Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

Drug addiction is a terrible public health problem, and a terrible personal problem for anyone facing it. Giving addicts a better chance to break the drug-taking cycle would be a great benefit, but that’s been an elusive goal. There’s a possible biochemical solution that’s been proposed for years, though, that is recently getting more attention: vaccination.

At first thought, that might seem like a weird idea. Drugs of abuse, such as heroin, cocaine, methamphetamine et al. are small molecules, and as such are too small to set off immune responses on their own. But a strategy could be to attach them to some larger protein that can raise antibodies – if those antibodies recognize the drug-labeled part of the protein conjugate, they may well retain activity against the drug molecule in its free state. There’s been a recent report in JACS on a heroin vaccine, from Kim Janda and co-workers at Scripps, that’s gotten a lot of media attention (as well it might). It uses just this sort of approach, but (as is so often the case with immunology), it’s taken a lot of work to get all the details right.

The vaccine has a tetanus toxoid core (as used in the well-known tetanus vaccine), with linkers coming off it that are attached to heroin molecules. Figuring out the right kinds of linkers (their chemistry, length, and flexibility) and the right loading of the core protein are nontrivial issues, as is the combination of this species with various adjuvants. Adjuvants are (to a chemist) the voodoo part of vaccine development. They’re additives (such as aluminum salts, squalene, or other substances) that increase the immune response, through mechanisms that are still not completely worked out, which means that there can be a lot of trial-and-error involved. This latest paper takes things from mice up to rhesus monkey studies, which are quite promising for human effects.

It’s been a long road. The first morphine immunoconjugate was described in 1970, and a morphine vaccine was tested in rabbits in 1975. But very little progress in the field occurred over the next twenty years or so, partly because methadone treatment for heroin addiction had become widely used. It’s interesting to note, though, that vaccine development work against amphetamine seems to have followed a roughly similar path – early reports in the 1970s followed by a drought, then renewed interest in the late 1990s and beyond, from the Owens group at Arkansas (who have also developed monoclonal antibodies as potential therapies) and from the Scripps group and others. I haven’t found any cocaine vaccine reports from the 1970s, but Janda has published a number of papers in that area, too. (Back in the opioid field, last year his group also published on a possible fentanyl vaccine as well).

It would seem that we really are getting close to human clinical trials for some of these, which will be quite interesting. A drug-abuse vaccine is not going to be magic, though. Because of the specificity of the immune response, someone who’s been vaccinated against heroin would almost certainly still respond to morphine, and most definitely would to compounds like fentanyl or oxycodone. It’s unclear how long the immune protection will last in humans (that is, how many booster shots would be needed), and that’s obviously going to vary from person to person no matter what (like everything else in immunology). But vaccines could, at the same time, provide the extra help needed for people to finally break free of a particular drug, and addicts who are really trying to quit need all the help that they can get.

I’d say that last part is the key. One of the big issues in drug addiction is (in the end) a philosophical argument about free will (which would explain why it never gets resolved!) Is drug addiction a disease, a choice, a behavior, a biochemical problem. . .the arguments go on forever, complicated by the way that different people attach different meanings to those terms. But it would seem clear that a desire to stop abusing drugs is a big part of the effort to stop abusing them. Otherwise, the person involved will probably just find new ways to go on abusing. I have no idea how to help anyone in that situation, but for people who’ve gotten on this awful treadmill (by whatever means) and want to get off, a drug vaccine might be a big step.

Update: see the comments. It looks like one of the cocaine vaccines has been into humans, with unspectacular results.