New Evidence on Gateway Drugs

Call me crazy (you won’t be the first), but the research results I like best challenge my preconceived notions. I ran across a good example in a study about nicotine as a gateway drug, published in the September 4, 2014 issue of The New England Journal of Medicine.

I’ve always thought all psychoactive drugs are gateway drugs. A good experience with one drug opens the mind to a new world of mood alteration and fosters the expectation other drugs will be fun, not dangerous. Thus, a gateway drug is whatever drug you use first, I thought.

I didn’t pay much attention to tobacco as a gateway drug because nicotine’s kick is so much more subtle than drugs like alcohol, pot and cocaine. Plus, my experience wasn’t that smoking made me want to take other drugs; it was the exact opposite. Alcohol and drugs induced a craving for a cigarette I wouldn’t otnucleus.accumbensherwise smoke.

I also wasn’t aware that studies showed smoking consistently preceded cocaine use. For example, “in 2012, among U.S. adults 18 to 34 years of age who had ever used cocaine, 87.9% had smoked cigarettes before using cocaine,” while only “5.7% began using cigarettes and cocaine at the same time,” a mere “3.5% used cocaine first, and 2.9% had never smoked cigarettes.”[1]

But it turns out there’s evidence nicotine is a gateway drug — it primes the brain in a way that intensifies the effects of later cocaine use.

The article, A Molecular Basis for Nicotine as a Gateway Drug, concludes: “We found evidence that there is a specific biologic mechanism that explains the sequence from cigarettes to cocaine in the population.”

Researchers Dr. Eric Kandel and Dr. Denise B. Kandel, fed nicotine to mice, then gave them cocaine and nicotine. They measured addiction-related behaviors, synaptic plasticity, and the activity of a transcription factor, called FOSB, which is central to the addictive process, and found:

  • In one addiction-related behavior, “locomotor sensitization,” mice given nicotine alone were no more active than a control group; nor were those fed nicotine for 1 day and given both nicotine and cocaine for 4 days. Mice given cocaine alone were 58% more active than controls, “but mice given nicotine for 7 days, followed by 4 days of nicotine and cocaine, were 98% more active than controls.”

  • Another behavior, “conditioned place preference” showed that “mice primed with 7 days of nicotine and then given both nicotine and cocaine for 4 days had a 78% greater preference for the chamber associated with cocaine than mice who were fed only water and then cocaine.”

  •  “Priming with nicotine appeared to increase the rewarding properties of cocaine” by impacting synaptic plasticity, increasing dopamine activity in a key part of the reward system (the ventral tegmental area).

The effect on FOSB gets into molecular detail which I can’t claim to understand, let alone explain (something about changing chromatin structure at the FOSB “promoter” by means of histone acetylation in the hippocampus…)iStock_000013785503XSmall[1].pot

Suffice it to say that the FOSB findings not only supported nicotine as a gateway drug, they also found, “the priming effect of nicotine does not occur unless nicotine is given repeatedly and in close conjunction with cocaine.”

In sum, “[t]hese results provide a biologic basis and a molecular mechanism for the sequence of drug use observed in people. One drug affects the circuitry of the brain in a manner that potentiates the effects of a subsequent drug.”

Whether drugs like alcohol and marijuana act in a like manner remains to be investigated. However, as Drs. Kandel point out, these results have significant implications for e-cigarettes, newly-popular nicotine-delivery systems, which have been promoted as less dangerous than traditional cigarettes.

Assuming the results of this study are replicated, anti-smoking efforts should incorporate nicotine’s role as a gateway to other drug use as yet another reason people, particularly young people, shouldn’t smoke.

And it may be a good time to reconsider our views on gateway drugs — with a more open mind.

 


[1] All quotes are from: A Molecular Basis for Nicotine as a Gateway Drug, The New England Journal of Medicine; 371:932-943, September 4, 2014.


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