Ketamine has an impeccable clinical safety profile and it was in researching this that I started embracing it as a psychoactive substance, first exploring it myself and now comfortably using it in clinical practice with patients. In its over 50 years of clinical use in the U.S., there have been less than ten ketamine-associated deaths or injuries, eight of those where ketamine was not explicitly implicated but also “could not be excluded as a contributing factor”, and all at anesthetic doses (1). The other two involved a combination of emergency situations, underlying medical conditions, and inappropriate dosing (2,3) Among recreational use, death or injury from ketamine misuse are rare and associated with multiple, simultaneous drug misuse and accidents from impairment (4). Anaphylaxis or allergy to ketamine is exceedingly rare, with the majority of allergy-responses involving multiple drug administration(5) and none resulting in death or injury.
While any associated death or injury is unsettling, it is helpful to acknowledge that a drug like acetaminophen (Tylenol) kills nearly 500 people every year (6). Additionally, the above instances included either recreational abuse/misuse, multiple drug involvement, hospital-admitted individuals, and anesthetic doses – situations far different from the sub-anesthetic doses and clinical settings we are speaking to with ketamine therapy (therapeutic ketamine doses are 4-6 times less than anesthetic amounts). Further, unlike many clinics that utilize ketamine as a therapy, my practice exclusively uses the IV route of administration enabling discontinuation of ketamine at any point in treatment.
Aside from the altered state of consciousness, side effects from ketamine are relatively mild and include: nausea/vomiting (mainly at larger, anesthetic doses), dizziness, grogginess, potential for increased blood pressure, and bladder irritation (associated with abuse and recreational use). In full transparency, I have had one patient respond paradoxically and experience worsening of mood the day following administration, returning to normal after 24 hours. Ketamine in the therapeutic setting is largely contraindicated for those with uncontrolled hypertension, heart disease, history of psychosis, and pregnancy. In my practice, I do not administer ketamine to patients with a history of psychosis, active suicidal thoughts, or major depressive disorder. While the latter two are actually indications for ketamine therapy, patients with this history are best overseen by a psychiatrist for ketamine administration.
Ketamine was not listed as a scheduled drug with the DEA until 1999 when use of it as a recreational drug grew, especially with news of its abuse in Southeast Asia and other parts of the world where it was particularly high. In the recreational world, ketamine is often used in powdered form which does not necessarily impart the same effects as IM or IV use. It is still classified as a Schedule III drug today which means it is viewed as a drug “with a moderate to low potential for physical and psychological dependence”. As a comparison, testosterone is also listed as a Schedule III drug.
I suspect a number of individuals that have hesitation around ketamine, if they really sat with their emotions around this, will find that this does not necessarily come from concerns around safety or physical risk (although they may phrase it this way) but instead from fear of the unknown and fear of loss of control, along with potential shame or guilt as a consequence of the unfortunate stigma surrounding “drugs”. If this resonates I will leave you with the perspective that alcohol is by far the worst recreational drug available to us (yes, it is a drug) yet because it is socially acceptable we do not view it this way. I encourage you to listen to Peter Attia’s The Drive podcast episode 182 with David Nutt for a more in-depth take on this, and I’ll dive further into this topic in future writing.