Immunotherapy Principles May Apply in Vaccine to Combat Methamphetamine Addiction

If you thought the principles of immunotherapy applied only in the fight against cancer, guess again. The same concepts that have been used to harness the immune system to battle tumors might soon be used to keep harmful drugs from wreaking havoc on the brain, said Thomas Kosten, MD, professor of psychiatry, neuroscience, pharmacology and immunology at Baylor College of Medicine.

On Saturday, Kosten offered an update to his talk last year on what’s in the pipeline to treat substance abuse in “New Anti-Addiction Medications: Exploring Pharmacogenetic and Immunotherapy Approaches to Managing Addiction,” part of the 28th US Psychiatric and Mental Health Congress being held in San Diego, California.

Especially exciting are the results of animal studies on a vaccine to control methamphetamine; studies have been so promising that human trials could start in May 2016, he said. Kosten has tested similar concepts for a cocaine vaccine in human trials for a while, although, as he explained, the element of getting cocaine addicts to buy into an actual cure for their disease has proved challenging.

As a concept, the methamphetamine vaccine is straightforward: the assembled mental health professionals understood how the drug travels from the bloodstream to the brain, which easily accepts the drug because of receptors waiting to capture it. If a process could be created to hold drugs in the bloodstream, that exchange would be interrupted, thus reducing brain concentrations of the drug.

Researchers have created a methamphetamine derivative called hapten, which is injected 3 to 5 times over a 3 month period to build antibodies that act to receive the drug. “When we vaccinate animals with this, it keeps the methamphetamine from getting into the brain,” Kosten said. “The locomotor behavioral effects are sharply reduced.”

The antibody effect peaks between 2 to 4 weeks after dosing, indicating the need for boosters during the course of the year. The effects of methamphetamine is reduced in the animals after the injections, and studies of a similar cocaine vaccine offer a road map for future work in human trials.

Cocaine Trials. Kosten updated the audience on work he first presented last year that involved 114 active cocaine abusers who were recruited to test the effectiveness based on a cholera vaccine.

Researchers have learned quite a lot from the trial. For starters, Kosten said, in subsequent research, they will start will participants who have been clean for 2 weeks instead of those who are still actively using.¹ While the vaccine did eliminate the ability of users to get high, it didn’t eliminate the desire to get high, and thus only 15 of patients were able to sustain clean urine sample for 2 weeks. No matter how little information they were given, addicts would try to guess whether they were in the control group, or whether they were at a point that their antibody had worn off so they could go out and get high, he explained.

“If you get them abstinent first, this can be an effective relapse prevention agent,” Kosten said.

Targeting Treatments. More and more is being understood about targeting treatments that have been used for addiction for some time, since research is showing that some patients are more genetically predisposed to respond to certain treatments for cocaine or alcoholism. Although it is not yet approved, pharmacogenetics is using the α-1A adrenergic receptor polymorphism to identify which patients might respond to doxazosin for cocaine dependence.²

And a clinical application nears for use of the OPRM1 Asn40Asp polymorphism to identify which severely alcoholic patients will respond best to naltrexone, which has been used for decades. An “as needed” version, nalmefene, has been used in Europe to facilitate moderated alcohol consumption but is not approved in the United States.

References

1. Kosten TR. Domingo CB, Shorter C, et al. Vaccine for cocaine dependence: a randomized, double-blind placebo-controlled trial. Drug Alcohol Depend. 2014;143:42-47.

2. Shorter DA, et al. A polymorphism of the alpha-1 adrenergic receptor influences the acute response to cocaine administration. In submission. 2015.