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Can Psychedelics Target Overly Rigid Brain Networks?

July 30, 2015

By Andrew Penn, RN, MS, NP, CNS, APRN-BC
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The opinions expressed by Psychiatry & Behavioral Health Learning Network bloggers and those providing comments are theirs alone and are not meant to reflect the opinions of the publication.

In this series of blog entries, I am discussing the emerging data on using psychedelic compounds, such as psilocybin (the active ingredient in “magic mushrooms”) and 3,4 methyelenedioxymethamphetamine (MDMA, commonly referred to as “ecstasy”) as a means of catalyzing psychotherapeutic change. 

The idea of using these drugs as catalysts for psychotherapeutic change challenges the historic assumption that these drugs are mere intoxicants, and it also challenges biological psychiatry’s predominant orientation towards mental disease as something that is managed or palliated, but not cured. 

The conditions for which psychedelics have been researched as treatments are a curious collection of seemingly unrelated disease states­­­—posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), alcohol and nicotine dependence, and anxiety experienced by patients with terminal illness. What do these conditions have in common, and what is it about these psychedelic drugs that might account for their beneficial effects?           

British neuroscientist Robin Carhart-Harris, PhD, made a compelling and intriguing hypothesis for this mechanism of benefit in a 2014 article entitled “The entropic brain: a theory of conscious states informed by neuroimaging with psychedelic drugs,” (1) in which he uses the measurement of entropy within brain network activity as a means of understanding the relative rigidity of different states of consciousness. 

He hypothesizes that certain psychiatric disease states, such as depression, OCD, and substance use disorders, represent an overly constrained and rigid pattern of functional brain network activity. I call these conditions “diseases of excessive psychic rigidity.” 

Dr. Carhart-Harris and his team have discovered that psychedelic drugs, such as psilocybin, may have the ability to temporarily disrupt these patterns, and when combined with a controlled psychotherapeutic experience, may produce changes in perception and behavior that persist long after the drug has worn off. 

Through use of fMRI (functional magnetic resonance imaging) and MEG (magnetoencephalography) scanning, Dr. Carhart-Harris and his colleagues have been able to study the stability of functional brain networks, such as the normally competitive relationship between the default mode network and the task-positive network. Studies suggest that psilocybin disrupts this normal competitive pattern. 

The task positive network is a problem solving, externally focused network comprised of the salience network (which determines what needs to be dealt with in the environment) and executive network (which determines what to do with this information). The structures involved with these networks, represented by the dorsolateral prefrontal cortex, lateral parietal cortex, and subgenual anterior cingular cortex, lie laterally in the brain. 

Along the midline, the default mode networkis more inwardly directed and is activated when we are introspective, engaged in theory of mind (ostensibly, empathy), or navigating complex social interactions. These midline structures consist of the mediotemporal lobe, the posterior cingulate cortex, the ventromedial prefrontal cortex, and the dorsomedial prefrontal cortex. 

It is important to understand that these two networks normally work in opposition to one another, so that when one is turned up, the other is turned down, like two sides of a seesaw.  In a non-depressed brain, the ability to shift between these networks should be relatively easy. 

For example, when one is “lost in one’s work,” the dominance of the task positive network over the default mode network is evident. Conversely, when one is engaged in inward-focused activity, such as meditation or reminiscing, there is little external work being done. 

However, in the context of depression it appears that the introspective capacity of the default mode network becomes “stuck” in a ruminative mode, and that this rigidity prevents the task positive network from working normally. I translate this to patients with depression by explaining that this is why they can spend all day thinking negatively about themselves but cannot shift focus and respond to all those emails that have been piling up. This hijacking of the default mode network by rumination has been called “pathological introspection” and this rigidity of network activity in depression has been referred to as “overstability.” (2-7) 

In the case of PTSD, the limbic structures of the brain that exist to alert us to danger (amygdala) and rally a protective response against a threat become persistently activated, leading to hypervigilance. In addition, structures that help us put information in context (hippocampus) are underactivated, leading to misperception of neutral stimuli as threats. Thus, the brain loses the ability to “put the brakes” on an overly excited limbic system as the medial prefrontal cortex loses the ability to exert top-down inhibition of these responses. Not surprisingly, activity in the default mode network decreases (probably resulting in difficulties with social cognition and introspection) while activity in the salience networks increases. (8-11) 

In my next blog entry, I’ll discuss how psilocybin may disrupt these overly rigid brain networks, and how this effect may be leveraged to help people change “stuck” behaviors such as OCD, alcohol or tobacco dependence, or anxiety at the end of life. I’ll also discuss how MDMA may help to reduce some of this limbic hyperactivity, allowing for an enduring reprocessing of traumatic memories. 

So stay tuned, and if this topic interests you, I hope you’ll join me in San Diego at the U.S. Psychiatric Mental Health Congress where I’ll be presenting a talk entitled “Re-imagining a brave new world: Can psychedelics be catalysts for therapy?” 


1. Carhart-Harris et al. The entropic brain: a theory of conscious states informed by neuroimaging with psychedelic drugs. Frontiers in Human Neuroscience. 2014 Feb 3;8:20.

2. Raichle R et al. PNAS. 2001;98(2).

3. Sheline et al. PNAS. 2009;106(6).

4. Leech et al. PLOS ONE. 2014;9(6).

5. Carhart-Harris et al. PNAS. 2012;109(6).

6. Maletic, Psych Congress Network Accessed 4/13/15

7. Sood A et al. Explore. 2013;9:136-141.

8. Shin LM et al. Neuropsychopharmacology. 2010;35(1):169-191.

9. Jovanovic T et al. Front Behav Neurosci. 2011;5:44.

10. Sripada RK et al. Psychosom Med. 2012;74(9):904-911.

11. van der Kolk B. The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma. New York, NY: Viking;2014.

Andrew Penn was trained as an adult nurse practitioner and psychiatric clinical nurse specialist at the University of California, San Francisco. He is board certified as an adult nurse practitioner and psychiatric nurse practitioner by the American Nurses Credentialing Center. Currently, he serves as an Assistant Clinical Professor at the University of California-San Francisco School of Nursing. Mr. Penn is a psychiatric nurse practitioner with Kaiser Permanente in Redwood City, CA, where he provides psychopharmacological treatment for adult patients and specializes in the treatment of affective disorders and PTSD. He is a former board member of the American Psychiatric Nurses Association, California Chapter, and has presented nationally on improving medication adherence, emerging drugs of abuse, treatment-resistant depression, diagnosis and treatment of bipolar disorder, and the art and science of psychopharmacologic practice.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors. Blog entries are not medical advice.

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