An Overview of Addiction
Drug addiction, also known as substance use disorder, is the inability to control impulses regarding drug-seeking and drug-using behavior. Addiction can result from knowingly overindulging in a substance, from being administered drugs in a clinical setting that are inherently addictive, and everywhere in between. Regardless of the cause of these behaviors, the brain is affected in a very similar way. Some drugs are addictive by their very nature, such as nicotine or opiates, and some are not addictive but the repeated administration can result in a dependency, leading to the same addictive outcome.
What are Gateway Drugs?
Gateway drugs are drugs that encourage the user to experiment with stronger, more dangerous drugs; not by the way of “I smoke cigarettes so now I want to try heroin” but by the way that these drugs are so addictive that they make the brain more susceptible to becoming addicted to new substances. This is best explained by the gateway-drug effect, which explains that the repeated use of particular psychoactive drugs increases the chance of using and becoming addicted to other substances, usually stronger and more dangerous, by altering neural connectivity throughout the brain (particularly the nucleus accumbens (NAc) and ventral tegmental area (VTA)). Some of these drugs include tobacco, alcohol, and marijuana, but the list is difficult to completely define.
Animal Models of Multi-Drug Addiction
While the gateway-drug effect has been shown in humans, it has been the most easily studied in animal models. Studies show that repeated THC injections in mice increase the self-administration of morphine, heroin, and nicotine. Nicotine addiction in mice was found to increase cocaine consumption and drug-seeking behavior compared to non-addicted mice. Alcohol was found to increase drug-seeking behaviors for cocaine and decreased the average time needed to become addicted to the substance. In all of these experiments, profound changes were seen in the reward regions of the brain in very similar ways, regardless of drug class.
Neurophysiology of Drug Addiction
Figure 1 – Reward, Plasticity, and Behaviors associated with Chronic Drug Use
Drugs become addictive largely by their effects on dopamine signaling in the NAc and VTA, which play overarching roles in reward, motivation, and addictive behaviors due to the large deposits of dopaminergic neurons in these areas. In the context of gateway drugs, even a single administration of a substance can increase dopamine release in the NAc and VTA, which can have immediate, long-term effects on both the affected neuron and synapse (Figure 1). Figure 1 shows that repeated drug exposure increases DA activity and encourages AMPA receptor migration to the post-synaptic domain and decreases NMDA receptor density, which ultimately increases long-term potentiation (LTP). By having a very high amount of AMPA receptors on the postsynaptic cell, it is much more sensitive to excitation, which strengthens the connections between the two neurons.
Conclusions
Ultimately, this explains that repeated drug use strengthens the connections between neurons in the NAc and VTA which makes it very difficult to stop the use of an addictive drug. Gateway drugs do exactly this. By becoming addicted to this small collection of substances, the brain can be altered for years, even permanently, encouraging the use of stronger, dangerous drugs. This is not to say that smoking marijuana or having a cocktail now and then will lead to drug addiction, but it is important to understand the risks of chronic use.
Sources
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898681/
- https://www.mayoclinic.org/diseases-conditions/drug-addiction/symptoms-causes/syc-20365112
- https://www.sciencedirect.com/science/article/pii/S0092867415009629
- https://bluefirewilderness.com/blog/gateway-drugs-nipping-drug-use-in-the-bud/
