Nicotine!

I smoke and wonder if it`s holding up my healing?  A friend sent me this link, can any of you understand if this maybe the case?

 

https://www.nature.com/articles/1300032

 

 

 

 

You can ask dm123. I think he would be able to give you a good explanation.

I quit and my sleep got so much better. Not easy but I used the step down method. I was also holding my Valium taper at the time after I finished my kpin taper. My BP got better too.

Smoking ampes  up my symptoms.  For me the compromise is a low nic ecig - no going outside - no bad smell- no other junk in it

I now use a 0.6% nicotine e cig - most ecigs in gas stations and smoke shops are 2% or higher. Those high amps me up too.

I buy mine online ( V2Cigs) they different strengths to chose from

I smoke and wonder if it`s holding up my healing?  A friend sent me this link, can any of you understand if this maybe the case?

 

https://www.nature.com/articles/1300032

 

Hi , I just found the link .  I will take a look and get back to you,

 

Nicotinic receptors are part of the acetylcholine family of receptors and we know that benzodiazaphines affect acetylcholine levels.   

Hi nevercantell,

 

Here is the information on that article and a lot more on brain neuro-anatomy that is involved.  I think smoking would affect your sleep, BP(see post above), hyper-arousal and possibly depression and addiction tendencies.  This is according to how the authors interpreted the effect that this could have on the PFC.  Let me know via PM if you have further questions, because I don't venture out much beyond the Chewing the Far post/thread.(can anyone explain this to a layperson thread)

 

 

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I haven’t  presented the module 4 of the Neural Circuits paper on brain neuro-anatomy yet, and in order to fully appreciate the article above on nicotinic receptors and glutamatergic excitability, we need to first understand how the thalamocortical projections or terminals (TC) into the PFC (prefrontal cortex ) affect our neurophysiology.

 

  The PFC is part of the brain region called the cerebral cortex. 

https://en.m.wikipedia.org/wiki/Cerebral_cortex

 

 

Quote

 

The cerebral cortex is the largest region of the cerebrum in the mammalian brain and plays a key role in memory, attention, perception, cognition, awareness, thought, language, and consciousness.[1]

 

 

The cerebral cortex contains a large number of neuronal and glial cell bodies, as well as their intricate dendritic formations and axonal projections, which connect at synapses to form basic functional circuits.[1] The cerebral cortex is entirely made of gray matter, contrasting with the underlying white matter, which consists mainly of axons traveling to and from the cortex, their myelinated sheaths, and the cell bodies of oligodendrocytes.[1]

End quote

 

Layers in the cerebral cortex

 

The cerebral cortex tissue is comprised of layers.  These layers convey and receive signals from the thalamus and thalamic structures of the brain.  The original article above pertains to pyramidal neurons in layer V

 

Visually the layers in the cortex look like this, with the layers noted on the left side of this picture.

 

 

 

https://en.m.wikipedia.org/wiki/Cerebral_cortex#/media/File%3AGray754.png

 

 

The thalamus is located between the midbrain and the cerebral cortex (cortex).  It kind of acts like a go between or regulator between information coming to and from the midbrain (a lower region of the brain) and the upper regions of the brain like the cortex.(it does a lot of other things beyond the scope of this paper)  It is a very critical part of the brain. 

 

There are Thalamic projections from the thalamus into the cortex.  These thalamocortical (TC) projections are what the article you cited are referring to.  Specifically the article refers to glutamatergic projections from the thalamus to the layer V neurons in the PFC (prefrontal cortex).  These projections are axon terminals from the thalamic neurons, that release glutamate into the synapses.  The layer V neurons in the PFC then take up the glutamate and this is the excitability in the PFC that the article refers to.

 

 

cortical Layer V

The article you cited is about layer V cortical neurons and thalamic cortical projections into this area of the cortex.

Quote

Layer V, the internal pyramidal layer, contains large pyramidal neurons which give rise to axons leaving the cortex and running down to subcortical structures (such as the basal ganglia). In the primary motor cortex of the frontal lobe, layer V contains Betz cells, whose axons travel through the internal capsule, the brain stem and the spinal cord forming the corticospinal tract, which is the main pathway for voluntary motor control.

