Ketamine and Psychedelic Drugs Change Structure of Neurons

Ketamine and Psychedelic Drugs Change Structure of Neurons

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.

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis. What is really exciting is that psychedelics seem to mirror the effects produced by ketamine,” said David Olson, assistant professor in the Departments of Chemistry and of Biochemistry and Molecular Medicine, who leads the research team.

Ketamine, an anesthetic, has been receiving a lot of attention lately because it produces rapid antidepressant effects in treatment-resistant populations, leading the U.S. Food and Drug Administration to fast-track clinical trials of two antidepressant drugs based on ketamine. The antidepressant properties of ketamine may stem from its tendency to promote neural plasticity — the ability of neurons to rewire their connections.

“The rapid effects of ketamine on mood and plasticity are truly astounding. The big question we were trying to answer was whether or not other compounds are capable of doing what ketamine does,” Olson said.

Psychedelics show similar effects to ketamine

Olson’s group has demonstrated that psychedelics mimic the effects of ketamine on neurons grown in a dish, and that these results extend to structural and electrical properties of neurons in animals. Rats treated with a single dose of DMT — a psychedelic compound found in the Amazonian herbal tea known as ayahuasca — showed an increase in the number of dendritic spines, similar to that seen with ketamine treatment. DMT itself is very short-lived in the rat: Most of the drug is eliminated within an hour. But the “rewiring” effects on the brain could be seen 24 hours later, demonstrating that these effects last for some time.

image shows neurons under psychedelics and ketamine

Behavioral studies also hint at the similarities between psychedelics and ketamine. In another recent paper published in ACS Chemical Neuroscience, Olson’s group showed that DMT treatment enabled rats to overcome a “fear response” to the memory of a mild electric shock. This test is considered to be a model of post-traumatic stress disorder (PTSD), and interestingly, ketamine produces the same effect. Recent clinical trials have shown that like ketamine, DMT-containing ayahuasca might have fast-acting effects in people with recurrent depression, Olson said.

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.


Additional coauthors on the Cell Reports study are Calvin Ly, Alexandra Greb, Sina Soltanzadeh Zarandi, Lindsay Cameron, Jonathon Wong, Eden Barragan, Paige Wilson, Michael Paddy, Kassandra Ori-McKinney, Kyle Burbach, Megan Dennis, Alexander Sood, Whitney Duim, Kimberley McAllister, and John Gray.

Olson and Cameron were coauthors on the ACS Chemical Neuroscience paper along with Charlie Benson and Lee Dunlap.

Funding: The work was partly supported by grants from the National Institutes of Health.

Source: Andy Fell – UC Davis 
Publisher: Organized by
Image Source: image is credited to Calvin and Joanne Ly.
Original Research: Open access research for “Psychedelics Promote Structural and Functional Neural Plasticity” by Calvin Ly, Alexandra C. Greb, Lindsay P. Cameron, Jonathan M. Wong, Eden V. Barragan, Paige C. Wilson, Kyle F. Burbach, Sina Soltanzadeh Zarandi, Alexander Sood, Michael R. Paddy, Whitney C. Duim, Megan Y. Dennis, A. Kimberley McAllister, Kassandra M. Ori-McKenney, John A. Gray, and David E. Olson in Current Biology. Published April 6 2018

UC Davis “Ketamine and Psychedelic Drugs Change Structure of Neurons.” NeuroscienceNews. NeuroscienceNews, 12 June 2018.


Psychedelics Promote Structural and Functional Neural Plasticity

•Serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis
•Psychedelics promote plasticity via an evolutionarily conserved mechanism
•TrkB, mTOR, and 5-HT2A signaling underlie psychedelic-induced plasticity
•Noribogaine, but not ibogaine, is capable of promoting structural neural plasticity

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.

Learn a new dance, movement , language to grow new brain cells

Surround yourself with people who will let you get the optimum potential that your brain can do to be successful in your own terms. You control your destiny, what your career will be , your finances and happiness.

Find an inspiration. I want to be a doctor before I reached the age of 80. I will use the internet for free skills and knowledge while I save for the time to be full time student as Nurse Practitioner first.

Every time we learn a new dance, movement , language or reach new accomplishments and solve new challenges, our brain cells grow.

