphetamine vaccine through rat trials; in 2013 they published a paper showing that one candidate gave evidence of protecting rats from becoming intoxicated with a robust antibody response.18

The Difficulties in Vaccine Development

The scientific challenges to developing an effective addiction vaccine have become all too clear since the 1990s. Most of the target molecules are so small that getting the immune system to “see” them, together with getting a high enough antibody level, is the highest hurdle.19


With methamphetamine, because it has a long half-life—it lingers in the nervous system—antibodies have to be especially robust to flush out the molecules.

Each substance poses its own unique set of problems. A vaccine for alcohol is thought to be improbable because the ethanol molecule is too small to be adequately targeted. With methamphetamine, because it has a long half-life—it lingers in the nervous system—antibodies have to be especially robust to flush out the molecules.20 As for cocaine, simply taking more of the drug overcomes the effect of the vaccine.21

In principle, a vaccine would make someone immune for a period of months. However, the vaccines currently in development have a much shorter effect. For a sustained effect, Janda says, a patient would need an initial shot followed by 2-4 boosters every 2-3 weeks over the first 6- to 8-week period. Even then, protection would last only 3-6 months.19


This holds true in the hierarchy of addictions, too. With 50 million nicotine addicts, 1.4 million cocaine addicts and 400,000 meth addicts in the U.S., it’s no wonder that there are multiple anti-smoking medications but none for cocaine or meth.

There are other, more general hurdles, too. A vaccine would probably not protect against other drugs, or diminish cravings, and its effects could likely be overridden, at least in part, when a person relapses and takes enough of the drug — which could pose a serious health risk. This underscores the fact that vaccination works best with patients who are motivated to quit.

Economic hurdles also stand in the way. Taking a new drug from early development to market costs $2.6 billion, according to the most recent survey from the Tufts Center for the Study of Drug Development. [22] Drugs for medical conditions that affect large numbers of people offer the best bet of a payoff; substance misuse and addiction are widespread, but the vast majority of people experience natural recovery.


Anti-addict stigma extends to drug development as well… This discourages funding for potential treatments for addiction medications…

Anti-addict stigma extends to drug development as well, says Janda. This discourages funding for potential treatments for addiction medications — “it’s a moral failing, not a medical disorder,” is the rationale — especially to illegal narcotics like heroin, cocaine and meth.23

The good news is that vaccines are cheap, at least compared to other medications. If they are not a magic bullet, they would at least offer a new approach that, when used in combination with other medications and behavioral therapies, could significantly raise the standard of addiction treatment.

Sources

  1. National Institute on Drug Abuse. (2014). Drugs, Brains, and Behavior: The Science of Addiction.
  2. Penn Medicine Neuroscience Center. (2016). Kyle M. Kampman, M.D.
  3. American Society of Addiction Medicine. (2014). Cocaine Vaccine: Research Review.
  4. The Janda Group: The Scripps Research Institute. (2016). Research Areas in the Janda Group.
  5. U.S. Department of Health and Human Services. (2008). Helping Patients Who Drink Too Much: A Clinician’s Guide.
  6. U.S. Food and Drug Administration. (2016). FDA 101: Smoking Cessation Products.
  7. National Institute on Drug Abuse. (2014). Heroin.
  8. PubMed. Nicotine receptor partial agonists for smoking cessation.
  9. Science Daily. (2014). Combining Treatments Boosts Some Smokers’ Ability to Quit.
  10. U.S. Food and Drug Administration. (2015). FDA Drug Safety Communication: FDA updates label for stop smoking drug Chantix (varenicline) to include potential alcohol interaction, rare risk of seizures, and studies of side effects on mood, behavior, or thinking.
  11. PubMed. (2010). Opioid antagonists for alcohol dependence.
  12. The Fix. (2014). Shortcuts to Recovery.
  13. Global News Wire. (2011). Nabi Biopharmaceuticals Announces Results of First NicVAX(R) Phase III Clinical Trial: Smoking Cessation Immunotherapy Failed to Meet Primary Endpoint.
  14. Irina Esterlis, Ph.D., Jonas O. Hannestad, M.D., et. al. (2012). Effect of a Nicotine Vaccine on Nicotine Binding to β2*-Nicotinic Acetylcholine Receptors In Vivo in Human Tobacco Smokers. The American Journal of Psychiatry, 170(4), 399-407.
  15. Oxford Journals. (2013). Niccine®, a Nicotine Vaccine, for Relapse Prevention: A Phase II, Randomized, Placebo-Controlled, Multicenter Clinical Trial.
  16. PubMed. (2014). Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial.
  17. EurekAlert! (2013). Preclinical study shows heroin vaccine blocks relapse.
  18. Miller, M.L., Moreno, A.Y., Aarde, S.M., Creehan, K.M., Vandewater, S.A., Vaillancourt, B.D., Wright, Jr., M.J., Janda, K.D. & Taffe, M.A. (2014). A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biological Psychiatry, 73(8), 721-728.
  19. Shen, X., Orson, F.M., Kosten, T.R. (2012). Vaccines for Drug Abuse. Clinical Pharmacology & Therapeutics, 91(1), 60-70.
  20. The Scripps Research Institute. (2012). Meth Vaccine Shows Promising Results in Early Tests.
  21. National Institutes of Health. (2004). Vaccines and Depot Medications for Drug Addiction: Rationale, Mechanisms of Action, and Treatment Implications.
  22. Tufts Center for the Study of Drug Development. (2016). Tufts CSDD Assessment of Cost to Develop and Win Marketing Approval for a New Drug Now Published.
  23. Time. (2015). Why You’ve Never Heard of the Vaccine for Heroin Addiction.
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