Discussion: Ketamine & Piracetam

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Ketamine & Piracetam​

Ketamine is a dissociative anesthetic with a variety of uses, including anesthesia, pain management, and, more recently, treatment-resistant depression and other psychiatric disorders. Its mechanisms of action are complex and involve multiple neural pathways.

Ketamine primarily functions as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor. By blocking NMDA receptors, ketamine inhibits excitatory neurotransmission, which can lead to its anesthetic and dissociative effects.

The blockade of NMDA receptors is also associated with an increase in synaptic plasticity. This can result in the formation of new synaptic connections, which is believed to play a role in its rapid antidepressant effects.

Although ketamine blocks NMDA receptors, it indirectly leads to the activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. This is due to an increase in extracellular glutamate levels, which then stimulates AMPA receptors. The activation of AMPA receptors is crucial for ketamine’s antidepressant effects.

Also ketamine interacts with opioid receptors, particularly the mu and kappa opioid receptors, contributing to its analgesic properties. However, this is not the primary mechanism for its psychiatric effects.

Ketamine may inhibit GABAergic interneurons, which results in increased excitatory neurotransmission. This paradoxical effect may contribute to its overall action on mood and perception.


Piracetam is a nootropic drug, often considered one of the earliest and most widely recognized cognitive enhancers. It belongs to the racetam family and is commonly used to improve cognitive functions, such as memory, attention, and learning.

Piracetam enhances the function of the neurotransmitter acetylcholine by increasing its receptor density in the hippocampus, a brain region crucial for memory formation and retrieval. This enhancement improves cholinergic transmission, which is essential for cognitive processes.

Also piracetam improves the fluidity of neuronal cell membranes, which enhances cell membrane permeability and receptor function. This results in more efficient neurotransmission and synaptic plasticity, contributing to better cognitive performance. Besides, piracetam modulates the glutamatergic system by influencing AMPA receptors, which play a key role in synaptic plasticity and long-term potentiation (LTP), mechanisms underlying learning and memory.

Piracetam has neuroprotective properties, protecting neurons from damage caused by oxidative stress and ischemia. It can enhance brain cell survival by reducing the damage caused by free radicals and improving blood flow to the brain. The drug improves microcirculation in the brain without causing vasodilation in other parts of the body. It enhances the rheological properties of blood, such as decreasing blood viscosity, which improves oxygen and nutrient delivery to brain cells.


The combination of ketamine and piracetam is an area of interest due to the distinct and potentially complementary mechanisms of action of both drugs.

The following points are not supported by scientific research, and are listed only as potential speculative possibilities:

• Enhanced Cognitive Function: Piracetam's enhancement of cholinergic and glutamatergic neurotransmission might support cognitive functions, potentially augmenting the cognitive clarity often dulled by ketamine’s dissociative effects.
• Improved Mood and Rapid Antidepressant Effects: The neuroplasticity and BDNF increase induced by ketamine, combined with piracetam's cognitive enhancement, might provide rapid and sustained antidepressant effects.

Combining ketamine and piracetam also carries the potential for side effects, based on the pharmacological profiles of both drugs:

1. Havy Dissociation: Ketamine is known for causing dissociative effects, which may include a sense of detachment from reality, hallucinations, and altered perception. Piracetam can alleviate some cognitive impairment, but dissociation can still occur and even increase.
2. Cognitive Impairment: While piracetam enhances cognitive function, ketamine can cause short-term cognitive impairment, especially in higher doses.
3. Mood Swings: Although both drugs can have antidepressant effects, they may also cause mood swings or emotional instability in some individuals.
4. Anxiety and Agitation: Both drugs can cause anxiety and agitation, particularly at higher doses. This effect might be amplified when the drugs are used together.
5. Seizures: Piracetam can lower the seizure threshold, particularly in individuals with epilepsy. Combining it with ketamine, which alters neural activity, might increase the risk of seizures.
6. Headaches: Both drugs can cause headaches, which could be more pronounced when used together.
7. Increased Blood Pressure In Brain Area: Ketamine can elevate blood pressure and heart rate, which could be exacerbated by piracetam’s effects on cerebral blood flow.
8. Cardiovascular Stress: Combining these drugs might increase cardiovascular stress, especially in individuals with preexisting heart conditions.
9. Gastrointestinal Issues: Both drugs can cause gastrointestinal discomfort. Ketamine is known to induce nausea and vomiting, which could be potentiated by piracetam's side effects.

The combination of ketamine and piracetam comes with a range of possible side effects. Given the multifaceted pharmacological profile of ketamine and the general tendency of piracetam to enhance the effect of psychoactive substances, it is worth having a lot of experience, understanding of what is happening, and all the principles of harm reduction if you irresistibly want to experiment with this combination.

In light of these considerations, we strongly recommend a meaningful approach to this combination.