March for science

Introduction

What is addiction? The National Institute on Drug Abuse, which supports about 90% of research in addiction worldwide, formally defines it as “a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences.”. It is rather easy to conclude that addiction is a disorder of the brain. But a more careful analysis of the neuroscience and behavioral psychology, would make it clear that it is actually an order rather than disorder of the brain.

Addiction is a self-reinforcing order in the brain building habits - which are, unfortunately, detrimental to the well-being of the person. Simply put, addiction is a deeply learned skill of the brain like other skills that the brain has learnt such as playing the guitar or brushing our teeth. When these skills have been learned, person can perform the complex movements required in these tasks automatically and effortlessly, without taxing mental energy. These skills serve the purpose of accomplishing some goals or desire of ours. For example, to maintain healthy teeth (which, in turn, is for our basic need for food), we brush our teeth. In the same way, to alleviate a difficult emotion or experience a desirable emotion, an addicted person would excessively indulge in, say, alcohol. As we will see in more depth below, learning addiction is usually more special than learning most other skills. It's driven by a lot more of the chemical fuel known as dopamine and makes special use of the reward-based feedback learning mechanism that is embedded in the blueprint of the brain.

Our brains are designed such that addiction can form in it. Neuroscience, through brain imaging, brain stimulation and behavioral experiments, has come a long way in understanding how this occurs as well as suggesting methods to overcome it. But first, we need to remark on the fundamental capacity of the brain to change and adapt.

The neuroplastic brain

Just as any computer program is stored as a series of magnetized spots in the hard-disk of the computer, everything we know and can do is stored as something physical in the brain. As an infant grows, he or she is acquiring new knowledge, memory or abilities, which are being recorded at a biological level in the brain. Thus, the brain is changing. This is the most fundamental function of brain - to change and adapt. This is known as the neuroplasticity of the brain - because the brain has a plastic nature that can be deformed into a different shape.

Neuroplasticity is a buzz word that has attracted a lot of attention in recent decades. This is because several myths have been severely debunked related to it. The most famous one debunked is that the adult brain does not change. Not only any new skill that an adult may learn changes the brain on a relatively small scale, it can change the brain at a large scale that is clearly visible through brain imaging techniques. For example, the taxi drivers who navigate through the vast network of roads in London have displayed larger than average size of hippocampus [5], a structure in the brain that is like the filing system for forming memories. Another remarkable example comes from the story of Connie Smiley, a 65 year old avid animal lover who worked in the Cincinnati Zoo [3]. She suffered a brain stroke that disabled the entire left side of the body, where she could move "not a finger, not a toe, nothing" as she recalls. The stroke was on the right side of the brain which controls the left side of the body, whereas the left side of the brain controlling the right side of the body was fully functioning. Driven by her motivation to return to her passion for animal kingdom, she began extensive rehabilitation at a facility in the US. Peter Levine, the researcher who worked closely with Connie explains, that she was able — “to drive her nervous system towards recovery far beyond any expectations.” They found in the MRI scans that the left side of the brain was controlling both the right and left sides of the body! Even after a senior age of 65 years old, she was able to define new brain circuits that trumped the in-built circuits we are all born with.

The main brain circuits are formed by the cells of the brain called neurons and their interconnections via arms called axons and dendrites. Dendrites are short and multiple for each neuron; they receive signals from other neurons. Axons are long and only one for each neuron; they connect to the dendrites of other neurons and send signals. The junction point of interconnections of the neurons - point of contact between an axon and a dendrite - is called a synapse. The signals travel across the arms as electrical pulses, resulting from an electrochemical process, but require chemical messengers - known as neurotransmitters - to send signal across the synapse, i.e. from one neuron to another. The most important neurotransmitter related to addiction is dopamine. These neurotransmitters are usually carried in some interior vessels near the synapse and are released into the synapse when they are triggered by the electrical pulse. When the dopamine has done its job of transmitting the message, it is sucked back into the vessels of the axon. This network of neurons with electrical pulses zapping through them is viewed as brain circuits. Since there are about 100 billion neurons in the brain and most of them have some 1000 - 10000 synapses, the cliché that brain is the most complex system known to us is no overstatement.

How do the neurons make connections? A golden rule of neuroscience was coined by Donald Hebb in his 1949 book “The Organization of Behavior”. Simply put, the Hebb's law says, "Neurons which fire together, wire together." These means that if two (nearby) neurons are firing at the same time - where firing means that it is persistently sending out electrical pulses through its arms - the chain of synapses connecting these neurons undergo a growth process or metabolic changes such that the efficiency of the signal transmission improves with repetition. These neurons become associated, the firing of one neuron causes the firing of the other, thereby they are wired together forming a synaptic pathway. Their strength depends on the repetition of their use. They may emerge distinctly strong if they have been exercised enough or they might weaken before eventually fading away with disuse. Most of the changes in the brain are changes in these synaptic networks, whereas all the neurons stay alive throughout our life (another debunked myth).

