Ketamine & MAOI
Ketamine is a dissociative anesthetic that has been increasingly studied and used for various purposes, including anesthesia, pain management, and treatment-resistant depression.
Ketamine primarily acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor in the brain. By blocking these receptors, ketamine disrupts the excitatory actions of glutamate, which can lead to its anesthetic and dissociative effects.
Beyond blocking NMDA receptors, ketamine increases the release of glutamate. This increased glutamate then stimulates the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. The activation of AMPA receptors is thought to enhance synaptic plasticity, which is crucial for learning, memory, and mood regulation.
At sub-anesthetic doses, ketamine can cause dissociative effects, where the individual feels detached from their body and surroundings. This is often described as a "k-hole" in recreational settings.
Monoamine oxidase inhibitors (MAOIs) are a class of medications used primarily to treat depression and some anxiety disorders. They work by inhibiting the activity of monoamine oxidase (MAO), an enzyme responsible for breaking down monoamine neurotransmitters in the brain. Here’s a detailed explanation of how MAOIs work, including examples:
MAO is an enzyme that breaks down monoamine neurotransmitters such as serotonin, norepinephrine, and dopamine. These neurotransmitters play a crucial role in mood regulation. There are two types of MAO enzymes: MAO-A and MAO-B. MAO-A primarily breaks down serotonin and norepinephrine, while MAO-B mainly breaks down dopamine.
By inhibiting the activity of MAO, MAOIs prevent the breakdown of these neurotransmitters, leading to increased levels of serotonin, norepinephrine, and dopamine in the brain. Elevated levels of these neurotransmitters help alleviate symptoms of depression and anxiety by improving mood, energy levels, and overall emotional stability.
Examples of MAOIs:
- Phenelzine (Nardil) is a non-selective MAOI, meaning it inhibits both MAO-A and MAO-B. It is used to treat major depressive disorder and anxiety disorders, especially when other treatments have failed.
- Tranylcypromine (Parnate) is another non-selective MAOI. It is effective in treating major depressive disorder and is often used in cases of treatment-resistant depression.
- Selegiline (Emsam, Zelapar) is a selective MAO-B inhibitor at lower doses and becomes non-selective at higher doses. It is used in lower doses to treat Parkinson’s disease and in higher doses for major depressive disorder (transdermal patch form known as Emsam).
Combining ketamine and MAOIs can have complex effects due to their individual pharmacodynamics and potential interactions.
- Cardiovascular Effects: Both drugs can have significant cardiovascular effects. Ketamine can cause tachycardia (increased heart rate) and hypertension (increased blood pressure). MAOIs can also cause similar cardiovascular changes. When combined, there is a potential for compounded cardiovascular stress, necessitating careful monitoring.
- Increased Risk of Hypertensive Crisis: MAOIs inhibit the breakdown of tyramine, a substance found in certain foods and drinks, leading to increased levels of tyramine in the body. High levels of tyramine can cause a hypertensive crisis. Ketamine, which can increase blood pressure and heart rate, might exacerbate this risk when used with MAOIs.
- Potential for Serotonin Syndrome: Serotonin syndrome is a serious condition caused by excessive serotonin activity in the brain. Combining ketamine, which indirectly increases serotonin levels, with MAOIs, which directly increase serotonin by inhibiting its breakdown, can raise the risk of serotonin syndrome. Symptoms include agitation, confusion, rapid heart rate, and high blood pressure.
- Neuropsychiatric Effects: Both ketamine and MAOIs can affect cognitive and psychiatric functions. Ketamine’s dissociative effects might be amplified by the mood-stabilizing effects of MAOIs. This can lead to unique alterations in mood, perception, and cognition, which could be beneficial in some therapeutic contexts but also pose risks of excessive sedation or altered mental states.
Due to the potential for serious side effects, combining ketamine and MAOIs requires close supervision. Blood pressure, heart rate, and mental status should be monitored. User on MAOIs must adhere to dietary restrictions to avoid tyramine-rich foods and reduce the risk of hypertensive crisis.
We have not come across confirmed data on acute and fatal conditions associated with this combination. At the same time, there are no signs of worthwhile positive recreational effects that could cover the risks of this combination.
It's also important to highlight that MAOIs are commonly prescribed for managing psychological and psychiatric conditions. Introducing psychoactive substances during treatment with such medications generally diminishes the efficacy of the therapy, further destabilizes compromised neural systems, and elevates the likelihood of exacerbations and negative side effects.
Considering the above, we recommend treating this combination with great caution. It would be better to avoid it.
Last edited by a moderator: