How do psychedelics affect the brain? © Martin Hieslmair

How do psychedelics affect the brain?

Though the specifics depend on the drug, psychedelics all increase the amount of disorganised activity across the brain.

‘Classic psychedelics’ like LSD and psilocybin (found in magic mushrooms) are chemically similar to the neurotransmitter serotonin produced by the brain. Serotonin is involved in many neural functions including mood and perception. By mimicking this chemical’s effects, the drugs exert their profound effects on subjective experience.


DMT (or dimethyltryptamine) too acts via serotonergic pathways (the system involving serotonin), but also through other routes – for instance, DMT binds with sigma-1 receptors that are involved in the communication between neurons.

Meanwhile, ketamine – among many other effects – blocks NMDA receptors that are involved in the functioning of the neurotransmitter glutamate.

A key brain area for psychedelic drugs’ effects appears to be the temporal lobe, the location of much emotional and memory functioning. For instance, removal of the front part of the temporal lobe (as a radical treatment for epilepsy) has been shown to prevent the psychological effects of taking LSD.

Interestingly, abnormal activity in the temporal lobe, such as during seizures, can lead to events similar to near death experiences.

An effect shared by different psychedelic substances is that they increase the amount of disorganised activity across the brain – a state that neuroscientists describe as being ‘higher in entropy’.

One consequence of this is a reduction in the activation of a group of brain structures known collectively as the ‘default mode network’, which is associated with self-conscious and self-focused thought.

One theory, then, is that psychedelics provoke a spiritual state of oneness with the world by increasing the brain’s entropy and suppressing the ego-sustaining activity of the default mode network.

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