MAOIs & Mephedrone
Monoamine oxidase inhibitors (MAOIs) are a class of antidepressants that work by inhibiting the activity of an enzyme called monoamine oxidase (MAO). This enzyme is responsible for breaking down neurotransmitters such as serotonin, dopamine, norepinephrine, and tyramine. These neurotransmitters are essential for regulating mood, emotion, and various physiological functions. When monoamine oxidase breaks them down too rapidly, it can result in a deficiency that contributes to depression, anxiety, and other mood disorders.
There are two types of monoamine oxidase enzymes: MAO-A and MAO-B. MAO-A preferentially breaks down serotonin, norepinephrine, and dopamine, whereas MAO-B focuses more on dopamine and phenylethylamine. Some MAOIs target both enzymes, while others are more selective. By inhibiting these enzymes, MAOIs increase the levels of neurotransmitters in the synaptic cleft, the space between nerve cells, which improves communication between neurons and helps alleviate the symptoms of depression and anxiety.
Examples of non-selective MAOIs include phenelzine and tranylcypromine, which inhibit both MAO-A and MAO-B. These drugs are commonly used to treat major depressive disorder, especially in cases where other antidepressants have failed.
Selegiline, on the other hand, is a selective MAO-B inhibitor, primarily used in low doses for Parkinson’s disease to increase dopamine levels, but at higher doses, it can also function as an antidepressant by inhibiting both MAO-A and MAO-B.
Mephedrone, also known as 4-methylmethcathinone or simply “meph,” is a synthetic stimulant belonging to the cathinone class, chemically related to amphetamines and structurally similar to the active compound found in the khat plant. It acts primarily by increasing the activity of the neurotransmitters dopamine, serotonin, and norepinephrine, which are critical in regulating mood, energy, motivation, and pleasure. Mephedrone achieves its effects by functioning as both a releasing agent and reuptake inhibitor for these neurotransmitters, meaning it promotes their release into the synapse and simultaneously blocks their reabsorption into presynaptic neurons, leading to a substantial buildup of these chemicals in the brain.
Dopamine is associated with feelings of reward, pleasure, and motor function. By increasing dopamine levels, mephedrone creates a sense of euphoria, heightened confidence, and enhanced sociability. This effect is similar to that of amphetamines, contributing to the stimulant properties of the drug. Serotonin plays a role in mood regulation, empathy, and emotional closeness. The increase in serotonin caused by mephedrone often results in feelings of emotional warmth, connectedness, and increased sensory perception, effects that can resemble those produced by MDMA. Norepinephrine influences arousal, alertness, and cardiovascular function. By elevating norepinephrine levels, the drug enhances energy, focus, and physical stimulation, often causing increased heart rate, blood pressure, and sweating.
The combination of MAOIs with mephedrone presents serious and potentially life-threatening risks. Both substances profoundly impact neurotransmitter systems, and their interaction can lead to severe complications, particularly serotonin syndrome and hypertensive crisis.
When taken together, this results in an excessive buildup of serotonin, drastically raising the risk of serotonin syndrome. Symptoms of serotonin syndrome include confusion, agitation, fever, sweating, muscle rigidity, tremors, and, in extreme cases, seizures, rhabdomyolysis, organ failure, and death. The syndrome can develop rapidly—often within hours of co-administration—and requires immediate medical attention to prevent life-threatening complications.
Additionally, mephedrone’s stimulant properties can provoke sympathetic overactivation, elevating norepinephrine levels, which, in combination with MAOIs, can trigger hypertensive crises. This acute rise in blood pressure may present with severe headaches, chest pain, palpitations, nausea, and potential stroke. The risk is especially high because both agents increase adrenergic activity, overwhelming cardiovascular control mechanisms.
Given the danger of these interactions, concurrent use of MAOIs and mephedrone is strongly contraindicated. Both substances should be avoided together under any circumstances due to the unpredictable and potentially fatal effects on the central nervous system and cardiovascular system. Users of MAOIs need to exercise caution with all serotonergic or sympathomimetic agents, not just stimulants, to avoid these extreme outcomes.
It's also important to highlight that MAOIs are 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.
All things considered, we recommend avoiding this combination.
Last edited by a moderator: