You’ve probably heard that smoking is bad for you. I mean duh, but lets talk about nicotine specifically, which isn’t so bad for you if you take it without the other harmful substances present in cigarettes.
So many gurus on x.com and other business forums will tell you to wake up, chuck a zyn in your mouth and start working. Does it actually work? Maybe there’s a real reason that they do it, apart from being degenerate dopamine addicts. What if nicotine legitimately makes you more motivated?
Lets explore everything about how nicotine works in the brain.
Nicotine receptors - What they do and effects.
Nicotine primarily affects the nAChR receptors in the brain, most strongly the α4β2 subtype, which are found throughout the brain. These receptors mediate the release of neurotransmitters, primarily dopamine.
Nicotine mimics the neurotransmitter acetylcholine and activates (agonizes) these receptors. Through various processes, the nAChR receptors further enhance the release of various neurotransmitters, primarily dopamine, through both direct and indirect means.
Most of these are presynaptic and have a neuromodulatory role, enhancing the release of neurotransmitters such as GABA, glutamate or dopamine, while others are postsynaptic and mediate fast excitatory synaptic transmission. - Dani, 2001
The regions of the brain most dense in these receptors are:
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Insula
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Cingulum ant
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Cingulum mid
You can see that the Cingulum, particularly the part encompassing the anterior mid-cingulate cortex (aMCC), is the defining region of the brain responsible for motivation. I’ve discussed this more in this blog post.
Everyone knows that over time, these receptors become desensitized through repeated nicotine exposure and become less responsive to stimulation (which forms the basis of addiction). However, it's more interesting to explore the effect on how it specifically alters the brain and inter-brain regions.
Cues - The secret of using nicotine smartly?
Why is nicotine really so addictive? The secret is Cues.
Nicotine by itself isn’t that very addictive. It’s like a weak magnet for your neurotransmitters. It pulls them in, but not very hard. The interesting part is that if you pair nicotine with cues like the act of checking your pocket to open a zyn, or walking to the window to smoke, or even after eating a meal, then it becomes much much more powerful. The cues make the pull of the nicotine much much more powerful.
When people establish these habits, then use nicotine around them, they become much more harder to break. In effect nicotine acts as a reinforcer. Usually, a habit is weak, but nicotine makes that habit much much more “habity”, as it more powerful.
That’s primarily why nicotine boosts motivation in some people and decreases it in others! Nicotine acts as a reinforcer of your environment. If you consume nicotine while working, it will reinforce you working more. If you consume nicotine while playing games, or scrolling social media, it will reinforce more of that same behaviour.
Whatever you choose to do while you take in nicotine, that behaviour will be rewarded. Overall it’s a very basic idea, but not many people intuitively have that ingrained in their brain, and they end up taking nicotine when they feel like it, instead of when it will truely be helpful to their life and work. The key really is to really be conscious of when you consume nicotine.
What’s even more powerful (and pernicious) about nicotine is that not only can nicotine reinforce cues, or the environment, but the environment can reinforce nicotine.
What that means is that nicotine is really really fucking hard to quit. If you associate with nicotine with work, that means that every time you go to work, you’ll also think of nicotine (it’s a reinforcer). What’s worse is that if initially paired with bad behaviour (watching instagram, procrastinating, ect), then every time that you try to quit nicotine, you’ll have an extremely difficult time not thinking of nicotine if you try to quit that behaviour.
they become conditioned reinforcers capable of eliciting self administration behavior on their own and they become triggers that lead to craving for the drug with which they were paired (Tiffany & Drobes, 1990).
a nicotine-associated cue is a more efficient primer than the drug itself in reinstating nicotine self-administration in an animal model of relapse (Lesage, Burroughs, Dufek, Keyler, & Pentel, 2004)
This really is the key for consuming nicotine, and what’s really ironic about consuming nicotine. If you already have a productive routine set up, you’re in a good position to consume nicotine - but if you’re already at this point without it, it’ll probably be a net negative in your life to start.
If you have a crap routine, watch tiktok all day and already consume ample nicotine, well you’re in a pickle, because your best bet to quit the bad habits is to quit both simultaneously. Nicotine makes it harder to “switch” to a good routine, rather than just to stop both activities.
You might notice in both scenarios, nicotine is a net negative for everyone involved. And although I’ve came to the conclusion via first principles thinking, it really is obvious by mainstream consensus. However you now know the exact mechanism of why nicotine is so hard to quit, and why some people continue to use it.
