Then (1979), LSD: My Problem Child
The Neuroplasticity Mechanism: What Hofmann Couldn't Have Known
Hofmann observed that a single LSD session produced psychological changes that persisted for months or years, changes in alcoholism, in neurotic patterns, in death anxiety. He could not explain the mechanism; the neuroscience of the 1970s offered no framework for how a single session could produce lasting change. He described the effect but had no mechanism.
confirmed
The neuroplasticity mechanism is now the primary hypothesis for how single psychedelic sessions produce lasting change. Shao et al. (Neuron, 2021): psilocybin produces rapid (within 24 hours) and persistent (lasting at least 4 weeks) growth of dendritic spines in mouse frontal cortex, the physical substrate of new synaptic connections. Carhart-Harris et al. (New England Journal of Medicine, 2021): in a six-week trial of 59 people with depression, psilocybin and the antidepressant escitalopram both reduced depression scores, with no significant difference between them on the main measure. Ly et al. (Cell Reports, 2018): multiple psychedelics promote structural and functional neural plasticity. Spine growth in mice is a candidate cellular mechanism for the lasting change Hofmann observed; it has not been shown to explain lasting change in people.