Ketamine

What it feels like

From a step removed to melting away.

As the dose rises

• About 15 minutes, Arriving: Snorted, it comes on in about a quarter of an hour; swallowed, 20 minutes to an hour.
• Light, A step removed: The room is unchanged, but you feel detached from it, and from yourself.
• Dissociating, Flat and doubled: The eyes jerk in small rhythmic beats and stop converging, so things double; the world flattens and stops feeling real.
• Heavy, Distorted: Perception bends further — distortions rather than true hallucinations — and little of it will be remembered.
• K-hole, Melting away: Melting into the surroundings and out-of-body experiences; unable to move, mind and body feeling separated — often very frightening.
• 30–60 minutes, Coming back: The buzz itself usually lasts 30 minutes to an hour.

What it can feel like

• Detached: From yourself and from everything around you.
• Melting: Into the surroundings — the effect users rate most appealing.
• Out of body: Seeing yourself from outside, or floating free of yourself.
• Giggly: Laughter comes easily.
• Numb: Pain doesn't register properly — it's an anaesthetic.
• Unsteady: Balance goes; the pulse rises.

What's happening in the brain

A blocked receptor, a loosened self — and, perhaps, new connections. The model lights each one as you read.

Ketamine blocks NMDA receptors, one of the main ways glutamate — the brain's chief accelerator — passes signals between neurons.

Detachment

It weakens the default mode network's connections, through its hub in the posterior cingulate, to the medial prefrontal and anterior cingulate cortex. The network that ties experience to you comes loose, and it's felt as standing a step away from yourself.

Not remembering

To store something new, the hippocampus relies on NMDA receptors: block them in rats, and it stops strengthening its connections and learning where things are is impaired. Ketamine blocks them. Low doses disrupt delayed recall but spare immediate recall: in studies, people on it could still pay attention, but what happened didn't get stored, and the higher the dose, the worse their memory. Words learned before the infusion were remembered fine; words learned during it weren't. It's the time on it that goes missing — which is why so little of a heavy session is remembered.

Regrowth

In rats, low doses of ketamine increase glutamate release in the prefrontal cortex and rapidly build new synapses there — which could be why it lifts depression in hours rather than weeks.

As a medicine

An anaesthetic, and now a depression treatment.

Ketamine remains an important medicine in anaesthesia and pain management. In a 2006 trial, a single infusion improved treatment-resistant depression within about two hours compared with placebo, and the difference lasted through the following week.

A related form, esketamine, is now approved as a nasal spray for adults whose depression hasn't responded to other treatment — given in certified clinics, with at least two hours of observation afterwards, because of its sedation, dissociation and misuse risks.

Risks and staying safe

The risks, plainly.

The real risks

• Mixing: With alcohol, benzodiazepines or opioids it's dangerous, and can be fatal.
• Injury: You can't feel pain properly, so you can get hurt without knowing.
• The bladder: Frequent use is linked to ulcerative cystitis, which can need surgery.
• Memory: Frequent, daily use is linked to lasting memory problems.
• Hard to stop: Tolerance builds, and many frequent users try and fail to quit.

Keeping it safer

• Never with alcohol, benzos or opioids.
• Sit somewhere safe, with someone sober, away from stairs, roads and water.
• If someone won't respond or is breathing strangely, put them on their side and get help — and say what they took.

Check what you know

Four questions about what ketamine does.

• On ketamine, the room looks exactly the same — but it feels like you're watching it from somewhere slightly behind yourself. What's happening in the brain? The default mode network, which ties experience to your sense of self, is coming apart. Ketamine weakened the default mode network's links through the posterior cingulate, and dissociation is its signature effect.
• The next morning, you remember the start of the night clearly and almost nothing from the middle — though you were talking the whole time. Why? Ketamine disrupts storing new memories while leaving moment-to-moment recall working. It impaired delayed recall while sparing immediate recall.
• Someone wonders how a party drug could possibly help depression. What's the leading idea? It rapidly grows new synapses in the prefrontal cortex, and works within hours. One infusion helped treatment-resistant depression within two hours, and in rats it rapidly built new prefrontal synapses.
• Someone's eyes are flicking side to side in small rhythmic jerks, and they say everything looks doubled. What's going on? Ketamine's typical eye signs: nystagmus, and the eyes failing to converge. Those were the typical signs of ketamine in people leaving discos.