Post from 3 years ago a Neurobiologist:

The first thing we need to establish is what a neurotransmitter is. Essentially, there are chemicals that exist within your brain that help transmit and modulate information. This happens by the chemicals binding to a site, similar to a lock and key, where the key (neurotransmitter) unlocks a lock (receptor) and this lets the brain know that certain information was exchanged. This information typically releases something known as an action potential, or essentially an electrical signal - basically it lets another part of the brain know that this part of the brain was 'activated'.

There are only so many neurotransmitters and they can do a variety of things in the brain.

LSD, or lysergic acid diethylamide has a structure that is very similar to a few neurotransmitters that are naturally produced. The key it is most similar to is a neurotransmitter known as serotonin. Serotonin is used to modulate and signal a variety of things in the brain. Visual processing (or what you see) utilizes a lot of serotonin. Almost all of the senses have some serotonin input as well. Emotional processing (sad, happy, excited, etc.) is also heavily serotonin influenced.

LSD happens to be even better at activating serotonin receptors than serotonin itself, so it essentially increases the normal levels of signaling by serotonin (it does this through a variety of mechanisms, not just limited to better binding - it actually releases extra serotonin, changes the lock to accept keys more readily, etc.). In a lot of ways its like turning up the volume on quiet music. Not only are the already audible pieces more audible, but things you previously could not hear are now audible (whispers you might have missed, or background noise might now become audible).

Because it increases the signal, it also increases the signal noise (if you turn the volume up on a microphone very high, you sometimes get feedback loops, or that annoying high pitched noise). In addition, if you have the volume extremely high, you may not be able to differentiate between the louder sounds very well. On LSD, this often results in hallucinations - hearing, seeing, touching, tasting, etc. things that are not actually there.

In addition, through a relatively unknown mechanism, LSD increases 'cross-talk' between areas of the brain. That is to say, it helps stimulate areas of the brain that don't normally talk to each other, to start talking to each other. Over the long term, it can even help create connections that previously didn't exist - much like putting up extra telephone or internet lines. This increased cross-talk while under the influence of LSD (combined with the increased sensory input) often results in something known as synesthesia, or a mixing of the senses. What this means is that people might experience a sense across multiple senses - they might see sound, taste colors, or feel smells.

Since the mechanism of cognition (what causes us to think the way we do) is not known, I cannot explain why it changes a person's mindset, only that it does. People often describe it as 'thinking outside the box'. Having done LSD myself many times, I agree that it shifts the paradigm of thought. It likely is associated with this 'cross-talk' mechanism, at least to some extent, but the increase in serotonin and dopamine likely has an effect as well. Other serotonergic drugs, such as ecstasy (which is very similar to hallucinogens), shift how you think as well because increased serotonin results in a sort of euphoria (happiness). It also seems to increase one's ability to empathize with someone else - that is to say, you more easily relate with someone else's emotional state. This increased empathy also changes how you think about things.

It's important to note that no hallucinogens have any proven addictive mechanisms (they are the only recreational drugs that have no addictive qualities). In addition, casual use is not associated with any permanent brain damage. Any use, casual or not, will reduce the relative abundance of serotonin (and other catecholamine receptors, such as dopamine) receptors. However, anecdotal evidence suggests that a single use of a moderate dose can be recovered from within about 1-2 weeks of abstinence.