Key points

Ketamine, a Schedule III substance, is FDA-approved for induction and maintenance of general anesthesia.

At-home, unsupervised injection of the drug is surging due to online "clinics" spawned by the pandemic.

Esketamine (Spravato) nasal spray is FDA-approved for monitored use in designated medical offices.

Spravato offers a novel, rapid-acting way to treat depression.

Actor Matthew Perry was addicted to intravenous ketamine when he overdosed and died in 2023, reminding us that ketamine is dangerous and too accessible. However, the drug Spravato, a form of ketamine and the first novel FDA-approved antidepressant in 50-plus years, can be lifesaving when used appropriately, under supervision, in those with severe and nonresponsive depression .

But what to make of unsupervised, home-injected ketamine, as in Matthew Perry’s case, made available as a result of telemedicine exceptions created during the pandemic?

Looking Back in Time

Ketamine was synthesized in 1962 (a mixture of two mirror-image molecules, R- and S-ketamine) and developed as an alternative to phencyclidine (PCP). Ketamine has anesthetic, hallucinatory, and dissociative effects similar to PCP but without respiratory depression and with a shorter duration of action. In 1964, Drs. Edward and Toni Domino tested ketamine in humans, coining the term “dissociative anesthesia” to describe its unique effects.In early rat testing, ketamine did not appear addicting. Still, nonhuman primate testing has shown it is addicting, depending on dose, route of administration, frequency, and current and past drug use. Reports of abuse and the dissociative and hallucinogenic effects of ketamine emerged in the 1980s. Known as “Special K,” ketamine was abused for psychedelic out-of-body experiences .In 1999, the Drug Enforcement Administration (DEA) classified ketamine as a Schedule III controlled substance. This meant it was similar to codeine and buprenorphine—having accepted medical benefits but abuse potential. John Krystal, MD Source: Yale University School of MedicineJohn Krystal, MDSource: Yale University Psychiatric Uses for Ketamine In 2000, Yale’s Dr. John Krystal and colleagues demonstrated that low-dose, intravenous racemic ketamine produced rapid, significant antidepressant effects in patients with treatment-resistant depression. This discovery sparked additional psychiatric research on ketamine.The late George Aghajanian, M.D. , collaborated with neuroscientist Ronald Duman […]

The Bright and Dark Sides of Ketamine