Psychedelics, DMN & depression
RESEARCH & Academic writing
Academic essay and research project for the course Various states of consciousness,
by the cognitive neuroscience department at the University of Skövde.
Content
Introduction
Psychedelics alter brain function, which alter the state of consciousness. It may be that by altering our state of consciousness with psychedelics, we can achieve long-lasting results with positive changes on our normal waking state of consciousness. Under the right circumstances, psychedelics have psychotherapeutic potential for mental health issues that are otherwise deemed treatment resistant, and there’s potential to uncover more knowledge and understanding about our minds and consciousness with psychedelics lighting up the way.
This essay looks into psychedelics and their effect, and how that can affect consciousness. The focus is set on the effect of classic psychedelics, and of those foremost the effects of psilocin and lysergic acid diethylamide (LSD). These compounds have a broad spectrum of effects, of which I’m focusing on the specific effects on the Default Mode Network of the brain, and how that connects to depression.
Psychedelics alter brain function, which alter the state of consciousness. It may be that by altering our state of consciousness with psychedelics, we can achieve long-lasting results with positive changes on our normal waking state of consciousness. Under the right circumstances, psychedelics have psychotherapeutic potential for mental health issues that are otherwise deemed treatment resistant, and there’s potential to uncover more knowledge and understanding about our minds and consciousness with psychedelics lighting up the way.
This essay looks into psychedelics and their effect, and how that can affect consciousness. The focus is set on the effect of classic psychedelics, and of those foremost the effects of psilocin and lysergic acid diethylamide (LSD). These compounds have a broad spectrum of effects, of which I’m focusing on the specific effects on the Default Mode Network of the brain, and how that connects to depression.
Psychedelics, consciousness & depression
Psychedelics
Psychedelics (meaning “mind revealing”) is a group of psychoactive chemicals known to impact consciousness by altering brain function (Presti, 2017; Carthart-Harris et.al, 2014). This class of substances are also known as hallucinogens (“generating hallucinations”), entheogen (“generating god within”), and psychotomimetic (“mimicking psychosis”) (Presti, 2017). The experience of the altered state during the influence of psychedelics is highly affected by set and setting, i.e. mindset and surrounding environment; such as preparation, expectations, intentions, and physical and social setting (Presti, 2017). Influencing perception, thoughts and feelings, psychedelics seem to have a promising utility in psychotherapeutic work by bringing material to the surface that’s otherwise not readily available to awareness (Presti, 2017).
LSD, psilocin (and pro-drug psilocybin), DMT and mescaline - known as the “classic psychedelics” - all have significant agonist activity at type-2A serotonin receptors (5-HT2AR) which are widely distributed throughout the brain. The 5-HT2AR is involved in functions such as learning, mood and anxiety, and it is believed that this receptor plays a primary role in the altered states of consciousness caused by psychedelics (Presti, 2017; Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018).
Default Mode Network
The Default Mode Network (“DMN”) is a brain network of which the major hubs are the posterior cingulate cortex (PCC), precuneus and medial prefrontal cortex (mPFC) (Ruban & Kołodziej, 2018). It is engaged in processing of self-reflection, mind-wandering and mental time-travel (Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018). The network is a resting-state network which is active during internal thoughts, while being relatively removed from sensory processing and anticorrelated with task performance; when focused on tasks or the outside world, task-positive networks of the brain are active and activity in the DMN is suppressed (Carhart-Harris et.al, 2014).
The connectivity of the DMN increases during the development from birth to adulthood, and the regions have undergone a major evolutionary expansion. During high functional connectivity (FC) within the DMN, an increase can be seen between the DMN and other brain networks; this centrality of the DMN is not shared with other brain networks, implying that the DMN serves as the highest level of hierarchy of global brain function (Carhart-Harris et.al, 2014). With this comes an extended ability to organise cognition and lower entropy (uncertainty). The suppression of entropy is an evolutionary beneficial function that supports realism, reflection, foresight and the ability to therefore overcome wishful thinking and paranoia (Carhart-Harris et.al, 2014).
