Tolerance to Hallucinogens
As the body becomes tolerant to the effects of a drug, users need to take ever-increasing quantities of the substance to achieve the same effects experienced at lower doses. This is why tolerance is such an important characteristic of dependence on certain drugs.
Multiple studies have shown that tolerance to hallucinogens such as LSD, mescaline, psilocybin, and psilocin builds very quickly; after three to four days of drug taking, the user does not experience any psychedelic effect regardless of the dose of the drug. Researchers have also discovered that once tolerance to these hallucinogens has been achieved, the user only has to abstain from the drug for about four days to once again experience the full effect of the hallucinogen. Experts therefore agree that tolerance-driven dependency upon these drugs is virtually unknown since tolerance tends to limit the frequency of their use.

MDMA is rather unique in this group of hallucinogens with regard to tolerance, and, to some extent, dependency. Tolerance to the euphoric sensations from Ecstasy develops quickly in a fashion similar to other hallucinogens. As a result, users sometimes take escalating doses of the drug to prolong their pleasant effects (called "stacking"). However, as tolerance builds, increased use of MDMA results in an escalation of the more stimulating aspects of the drug (described as "unpleasant") along with a decrease in the euphoria and openness associated with Ecstasy. Users also report combining alcohol, marijuana, or other drugs with these stacked doses of MDMA. Researchers and physicians cite evidence that many of these accelerated efforts to sustain a good trip with MDMA can pose unpredictable physical and psychological dangers to the user, and more often than not result in a bad trip.
Interestingly, when users are tolerant to LSD, they also become tolerant to mescaline and psilocybin as well. This is called cross-tolerance—one becomes tolerant to the effects of all hallucinogens simply by taking one frequently. It is unclear whether MDMA is cross-tolerant with any other hallucinogens. Its structural and chemical similarity to mescaline leads some researchers to conclude that MDMA may very well be cross-tolerant with these other hallucinogens. However, other researchers disagree and base their hypothesis on evidence that there is no cross-tolerance between LSD (and other related hallucinogens) and non-hallucinogenic amphetamines. Since MDMA is an amphetamine derivative, these researchers conclude that MDMA cannot be cross-tolerant with the other hallucinogens.
Continue reading here: Serotonin Dopamine And Norepinephrine Psychedelic Messengers
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