So, on a macroscopic level, what is the key to cranking up or down the firing rates of these neurons? The emotional intensity, attention and repetition of activation are the driving forces that build the synaptic pathways in the brain, representing new memories or learning. The more these forces are applied, the deeper the learning becomes. When our experiences are stained with strong emotions such as threat, attraction, pleasure, or relief, neuroplasticity takes on extra momentum. Emotions focus our attention and cognitive activity around the learning process, and when these emotions repeat over and again, the brain inevitably changes in the direction of the experience, entrenching the experience a little more each time. This is what is implemented in addiction with a strong feedback loop.

The brain anatomy for addiction

Our brain has various sectors that have been identified to specialize for one cognitive aspect or the other, but all the time they must collaborate with each other to perform specific tasks that we do. The brain is divided in two hemispheres that are identical anatomically (not functionally though). The outer structures on each of them are made up of cortices (plural of cortex) which are dedicated to sensory, motor or visual processing. It also houses prefrontal cortex (PFC), which is uniquely sophisticated in humans, and gives us our capacity of planning, judgement, decision-making, error-detection and the fundamental sense of self. So, in short, we can regard the PFC as the executive center of the brain. It is more recent in the evolutionary timeline and gives humans the advantage of the intellect that no other creature has.

Under this advanced cortex of the brain is the 'subcortical' region called the limbic system. It is more primitive in the evolutionary timeline and is in common with the rest of the animal kingdom. Broadly speaking, it is at a low-level consciousness with basic mechanisms for our survival and operation, but functions very efficiently and rapidly compared to the higher cortex. It constitutes a wide range of distinctive tissues which (1) processes and regulates emotions, (2) deploy stress response signals for fight or flight, (3) process memory for storage, (4) register basic needs and rewards, (5) instigate motivation, (6) command actions to the motor cortex which controls our bodies and (7) form habits, both physical and mental. Habits are very necessary for us to spend our daily lives without overtaxing our mental and physical energy, so that we can concentrate on other more meaningful tasks like thinking, exploring, talking, evaluating, and planning. The habit center can be mostly located in the striatum of the limbic system. Since addiction is basically a habit that has gone rogue to the point of being detrimental, striatum is also crucial to the mechanism of addiction.

Striatum is like a headquarter of the limbic system. It is remarkably multi-functional - (1) it coordinates our actions by communicating with the motor cortex of the brain (2) process our motivation (3) communicates with other parts of the limbic system such as amygdala and hippocampus (4) exchanges information with the prefrontal cortex. What is motivation? It is basically desire - a desire to for an action. Therefore, it is highly convenient for the brain to have the motivation center (2) close to the action center (1). Amygdala are structures which acquire and maintain emotional attributes - whether something feels happy or frightening - and accordingly transmits the information to the striatum and hippocampus. It steers the attention towards whatever is making us feel those emotion, and its impact is stronger for stronger emotions. Hippocampus processes experiences bundled with the accompanying emotional information from amygdala and registers them as memories in the other parts of the brain.

Below the limbic system is the midbrain - a part of the central nervous system associated with vision, hearing, motor control, sleep, arousal and temperature regulation. It is also the source of dopamine - a neurotransmitter - that enables functioning of the limbic system and the prefrontal cortex. Whenever there is an increased activity in the limbic system, dopamine shoots through certain in-built pathways and irrigates the striatum, hippocampus, amygdala and prefrontal cortex. These paths are the lifeline of the formation of habits and addiction, among other functions.

The machinery of addiction

As the motivational center of the brain, the strong feeling of attraction or desire of anything specific, say alcohol, is felt in the striatum and then - it develops with experience. It adjusts its neural circuits according to what seemed rewarding in the past and thereby, it interprets past pleasures into present desires. These desires are identified as goals. Accordingly, the striatum orchestrates neural activity in (1) the prefrontal cortex to manufacture meanings and expectations, (2) the back of the cortex to form imagery and enliven memories, (3) the amygdala to spark emotional responses, (4) the hippocampus where this moment of pleasure with all the sensory cues such as the sight of the bottle of alcohol and its sweet smell, (5) the brain stem where the emotional feeling is communicated to the rest of the central nervous system, maybe, as a smile or a shudder of fear. In this manner, all the associated firings of neurons are wired together. The necessary fuel is the neurotransmitter dopamine which is summoned from the midbrain when these activities begin. If the amount of dopamine increases, each of the above neural activities intensify. The focus on the addictive activity is intense, the feeling of attraction is stronger, the memory of the bottle and smell of alcohol is more vivid, the euphoric experience feels more real than anything else.

