Psychedelic drugs can aid fast and lasting remission from various neuropsychiatric disorders, presumably by increasing neuroplasticity. Growing evidence shows enhanced neuronal plasticity in the first week post-treatment, but it is unclear if these changes are integrated across higher levels of analysis to explain the long-term shifts in behaviour. We searched for signatures of enhanced plasticity at behavioural, cognitive, and structural levels to determine if a single dose of the psychedelic drug DOI induces a comprehensive and lasting high-plasticity state in young adult C57BL/6 male mice. On a behavioural level, high-plasticity states are environmentally sensitive, so we tested whether the acute psychedelic state in mice is context-dependent. We compared DOI’s dose-response curves in a familiar and novel context and found that novelty modulated the frequency of psychedelic-like behaviours without modulating the drug’s effects on exploration. On a cognitive level, high plasticity implies better cognitive flexibility, so we tested reversal learning in a two-step decision-making task in the weeks after a single moderate dose of DOI. Adaptability to a novel reversal one day after DOI was comparable to the controls. But when we initiated a novel reversal one week after treatment, allowing for consolidation of putative neuronal plasticity, DO-Itreated mice adapted faster and developed a richer choice strategy. On a structural level, high and extensive neuronal plasticity would lead to regional changes in grey matter volume. Using ex vivo magnetic resonance imaging, we showed increased volumes of several sensory and association cortices 24h, but not three weeks, after one moderate dose of DOI. In conclusion, we found signs of DOI-induced higher brain plasticity at several levels of analysis that are correlated but not necessarily coincidental with known neuronal plasticity. We suggest that while DOI’s neuronal plasticity can initiate higher-level plasticity, its consolidation might be required for any enduring cognitive and behavioural change.