Regions of the DMN consume more energy and receive more blood than other parts of the brain; only in the PCC the cerebral blood flow (CBF) and energy consumption is around 40% higher than average of the rest of the brain. It also seems to have a consistently high level of activity and receives more blood flow than other regions of the brain, even when suppressed during task-focused cognition. With its processes and constant presence it is believed that it is from the DMN that a sense of self and ego emerge (Carhart-Harris et.al, 2014), and it is the formation of an ego that provides an ability to reflect about one’s own introspection; metacognition (Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018).
Ego & depression
The primary function of the DMN to support metacognition has evolutionary benefits for survival (learning, plan, reason, reality-testing) (Killingsworth & Gilbert, 2010; Carhart-Harris et.al, 2014), and can lower uncertainty. Humans spend a lot of time mind-wandering, and it seems to be the default mode of the brain when not engaging in any other task. However, people are less happy when the mind is wandering, compared to when being present in the moment. The human mind is a wandering mind, and a wandering mind is an unhappy mind (Killingsworth & Gilbert, 2010). What can be gained by the cognitive achievements of the DMN, can come with a decrease in flexible and divergent thinking, and at an emotional cost (Carhart-Harris et.al, 2014). Dysfunction of the DMN seems to be connected to several different mental health issues and disorders. Activity in the DMN is elevated in depression, and greater DMN activity than task-positive network activity has been found in patients with major depressive disorder (MDD). DMN functional connectivity has a positive correlation with ratings of self-awareness, trait neuroticism, and is associated with an impaired ability to suppress depressive rumination. The inability to suppress DMN activity is also suggested to interfere with the ability to concentrate on a task (Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018).
Magical thinking is the description of cognition in which interpretations are made; the kind of thinking that is likely to happen in situations of high uncertainty since that provides for an opportunity to dream up explanations that lack a base in evidence. This includes wishful beliefs, but also includes paranoia where an individual jumps to negative conclusions since that effectively suspends uncertainty (Carhart-Harris et.al, 2014).
By reinforcing stable patterns of activity uncertainty is lowered. However, depressed individuals’ cognitive style can become too fixed and one state comes to dominate cognition; it’s easier to go back to the same thought patterns since that particular activity has been entrenched. The DMN processes may have beneficial aspects for survival, but when it becomes hyper-active, such as in depression, cognition is no longer optimal. During depression, cognition is characteristically inflexible. Focus is often turned inward (related to DMN processes) and is critical of the self, ability to remove oneself from this state is often restricted, and everything is perceived through pessimism (Carhart-Harris et.al, 2014).
5-HT2AR expression is up-regulated in depression. Studies have found correlations between the 5-HT2AR binding and neuroticism and pessimism, and there might be a connection to deficient 5-HT2AR stimulation which contributes to inflexible patterns of thought (Carhart-Harris et.al, 2014).
Psychedelics & DMN
Changes in the Default Mode Network seem to be a common trait in several mood disorders, which means that treatment targeting alterations of the DMN can become a focus for psychedelic-assisted psychotherapy of e.g. depression, anxiety, OCD, addiction and PTSD (Ruban & Kołodziej, 2018; Carhart-Harris et.al, 2014) - and there are associations between psychedelic drug use and reduced psychological distress and suicidality (Ruban & Kołodziej, 2018). There’s evidence that the effects of psychedelics produce long-lasting positive changes on personality and outlook (especially trait “openness”), something otherwise known to be relatively fixed (Carhart-Harris et.al, 2014).
