Falling down the K-Hole. Taking “Special K.” Ketamine has quite the reputation as a recreational club drug. But research is showing its promising potential as a treatment for severe cases of depression.
Jesse talks to Dr. Panos Zanos, Postdoctoral Researcher at the University of Maryland School of Medicine, (who has possibly the best name of any Smart Drug Smarts guest to date) about his research on ketamine and depression.
Medical and Recreational Uses
Ketamine was originally synthesized in a lab as a safe anesthetic and continues to be approved in many countries (including the US) for anesthesia and sedative use. In the US, it’s classified as a Schedule III drug, meaning it has currently accepted medical uses, but carries a danger of abuse.
It’s the dissociative effects — feeling detached from the environment and users’ own selves, as well as experiencing sensory distortion — of ketamine that’s made it popular as a recreational club drug. Users report feeling numb and serene, like they’re in another world or walking on clouds. Important note: while there’s no current evidence of any addiction potential, there’s certainly abuse potential.
A New Use For Ketamine: Treating Depression
For sheer speed of efficacy, ketamine blows conventional antidepressant therapies out of the water. Patients feel relief within two hours after a single ketamine injection, while traditional medicine can take up to three months to work. It’s no surprise, then, that ketamine is often used as an emergency treatment in crisis situations to disperse suicidal thoughts.
But ketamine has potential as a long-term treatment as well. The antidepressive benefits from one injection last up to two weeks. Multiple studies have confirmed these antidepressive effects. Unfortunately, you’ll have to contend with all the side effects as well. The dissociative effects of ketamine may become more pronounced and enduring with repeated treatment. This is something that needs to be researched further — no one knows the long-term effects of persistent ketamine treatment.
How Does Ketamine Work?
There’s a lot we don’t know about ketamine yet, and it contains a shit ton (that’s the technical term) of substances, each with its own effect. Here’s what we do know:
Once ketamine enters the body, the liver quickly breaks it down, creating metabolites (a chemical byproduct of the breakdown process), which stay in the body for up to a week.
Metabolites are responsible for the mood-boosting effects of ketamine, without all the side effects (anesthesia, dissociation). Dr. Zanos’s recent research shows that a metabolite called (2R, 6R)-hydroxynorketamine is at least partially responsible for ketamine’s antidepressant benefits.
This is good news for depression sufferers, since if the active metabolites can be isolated, they can be used to treat depression without the ketamine high.
As for how ketamine metabolites lift depression, the jury’s still out, but a few likely theories have emerged. Ketamine may work by…
- Increasing levels of glutamate, an excitatory neurotransmitter that may be linked to depression.
- Inhibiting NMDA receptors, a type of glutamate receptor. NMDA receptors are a component of the glutamate pathway, involved in memory and cognition. However, human trials of non-metabolite NMDA-receptor blockers were unable to replicate ketamine’s powerful antidepressant effects.
- Promoting the release of brain-derived neurotrophic factor (BDNF). Depression damages neurons and synapses, while BDNF promotes neurogenesis and strengthens existing synapses.
Perhaps the most promising theory so far: activation of AMPA receptors (another type of glutamate receptor). Dr. Zanos’s recent research shows that, at least in mice, antidepressant effects depend on activating AMPA receptors.
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Ketamine and depression
This Week in Neuroscience: Why We Sleep Badly on Our First Night in a New Place
The audience interaction section
Dr. Panos Zanos and his work with Ketamine
Ketamine as an anaesthetic
Recreational versus medical use
Are there downsides with repeated use?
Acute effects of ketamine
The legality of ketamine in different parts of the world
Which metabolites are pharmaceutically active?
How was ketamine discovered?
How ketamine treats depression
Are there any contraindications?
How long have scientists been researching ketamine as an antidepressant?
Ketamine as an off-label therapeutic treatment
Scheduling of ketamine in the U.S.
Ketamine’s additive effects
A first-hand account of ketamine treatment for depression
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