Short-term physical health risks of MDEA consumption include dehydration, insomnia, hyperthermia, and hyponatremia. Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.
The exact toxic dosage is unknown, but considered to be far greater than its active dose.
Neurotoxicity
As with MDMA, the neurotoxicity of MDEA use has long been the subject of debate. Scientific study has resulted in the general agreement that, although it is physically safe to try in a responsible context, the administration of repeated or high dosages of MDEA is likely to be neurotoxic and cardiotoxic in some form.
Like other powerful serotonin releasing agents, MDEA is thought to cause down-regulation of serotonin reuptake transporters in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in some animals exposed to MDMA, which likely applies to MDEA as well. Other studies have suggested that the brain may recover from serotonergic damage.
Cardiotoxicity
Like with MDMA, the long-term heavy use of MDEA is likely similarly cardiotoxic, leading to valvulopathy through its actions on the 5-HT2B receptor. In one study, 28% of long-term MDMA users (2-3 doses per week for a mean of 6 years, mean of age 24.3 years) had developed clinically evident valvular heart disease.
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As with other stimulants, the chronic use of MDEA can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of MDEA develops with prolonged and repeated use. This results in users having to administer increasingly larger doses to achieve the same effects. After that, it takes about 1-1.5 months for the tolerance to be reduced to half and 2-3 months to be back at baseline (in the absence of further consumption). MDEA presents cross-tolerance with all dopaminergic and serotonergic stimulants and entactogens, meaning that after the consumption of MDEA all of these will have a reduced effect.
Dangerous interactions
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with MDEA should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
Stimulants - MDEA may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
Tramadol - Tramadol is known to lower the seizure threshold and combinations with stimulants may further increase this risk.
MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.
Stimulants - The neurotoxic effects of MDEA may be increased when combined with other stimulants.
Cocaine - This combination may increase strain on the heart.
Serotonin syndrome risk
Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.
MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.
Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
SSRIs - Such as citalopram and sertraline
SNRIs - Such as tramadol and venlafaxine
5-HTP
There is an increased risk of serotonin syndrome when MDEA is taken with many antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Additionally, if MDEA is taken with SSRIs and SNRIs, the MDEA will be significantly less powerful or may have no distinguishable effects at all.