Natural and Unnatural Highs

If you think about it, it’s so interesting that your brain’s neurons talk with each other via small molecules. This was a pretty outside of the box theory prior to the 1920s. A more intuitive hypothesis was that synaptic transmission (direct communication between neurons) was just a flow of electrons from one neuron to the next. These electrical synapses actually do exist, but there are also chemical synapses, as proven by one Otto Loewi in 1921.

Basically, Otto woke up in the middle of the night to a grand epiphany, wrote it down, and then promptly fell back asleep. The next morning, he couldn’t read his own writing. This has happened to the best of us. He wrote of that day, “That Sunday was the most desperate day in my whole scientific life.” However, the next night at 3:00 am, he woke again and remembered the idea. Instead of trusting his clearly terrible penmanship, he got up immediately and went to his lab to perform the experiment his subconscious had conceived, which was this:
1. Electrically stimulate the vagus nerve of a frog (which results in slowing of the frog’s heartbeat).
2. Take the “solution that bathed the heart” and apply it to a new frog heart.
3. Observe.

The idea that there would be sufficient chemical messengers released into the fluid around the heart during electrical stimulation that the fluid would elicit the same response in the second heart as the electrical stimulation did in the first was borderline insane, even to Otto. He said afterwards that “careful consideration in daytime would undoubtedly have rejected the kind of experiment I performed.” I totally get this. I can’t describe how many good ideas I’ve woken up with, only to discover seconds later in the cruel light of lucid reasoning that my idea makes absolutely zero sense and probably involves colors outside of the visible spectrum. But Otto’s idea did work–the fluid from the first heart indeed slowed the second heart’s rate–and now we know that neurotransmitters are a thing.

In order to have any effect when released from a neuron, there must be a type of “receptor” at the neurotransmitter’s destination that it can bind to. And you know what else can bind to these receptors? Drugs. It makes sense that in order for drugs to have any effect on your brain, they must have to somehow affect communication between neurons. Many drugs are counterfeit neurotransmitters, or “agonists,” which can bind to and activate a subset of their endogenous counterparts’ receptors. Other drugs can induce release of certain transmitters or prevent their re-uptake (removal) from the synapse. Here I present an incomplete list of drugs, their corresponding or affected transmitters, and related effects:


I. Cannabinoidergic
A. Endocannabinoids: Stimulate hunger. A certain variety found in the developing brain and in breast milk are shown to actually control oral motor function so babies will make the suckling motion in order to feed.

  • THC from marijuana: munchies.

II. Cholinergic
A. Acetylcholine: Attention, learning, arousal, reward, muscle contraction, slowing and speeding of heart rate, etc.

  • Nicotine: activates reward system, increases concentration, increases heart rate.
  • Muscarine: stimulates intestinal muscles, slows heart rate.

III. Catecholaminergic
For a natural high: sex, thinking about your crush, trying something new
A. Dopamine: Alertness, euphoria, and decrease of appetite.

  • Cocaine: increases dopamine, serotonin and norepinephrine levels.
  • Amphetamines: More dramatically increases the same neurotransmitter levels.

B. Norepinephrine: increases heart rate, alertness, and happiness; decreases blood circulation and pain.

  • Cocaine
  • Amphetamines

IV. Serotonergic 
For a natural high: exercise, sex, confidence-boosting activities
A. Serotonin: increases happiness, fullness, feeling of satisfaction; decreases pain. Interestingly, too much (for example from excessive exercise) can cause mental fatigue.

  • Ecstasy (MDMA): increases dopamine, norepinephrine, and causes an extremely dramatic increase in serotonin levels.
  • Amphetamines
  • Cocaine

V. Opioidergic
For a natural high: sex, exercise, listening to music, laughing (this is incidentally why laughter is the best medicine)
A. Endorphins, enkephalins, and dynorphins: euphoria, pain relief, calmness, relaxation, sleepiness, appetite suppression.

  • Morphine & heroin: activate all opioid receptors, so effects are the same as above.

VI. Oxytocinergic:
For a natural high: sex, cuddling, thinking about your loved ones. Click here to read a hilarious article on how to trick yourself into feeling in love, i.e. to increase your oxytocin levels.
A. Oxytocin: increases happiness, feelings of attachment, trust, heart rate, and social skills; increases strength of bad and good social memories; induces labor; helps prevent obesity, relieves stress, speeds the healing process, and decreases pain. Read more here.

  • Pitocin: induces labor
  • Apomorphine: increases oxytocin and dopamine levels

As you can see, sex and love have similar effects as many drugs and they are very addictive. When you’re deprived of the related neurotransmitters, you will experience legitimate withdrawal. Also, like with any prolonged exposure to drugs, you eventually build up a desensitization, or “tolerance”–the amount of neurotransmitters involved in the neural reward system that are released during the same stimulus (i.e. thinking about your significant other) decrease.

Discussion Topic: If you had to get a tattoo of a neurotransmitter (or an item of neurotransmitter jewelry), which one would you choose?

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