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The demand for ketamine has surged in recent years as interest in its off-label use for treating depression, anxiety and PTSD has grown.

Ketamine has been “shown to be very effective,” said Linnea Butler, founder and CEO of Bay Area Mental Health (Campbell, California), which recently began offering ketamine-assisted psychotherapy.

Also this week, Earlier this week, Pasithea Therapeutics Corp. (NSDQ:KTTA), announced the launch of the first U.K.-based ketamine infusion clinic.

And separately, Delic Holdings (CSE: DELC) announced two new alliances between Ketamine Wellness Centers (KWC) and the Veterans Administration Community Care Networks of Illinois and Minnesota. KWC plans to provide ketamine for PTSD, depression and chronic pain to veterans at no out-of-pocket cost at their locations in Naperville, Illinois, and Burnsville, Minnesota.

Parke-Davis, now a Pfizer (NYSE:PFE) subsidiary, first discovered the dissociative anesthetic ketamine in 1962. The result of combining a ketone with an amine, the drug won FDA approval as a field anesthetic during the Vietnam War, but its medical use in humans began to wane by the end of the 1970s. In 1999, the U.S. classified the drug as a Schedule III non-narcotic substance.

Linnea Butler

Linnea Butler

Butler notes that ketamine first found use in mental health for treatment-resistant depression (TRD) using IV delivery in an inpatient setting for the most severe cases of suicidal ideation.

“Ketamine-assisted psychotherapy (KAP) is done with sublingual or intramuscular (IM) ketamine,” Butler notes. The therapy uses the dissociative state to facilitate delving into “extremely painful issues that clients can’t tolerate without the ketamine,” she added. “It gives them an ‘emotional skin’ of sorts.”

The idea behind KAP, similar to proposed indications of other psychedelics for therapeutic indications, is to “facilitate neuroplasticity, and in combination with therapy, we can help break old patterns that have been stuck for years leading to long term change,” Butler said.

“In terms of determining who is appropriate for KAP, there are a couple of specific rule-outs: current episodes of mania or hypomania, presence of a dissociative disorder or psychosis, and poorly managed high blood pressure,” Butler said. “Ideal candidates are people struggling with depression, anxiety, trauma or PTSD, rigid thinking and rumination, grief and loss or facing end of life.”

Ketamine is currently the only legal form of psychedelic-assisted psychotherapy in the U.S.

The Drug Enforcement Agency (DEA) lists psychedelics such as psilocybin, ​​LSD and MDMA as schedule I substances of the Controlled Substance Act, concluding they have no medical value and high abuse potential.

DEA has concluded that ketamine, as a schedule III drug, has “a moderate to low potential for physical and psychological dependence.”

The related drug esketamine, the S-enantiomer of ketamine, won FDA approval for treatment-resistant depression in 2019. Johnson & Johnson developed the drug, which it markets as Spravato.

As ketamine has long been off-patent, it has limited potential for the pharmaceutical industry. “Spavato was launched with a unique delivery system, but the effects are no greater than with IV Ketamine or with KAP,” Butler notes. “Right now, it is the only delivery system covered by insurance, however, I don’t think it will be the preferred method over time.”

Ketamine has several advantages over substances that require extended psychotherapy sessions. “For example, MDMA therapy sessions are eight hours long with two therapists,” Butler said. “Ketamine is relatively short, and that makes it more accessible timewise.”

The heightened focus on psychedelic medicine has piqued the interest of a growing number of pharmaceutical companies.

“Some drug developers are looking to find compounds that can deliver the mental health benefits without the psychedelic effects, but I do not think they will be successful,” Butler said. “Part of the effectiveness of the medication is experiencing an expanded state and feeling a sense of connection to something greater than the self,” she said.

Butler sees other opportunities in the psychedelic space. Plants used for indigenous ceremonial use, such as the African shrub iboga or mescaline, found in some cacti in the Americas, have relatively small yields.

“Finding a synthetic alternative could be compelling since there is a lot of attention on protecting indigenous cultures from outside involvement,” Butler said.

Butler also envisions that there could be a large market for a true psychedelic with a shorter half-life than traditional drugs such as psilocybin or LSD. “Imagine a compound similar to psilocybin in effect but with a half-life of 30 minutes,” she said.

While ketamine may offer significant potential as an adjunct to psychotherapy, there is little in the way of rigorous evidence for KAP. “Most of the research has been done with IV ketamine or Spravato from the lens of the medical model, so it’s a bit of the wild west at the moment with lots of anecdotal evidence,” Butler said.

But KAP can lead to a “drastic reduction in symptoms for clients who have been unresponsive to other medical and psychotherapy treatments,” Butler added.

“The adoption is fast and accelerating. Because there are limited facilities that offer ketamine-assisted psychotherapy, many have long waitlists,” Butler said. “It’s easier for people to get IV ketamine or Sopravato, but they are more short-term treatments than transformative.”