So, grow your brain cells and be in control. Do not use the excuse that someone introduced you to a path that later on is a failure. Use that failure to get up and do a meaningful project you own and be proud of. I believe in the human potential and the power of the mind to control the brain to move and do some learning.


motor neurons


WUSTL researchers have converted skin cells into motor neurons without going through the stem cell state. The new technique could help in the development of devastating neurodegenerative diseases, like ALS, that affect motor neurons. READ MORE…
Image shows a neuron.


Researchers have developed a robotic system that allows them to focus in on specific neurons in the brain. The technology could help answer questions such as how neurons interact with each other as we recall a memory. READ MORE…

Every Experience the Brain Perceives is Unique

Every Experience the Brain Perceives is Unique

Summary: A new study reports neural activity in the prefrontal cortex reacts as though every experience is brand new, even if the event is similar to ones that have previously occurred. Researchers say this could account for feelings of déjà vu.

Source: Medical University of Vienna.

Neuronal activity in the prefrontal cortex represents every experience as “novel.” The neurons adapt their activity accordingly, even if the new experience is very similar to a previous one. That is the main finding of a study conducted by researchers from MedUni Vienna’s Division of Cognitive Neurobiology and recently published in the leading journal Nature Communications.

“As far as the brain is concerned, every experience is unique, no matter how similar it is to an earlier one. The neurons in the prefrontal cortex will be active each time – just as if the experience was entirely new,” explains study author Hugo Malagon-Vina from the Division of Cognitive Neurobiology at MedUni Vienna’s Center for Brain Research. Potential neuronal activity “mismatching” during this process might lead to the phenomenon of déjà vu, explains Malagon-Vina.

This has now been demonstrated by the MedUni Vienna researchers for the first time, using an animal model. They recorded and analysed the activity of around 300 neurons.

Nothing is ever perceived in the same way twice

“Of course, there is memory,” says Malagon-Vina. “But the brain needs flexibility, so that it can constantly adapt. This is achieved by each event being perceived as new.” From a philosophical perspective, says the MedUni Vienna researcher, an analogous explanation is provided by a quote from the old Greek philosopher Heraclitus: “No man ever steps in the same river twice, for it’s not the same river and he’s not the same man.” Malagon-Vina explains that “He (Heraclitus) was referring to the ambiguity that deliberate actions and plans are never perceived in the same way, no matter how similar they were to each other.”

a brain

At the same time, this flexibility, and the experience of uniqueness, allows people to experience feelings of joy or surprise, or the so-called “wow” effect, says Malagon-Vina. The results also show that the brain is able to perceive lifelong experiences as something new, so long as the neuronal activity is not impaired by a disease. According to the MedUni Vienna brain researcher, this is an argument in favour of staying mentally active into old age. Neurons are always ready to “adapt” in the face of new knowledge and to process new experiences as unique.


Source: Medical University of Vienna
Publisher: Organized by
Image Source: image is adapted from the Medical University of Vienna news release.
Original Research: Open access research in Nature Communications.

Medical University of Vienna “Every Experience the Brain Perceives is Unique.” NeuroscienceNews. NeuroscienceNews, 20 February 2018.


Fluid network dynamics in the prefrontal cortex during multiple strategy switching

Coordinated shifts of neuronal activity in the prefrontal cortex are associated with strategy adaptations in behavioural tasks, when animals switch from following one rule to another. However, network dynamics related to multiple-rule changes are scarcely known. We show how firing rates of individual neurons in the prelimbic and cingulate cortex correlate with the performance of rats trained to change their navigation multiple times according to allocentric and egocentric strategies. The concerted population activity exhibits a stable firing during the performance of one rule but shifted to another neuronal firing state when a new rule is learnt. Interestingly, when the same rule is presented a second time within the same session, neuronal firing does not revert back to the original neuronal firing state, but a new activity-state is formed. Our data indicate that neuronal firing of prefrontal cortical neurons represents changes in strategy and task-performance rather than specific strategies or rules.

Star-like cells – astrocytes – may help the brain tune breathing rhythms

Star-like cells , astrocytes,  may help the brain tune breathing rhythms

NIH study in rats suggests that support cells modulate brain circuit activity.

Traditionally, scientists thought that star-shaped brain cells called astrocytes were steady, quiet supporters of their talkative, wire-like neighbors, called neurons. Now, an NIH study suggests that astrocytes may also have their say. It showed that silencing astrocytes in the brain’s breathing center caused rats to breathe at a lower rate and tire out on a treadmill earlier than normal. These were just two examples of changes in breathing caused by manipulating the way astrocytes communicate with neighboring cells.

