How do hallucinogens work on the brain?
What do we know about how hallucinogens work on the brain to produce their characteristic subjective effects? This question can be approached from a number of different levels. At the lowest functionally relevant level, how do the hallucinogenic compounds themselves interact with a certain neurotransmitter receptor to alter neuronal activity? Then at the neuronal population level, how does a drug-induced change in neuronal firing interact with the integrated oscillatory activity of large populations of neurons? Finally, how does this all play out at the level of large-scale systems or networks in the brain; and of how do changes in the functional behaviour of these systems map on to specific psychological experiences?
The ‘classic’ hallucinogens – such as LSD (derived from ergotamine found in ergot fungi), dimethyltryptamine (DMT, the major hallucinogenic component of ayahuasca) and psilocybin (from magic mushrooms) – possess a unique and arguably unrivalled potential as scientific tools to study the mind and the brain. For those of us who are currently fortunate enough to be researching them, there is a real sense that we are exploring something destined to become the ‘next big thing’ in psychopharmacology. But how much do we really know about how they act on the brain to produce their many unusual effects? Here, we summarise the relevant research, beginning at the level of single neurons and moving towards networks in the brain.