Mephedrone Tolerance – How To Beat It?

Safety in use

We are often asked: “How to get rid of mephedrone tolerance?”. People are concerned about the situation in which the usual recreational effects begin to disappear. Well, we have the answer. Even two.

Quick Answer

If you notice an increase in your tolerance to mephedrone, you need to gather your strength and take a break of at least 1 week. With complete abstinence during this time, tolerance should decrease by about half. It will take 2-3 weeks to return to the near-initial level. These are very approximate figures, it all depends on the individual, the pattern of use, and other factors.

Long Answer

Tolerance in pharmacology is when the response to repeated administration of the usual doses of a substance ceases to produce the expected effect.

This happens because receptors and cells change their work due to new living conditions. And the regular intake of substances from the outside is a very new condition for any cell/organism.

Have you ever seen a child who tastes something sweet for the first time in life? Or maybe you remember the impressions of the first sip of strong coffee, the first joint, the first track?

The truth is said that the first time is most often unforgettable. And any addicted person is chasing just this feeling – to make it feel like the first time.


Mephedrone Tolerance Guide: Cross & High Tolerance, Recovery

But biochemistry cannot be deceived. The body as a system strives for balance. When a substance in sufficient concentration binds again and again to cell receptors, it can rebalance the system in several ways:

  • Reduce the sensitivity of receptors to the substance.
  • Reduce the density (read number) of receptors in cells.
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This is pharmacodynamic tolerance. It has other mechanisms, but these two are the main ones. And all of them are likely to occur simultaneously – the system must come into homeostasis.

Mephedrone Tolerance Guide: Cross & High Tolerance, Recovery

We normally perceive sweets throughout life. We do not fall into a sugar high every time, because sugars enter our body regularly, and it adapts to this. Some are better, some are worse.

To reverse the process, you must change the “conditions” for receptors, cells, and the body again. This means removing from the equation the substance that was the root cause of the rebalancing. Remove for a long time, and hopes the changes were not so deep, and it would not take years to return to the original state.

So, to reduce tolerance to mephedrone (and to any other substance), you need to spend a Drug holiday is a medical term, but we like the way it sounds. And quite suitable for our purposes.

Above, I outlined the approximate timing of the decrease in tolerance to mephedrone. But the following rule seems more realistic:

With long-term (more than a month) and regular (more than once a week) mephedrone use with high tolerance, the Drug holiday should be at least half of the period of regular use. The longer the better.

There is a second type of tolerance – pharmacokinetic tolerance. It concerns mainly oral consumption and is associated with the work of CYP450 enzymes, which in theory can be influenced. I have met experiments of this nature, but so far everything looks very damp. And the role of pharmacokinetic changes in the formation of tolerance to mephedrone seems to be minimal. Nevertheless, I am following this trend with interest.

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Mephedrone Tolerance Guide: Cross & High Tolerance, Recovery
Monoamine molecules are responsible for most of the effects of stimulants and euphoretics

In the end, I will also touch on cross-tolerance – when a particular substance increases tolerance for other substances from its pharmacological group.

Mephedrone shows cross-tolerance with all stimulants that increase dopamine levels. Amphetamine, methamphetamine, and cocaine will work worse if taken shortly after mephedrone or while regularly using mephedrone. Plus, side effects and post-effects will be stronger.

If you are interested in this topic, I recently came across a discussion on Reddit.

That’s all for today. Thank you for your time!