Ketamine has been used for the past 50 years as an important anesthetic with a variety of uses. The discovery of the rapid-acting antidepressant effects of ketamine has results in a surge of interest towards understanding the precise mechanisms driving its effects. The ability of ketamine to provide a rapid relief of depressive symptoms, often within just hours, has brought it to the forefront of treating severe treatment-resistant depression as well as a variety of chronic pain conditions and neurodegenerative disorders.

Ketamine was first synthesized in 1962 at the Parke-Davis pharmaceutical company following the discover of phencyclidine (PCP), another anesthetic belonging to the arylcyclohexylamine chemical class. Ketamine differed because it lacked the unwanted psychotrophic effects of PCP.

The main mode of ketamine’s pharmacologic action is the non-competitive blockade of N-methyl-D-aspartate (NMDA) receptors, ion channels mainly involved in the excitatory glutaminergic neurotransmission. It has been proposed that it also affects many other targets, including dopaminergic, seroterngic, adrenergic, opioidergic, cholinergic, and sigma receptors.


Ketamine is unique, compared to other sedatives and anesthetics, because of the dissociative anesthesia produced when NMDA receptors are blocked at higher doses. Most of the other anesthetics that possess sedative or hypnotic properties act primarily through gamma-aminobutyric acid (GABA) receptors. The dissociative effects of ketamine can be described by the experience of being conscious while being drawn away from sensory perceptions. Higher doses produce a dose-dependent deepening of the dissociative state towards dream-like states of open- and closed-eye visuals and strong perturbation of thought and bodily sensations.

Ketamine can be efficiently administered via multiple routes, including oral, sublingual, intranasal, intramuscular, intraosseous, rectal, and subcutaneous routes, but the highest bioavailability and fastest onset are achieved by intravenous administration.

A large Cochrane review found that perioperative intravenous ketamine reduces the need for postoperative analgesics and decreases perceived pain intensity. In addition to its use in treating acute pain, ketamine is also used in chronic pain syndromes, where it exerts beneficial effects through the inhibition of NMDA receptors. Ketamine has been suggested to be effective in treating many different types of chronic pain, such as neuropathic pain, phantom limb pain, cancer pain, and migraines with prolonged aura. It may be particularly useful in instances where opioids no longer provide sufficient pain relief because it has been suggested to reduce opioid tolerance and pain hypersensitivity. Moreover, the antidepressant effects of ketamine may be beneficial when treating patients with chronic pain because depression and pain syndromes often coexist.

At InVita Health and Wellness, we are often asked, “why do I have to have a series of infusions? Why can I not have just one?” The first randomized controlled study in this context demonstrated that a ingle dose of IV ketamine was superior to midazolam in rapidly reducing PTSD and depressive symptoms within 24 hours, however, PTSD symptoms often started to recur within 24 hours, however, PTSD symptoms often started to recur 48 hours post infusion, and there was no significant difference was detected at 1 week post-infusion. Another open-label trial studied repeated IV ketamine infusions at the same low dose for six infusions over 12 days and found rapid improvement in both PTSD and depressive symptoms, with the median time to relapse in PTSD remitters being 41 days.

If you or someone you know could benefit from ketamine therapy, please call InVita Health and Wellness at 314-394-0950.