“For decades we thought that breathing was exclusively controlled by neurons in the brain. Our results suggest that astrocytes actively help control the rhythm of breathing,” said Jeffrey C. Smith, Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published in Nature Communications. “These results add to the growing body of evidence that is changing the way we think about astrocytes and how the brain works.”

Dr. Smith’s lab investigates how breathing is controlled by the rhythmic firing of neurons in the preBötzinger complex, the brain’s breathing center that his lab helped discover. For this study, his team worked with Alexander Gourine, Ph.D., professor at University College London (UCL), whose lab found that astrocytes in neighboring parts of the brain may regulate breathing by sensing changes in blood carbon dioxide levels.

At least half of the brain is comprised of cells called glia and most of them are astrocytes. Recently scientists have shown that astrocytes may communicate like neurons by shooting off, or releasing, chemical messages, called transmitters, to neighboring cells.

In this study, the scientists tested the role of astrocytes in breathing by genetically modifying the ability of astrocytes in the preBötzinger complex to release transmitters. When they hushed the astrocytes in rats by reducing transmitter release, the rats breathed and sighed at a lower rate than normal. In contrast, if they made the astrocytes chattier by increasing transmission, the rats breathed at higher resting rates and sighed more often.

The team also tested how silencing astrocytes affected the rats’ responses to changes in oxygen and carbon dioxide levels. Although the rats’ breathing rate increased when oxygen levels were lower or carbon dioxide levels higher, it was still lower than normal. Silencing astrocytes also decreased the rate at which the rats sighed under lower oxygen levels. Moreover, the rats became exhausted much earlier than normal. They could only run half the distance that normal rats could run on a treadmill before tiring out.

“The primary goal of breathing is the exchange of carbon dioxide and oxygen that is critical for life. Our results support the idea that astrocytes help the brain translate changes in these gases into breathing,” said Shahriar Sheikhbahaei, Ph.D., formerly a doctoral student at UCL and participant in the NIH Graduate Partnership Program, and the lead author of the study.

Finally, the team showed that these astrocytes used adenosine triphosphate (ATP) to communicate with other cells in the brain. Inactivating released ATP reduced resting breathing rates and the frequency of sighs under normal and low oxygen levels.

“Our results expand our understanding of how the brain controls breathing under normal and disease conditions,” said Dr. Smith. “We plan to follow this path to understand how astrocytes help control other aspects of breathing.”

This study was supported by the Intramural Research Program at the NINDS, the Wellcome Trust, British Heart Foundation (Ref. RG/14/4/30736), BBSRC (Refs. BB/L019396/1, BB/K009192/1), the Medical Research Council (Ref. MR/L020661).

NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

Snapshots of Life: The Birth of New Neurons

Radial Glia in Oil

Snapshots of Life: The Birth of New Neurons

After a challenging day at work or school, sometimes it may seem like you are down to your last brain cell. But have no fear—in actuality, the brains of humans and other mammals have the potential to produce new neurons throughout life. This remarkable ability is due to a specific type of cell—adult neural stem cells—so beautifully highlighted in this award-winning micrograph.

Here you see the nuclei (purple) and arm-like extensions (green) of neural stem cells, along with nuclei of other cells (blue), in brain tissue from a mature mouse. The sample was taken from the subgranular zone of the hippocampus, a region of the brain associated with learning and memory. This zone is also one of the few areas in the adult brain where stem cells are known to reside.

Kira Mosher, a postdoctoral fellow in the NIH-supported lab of Dave Schaffer at the University of California, Berkeley, captured this striking image using a confocal microscope. Then, to make it really pop, Mosher used photo-editing software to add a few “oil painting” effects. For her efforts, the micrograph was named a winner in the UC Berkeley 2017 MIC Image Contest.

Images like this one are helping the Schaffer lab pinpoint the locations of neural stem cells and map their interactions with other cells, providing clues to their potential roles in health and disease.The researchers also plan to use CRISPR gene-editing tools to tinker with neural stem cells and learn more about the molecular signals needed for them to function normally.

As scientists gain a more detailed view, the hope is they’ll be in a better position to figure out how to transplant or activate neural stem cells for possible use in brain repair. Such research might lead to new strategies for helping people with stroke, Alzheimer’s disease, Parkinson’s disease, and other conditions in which neurons are lost.


