The science

Tolerance, and why it moves

Tolerance is not a character flaw or a sign you are doing it wrong. It is a measurable change in your brain, and unlike most such changes, this one appears to undo itself.

What changes

A PET imaging study of 30 chronic daily cannabis smokers against 28 controls found reversible, regionally selective downregulation of CB1 receptors in cortical regions, with the degree of downregulation tracking how long someone had been using.

CB1 is the receptor THC acts on. Fewer available receptors is a straightforward mechanical explanation for why the same dose does less over time.

It comes back

In the same study, the 14 smokers who completed follow-up scans after roughly four weeks of monitored abstinence had CB1 receptor density back at normal levels.

Four weeks is a real inconvenience and it is also not very long. This is the basis for the tolerance break as a practical idea, and it is better supported than most folk wisdom in this area.

What tolerance does not do

Heavy users in a controlled study showed no impairment on certain tracking, stop-signal and planning tasks that reliably impair occasional users. Real tolerance, genuinely measured.

Those same users had no cross-tolerance to alcohol whatsoever, and alcohol potentiated THC's effects on divided attention. Tolerance is specific to the thing you built it against. It is not a general robustness, and it buys you nothing the moment a second substance enters. That is covered properly in THC and alcohol.

The practical read

• If drinks have stopped doing much, the answer is usually a break, not a bigger can. Going up a tier raises the cost and the calories and the risk of an unpleasant evening, and it treats a receptor problem with arithmetic.
• Coming back from a break, go back to beginner doses. Your receptors did. This is where people who have been doing this for years get caught out.
• One figure to distrust: you will see "roughly 20 percent lower CB1 availability in chronic users" quoted widely. We could not confirm that specific number in the source material and we are not going to repeat it.