End quote

 

 

Summary of the article

 

Just a bit on nAChRs.  They do have a direct effect on the modulation of BP(someone posted earlier in this post regarding  their BP being affected by nicotine), sleep, and , arousal, and attention.

 

Quote

 

The nicotinic receptors are considered cholinergic receptors, since they respond to acetylcholine. Nicotinic receptors get their name from nicotine, which does not stimulate the muscarinic acetylcholine receptor, but instead selectively binds to the nicotinic receptor.[3][4][5] The muscarinic acetylcholine receptor likewise gets its name from a chemical that selectively attaches to that receptor — muscarine. Acetylcholine itself binds to both muscarinic and nicotinic acetylcholine receptors.

As ionotropic receptors, nAChRs are directly linked to ion channels. New evidence suggests that these receptors can also use second messengers (as metabotropic receptors do) in some cases.[6] Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors.[3]

Since nicotinic receptors help transmit outgoing signals for the sympathetic and parasympathetic systems, nicotinic receptor antagonists such as hexamethonium interfere with the transmission of these signals. Thus, for example, nicotinic receptor antagonists interfere with the baroreflex that normally corrects changes in blood pressure by sympathetic and parasympathetic stimulation of the heart.

End quote

 

Now back to the original article

 

https://www.nature.com/articles/1300032

 

 

 

The findings implicate high sensitivity α4β2 nicotinic receptors in the thalamus that project glutamate release from their axon projections into the cerebral cortex.  This would cause excitatory activation of the prefrontal cortex according to the article, increasing attention and cognitive processing. 

 

The article you posted is significant because it’s stating that projections into deeper layers of the cortex are affected by these thalamic projections.  They have known about superficial layers, but layers V and VI are deeper layers .  Layers V and VI output to a lot of other structures (I get into the other layers below)

 

What they did to isolate the nicotinic receptor in these experiments was to administer a muscarinic blockade, which blocks another type of acetylcholine receptor called a muscarinic receptor.  They then were able to produce the glutamate release from the thalamic projections into layer V via either nicotine alone, or acetylcholine plus the muscarinic blockade.  Thus, it is nicotinic receptors and not muscarinic receptors that are responsible for this effect.

 

The β2 Subunit nicotinic receptor knockout mice were used to isolate the high sensitivity nicotinic receptors (α4β2) in the thalamus as causing the glutamate release in layer V of the PFC. As mentioned above this is via thalamic projections into layer V of the PFC..

 

The most interesting part of the article is that these are nAChRs located on the terminal aspect of the axons of these projections.  Thalamocortical terminals in the PFC are terminals from the thalamus. 

 

In the article they tested if nicotine and ACh could depolarize these thalamocortical terminals in the PFC sufficiently to induce an action potential (AP) directly in the terminal (note, as mentioned the nAChRs are located on the axon itself, and at the terminal aspect close to the terminal end where the neurotransmitters (in this case glutamate) are released)

 

These types of APs are called local terminal APs.  Thalamocortical axon projections have been known to do this.  These APs can be induced even if the soma is inhibited or severed from the axon!

 

Just the terminals need to be intact.  They prove that the mechanism for the release was via direct  depolarization of the terminal.  Note once again, these are nAChRs that are located in the terminal field of the thalamocortical axon projection in layer V of the cortex.

 

They confirmed that low levels of nicotine could cause this at blood levels consistent with those of smokers, due to the very highly sensitive α4β2 Subunit nAChRs.

 

Layer V stimulation would affect arousal, attention, affective processing to sensory stimuli, and excessive stimulation would cause poor sleep, hence the connection of nicotine to sleep issues.

Layer V defects in α4β2 nAChRs has been implicated in depression, addiction, and aberrations in reward expectancy.

 

 

 

cortical Layer 1

 

I won’t get into the details, but layer 1 receives input from thalamus cells as well.

 

Quote

 

While it was once thought that the input to layer I came from the cortex itself,[7] it is now realized that layer I across the cerebral cortex mantle receives substantial input from ‘‘matrix or M-type thalamus cells[8]

quote

 

 

The citation below tells us about how the TC projections into the cortex  affect layer 1 circuits in the PFC.