Focus on Stem Cell Research (National Institute of Neurological Disorders and Stroke/NIH)

Schaffer Lab (University of California, Berkeley)

NIH Support: National Eye Institute; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke

MS and Sphingomyelin in blood for early detection


Abnormalities and associated diseases

Sphingomyelin can accumulate in a rare hereditary disease called Niemann–Pick disease, types A and B. It is a genetically-inherited disease caused by a deficiency in the lysosomal enzyme acid sphingomyelinase, which causes the accumulation of sphingomyelin in spleenliverlungsbone marrow, and brain, causing irreversible neurological damage. Of the two types involving sphingomyelinase, type A occurs in infants. It is characterized by jaundice, an enlarged liver, and profound braindamage. Children with this type rarely live beyond 18 months. Type B involves an enlarged liver and spleen, which usually occurs in the pre-teen years. The brain is not affected. Most patients present with <1% normal levels of the enzyme in comparison to normal levels.

As a result of the autoimmune disease multiple sclerosis (MS), the myelin sheath of neuronal cells in the brain and spinal cord is degraded, resulting in loss of signal transduction capability. MS patients exhibit upregulation of certain cytokines in the cerebrospinal fluid, particularly tumor necrosis factor alpha. This activates sphingomyelinase, an enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide; sphingomyelinase activity has been observed in conjunction with cellular apoptosis.[17]

An excess of sphingomyelin in the red blood cell membrane (as in abetalipoproteinemia) causes excess lipid accumulation in the outer leaflet of the red blood cellplasma membrane. This results in abnormally shaped red cells called acanthocytes.

From Wikipedia, the free encyclopedia

General structures of sphingolipids

Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipidfound in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cellaxons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids.[1] In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.

Sphingomyelins contain phosphocholine or phosphoethanolamine as their polar head group and are therefore classified along with glycerophospholipids as phospholipids. Indeed, sphingomyelins resemble phosphatidylcholines in their general properties and three-dimensional structure, and in having no net charge on their head groups . Sphingomyelins are present in the plasma membranes of animal cells and are especially prominent in myelin, a membranous sheath that surrounds and insulates the axons of some neurons—thus the name “sphingomyelins”.[1]

Sphingomyelin was first isolated by GermanchemistJohann L.W. Thudicum in the 1880s.[2] The structure of sphingomyelin was first reported in 1927 as N-acyl-sphingosine-1-phosphorylcholine.[2] Sphingomyelin content in mammals ranges from 2 to 15% in most tissues, with higher concentrations found in nerve tissues, red blood cells, and the ocular lenses. Sphingomyelin has significant structural and functional roles in the cell. It is a plasma membrane component and participates in many signaling pathways. The metabolism of sphingomyelin creates many products that play significant roles in the cell.[2]

Physical characteristics

Blue:Fatty acid

Top-down view of sphingomyelin, demonstrating its nearly cylindrical shape


Sphingomyelin consists of a phosphocholine head group, a sphingosine, and a fatty acid. It is one of the few membrane phospholipids not synthesized from glycerol. The sphingosine and fatty acid can collectively be categorized as a ceramide. This composition allows sphingomyelin to play significant roles in signaling pathways: the degradation and synthesis of sphingomyelin produce important second messengers for signal transduction.

Sphingomyelin obtained from natural sources, such as eggs or bovine brain, contains fatty acids of various chain length. Sphingomyelin with set chain length, such as palmitoylsphingomyelin with a saturated 16 acyl chain, is available commercially.[3]


Ideally, sphingomyelin molecules are shaped like a cylinder, however many molecules of sphingomyelin have a significant chain mismatch (the lengths of the two hydrophobic chains are significantly different).[4] The hydrophobic chains of sphingomyelin tend to be much more saturated than other phospholipids. The main transition phase temperature of sphingomyelins is also higher compared to the phase transition temperature of similar phospholipids, near 37 C. This can introduce lateral heterogeneity in the membrane, generating domains in the membrane bilayer.[4]

Sphingomyelin undergoes significant interactions with cholesterol. Cholesterol has the ability to eliminate the liquid to solid phase transition in phospholipids. Due to sphingomyelin transition temperature being within physiological temperature ranges, cholesterol can play a significant role in the phase of sphingomyelin. Sphingomyelin are also more prone to intermolecular hydrogen bonding than other phospholipids.[5]