Deep dive into mechanistic action of reinforcement effects [nerds only]
Generally, a very small amount of nicotine is needed to reinforce these patterns. That’s why people have very fond memories of smoke filled places as kids or teens. The effect on them was still very effective even from secondhand smoke. In fact, even 0.1 cigarettes significantly altered many regions of the brain.
Desensitization of β2* nAChRs decreases DA release when the DA neurons are firing tonically, but enhances DA release when DA neurons are in a phasic state (Rice & Cragg, 2004), as one would expect during the presentation of a reward (Schultz, 2002).
What this means is essentially, is that the amount of dopamine release during normal activity (low frequencies) is supressed, and hence what it means physically is that you feel worse off. That might be the basis of why people in general hate nicotine. It makes usually minimally pleasurable activities unpleasasurable. You may tolerate washing the dishes, nicotine makes that untolerable due to the low amount of dopamine released in tonic DA neuron release (low slow dopamine drip while you do an activity).
What’s more significant is that nicotine increases phasic, or high frequency dopamine release, and that is likely the reason of the addictive properties of nicotine. The (a) graphic below shoes that the peak increases for 100Hz release (the most pleasurable activities) almost increase twice. No wonder you’ll get addicted to this!
Some other resources to find how the brain changes specifically due to environmental cues
As environmental cues gain more control over behavior following repeated presentation of cues with a primary reinforcer, there is a transition from phasic activity of DA neurons in response to the primary reinforcer, to phasic activity in response to the cue (Schultz, 2002). Thus, desensitization of nAChRs may enhance the response to environmental cues paired with smoking and make them more salient.
The ability of the nicotine-paired chamber to increase phosphorylated or active CREB (pCREB) in the NAc (Walters et al., 2005) suggests that this neuroadaptation could be associated with the ability of nicotine to increase conditioned reinforcement. Chronic nicotine exposure results in upregulation of total CREB levels in the NAc of mice (Brunzell et al., 2003), perhaps further promoting incentive salience of nicotine-associated cues. Post mortem studies on human brain indicate that protein kinase A (PKA) activity is elevated in the NAc and ventral midbrains of smokers (Hope, Nagarkar, Leonard, & Wise, 2007). PKA could promote synaptic plasticity via phosphorylation of CREB leading to CRE-mediated transcription. Reductions in NAc pCREB observed following chronic nicotine in rodents, however, suggest that homeostatic mechanisms occur in the NAc (Brunzell et al., 2003; Pandey et al., 2001).
suggesting that by virtue of their association with nicotine, cues become capable of altering new gene transcription in areas of the brain that regulate reward. As indicated above, nicotine-associated cues elicit arc and c-fos immediate early gene activity in the PFC, amygdala, and nucleus accumbens (Schiltz et al., 2005; Schroeder et al., 2001),
Nicotine on NAcc
a NAcc activity between nicotine and placebo visits. Acute nicotine administration significantly increased participants’ NAcc activity during reward anticipation. All voxels passed an initial cluster-forming threshold of z = 3.1, with small-volume correction within the anatomical NAcc using a cluster-extent threshold of p< 0.05. b PPI analysis of functional connectivity between NAcc and other brain regions. Acute nicotine administration significantly decreased the functional connectivity between NAcc and the ACC/MCC during reward outcome but not anticipation. c After adding in participants’ NAcc activation during reward anticipation as a covariate, the PPI model revealed that acute nicotine administration significantly decreased the functional connectivity between NAcc and three cortical regions (i.e., ACC, OFC and insula) during the reward outcome phase. All areas of activation passed an initial cluster-forming threshold of z = 2.3, with whole-brain cluster-extent threshold at p< 0.05.
a In the placebo visit, participants’ NAcc activity during reward anticipation and outcome did not show any significant relationship. b Following acute nicotine administration, participants’ NAcc activity demonstrated a significant negative relationship between the reward anticipation and outcome phases. There was a significant difference in the two correlation coefficients for the placebo and nicotine visits.
These results suggest nicotine alters both the anticipation and experience of rewards, potentially contributing to its addictive properties by enhancing expectation while modulating the reward experience itself.
Connectivity to brain regions
What’s more interesting is to examine how nicotine affects the connectivity of different brain regions. By connectivity, we mean functional connectivity, which is the degree of synchronicity, and not necessarily more physically connected.
