Gateway Drugs: Psychology or Physiology

As most people know, a gateway drug is a drug that may lead to the use of other, possibly more addictive drugs down the road.  What many incorrectly assume however, is that a gateway drug is simply of behavioral consequence.  Of course, it makes sense in a vacuum.  A person drinks, then maybe they try smoking a cigarette, then possibly they are more likely to move into illicit substances as they progress.  While this is not untrue, it only paints part of the picture. The physiological changes that occur during the use of “gateway drugs” also can play a huge role in the progression of, and addiction to, these substances. These two parts of the picture added into the role that environments and genetics play in the occurrence of substance use and abuse, give us a clearer idea of the causation behind addiction.

Nicotine

Studies on nicotine have given us tangible evidence of the changes a “gateway drug” can make in the brain. Early research has shown that FosB expression levels in the brains reward centers can be linked to cocaine addiction.  A study of mice published in 2011 compared FosB expression in mice under various treatment methods.  The experimental group was treated with Nicotine for 7 days, while the control group was not.   The findings showed a 61% increase in FosB expression over the control group.  As a stimulant, which is also addictive, this adds up.  However, when both groups were then treated with cocaine, the experimental (nicotine) group had an additional 74% increase in FosB expression over the control (cocaine only) group.  The “priming” by nicotine of the receptors also responsible for cocaine is what is believe to cause this effect.   Further, cocaine is known to affect the expression of FosB via altering chromatin structure, typically near the FosB promoter.  What was found is that nicotine causes accelerated acetylation of histones H3 and H4.  Cocaine was only responsible for increases in acetylation in H4.    It is believed that this hyper-expression/acetylation is due to the nicotine acting as an HDAC (histone deacetylase) inhibitor.  When HDAC was inhibited, and cocaine administered, there was again a 71% increase in FosB expression, consistent with the previous study done with nicotine and cocaine.

Marijuana

The research on marijuana as a gateway drug in a physiological sense is still ongoing.  In rodents, early exposure to cannabinoids resulted in a change in the dopamine receptors in the brains reward centers later in the brain.  This finding is concurrent with the studies of people who began marijuana use at a young age and later developed substance-related problems.  Another fact which puts marijuana into the gateway drug category, is that animal experiments have shown that THC has a similar ability to nicotine to “prime” the brain.   This priming leads to an enhanced response when the body is exposed or subjected to a new drug. While much of the argument surrounding marijuana is circumstantial, there are certainly some parellels to the effect of nicotine on the brain’s reward center.

 

Other Possibilities

While these substances are shown to have a correlation, and there is a physiological change to back it, it is vital to remember the other possibilities involved. The impacts of environments, and genetics cannot be overlooked.  It is well-known that addiction, and addictive behaviors are a largely heritable genetic predisposition, not just a behavioral phenomenon.  Some people are environmentally more likely to engage in drug use, and some are genetically more likely to develop an addiction of some sort.  The next phase of this research can hopefully expand into a human model.  Comparing the brain activity and expression of an addiction-predisposed individual to a person who likely has no predisposition could give the gateway drug hypothesis verity.  Or it could show that while a gateway drug “primes” the brain’s reward centers, it does it completely differently in varying types of people.  While there may be no definitive answer yet, there is certainly a consequential future in researching this conversation.

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