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Neurotransmitters: God’s Way of Getting You High

Considering the fact that the human brain comes equipped with the desire as well as all the necessary neurological equipment to get us high, it’s not surprising that ever since humanity began, we’ve been searching out more and more creative ways of doing so. Earth’s abundant flora, of course, have been only too happy to oblige.

Plants produce a number of medicinally important compounds. Medical marijuana use dates back to 2800 BC; opium poppies (from which morphine, heroin, and OxyContin are derived) were ubiquitous in ancient Mesopotamia, and still are today. Aspirin (salicylic acid) is derived from a tree, and Taxol, a chemotherapeutic drug used to treat breast cancer, is derived from the bark of the yew. Pscilocybin, a hallucinogenic compound similar to mescaline, is created naturally by mushrooms, just as mescaline is by cacti.

Coca plants have been cultivated for centuries in Peru, Bolivia, and Mexico. The leaves of the plants are chewed by the harvesters of the precious crop to increase stamina and decrease appetite, in the same fashion that we in the States consume nicotine and caffeine. Heck, we even structure our workdays around these drug-consuming activities, such as cigarette and coffee breaks. Though we might not even realize it, caffeine, just like marijuana and cocaine, is a psychoactive drug—that is, it has an effect on our central nervous system by increasing attention span and concentration. It does this by altering the action of neurotransmitters.

Neurotransmitters are used in neuronal communication—they exert a direct effect on mood and alter our perceptions. The neurons communicate by either permitting or preventing the sending of neurotransmitters to the next neuron, where each of them binds to an appropriate receptor, a “landing site” for a neurotransmitter. For example, in order to experience an amphetamine-like high, you would need to initiate a cascade of chemicals that together would result in the release of, in this case, dopamine, the pleasure neurotransmitter. Opiates, alcohol, cocaine and the amphetamines all share the same neurotransmitter, dopamine. An essential ingredient in this chemical cascade is the precursor L-dopa, which is converted to dopamine, stored in the vesicles and released into the synaptic cleft. But the mechanisms of actions vary: For cocaine, the effect is to prolong the time it stays in the gap between the synapses, the synaptic cleft. Amphetamine is slightly different—it essentially “dumps” all the dopamine at once, and goes to sleep for a while.

Aside from being the pleasure neurotransmitter, dopamine also plays a crucial role in cognition, motivation and reward-punishment systems. An overload of dopamine in a schizophrenic’s substantia nigra (an area of the brain rich in dopamine-producing cells) is the cause of the devastating constellation of symptoms that is schizophrenia, an incurable disease where the brain is essentially hijacked into a chronic state of paranoia, auditory and visual hallucinations, delusions, incomprehensible speech or logic, and the belief that one is being persecuted. The medications used to treat (and frequently reverse) the schizophrenic’s symptoms all reduce the amount of dopamine in the brain, since excess dopamine is the causal factor.

By comparison, when a “healthy” brain is given toxic doses of cocaine, a cocaine-induced psychosis will result. In other words, you can create a temporary schizophrenic state in anyone by giving them high doses of either cocaine or amphetamine. The symptoms match those of the real schizophrenic almost identically, discernible only by the educated eye and a quick urinalysis test.

The paranoia, in the case of cocaine users, is the dominant symptom: Their worst fear—the FBI is coming! Hundreds of thousands of dollars of cocaine have been flushed into the sewer systems of New Jersey due to the insidious nature of cocaine-induced psychosis—the horrific fear that at any moment, at any second, they can bust down the door to get YOU!

Now, all of this begs a singular question: Why would plants make substances that mess with our perceptions of time, space, and self? In self-defense, of course: A drugged herbivore is a harmless herbivore. Plants have evolved to manufacture toxins specifically designed to target their herbivore predators. These plant toxins attack our digestive system, heart rate, and respiration; it only makes sense that they would eventually get to our brain and central nervous system. Most herbivores (the sensible ones) do not like the plant’s defense, and learn to avoid consuming it and its noxious effects. Alas, most humans do not. Instead of avoiding them, when humans became aware of the compounds, they discovered, through trial and error, the best ways to extract, isolate and administer them for a maximum high. We seek them out and sometimes risk our lives to procure them.

As an interesting side note, for every mood-altering substance we find in nature, there is a corresponding endogenous brain compound that is created by all of us: In essence, we create our own drugs. For instance, many have experienced “runner’s high”—the euphoric elation that occurs when we push our bodies to their physical limits. Under stress, the body releases a flood of endorphins and enkephalins, the body’s natural opiates. Marathon runners’ anecdotal accounts of surpassing their pain thresholds and pushing themselves beyond expectations have been widely described in literature. These remarkable athletes have trained their bodies to turn on their cascade of opiates (which are much more potent than morphine) in response to extreme physical exertion or pain. Moreover, they have manipulated their neurochemical cascades to enhance their performances. And from an evolutionary perspective, you can see how an ability to run from a predator while ignoring an ankle injury’s crippling pain could have been adaptive, not to mention useful. Drug abuse, however, is anything but.

Of course, drugs don’t affect all of us the same way.  Marijuana, the most commonly used drug, affects our cannabinoid receptors, identified as CB1 and CB2 receptors. We all have these receptors, just like the mu receptor (for opiates) and GABA receptors (for alcohol and benzodiazepines). The question is: Why doesn’t everyone who smokes pot, drinks, or pops a Xanax become addicted? Depends on what you mean by “addicted.” A cancer patient on a maintenance dose of morphine does develop tolerance and could develop physical dependence, but the ultimate pathology in substance dependence is the inability to regulate drug use. Physical dependence and tolerance are essential components of dependency but the added dimension of obsessional use is a determining factor (according to the DSM-IVR) of Substance Dependence. Thus, a cancer patient who needs his morphine for pain and uses it according to doctor’s advice is not an addict. He may be physically dependent and go through opiate withdrawal when he no longer needs the pain relief, but only 2-6% of such patients are diagnosed with Substance Dependence.

But searching for the causes of drug dependency seems like a trip down the rabbit hole. Myriad factors play a role in whether one develops an addiction or not. In general, age of onset (one is more prone to becoming addicted if one begins drug use as a youth), social setting (one is more prone to becoming addicted if one is raised with addict parents), and psychiatric co-occurring disorders like Attention Deficit Disorder increase the risk of becoming an addict. And despite years of debate, there has been little evidence to support genetic predisposition, a notion bandied about so carelessly. The causal link is, at best, tenuous. However, as a general rule, the quicker the drug passes your blood-brain barrier (a protective device intended to keep certain things out of our brains), the greater the euphoria, and, consequently, the increased chance of using it repeatedly, which can result in substance dependence. For example, heroin—itself an invention of Bayer—is more euphoric than morphine because it crosses the blood-brain barrier quicker.

But the truth is, sooner or later, if one is persistent and has enough money, addiction can follow.  People become addicts because they never think it will happen to them. It’s really that simple. And as far as treatment is concerned, a multitude of attempts at eradicating alcohol and drugs have been exhaustively documented and yield limited success.

So it would be safe to say, yes, we have a long way to go, and no, we are not going to see any cessation of drug use on a grand scale anytime in our lives.  The plants may be eradicated, but synthetics are here to stay. In the future, expect more of the same—highly potent drugs being administered directly to their corresponding receptors. Sound like science fiction?  Or just like Prozac!

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Christopher Sedia

Christopher SediaChristopher Sedia has over a decade of experience in pharmaceutical research and as a substance abuse counselor. He resides in NJ with the best wife ever, the novelist Ekaterina Sedia. They are alumni of Rutgers University.