A positive t-value suggests that the activity in two brain regions tends to increase or decrease together, while A negative t-value suggests that as activity in one region increases, activity in the other tends to decrease, and vice versa.
Lets explore each brain region according to these findings, and make an educated guess on the likely effect of synchronising both.
Lt. IPS and MO
The Left Intraparietal Sulcus (Left IPS) is:
Part of the dorsal attention network
Involved in numerical processing and magnitude representation
Plays a role in spatial attention and working memory
Contributes to goal-directed behavior and motor planning
while the Medial Orbitofrontal cortex (MO) is:
Involved in reward processing and value-based decision making
Plays a role in emotional regulation
Contributes to expectation and outcome evaluation
Important for behavioral flexibility and adaptive learning
What that means is that likely, more functional connectivity better integrates attention and reward, more effectively rewarding valuable stimuli (which nicotine is likely to do)
also it might improve numerical decision making, and possible improve goal directed behaviour to focus on valuable goals.
However there might be difficulty disengaging from reward stimuli, and attention might be directed towards rewards, even when it is not appropriate of not ideal to do so. Additionally, there might be negative effects including
Over-emphasis on quantitative aspects in decision-making: Could result in neglecting qualitative factors in favor of numerical or quantitative information.
Rigidity in goal pursuit: Might lead to difficulty in switching away from previously rewarding goals, even when they're no longer adaptive.
Spatial-reward fixation: Could potentially lead to compulsive behaviors related to specific spatial locations associated with rewards.
Working memory bias: Might result in preferential storage and manipulation of reward-related information at the expense of other important data.
Lt. & Rt. NAc and MO
The Left Nucleus Accumbens (Lt. NAc) and the Medial Orbitofrontal cortex (MO) also have increased functional connectivity.
Potential Positive Effects:
Enhanced reward processing: May lead to better recognition and appreciation of rewards, potentially improving overall mood and life satisfaction.
Improved motivation: Could result in increased drive to pursue goals, especially those associated with positive outcomes.
More efficient decision-making: Might lead to quicker, more reward-oriented decisions in certain contexts.
Better emotional regulation: Could enhance the ability to use reward-related information to modulate emotional states positively.
Increased cognitive flexibility: Might improve the ability to adapt behavior based on reward feedback.
Potential Negative Effects:
Risk of addictive behaviors: Heightened reward sensitivity could increase vulnerability to substance abuse or behavioral addictions.
Impulsivity: Might lead to hasty decision-making based on immediate reward prospects without full consideration of long-term consequences.
Emotional volatility: Could result in mood fluctuations based on the presence or absence of rewarding stimuli.
Bias in information processing: Might lead to an overfocus on positive information, potentially ignoring important negative cues.
Anhedonia risk: Paradoxically, sustained heightened connectivity might lead to decreased sensitivity to everyday rewards over time.
SCC to Rt. IPS
The Subgenual Cingulate Cortex (SCC) is:
Part of the limbic system
Involved in mood regulation and emotional processing
Plays a role in the stress response
Implicated in the pathophysiology of depression
Involved in autonomic regulation
While the Right Intraparietal Sulcus (Rt. IPS) is part of the Dorsal Attention Network (DAN):
Involved in top-down directed attention
Plays a role in visual-spatial attention and working memory
Important for goal-directed behavior
Particularly involved in spatial attention and spatial working memory
Contributes to motor planning and action observation
May have a more prominent role in global attention compared to the left IPS
The potential Potential positive effects of increased connectivity of these regions are:
Enhanced spatial-emotional integration: The connection could allow emotional states to appropriately influence spatial attention, potentially enhancing awareness of emotionally relevant spatial information.
Improved emotional context for spatial tasks: During tasks involving the Rt. IPS (e.g., spatial navigation), emotional context from the SCC could inform more balanced decisions.
Adaptive stress response during spatial cognitive tasks: The connection might allow stress levels to appropriately modulate spatial attention, potentially enhancing performance under pressure in spatial tasks.
Integrated motivation and spatial attention: Emotional states could positively influence motivation for spatially demanding tasks, potentially improving engagement and performance.
Enhanced emotional learning in spatial contexts: The connection could facilitate learning from emotional experiences in a way that informs future spatial attentional priorities.
Potential negative effects:
Increased emotional bias in spatial attention: Strong connectivity might lead to excessive influence of mood on spatial attentional processes, potentially disrupting objectivity in spatial tasks.
Vulnerability to mood-related deficits in spatial cognition: In cases of mood disorders, altered SCC activity could negatively impact spatial attention processes mediated by the Rt. IPS.
