Ketamine Dextromethorphan (DXM) Red Discussion: Ketamine & Dextromethorphan (DXM)

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Ketamine & Dextromethorphan (DXM)​

Ketamine is a medication primarily used for anesthesia and pain management, but it also has applications in treating depression and other mental health conditions.

Ketamine primarily acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. NMDA receptors are involved in the transmission of excitatory signals in the central nervous system and play a key role in synaptic plasticity, memory, and learning. By blocking NMDA receptors, ketamine decreases the activity of glutamate, the primary excitatory neurotransmitter in the brain. This results in a rapid antidepressant effect by enhancing synaptic connections and neural plasticity.

Ketamine induces a trance-like state characterized by sedation, immobility, amnesia, and marked analgesia. It causes dissociation between the thalamocortical and limbic systems, meaning the brain cannot process external stimuli. At higher doses, ketamine can cause hallucinations, dissociation, and out-of-body experiences, which are generally referred to as the "K-hole."


Dextromethorphan (DXM) is a common active ingredient in many over-the-counter cough medications. It works primarily as a cough suppressant but also has other pharmacological effects. Like ketamine, DXM acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. By blocking these receptors, it can produce dissociative and hallucinogenic effects at higher doses.

DXM binds to sigma-1 receptors, which are involved in modulating neurotransmission and have a role in neuroprotection and neuroplasticity. DXM inhibits the reuptake of serotonin, increasing its availability in the brain, which can contribute to mood enhancement and, at high doses, serotonergic syndrome if combined with other serotonergic drugs. DXM also inhibits the reuptake of norepinephrine, which can contribute to its stimulant effects.

At higher doses, DXM’s NMDA receptor antagonism can lead to dissociative effects similar to those of ketamine and phencyclidine (PCP). These effects can include altered perception of time, space, and self, as well as visual and auditory hallucinations.


Combining ketamine and DXM can lead to significant interactions and potential side effects.

1. Cognitive Impairment: The combination can impair cognitive functions, leading to confusion, difficulty concentrating, and impaired judgment and motor coordination.
2. Increased Dizziness and Drowsiness: Users may experience significant dizziness and drowsiness, increasing the risk of falls and accidents.
3. Psychological Effects: Both drugs have dissociative properties due to their NMDA receptor antagonism. When used together, they can enhance each other’s dissociative and hallucinogenic effects, which might result in intense and potentially distressing psychological experiences. The intense dissociative effects can be psychologically distressing, potentially leading to panic attacks, paranoia, or exacerbation of underlying mental health conditions
4. Serotonin Syndrome: Since DXM inhibits the reuptake of serotonin, combining it with ketamine (which also has some serotonergic effects) increases the risk of serotonin syndrome. This condition is characterized by symptoms such as agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, and muscle rigidity.
5. Additive Neurotoxicity: The neurotoxic effects of each drug could be amplified when taken together, potentially leading to long-term cognitive and neurological issues with prolonged or repeated use.

Due to the high risk of severe side effects, it is generally recommended to avoid using ketamine and DXM together due to their overlapping mechanisms of action and potentiation of each other's side effects.

All things considered, we recommend avoiding this combination under any conditions.