– Nicotine is a tropane alkaloid, it has the ability to release dopamine in the reward pathways of the brain, why does it not produce consistent euphoria like cocaine; alkaloid or speed: amphetamine?


EDIT – Something I forgot to mention which may add context is that after a period of abstinence I feel a sharp euphoric wave of dopamine which goes away within less than a few minutes and results in dysphoria, even with redosing.

Unlike cocaine, which I’m comparing since both are alkaloids, it seems to build a very unusually fast tolerance and any positive effects dissipate, unlike the latter.

In: 3379

As someone who has a cigarette or two once every few years – it *absolutely* affects me that way.

Relative strength.

Nicotine’s impact on dopamine production in the brain is actually very mild. Euphoric states like we see with cocaine and amphetamine use are the results of considerably stronger chemical interactions in the brain – nicotine remains incredibly addictive though because a mild and consistent “high” still becomes incredibly difficult for the user to give up.

More to the point, the reward from smoking is often amplified by other activities and triggers – alcohol, caffiene, etc. all interact with nicotine and can reinforce dependence on the substance.

Nicotine’s addictive quality can’t be overstated but it actually isn’t a very strong drug – cocaine and amphetamines aren’t really comparable in regards to their impact on the brain.

There are actually lots of reasons but I think that one one of the reasons that is most related to what is OP is asking is that nicotinic receptors rapidly desensitize and some internalize. What that means is the acute high levels of nicotine that would be generated by smoking or vaping would cause the actual nicotine receptors to stop functioning for a brief period of time or even to be reabsorbed into the cell such that nicotine has no place to work until these things come back on-line.

Also, nicotine does release dopamine within the ‘reward pathway’ but it doesn’t do it to the same degree along each of the nodes of that pathway.

The first cigarette after a long break from them *is* euphoric.

I think we’re just good at building a tolerance/dependence on it.

Magical thing called “tolerance”, smoking does produce euphoria but only initially when you start. And it goes quick. The brain is amazing in that it can “turn off” indicating things to you that become “normal”. Also why drug addicts have to take more and more of the drug to get high, eventually going passed how much organs can tolerate and ending in OD.

Just to add to what has been said: Alkaloids are a huge, heterogeneous group of plant-made molecules. Comparing different effects of different alkaloids is similar to comparing different effects of different proteins or steroids. Yes, they are the same chemical class. No, their method of acting of the body is very different. Even though steroidal alkaloids are a more specific subgroup, the same is generally true.

Can you ask the question like ***IM*** 5?

I am working with pure nicotine… After small dose I feel very weak and bad overall. Nicotine as a pure co pound is rather bad for people who don’t smoke it.

Amphetamines very much do not consistently produce euphoria. That *first-got-diagnosed-with-ADHD* brightness lasted for maybe a week or two.

Tolerance brings the hum drums back.

Even caffeine produces euphoria if you quit long enough for your body to return to normal and then consume some again without any tolerance buildup.

They affect the dopamine system in different ways. Cocaine prevents natural dopamine from being broken down (effectively increasing the amount of dopamine) while nicotine indirectly affects dopamine pathways. Nicotine is also broken down far quicker in the brain than cocaine which is why the effects are shorter.

Nicotine is not a tropane alkaloid. Tropane is a fused bicylic compound, the chemical rings are connected at 2 points. Nicotine is not a fused ring, the chemical rings are only connected at 1 point. It is difficult to explain without pictures but the structures are available on wiki.

Speed and related amphetamines are also not tropane alkaloids.

As for why the effects are different, brain receptors are different shapes and are activated by chemicals which fit their shapes. The better the chemical futs, the stronger the reaction. Simplely put coke will activate 1 of receptors and nicotine a different set hence the different effects.

Nicotine at the level of a cigarette is not quite as strong as the caffeine dose you get from drinking a cup of coffee, and you build up a tolerance very quickly. It’s highly addictive, but quite weak.

An alkaloid is just a chemical class of molecule, generally, we use it to describe natural products (secondary metabolites from plants) which contain a Nitrogen atom. This was done in early chemical studies as it was thought that alkaloids had similar properties and effects, which as we learned more about molecules, we found was quite an oversimplification. Cocaine and nicotine both being alkaloids does not say that they will have similar chemical or pharmacological properties. For example, LSD is also an alkaloid, but has completely different properties in the body. Penicillin antibiotics can also be classified as alkaloids. You see what I mean.