Difficulty disengaging from emotional spatial stimuli: Strong connectivity might make it harder to shift attention away from emotionally salient spatial information when necessary.
Amplified stress effects on spatial cognitive performance: During high-stress situations, the connection might lead to exaggerated effects of stress on spatial attention and cognitive processes.
Potential for spatially-oriented rumination: The connection could facilitate a cycle where negative mood influences spatial attention, which in turn reinforces the negative mood.
SCC to Lt. IPS
Subgenual Cingulate Cortex (SCC):
Part of the limbic system
Involved in mood regulation and emotional processing
Plays a role in the stress response
Implicated in the pathophysiology of depression
Involved in autonomic regulation
Left Intraparietal Sulcus (Lt. IPS) as part of the Dorsal Attention Network (DAN):
Involved in top-down directed attention
Plays a role in visual-spatial attention and working memory
Important for goal-directed behavior
Involved in numerical processing and magnitude representation
Contributes to motor planning and action observation
Given their positive connectivity, let's consider the potential effects:
Potential positive effects:
Enhanced emotional saliency in attention: The connection could allow emotional states to appropriately influence attentional processes, helping to focus on emotionally relevant stimuli.
Improved emotional context for decision-making: During tasks involving the Lt. IPS (e.g., numerical processing), emotional context from the SCC could inform more balanced decisions.
Adaptive stress response during cognitive tasks: The connection might allow stress levels to appropriately modulate attention, potentially enhancing performance under pressure.
Integrated motivation and attention: Emotional states could positively influence motivation for attention-demanding tasks, potentially improving engagement and performance.
Enhanced emotional learning: The connection could facilitate learning from emotional experiences in a way that informs future attentional priorities.
Potential negative effects:
Increased emotional bias in attention: Strong connectivity might lead to excessive influence of mood on attentional processes, potentially disrupting objectivity.
Vulnerability to mood-related attention deficits: In cases of mood disorders, altered SCC activity could negatively impact attention processes mediated by the Lt. IPS.
Difficulty disengaging from emotional stimuli: Strong connectivity might make it harder to shift attention away from emotionally salient information when necessary.
Amplified stress effects on cognitive performance: During high-stress situations, the connection might lead to exaggerated effects of stress on attention and cognitive processes.
Potential for rumination: The connection could facilitate a cycle where negative mood influences attention, which in turn reinforces the negative mood.
SCC to MPFC
Subgenual Cingulate Cortex (SCC):
Part of the limbic system
Involved in mood regulation and emotional processing
Plays a role in the stress response
Implicated in the pathophysiology of depression
Involved in autonomic regulation
Medial Prefrontal Cortex (mPFC):
Involved in self-referential processing and introspection
Plays a key role in social cognition and theory of mind
Contributes to decision-making and reward evaluation
Involved in emotional regulation and mood control
Part of the default mode network
Potential positive effects:
Improved emotional regulation: Both regions are involved in emotional processing. Reduced connectivity might help in balancing emotional responses.
Reduced rumination: SCC's involvement in mood regulation and mPFC's role in self-referential processing. Less coupling might decrease excessive negative self-focus.
Enhanced stress resilience: SCC's role in stress response and mPFC's involvement in emotional regulation. Anti-correlation might allow for better stress management.
Balanced autonomic response: SCC's role in autonomic regulation and mPFC's involvement in emotional control could lead to more balanced physiological responses.
Potential negative effects:
Impaired mood regulation: Both regions are crucial for mood control. Reduced connectivity might disrupt normal mood regulation processes.
Altered self-referential processing in emotional contexts: mPFC's role in self-reference and SCC's involvement in emotional processing. Decreased connectivity might affect how emotions are integrated into self-concept.
Disrupted social-emotional processing: mPFC's role in social cognition and SCC's involvement in emotional processing. Reduced connectivity might affect emotional aspects of social interactions.
Altered reward processing in emotional contexts: mPFC's involvement in reward evaluation and SCC's role in mood regulation. Reduced connectivity might affect how rewards are processed in different emotional states.
Dysregulated stress response: SCC's involvement in stress response and mPFC's role in decision-making. Decoupling might lead to difficulties in making decisions under stress.
PCC to MPFC connectivity
the t value is negative, hence nicotine makes them inversely correlated.
