Filling an order for a lethal drug cocktail has been getting harder for quite some time. Four years ago companies in the European Union stopped shipping pharmaceuticals to the U.S. when they would be used for executions, leading to a shortage of sodium thiopental, a once-common general anesthetic. Then there were issues getting pentobarbitala backup drug that is also a staple in many animal euthanasia mixes.

The drug at the center of the U.S. Supreme Court case Glossip v. Gross, which the high court ruled on last month, was the sedative midazolama backup for the backup. The Court ruled that Oklahoma could continue using the drug but it left most big questions about capital punishment in the U.S. unanswered. No matter what the court said, however, it is only going to become harder to obtain drugs for use in executions, largely because the pharmaceutical companies that make them are increasingly refusing to sell them for that purpose.

By the time Glossip v. Gross reached the court there had already been several botched executions using the drug. In Ohio, where the execution drug replacement was not tested before use, convicted rapist and murderer Dennis McGuire struggled and gasped for breath and took more than 25 minutes to die (see Scientific American’s related editorial). The defendants in the case before the Supreme Court, however, were three prisoners from Oklahoma who are slated for execution. Their legal defense was that the sedative midazolam cannot be consistently relied on to make a prisoner unconscious before he receives the second and third drugs that are part of the three-drug lethal injection protocol in the state.

The Supreme Court justices rejected that argument. They concluded in their 5–4 decision that midazolam use is constitutional and stood by the decision of the lower court. The majority wrote that the petitioners “failed to establish that any risk of harm was substantial when compared to a known and available alternative method of execution.” They also noted that the lower court “did not commit clear error when it found that midazolam is likely to render a person unable to feel pain associated with administration of the paralytic agent and potassium chloride.” Therefore, Oklahoma can continue to use midazolam.

If it can find any. “The market has rejected the policy,” says Robert Dunham, executive director of the Death Penalty Information Center. American pharmaceutical companies have been withdrawing their product from the market or taking steps to block them from being used for executions. That’s where the difficulty may be going forward. Following in the footsteps of the E.U., Akorn, an Illinois.-based maker of midazolam, already asked Oklahoma to return its drug for a full refund earlier this year because it “strongly objects to the use of its products in capital punishment.” It also instituted a policy barring direct shipments of its product to prisons.

Akorn, of course, is not the only maker of midazolam, but other pharmaceutical companies are taking similar actions. London-based Hikma Pharmaceuticals—a firm which also has U.S. operations—told Scientific American in a statement that it “strongly objects” to its drugs being used for executions and now takes several steps to block such use: It does not usually sell its products to prisons or correctional facilities at all, they said. The firm also requires its distributor and wholesale partners to sign an agreement saying it will not sell the products to any prison or department of corrections for “use in any manner that is inconsistent with approved product labeling.” Further, the company said that if it learns its products were used in unapproved ways, it would work to “aggressively reclaim such products in exchange for a full refund.”

There are other ways states can get these drugs, though. Compounding pharmacies—those that traditionally combine or mix drugs from scratch to meet the needs of individual patients—may fill that niche, especially if privacy laws protect them from the negative publicity that could come from being makers of lethal drug cocktails. Yet compounding drugs for this purpose may itself violate the law because “both state and federal laws require a patient-specific prescription before a pharmacy can provide a compounded drug,” notes Dale Baich, a lawyer who represents death row prisoners at the Office of the Federal Public Defender for the District of Arizona Capital Habeas Unit. Because there is no unified oversight of compounding pharmacies, he says, there is also no way to guarantee that the drug is what it purports to be and is indeed safe and effective. The International Academy of Compounding Pharmacists declined to respond to specific questions from Scientific American but said in a statement, “IACP discourages its members from participating in the preparation, dispensing or distribution of compounded medications for use in legally authorized executions.”

The market is not the only remaining obstacle for capital punishment—there will probably be further court challenges, too. Justices Stephen Breyer and Ruth Bader Ginsburg signaled in their dissent to Glossip that they would like to reconsider the constitutionality of the death penalty. “Rather than try to patch up the death penalty’s legal wounds one at a time, I would ask for full briefing on a more basic question: whether the death penalty violates the Constitution,” they wrote. The two justices laid out a legal argument about why it may be considered cruel and unusual because of its unreliability, arbitrariness in application and unconscionably long delays that undermine the point of capital punishment. That may be the blueprint for a future challenge.