Fundamentally however, nicotine and cocaine have different mechanisms of action in the brain; they both effect the signalling of neurotransmitters, but different neurotransmitters, and at different parts of the brain, in different ways etc. The whole concept that dopamine is the ‘happy’ or ‘addictive’ neurotransmitter is an oversimplification of something that we understand relatively little about to begin with.

There is a specific ‘circuit’ in the brain that is shown to be associated with addiction, of which dopamine is the primary neurotransmitter, but different ‘addictive’ drugs impact this pathway from different parts of the brain, in different ways. We can understand this, but not understand why certain drugs are more/less addictive because of this.

TL;DR. An alkaloid is just a classification of molecule (containing a nitrogen atom). Nicotine and cocaine are different drugs with different actions in different parts of the brain. They also interact with the ‘addiction circuit’ in the brain in different ways.

If I understand your question right, the answer is evolution.

If we sat in a constant state of euphoria our species would have gone extinct long long ago. Euphoria and dopamine are reward signals, but they are used in our brain to reward actions that from an evolutionary perspective help both the individual and the species.

Find some honey and get a caloric hit of sugar, dopamine. Get laid and potentially reproduce, dopamine.

Go hungry because you haven’t hunter/foraged and are out of food, no dopamine, go find food first. No mate and thus no chance of reproduction, no dopamine, go find a mate first.

It is important to remember all these neurobiological and physiological systems evolved for life in the savannah and the woods. We did not evolve for modern life with constant food and easily accessible sexual pleasure. If we had a constant supply of dopamine we would just sit around smiling until we died and our species along side us.

Did you mean to post this in /r/AskScience? Because that’s not an ELI5 question.

Just another reason for society to abandon tobacco as a valid drug.

All it gives is 5 minutes of happiness and in turn, it gives you a lifelong addiction, and lung cancer, makes everything smell, makes people dislike you, cause passive smoking in people around you, ruin your voice, waste your money and so much more.

Cocaine might be bad, but atleast it has some real effects…

Wow. For a 5 year old you sure know some big words.

But, as others have said, it’s relative strength.

Picture it like this: if cocaine is sulphuric acid, which, given enough time, can eat through steel, nicotine is like white vinegar. Sure, it’s an acid, but we use it as a food ingredient.

The point is, one of them is just stronger than the other. So, it takes a lot longer for your body to acclimatize to cocaine than it does to nicotine.

Do enough coke, and, eventually, you’ll need more and more to get the same level of high.

With nicotine it might be that if you smoked enough you could get that euphoria feeling again, but I suspect you would feel ill before you got to that point.

Amphetamines like methamphetamine shut down Vesicular Monoamine Transporter type 2 (VMAT2) which shuttles monoamines like dopamine from the synaptic cleft back into storage vesicles in the neuron, essentially leaving the monoamines to build up and continuously activate receptors until the drug is metabolized out of the body.

Dopamine is more about wanting than liking. It is more about seeking than it is pleasure.

Really none of these compounds you mention produce much of a sense of pleasure. We typically think of dopamine as a pleasure neurotransmitter…it isn’t. If you want pleasure, look more at the opioid system.

In the pathway that drugs of abuse, sex, drugs, gambling, etc work on, dopamine is a *seeking* neurotransmitter. It is about motivating the brain to seek out something. Ideally this is supposed to be things like food and water and sex, but many drugs of abuse hijack this pathway. Some of these drugs may have other pleasurable effects (ie alcohol and opioids both engage with mu opioid receptors which feel pleasurable) which may drive the start of an addiction…but addictions are essentially mediated by dopamine in the seeking system.

Indeed, nicotine is not pleasurable so much as staving off nicotine withdrawal is a relief and thus feels good to someone with a nicotine dependency, who likewise has had their seeking system hijacked to seek nicotine as if its a biological need like food or drink. Psychostimulants might make a user energized and this might result in a heightened mood and an illusion of euphoria (not so much pleasure), but what keeps people coming back is rewiring of the seeking system which will drive people to continue to use.

Most of the time in life what we like and what we want more or less line up and most people don’t conceive the difference between pleasure and seeking. Thus people with addiction to things that aren’t very pleasurable might be confused and think that because they *want* the thing, be it nicotine, or compulsive gambling, or repeated relationships with abusers…they believe they must also *like* that thing. But this is a mere illusion.

The reality is liking and wanting are mediated by entirely different circuits in the brain and we can end up intesely wanting things that we may not exactly like or find pleasurable. This is not an easy thing at all to wrap one’s head around.

Source: Am psychiatrist who got over a gnarly vaping habit.