Posterior Cingulate Cortex (PCC):
Part of the default mode network
Involved in self-referential thinking and internal focus
Plays a role in autobiographical memory retrieval
Contributes to consciousness and awareness
Involved in regulating the focus of attention
Medial Prefrontal Cortex (mPFC):
Also part of the default mode network
Involved in self-referential processing and introspection
Plays a key role in social cognition and theory of mind
Contributes to decision-making and reward evaluation
Involved in emotional regulation and mood control
Potential positive effects:
Improved task focus: Reduced connectivity between PCC (part of the default mode network associated with self-referential thinking) and mPFC might help in focusing on external tasks rather than internal thoughts.
Reduced rumination: Less coupling between these regions might decrease excessive self-focused thinking, potentially reducing negative rumination common in depression.
Enhanced cognitive flexibility: The anti-correlation might allow for better switching between internal and external attention modes.
Emotional regulation: Decreased connectivity might help in disengaging from negative self-focused thoughts, potentially aiding emotional regulation.
Potential negative effects:
Impaired self-referential processing: The PCC and mPFC are both key parts of the default mode network. Reduced connectivity might impair normal self-reflection and autobiographical memory processes.
Disrupted social cognition: The mPFC is involved in social cognition and theory of mind. Decreased connectivity with the PCC might affect these processes.
Altered reward processing: The mPFC is involved in reward evaluation. Reduced connectivity with the PCC might affect how rewards are processed in relation to self-relevant information.
Memory consolidation issues: Both regions are involved in memory processes. Decreased connectivity might affect the integration of new memories with existing self-knowledge.
Mood regulation difficulties: Both regions are implicated in mood regulation. Their decoupling might contribute to mood instability.
The PCC-LPFC functional connectivity also goes down the more addicted you are - what does this mean?
Fig. 6. Scatter plot between the Fagerström Test for Nicotine Dependence (FTND) scores and the posterior cingulate cortex (PCC) – right lateral prefrontal cortex (LPFC) in smokers. Significant at P < .017.
that means over time, nicotine decreases the connectivity between the PCC and LPFC.
this is pretty interesting because while the PCC is responsible for attention and focus, memory retrieval and cognitive control (reconfigures itself in response to changes in task demand).
It’s also imporant in processing emotional salience, and awareness.
while the lateral prefrontal cortex (LPFC) is essential for Working Memory and Reasoning, Executive Functions, and Hierarchical Organization as well as Speech and Language
Again, there are numerous positives and negatives to reduced functional connectivity of decreased connectivity. The positices are:
Enhanced Emotional Processing: In some cases, reduced connectivity between the amygdala and prefrontal cortex (PFC) may allow for more direct and intense emotional experiences. This could potentially lead to:
Increased emotional sensitivity and awareness
More vivid emotional memories
Enhanced empathy in certain situations
Improved Intuitive Decision Making: Decreased PFC connectivity might reduce overthinking and allow for more intuitive or "gut feeling" based decisions in some contexts.
Creativity and Divergent Thinking: Some studies suggest that reduced prefrontal control can lead to enhanced creativity and divergent thinking by allowing more spontaneous and less filtered thoughts.
Stress Resilience: While chronic stress generally impairs PFC function, some research indicates that moderate, controlled stress exposure leading to temporarily decreased PFC connectivity might promote resilience to future stressors.
Flow States: Reduced prefrontal activity has been associated with flow states, where individuals are fully immersed in a task, potentially leading to peak performance in certain activities.
Adaptive Responses in Threatening Situations: In acute danger, decreased PFC control over the amygdala might allow for faster, instinctive responses necessary for survival.
Depression effects
I’ve often notices that nicotine helps depression, and personally it helps me to. This decreased connectivity may also explain why nicotine aids in depression. This Study contends that increased connectrivity of the posterior cingulate cortex (PCC) and the lateral orbitofrontal cortex (close to the LPFC) reduces depression.
The findings support a theory that depression involves increased effects of the non-reward system (lateral OFC) on memory systems (via PCC), contributing to negative rumination. Reducing connectivity helps reduce negative rumination…
Just food for thought.
Takeaway
Nicotine's effects on the brain are complex and multifaceted. Use it smartly, and it will probably help you win, but using it smartly requires so much prior discipline and motivation that most normal people will probably not be able to consciously use it in the correct way.
Let me leave you with this tweet, which prompted me to write this post:
Hi! I’m the founder of xzqt.it and I’m passionate about researching cutting edge topics about money, motivation and business, and sharing them with you for free!
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