Sphingomyelin is synthesized at the endoplasmic reticulum (ER), where it can be found in low amounts, and at the trans Golgi. It is enriched at the plasma membrane with a greater concentration on the outer than the inner leaflet.[6] The Golgi complex represents an intermediate between the ER and plasma membrane, with slightly higher concentrations towards the trans side.[7]



The synthesis of sphingomyelin involves the enzymatic transfer of a phosphocholine from phosphatidylcholine to a ceramide. The first committed step of sphingomyelin synthesis involves the condensation of L-serine and palmitoyl-CoA. This reaction is catalyzed by serine palmitoyltransferase. The product of this reaction is reduced, yielding dihydrosphingosine. The dihydrosphingosine undergoes N-acylation followed by desaturation to yield a ceramide. Each one of these reactions occurs at the cytosolic surface of the endoplasmic reticulum. The ceramide is transported to the Golgi apparatus where it can be converted to sphingomyelin. Sphingomyelin synthase is responsible for the production of sphingomyelin from ceramide. Diacylglycerol is produced as a byproduct when the phosphocholine is transferred.[8]

Sphingomyelin de novo synthesis pathway


Sphingomyelin breakdown is responsible for initiating many universal signaling pathways. It is hydrolyzed by sphingomyelinases (sphingomyelin specific type-C phospholipases).[6] The phosphocholine head group is released into the aqueous environment while the ceramide diffuses through the membrane.



The membranous myelin sheath that surrounds and electrically insulates many nerve cell axons is particularly rich in sphingomyelin, suggesting its role as an insulator of nerve fibers.[1] The plasma membrane of other cells is also abundant in sphingomyelin, though it is largely to be found in the exoplasmic leaflet of the cell membrane. There is, however, some evidence that there may also be a sphingomyelin pool in the inner leaflet of the membrane.[9][10] Moreover, neutral sphingomyelinase-2 – an enzyme that breaks down sphingomyelin into ceramide – has been found to localise exclusively to the inner leaflet, further suggesting that there may be sphingomyelin present there.[11]

Signal transduction

The function of sphingomyelin remained unclear until it was found to have a role in signal transduction.[12] It has been discovered that sphingomyelin plays a significant role in cell signaling pathways. The synthesis of sphingomyelin at the plasma membrane by sphingomyelin synthase 2 produces diacylglycerol, which is a lipid-soluble second messenger that can pass along a signal cascade. In addition, the degradation of sphingomyelin can produce ceramide which is involved in the apoptotic signaling pathway.


Sphingomyelin has been found to have a role in cell apoptosis by hydrolyzing into ceramide. Studies in the late 1990s had found that ceramide was produced in a variety of conditions leading to apoptosis.[13] It was then hypothesized that sphingomyelin hydrolysis and ceramide signaling were essential in the decision of whether a cell dies. In the early 2000s new studies emerged that defined a new role for sphingomyelin hydrolysis in apoptosis, determining not only when a cell dies but how.[13]After more experimentation it has been shown that if sphingomyelin hydrolysis happens at a sufficiently early point in the pathway the production of ceramide may influence either the rate and form of cell death or work to release blocks on downstream events.[13]

Lipid rafts

Sphingomyelin, as well as other sphingolipids, are associated with lipid microdomains in the plasma membrane known as lipid rafts. Lipid rafts are characterized by the lipid molecules being in the lipid ordered phase, offering more structure and rigidity compared to the rest of the plasma membrane. In the rafts, the acyl chains have low chain motion but the molecules have high lateral mobility. This order is in part due to the higher transition temperature of sphingolipids as well as the interactions of these lipids with cholesterol. Cholesterol is a relatively small, nonpolar molecule that can fill the space between the sphingolipids that is a result of the large acyl chains. Lipid rafts are thought to be involved in many cell processes, such as membrane sorting and trafficking, signal transduction, and cell polarization.[14] Excessive sphingomyelin in lipid rafts may lead to insulin resistance.[15]

Due to the specific types of lipids in these microdomains, lipid rafts can accumulate certain types of proteins associated with them, thereby increasing the special functions they possess. Lipid rafts have been speculated to be involved in the cascade of cell apoptosis.[16]

Connie’s comments: Toxic substances  (metals, chemicals,etc) for the liver can destroy the myelin sheath that covers our neurons.