Our brains have evolved with a dopamine-based reward system that values behaviors such as eating, procreating, and interacting socially as rewards, to motivate us towards these behaviors for our survival. Modern world offers several hard drugs that can hijack this reward system to artificially flood it with dopamine. Dopamine would then drive to rewire your brain to want more drugs, which in turn would pump in more dopamine and keep driving the cycle, leading to addiction. For the release of dopamine, there are several microscopic components in this process - dopamine inhibitors, dopamine carrying vessels and dopamine receptors. Each type of hard drug, like heroin cocaine etc., increases the dopamine level in the synapse in a unique way. Heroin disables the dopamine inhibitors in the midbrain, thereby keeping on flooding the dopamine to the rest of the brain. Methamphetamine reverses the flow of dopamine into neurons, forcing dopamine to rush into synapses instead. Cocaine manipulates dopamine flow preventing removal of excess dopamine from synapses. Abstaining from these substances is extremely hard not only cognitively, but also physiologically as in withdrawal symptoms. However, it does not entirely explain why people get addicted to wide array of other modern world activities as video games, internet or even gambling. These addictions have been well studied in the lower primates where the same mechanisms of limbic system play out addiction. In an experiment, rats are conditioned by flashing lights and throbbing sounds, like what keep humans playing in casinos. With the reward payed in sugar pellets, the rat will consistently press at levers with the highest payoff but the smallest probability of winning. So, the main ingredients for addiction are desire and reward-based learning in a feedback loop.

Feedback loop for reinforcement learning is very important for addiction to set. Addiction is a self-sustaining, self-perpetuating set of behaviors, both mental and physical, that strengthens with each cycle of the following feedback loop, that was sparked by a desire. A cue, which may be a white powder reminiscent of the substance such as cocaine, would register to the sensory cortex and makes it way to the striatum. Sometime during the formation of addiction, striatum had learnt that a white powder is same as cocaine so the cue itself triggered it to buzz loudly with activity (as seen in fMRI scans showing increased metabolism). This is craving. The craving instigates thoughts in the prefrontal cortex with mental imagery and other bodily process such as restlessness or shortness of breath. When the cocaine has been finally obtained and consumed, the craving subsides giving pleasure or relief - basically the reward. Often the cue is simply the feeling of void which needs to be filled with this substance. So at times the craving appears out of nowhere and then the cycle has to be repeated. In summary, trigger - behavior - reward - repeat. This loop plays again and again, each time entrenching itself into the brain. The brain has, essentially, learnt the reward as its goal, operates as if this is necessary for survival and has become very efficient in it. How efficient could it be? In a study, brains of 22 recovering cocaine addicts, photos of crack pipes and other drug cocaine related objects were flashed to them on a display screen for 33 milliseconds, one-tenth of the time it takes to blink. They didn’t “see” anything consciously, but the images activated the same parts of the reward circuitry that visible drug cues excite [4]. Addiction, once set, is extremely stubborn and tends to relapse after rehab. So, it's very easy to do it. But why is it so hard to NOT do it?

This brings us to the executive role of the prefrontal cortex. A component of this is the dorsolateral prefrontal cortex (DLPFC) which is like the captain of the ship. This is the one which is active when you are being your rational self as you are reasoning, evaluating your choices, planning and making decisions about your actions. In normal brains (non-addicted brains), there is a healthy number of neural interconnections in the region between DLPFC and striatum, which includes anterior cingulate cortex (ACC), allowing two-way traffic. A healthy amount of neural fibers here ensures good self-regulation, self-monitoring and behavior control. This region becomes highly active in the early stages of addiction, probably because people are trying to regulate their behavior. At some stage, the gears shift dramatically such that the PFC begins to disengage from the striatum when the addictive behavior is being experienced - where you would "just feel like doing it, so why not?". The disengagement leads to disuse of these self-regulation neural channels, and the disuse leads to dissolution. Research has shown that when the addiction grows over months and years, the grey matter density (quantifying the synaptic pathway density) in the PFC is lost by as much as 20 percent, irrespective of whether the addiction is to heroin, alcohol or tobacco [8,9]. The amount of loss seems to correlate with the length and severity of the addiction. Therefore, the self-control during addiction is biologically severed, fragmented or inaccessible. To resist a craving, the DLPFC must overpower the automatic and powerful commands of the limbic system. This is not easy. This process takes a lot of effort and concentration, and therefore it depletes energy. Therefore, when a person is tired or stressed, the prefrontal cortex is the first one to go offline whereas the learned and automatic behaviors of the limbic system would take over. This results in ego fatigue - where the act of resisting, resulting from willpower, has left you depleted of the capacity to resist the craving next time. That's why "just saying NO to drugs or alcohol or tobacco" is a very poor strategy to overcome addiction.

