20:00 – Psilocybin’s effect on the serotonin pathway. It is known as a serotonergic agonist; it activates the 5-HT2A receptor.
20:54 – Swiss study on psilocybin’s effects on neurogenesis. Administering psilocybin to animals increased neurogenesis in the dentate gyrus region of the brain and caused fear extinction.
21:21 – Neurogenesis and how it treats PTSD. There was another study that did not involve psilocybin. The study showed that to form new connections, others connections had to break. The PTSD study showed, for some reason, that the connections responsible for traumatic recollection would degrade as new ones formed when neurogenesis was increased. It appeared as if the brain had a way of economically cleansing the connections.
22:11 – Dr. Griffiths explains an unpublished study from Barcelona examining classic hallucinogens and neurogenesis. He believes a signal between the two exists and we will be hearing more about it.
22:38 – Mechanisms of action of these effects. Psilocybin binds to 2A and 2C receptors of the 5-HT category of receptors. Psilocybin’s long term/”downstream” effects are glutamate mediated. Glutamate is the most abundant neurotransmitter in humans; glutamte accounts for well over 90% of the synaptic connections in the human brain.
24:40 – Ketamine. Ketamine is a dissociative anesthetic but is sometimes considered a psychedelic; though it is typically used to treat depression.
26:22 – What we know about psilocybin. We know the receptors that it binds to (5-HT2A and 5-HT2C). We know the areas that are activated and deactivated.
Here is a quote from a study looking at the neural correlates of the psychedelic state (determined by fMRI):
“These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enables a state of unconstrained cognition”
The photos gathered from the fMRI are quite telling as well – they show significant activity over the placebo.
26:39 – Default mode network. Psilocybin seems to decrease activity (acutely) within the default mode network. The default mode network (DMN) is a series of connection typically active when an individual is not focused on the outside world and is in a state of wakeful rest. Typically the DMN is active when an individual is daydreaming, mind-wandering, recalling autobiographical information, engaging in self-reference, and experiencing emotions of one’s self and others.
When someone is depressed, there is an increased level of activity in the DMN. Two major areas of the brain decrease in activity when the DMN is active; these regions are typically associated with planning, decision making, and moderating social behavior. Areas such as the prefrontal cortex and posterior cingulate cortex. This part of the discussion may be a bit confusing because I (at least) always understood the DMN to consist of these regions involved in long term planning and for these regions to be active when in a state of self-reflection. Perhaps what is important the the fact that the DMN is a network of connectivity and certain things can be done to activate it or deactivate it. Another important thing to note is that the DMN is often associated with rumination which gets a negative connotation because the act of ruminating is considered unproductive.
28:21 – Activity in the DMN is decreased in long term meditators. This can be understood as a surrender of the self and dropping of the ego.
A quote from a study out of Yale School of Medicine:
“Results indicate that meditation is associated with reduced activations in the default mode network relative to an active task in meditators compared to controls”
28:48 – Psilocybin looks a lot like meditation in regards to how active the DMN is. Subjects who take psilocybin are encouraged to “let go” and surrender ego and be present in the present moment. This is similar to one of the key features of psilocybin induced experiences; the feature of feeling as though you are getting out of past and future and you’re present. Dr. Griffiths addresses the hippie-like framework typically used to describe these psychological processes. He understands that this framework falls short of the empirical scientific standards set forth. There is a lot of metaphor; perhaps this is telling of the true significance of the experience.