Ketamine and Psychedelic Drugs Change Structure of Neurons

[Indigophoton]

I thought this was generally interesting, shedding some light, as it does, on how ketamine and psychedelics affect the brain structurally, and suggesting the possibility of new drugs for depression and anxiety based on these chemicals.

Ketamine was also suggested and tried as a treatment for ME by Dr Jay Goldstein; he found it useful for patients, but I think did not publish peer-reviewed work.

Summary: A new study reveals psychedelics increase dendrites, dendritic spines and synapses, while ketamine may promote neuroplasticity. The findings could help develop new treatments for anxiety, depression and other related disorders.

Source: UC Davis.

A team of scientists at the University of California, Davis is exploring how hallucinogenic drugs impact the structure and function of neurons — research that could lead to new treatments for depression, anxiety, and related disorders. In a paper published on June 12 in the journal Cell Reports, they demonstrate that a wide range of psychedelic drugs, including well-known compounds such as LSD and MDMA, increase the number of neuronal branches (dendrites), the density of small protrusions on these branches (dendritic spines), and the number of connections between neurons (synapses). These structural changes suggest that psychedelics are capable of repairing the circuits that are malfunctioning in mood and anxiety disorders.

...
These discoveries potentially open doors for the development of novel drugs to treat mood and anxiety disorders, Olson said. His team has proposed the term “psychoplastogen” to describe this new class of “plasticity-promoting” compounds.

“Ketamine is no longer our only option. Our work demonstrates that there are a number of distinct chemical scaffolds capable of promoting plasticity like ketamine, providing additional opportunities for medicinal chemists to develop safer and more effective alternatives,” Olson said.

https://neurosciencenews.com/ketamine-psychedelics-neuron-structure-9314

And an article with more detail,

The researchers did not do any human experiments, but experiments in both vertebrates and invertebrates showed psychedelics produced similar effects across species. This indicates the biological mechanisms that respond to psychedelics have remained the same across eons of evolution and that psychedelics will likely have the same brain growth (neural plasticity) effects in humans.

Psychedelic drugs such as LSD and ayahuasca change the structure of nerve cells, causing them to sprout more branches and spines, UC Davis researchers have found. This could help in "rewiring" the brain to treat depression and other disorders. In this false-colored image, the rainbow-colored cell was treated with LSD compared to a control cell in blue. Credit: Calvin and Joanne Ly


Olson and colleagues also set out to test how these psychedelics promoted neural plasticity, meaning they explored which biological pathways psychedelics activate that lead to neural growth. Ketamine's neural plasticity effects were previously shown to be dependent on a protein called brain-derived neurotrophic factor (BDNF). When the researchers blocked BDNF signaling, psychedelics lost their ability to promote neurite growth. BDNF binds to a receptor, called TrkB, that is part of a signaling pathway that includes mTOR, which is known to play a key role in the production of proteins necessary for the formation of new synapses. When the researchers experimented by inhibiting mTOR, it also completely blocked the psychedelics' ability to promote neurite growth. Olson thinks identifying the signaling pathways at play in psychedelic-induced brain changes will help future research identify compounds that could be developed into depression treatments.

https://www.google.co.uk/amp/s/medi...-psychedelic-drugs-neural-plasticity-rats.amp

 

[Wonko]

Interesting that they choose to indicate the potential use for depression but don't mention other cases where increasing neural plasticity would be helpful, such as stroke victims.

 

[nonstopflu]

Michael Pollan just wrote a book on psychedelics (out May 2018, see amazon). He's doing a big publicity tour. I haven't dug into it yet, but here's the info.

Here's the NPR interview
https://www.npr.org/sections/health...llan-embraces-the-new-science-of-psychedelics

....And 3 re-broadcasts next week of the interview he had in SF recently as part of the City Arts & Lectures series
https://www.cityarts.net/radio-broadcasts/

 

[anciendaze]

In general, I am not a fan of psychedelics, I had too much interaction with the walking wounded from the initial enthusiasm for LSD. I have some wild stories based on direct experience with the people, not the drugs.

That said, there is a possibility the entire idea of changing what is going on in the brain is based of misunderstanding of the mechanism of action. For example some people with antibodies to NMDA receptors have had the kind of symptoms that would have permanently confined them to locked wards prior to sophisticated biochemical tests. Resetting immune response to NMDA receptors might benefit them.

Of course the whole idea of "psychological problems" being centered inside the brain ignores the substantial nervous system interacting with other parts of the body. I've known people who had the vagus nerve surgically cut in an attempt to treat ulcers. Their gut went right on digesting food with no input from upper management.

Still another subsystem controls vascular response. Again, this takes place in the walls of blood vessels, without waiting to consult the brain.

You could make a checklist for symptoms deriving from parts of the nervous system least connected to the brain. Compare this with standard medical advice for diagnosing "mental problems" and you would find a surprising overlap. Gut disturbances, sphincter control, blood pressure, circulation and even sweating (diaphoresis/hidrosis) are all considered signs of emotional problems. Maybe we have cause and effect reversed.

A friend sometimes shows me things that Paul Cheney is exploring. I am cautious about separating his enthusiasms from replicable evidence. He has long said that ME/CFS patients show a distinctive pattern of changes on echocardiograms, and I've been frustrated that nobody else has even tried to reproduce this, so far as I know. The changes he describes fit with the work by David Systrom et al. about low pressure on venous return and exertional dyspnea. In both cases we are talking about measurements independent of assumptions about patient emotional state.

I will also note that the brain is highly sensitive to changes in the supply of oxygenated blood, even in people thought to have no fundamental psychological problems. There is a considerable literature on weird symptoms of hypoxia. ME/CFS patients don't have ordinary hypoxia, but there seems to be a problem at the tissue or cellular level in using oxygen.

Cheney has recently run before and after echocardiograms on a few patients treated via ketamine infusion for presumed psychological problems. The known dissociative effects of ketamine were significant negative factors in the treatment, and were not necessary for improvement. It looks like lower doses that don't produce dissociation still have a substantial measurable effect on cardiovascular function, seen on echocardiograms, and this is quickly apparent in orthostatic tolerance.

This is very early, and not ready for publication. Still, I think the idea that the drug is acting directly on a neglected part of the nervous system having little interaction with the brain, and producing measurable changes in a key symptom, is worth investigation.

I'm sorry that I can't link any references to sources. Perhaps others can turn up useful research.