Ketamine (K, Special K)
Ketamine is a dissociative anaesthetic that acts on NMDA receptors. It may interact with several antiretrovirals that change its levels, increasing the risk of deep sedation or reduced effectiveness.
What is it?
Ketamine is a dissociative anaesthetic originally developed for medical and veterinary use. At low doses it may change perception, create body disconnection, and alter consciousness. It may also increase dopamine and noradrenaline levels. It is mainly metabolised by the liver enzymes CYP3A4 and CYP2B6.
How is it used?
- Snorted (powder): the most common route in recreational settings
- Inhaled or vaporised
- Injected (intramuscular or intravenous): greater intensity and risk
- In pills or tablets
- Dissolved in drinks
The route of use affects the intensity and duration of effects. Injection produces the fastest and most intense effect.
How does it work?
Ketamine works by blocking NMDA glutamate receptors in the brain, producing a dissociative state characterised by:
- Disconnection from the body (floating sensation or separation from the environment)
- Changes in sensory, visual, and auditory perception
- Hallucinations at medium to high doses (the so-called “k-hole”)
- Relaxation and sedation
- Euphoria and distortion of time and space
- Analgesia (reduced pain sensation)
Effects start quickly (seconds if injected, 5-15 minutes if snorted) and last between 30 minutes and 2 hours depending on dose and route.
Interactions with antiretrovirals
Ketamine is metabolised by CYP3A4 and CYP2B6. Several antiretrovirals inhibit or induce these enzymes, which may significantly change ketamine blood levels.
It may INCREASE ketamine levels
Higher levels may cause:
- Deep sedation and inability to respond
- Severe confusion and disorientation
- Respiratory depression (life-threatening)
It may DECREASE ketamine levels
Lower levels may cause:
- Reduced effect and a perceived need for higher doses to get the same effect
- More toxicity from unintentional redosing
Medicines requiring more caution
| Group / Medicine | Interaction risk | Notes |
|---|---|---|
| Protease inhibitors (PI): lopinavir/ritonavir, atazanavir, darunavir | High | CYP3A4 inhibition; may increase ketamine levels and sedation/toxicity |
| NNRTIs: efavirenz, nevirapine | Moderate | Efavirenz may induce CYP3A4 and lower ketamine levels; nevirapine has a similar but smaller effect |
| Integrase inhibitors: elvitegravir, raltegravir, dolutegravir | Moderate | Elvitegravir boosted with cobicistat has greater interaction potential through CYP3A4 inhibition |
| Maraviroc | Moderate | Metabolised by CYP3A4; levels may be affected |
Harm reduction
- Use the smallest amount possible
- Avoid combining with alcohol, benzodiazepines, GHB, or other CNS depressants (the risk of respiratory depression rises a lot)
- Hydrate and rest during and after use
- Do not use alone: the dissociative state may stop you from asking for help
- Have a safe setting and trusted people who know the situation
- Tell your healthcare team about ketamine use
Warning signs
- Intense confusion or disorientation that does not improve
- Hallucinations or severe paranoia
- Trouble coordinating or moving safely
- Intense nausea or vomiting
- Respiratory depression: slow, shallow, or paused breathing
When should you seek medical care?
- Trouble breathing or very slow breathing
- Loss of consciousness or inability to respond
- Seizures
- Chest pain
- Extreme agitation or violent behaviour that puts the person or others at risk
If any of these happen, call emergency services immediately.
What does the evidence say?
Ketamine interactions with protease inhibitors boosted with ritonavir are related to CYP3A4 inhibition, which may significantly raise ketamine plasma levels. Efavirenz, in contrast, may induce this same enzyme system and lower levels. Direct clinical evidence in people living with HIV using ketamine recreationally is limited. Chronic or frequent ketamine use is associated with bladder harm (ketamine cystitis) regardless of ART.