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535493/

 

Quote

 

A longstanding hypothesis is that matrix TC systems are crucial for regulating neocortical excitability during changing behavioral states, yet we know almost nothing about the mechanisms of such regulation. It is also unclear whether synaptic and circuit mechanisms that are well established for core sensory TC systems apply to matrix TC systems.

 

……

 

Contrary to conventional views, we found that matrix TC projections to layer 1 could transmit relatively strong, fast, high-fidelity synaptic signals. Layer 1 TC projections preferentially drove inhibitory interneurons of layer 1, especially those of the late-spiking subtype, and often triggered feedforward inhibition in both layer 1 interneurons and pyramidal cells of layers 2/3.

 

 

End quote

 

 

 

cortical Layer IV

 

 

In general, glutamate seems to be prevalent in thalamic cortical terminals

Terminals projecting into layer IV of the cortex:

https://www.sciencedirect.com/science/article/pii/0304394093907273

 

Quote

Levels of glutamate in thalamocortical terminals, and in dendritic spines postsynaptic to them, were significantly higher than in nearby dendrites, astroglia, or in GABAergic terminals (identified by double immunostaining). These results support glutamate as neurotransmitter in thalamocortical fibers, and suggest that dendritic spines may take up glutamate released by these terminals.

End quote

 

 

 

cortical layer VI

 

 

Cortical Layer VI sends excitatory feedback to the thalamus. Layer VI contains large and small pyramidal neurons.

At the same time layer VI sends collaterals , i.e. Adjacent projections, to an area of the brain called the thalamic reticular nucleus that inhibit the neurons in this thalamic region.

 

This inhibitory input is reduced by cholinergic input to the cerebral cortex , and I’m assuming nicotinic receptors are playing a role here as the cholinergic input, based on the article you posted.

 

The above provides fine tuning gain control or throttling of the relay of sensory input (fine touch and sensory  location) coming into the thalamus to the prefrontal cortex from the skin and joints.

See blue lines in this diagram

https://en.m.wikipedia.org/wiki/Posterior_column%E2%80%93medial_lemniscus_pathway#/media/File%3AGray759.png

 

 

 

 

Quote

 

Pyramidal neurons (pyramidal cells) are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract.

…..

Neurons send excitatory fibers to neurons in the thalamus and also send collaterals to the thalamic reticular nucleus that inhibit these same thalamus neurons or ones adjacent to them.[11] One theory is that because the inhibitory output is reduced by cholinergic input to the cerebral cortex, this provides the brainstem with adjustable "gain control for the relay of lemniscal inputs".[11]

 

 

End quote

 

 

 

 

 

I smoke and wonder if it`s holding up my healing?

 

You've been benzo free since 2015, as per your signature.  I would quit smoking, it can only help your healing and improve your general health.  I wouldn't necessarily recommend quitting smoking to people in early benzo withdrawal/acute, because putting body through two withdrawals at the same time is very taxing on the body, as nicotine withdrawal has symptoms of its own that can be tough.  'The Ashton Manual' recommends the same thing.  I quit smoking 4 years ago (on my second attempt), way before I quit benzos, thank God I don't have to deal with cigarettes now during my benzo withdrawal.  Quitting smoking improved my health vastly, lower blood pressure, better breathing, better stamina, and better skin.  I would definitely recommend quitting for you now, as you have been benzo free since 2015.

I smoke and wonder if it`s holding up my healing?

 

You've been benzo free since 2015, as per your signature.  I would quit smoking, it can only help your healing and improve your general health.  I wouldn't necessarily recommend quitting smoking to people in early benzo withdrawal/acute, because putting body through two withdrawals at the same time is very taxing on the body, as nicotine withdrawal has symptoms of its own that can be tough.  'The Ashton Manual' recommends the same thing.  I quit smoking 4 years ago (on my second attempt), way before I quit benzos, thank God I don't have to deal with cigarettes now during my benzo withdrawal.  Quitting smoking improved my health vastly, lower blood pressure, better breathing, better stamina, and better skin.  I would definitely recommend quitting for you now, as you have been benzo free since 2015.

 

:thumbsup: