First, some housekeeping. This series has permanently moved to 9:00 PM Sunday evenings. There are a couple of reasons, mostly because I was having trouble having a proper dinner posting at 7:00. Another reason is to give our west coast friends a better opportunity to participate, since most folks have better things to do at 4:00 PM on a Sunday afternoon than to read my ravings.
I was going to continue my boring series on fuels or food additives, but happened to listen to the very good series on VH1 Classics, The Drug Years, whilst doing something else. That series is excellent, and they run it from time to time. If you like historical documentary films, this is a pretty good series to watch.
In any event, I would like to establish some ground rules for the comments for this series. All of you know that I welcome any and all, but PLEASE refrain from ones that speak to direct personal experience with illegal substances unless the statute of limitations has expired, or if your employer would not be interested. It is dangerous for you, and also might put me in the uncomfortable position of having to rat you out if any comment might come to examination by the authorities.
As Tommy says, "Here we go!"
First some background is necessary. We still do not know everything about brain chemistry, but we have elucidated that the pleasure response is mediated, in large part, by several neurotransmitters. By far the most important one is dopamine. Here is a picture of the dopamine molecule as we organic chemists understand the graphics, and the ones for methamphetamine and Ecstasy for comparison. More about these agents will be following in further installments, if there is enough interest. By the way, the wedge and line mean the same thing as the "CH3", just different representations. The reason that Ecstasy and methamphetamine work so powerfully is that they have strong structural similarity to dopamine.
Dopamine
Methamphetamine
Ecstasy
Almost every expert agrees that the release of dopamine stimulates pleasure in mammals. Some other neurotransmitters do that as well, but most, if not all, cause a cascade of dopamine to be released to the pleasure centers of the brain. Take a couple of puffs of a cigarette? Dopamine cascade. Some some Cannabis? Dopamine cascade. Ingest some meth? Dopamine cascade. Have sex? Dopamine cascade. Eat food? Dopamine cascade.
The point is that the pleasure center is run by dopamine. Some others are, as well, in particular the voluntary muscle centers, and the degeneration of dopaminergic cells there cause Parkinson's disease. Those centers are not necessarily the same ones connected with the pleasure centers, and specific destruction of the substansia nigra cells leads to Parkinson's disease. Dopamine is still being produced in the brain, but just not in the places that need it for movement.
Dopamine release is not all bad: it is an important part of the survival instinct, because otherwise eating would be nothing but a chore, and having sex would really be a chore. Both of these activities are necessary for species survival, however. The problem arises when dopamine is released for too long, in greater than normal amounts, or both. Take the case of Ecstasy for example. So much dopamine is released, and for so long, that it becomes depleted (the body can make it only so fast), and there follows a depression until dopamine stores are regenerated. Methamphetamine is even worse, with the "crash" following high doses being incapacitating in many cases.
Other activities can cause a dopamine cascade, but not in everyone and to different degrees. As most of you know, I am a coin collector, and get a "rush" when I find a particularly rare of particularly nice old coin. However, the pleasure is not so intense that I pursue that activity to the exclusion of all others. However, certain behaviors are addicting to some people. Gambling is a well known one, and can make a certain fraction of society lie, cheat, steal, or even kill to keep getting the rush. In others, sex has the same effect. Infatuation ("love" in the early, exciting stages) is an extremely powerful trigger for dopamine cascades, and I daresay that many reading here have done some, in retrospect, extremely stupid things under this influence.
Likewise, some people do not get much pleasure from drugs. For example, a person in extreme pain does not usually get a rush from narcotics, just some pain relief. Many children with ADHD do not get a rush from stimulants, just better focus (although my personal opinion is that drug therapy in children for behavioral disorders is given much too causally, rather than being the treatment of last resort, but that is quite another subject).
However, I believe that it is fair to say that most people receive a pleasure response from intake of drugs of abuse. This is particularly true of the stimulants, some of the most addictive drugs known. Most studies show that methamphetamine addiction is the most difficult addiction to treat, and the relapse rate is high.
Well, I think that we have established that dopamine is the dominant "good feel" neurotransmitter, and most of those involved in the research will not disagree. In most cases the dopamine cascade is indirectly precipitated by a drug's action on a different neurotransmitter. For example, nicotine affects a completely different neurotransmitter, but the pleasant sensations (for those initiated enough not be be rendered nauseous) from this causes a dopamine cascade as the reward system engages. This is why different classes of drugs have different effects, but it is generally agreed that the single most important addictive aspect of drug use is the dopamine cascade, because this is the brain's reward system. In the case of methamphetamine, the drug directly causes a dopamine cascade.
How powerful can this be? There have been animal studies that show that rats and primates will self-administer stimulants to the point of death, not from overdose (in some studies the amount of drug was limited to prevent overdose mortality), but rather from lack of eating, drinking, or sleeping. The animals would self-administer the drugs until they starved to death. Why? Because the drugs gave a more powerful dopamine cascade than eating or drinking would, so they would keep hitting the drug lever rather than partake in other activities.
Since this is the introductory post in this series, a few definitions are in order. In future posts, if there is enough interest, I will provide a link back so it is easy to find the definitions.
Habituation: the phenomenon of tending to repeat a given behavior because of some sort of reward. This is not always negative. For example, many people are habituated to going to work (behavior) because of a paycheck, satisfaction with their work, or both (reward).
UPDATE: As Compound F points out in the comments, this term has a different meaning in the psychological literature, where it means the reduction of sensitivity to a given stimulus, such as when one stares at the same spot for a while, and it tends to disappear. In drug abuse circles, this term is as I describe. Thanks to Compound F for the suggestion.
Tolerance: the phenomenon of requiring increasing amounts of a drug, or behavior, to cause the same subjective effect that a smaller amount has at an earlier time. This often happens with narcotic addiction, and many addicts where have been jailed, upon release, take their old dose and overdose, although they would not have before because of tolerance. It is very much like the definition of habituation from Compound F.
Addiction: a severe form of habituation characterized by the lack of ability to stop a given behavior even though the person realizes that the behavior is having adverse effects on other aspects of her or his life. Addictions can by physical (the person becomes physically ill when the behavior is discontinued, such as narcotic or alcohol addiction) or psychological (the mental anguish is so great that the person becomes agitated, despondent, or displays other severe mental pain). Methamphetamine causes no physical addiction, but the psychological addiction is extreme. Many drug addictions have both components to a greater or lesser degree.
Neurotransmitter: a chemical messenger that allows nerves to communicate with each other. There are many, some of which we probably do not know yet. Drugs of abuse affect one or more nerve systems by interfering with or enhancing one or more neurotransmitters. A given neurotransmitter can have more than one action.
In future posts, if there is enough interest, I will detail how alcohol, cannabis, narcotics, sedatives, stimulants, and other classes of drugs work on the brain. If readers are interested, please post comments to that effect. I get my dopamine rush from good response and questions from you. And, even though I know it stops your dopamine cascade when I say this, I learn much more than I ever teach writing these posts because of your comments, corrections, and questions. No scientific nor technology subject is off topic in the comments.
Warmest regards,
UPDATE: thank everyone who commented for the input. I would not keep writing this series without input. Any suggestions for the next installment are welcome, but, short of a compelling argument, I will post about the most widely, and likely, for most cultures, the most ancient drug of abuse, alcohol.
Final update: as of seven minutes ago, I am now legally two score and twelve years of age. Please, no flowers, just lamentations.
Doc