Paths to rise above addiction

Since it is clear which parts of the brain are responsible for addiction and self-control, is it possible to turn them on or off? Modern techniques can do exactly that. One of them is optogenetics. With the aid of gene therapy, it is possible to lace specific parts of the brain with photo-responsive molecules in rats and then shine light using optical fibers to excite or inhibit these brain parts. These techniques have only been used in lower primates like rats so far. Having identified the quiet parts of prefrontal cortex in the addicted rats, Dr. Antonello Bonci and his team from NIDA used this technique to activate them. The result - “Their interest in cocaine basically vanished,” Bonci says. This research suggested that stimulating the region of the human brain responsible for inhibiting behavior, in the prefrontal cortex, might quell an addict’s insatiable urge to get high.

Transcranial magnetic stimulation (TMS) is a non-invasive and safe technique that works on humans. It is basically a coil of wires where a passing current produces a magnetic field. When this coil is placed near a brain region, the magnetic field tinkers with the underlying brain circuits to activate them. Dr. Luigi Gallimberti in Italy and his team recruited a group of cocaine addicts to test this method on their prefrontal cortex. Sixteen addicts underwent one month of TMS while thirteen received standard treatments, with medication for anxiety and depression. At the end of the trial, 11 from the stimulation group were drug-free whereas only three in the other group were successful [10]. This study gained wide publicity drawing hundreds of cocaine users to the Gallimberti. It is important to note that TMS does not heal the brain by itself. It just jacks up by powering all the neural circuitry, temporarily. The stimulation has to be coupled with psychotherapy for the right pathways to form for independent functioning. There are still more studies to be done before this method becomes more widespread, but researchers around the world are trying it out in other types of addictions [11]. TMS is already being used to treat anxiety and depression and is also used in military training to enhance cognitive skills for warfare [12].

But latest perspectives on addiction suggests that addiction is something one needs to rise above by building other skills. Dr. Judson Brewer is a psychiatrist specializing in addiction and is inspired by Buddhist philosophy which regarded craving as the root of all suffering. His main idea has been to implement mindfulness, the practice of keeping keen awareness of what the person is doing, feeling and experiencing at the present moment, supplemented with meditation exercises. He taught the volunteers who joined his program to quit smoking that he does not want them to resist smoking each time they smoke, but to give curious attention to the act of smoking. They right away notice that the act of smoking feels awful - the smoke is disgusting; the taste is like chemicals - so that the act of smoking becomes repulsive. Smoking is the most sticky of substance addictions - cocaine, marijuana, alcohol would typically be abandoned by an addict after on average in 4, 6, 16 years respectively [13] because these substances damage lifestyles that no other option is left - but smoking is a stimulant so that the person can continue to function without any cognitive decline. It can persist for 25 years on average [13]. Brewer's program turned out to be twice as successful as the gold-standard therapy for quitting smoking [2]. There is other growing evidence that mindfulness can, in general, regulate dopamine in modern life. Other researchers, at the University of Washington, also devised a program based on mindfulness that was more effective in preventing drug-addiction relapse than the popular 12-step programs in the US.

There are a few FDA-approved medicines which can help during the extreme withdrawal symptoms while abstaining from addictive substances. Nevertheless, some form of cognitive behavioral therapy is required to overcome it. A highly successful therapy is devised by Dr. Jeffrey Schwarz, a research psychiatrist at the University of California at Los Angeles and one of the world’s leading experts in neuroplasticity. He explains his 4-step solution program in his book "You are not your brain" to combat any unhealthy habit [3]. They can be applied to a craving as follows - (1) Relabel the craving as a deceptive message from the brain (2) Reframe them as useless and unhealthy signals from the brain that should be ignored (3) Refocus on something productive and meaningful to you (4) Revalue your experiences. The third step is particularly important - to refocus on something meaningful and engaging. The strategy is not to simply distract from the craving or resist, because ultimately it will cause fatigue to the brain. Instead, it is to allow the brain to rewire itself. As a past addict and an eminent expert on addiction, Dr. Marc Lewis, a development neuroscientist in the Netherlands, has shared his personal experiences and others he interacted about their journey through addiction in his book, "The biology of desire" [1]. He believes that addiction is a development learning which cannot be reversed but can be built upon towards a brighter future.