The reason you can't become physically addicted to psychedelics

Tolerance is a person's diminished response to a drug with repeated use. Classic psychedelics, like LSD and psilocybin from psychedelic mushrooms, activate 5-HT2A receptors and?induce rapid tolerance.?For example, taking the same dose of LSD daily reduces its psychedelic effects almost completely after several days.?

"In an early human study from the mid-1950s, psychedelic doses of LSD were given daily for two to three weeks, or even up to three months. By the end of the repeated LSD dosings, tolerance was so profound that when researchers replaced the drug with mere water, subjects did not even recognise that it was not LSD they had received."?-?Mind Foundation.

However, tolerance is also quickly abolished, and maximal effects return?after 3-7 days of abstinence.

Interestingly, cross-tolerance occurs between different psychedelics that are?5-HT2A agonists.?For example, taking LSD on day 1 will reduce response to psilocybin on day 2 and visa versa.

Tolerance is thought to occur because “psychedelic” 5-HT2A receptors are down-regulated (transported back into the cell for recycling) after excessive stimulation and there are fewer receptors?to stimulate on the cell surface. These receptors are recycled and returned to the surface of the cell after a few days.

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Written by Dilara Bahceci, PhD