Psychedelics have an effect on consciousness and alter the state of it. Findings show that psychedelics can help to achieve changes on a neural level on mechanisms that are usually connected to mental dysfunction. These alterations are observed in the set of regions connected to the activity of the DMN, and the changes are characterised by functioning in an opposite way to that seen in the pathology of mood disorders (Ruban & Kołodziej, 2018). The changes under the influence of psychedelics seem to be connected to a decreased activity and connectivity in areas of the brain which are usually highly metabolically active, functionally connected and organised in their activity (Ruban & Kołodziej, 2018; Carhart-Harris et.al, 2014) - and usually over-engaged in depression, but normalised after a range of effective psychedelic-assisted treatments (Carhart-Harris et.al, 2014). The decreased activity in otherwise highly active and connected brain regions also implies that the mechanisms by which psychedelics alter brain functions to alter consciousness, are connected to increasing entropy by a lowered activity in the DMN - meaning that psychedelics alter consciousness by disorganising brain activity (Carhart-Harris et.al, 2014).
Psychedelics work by disrupting the entrenched patterns of negative thought and behaviour by altering the functioning of the structures that are engaged in emotion processing and the sense of self. With the lowered activity of the DMN follows a positive correlation to the feelings of disintegration of self or ego. By relinquishing the ego’s usual hold on reality it is suggested that psychedelics might reduce symptoms connected to maladaptive self references, with evidence of long-lasting changes in behaviour - which account for their therapeutic potential (Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018).
Discussion / conclusion
Challenges & the future
The use of psychedelics in psychotherapy is a relatively new field, and one that faces many challenges. Psychedelics have a controversial history of use, still making it difficult to do extensive research. Gaps include the low amount of both replications, participants, studies on clinical populations and the lack of an analysis and data collection approach that is widely accepted (Ruban & Kołodziej, 2018). On top of that, this essay in particular is based on review of only a few articles, which might provide limiting results. It is also important to remember that the science about psychedelics is an ongoing quest (Carhart-Harris et.al, 2014), inconsistencies on outcomes are already appearing, and it’s hard to acquire a complete overview of DMN alterations. At the same time differences in depression subtypes are usually not taken into account yet, although that would be interesting for future research (Ruban & Kołodziej, 2018).
One thing research has concluded is that set and setting is very important for the outcome of psychedelic use (Presti, 2017). When working with mental health issues such as depression - where the general mindset is already pessimistic - how do we fight the risk of bad trips with adverse effects and negative outcomes? The use of psychedelics may come with risks. In order for psychedelic-assisted therapy to be beneficial it is crucial that it’s mediated by appropriate therapeutic care and preparations - which makes research and knowledge about psychedelics even more important (Carhart-Harris et.al, 2014; Ruban & Kołodziej, 2018).
There are many challenges involved when it comes to broadening our understanding about psychedelics, and how psychedelics affect the brain to alter consciousness (Carhart-Harris et.al, 2014). However, with controlled studies psychedelics may provide us with new insights into the nature of how our minds and consciousness work, and how it arises from brain activity (Carhart-Harris et.al, 2014). If done right, the future of psychedelics and their effect on mental health issues - including those deemed treatment resistant - looks promising.
References
Carhart-Harris, R. et.al (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 03 February 2014, https://www.frontiersin.org/articles/10.3389/fnhum.2014.00020/full
Killingsworth, A. & Gilbert, D. (2010). A Wandering Mind Is an Unhappy Mind. Science, vol.330, p.932, https://jimdo-storage.global.ssl.fastly.net/file/629ab9a5-b3ee-4cad-ba4f-5a6dc28b592d/KILLINGSWORTH%20&%20GILBERT%20(2010).pdf
Presti, D. E. (2017). Altered states of consciousness: Drug-induced states. In S. Schneider & M. Welmans (Eds.), The Blackwell Companion to Consciousness (2nd ed.), p.171-186. John Wiley & Sons Ltd.
Ruban, A & Kołodziej, A. (2018). Changes in default-mode network activity and functional connectivity as an indicator of psychedelic-assisted psychotherapy effectiveness. Neuropsychiatria i Neuropsychologia (Neuropsychiatry and Neuropsychology), vol.13(3), p.91–97, https://doi.org/10.5114/nan.2018.81249
Research & academic writing