Saturday, December 24, 2011

The Genetics of Drug Addiction

     Drug addiction is a chronic disease associated with alterations in the brain that result in compulsive behaviour and the urge to use one or more particular drugs. Whether the drug involved is cocaine, amphetamines, narcotics (opioids), cannabis, alcohol or even nicotine, the affliction can be a chronic, relapsing disorder in which these compulsive drug-seeking and drug-taking behaviours persist despite serious negative consequences.
The Effects of Drug Abuse

     Even the tobacco smoker, well aware of the potentially deadly effects and faced with gruesome pictures of the results of smoking ignores, overlooks or 'blanks out' these warnings, overwhelmed by the need for nicotine.
     All these addictive substances induce pleasant states or relieve distress, effects that contribute to their recreational use (see post: Altered States of Consciousness). There really is a 'reward center' in the brain. It sits centrally, in the deep brain structures and is responsible for our feelings of motivation and reward. Performing healthy activities such as eating, drinking and sex, activities that aid in survival, results in stimulation of this central area of the brain. 
Dopamine Pathways and Central Reward Center of the Brain

     Bombarded by the senses of smell, touch, taste, and sight of a morsel of food, for instance, results in the release of the neurotransmitter dopamine, producing the sensation of pleasure and 'wiring' the brain to seek out this same pleasure again.    

     Dopamine has many functions in the brain including roles in motivation, regulation of body temperature, memory, voluntary movement (it is the neurotransmitter that is low in certain areas of the brain in cases of Parkinson's Disease), mood, learning, punishment and reward.
     Nature has programmed us to repeat behaviours that maximize rewards and thus, in a perverse way, it is dopamine that is critically involved in the drug addiction process.
Parkinson's Disease with Forward-Stooped Posture

     A neurotransmitter (such as dopamine, GABA, epinephrine, norepinephrine) is a chemical substance that is released from a nerve ending that then attaches itself to contact points on the next nerve cell(s). These contact points are called receptors but, to add to the confusion, there is often more than one receptor type for the various different neurotransmitters and even more than one receptor site for any one specific neurotransmitter, such as dopamine.
     The role(s) of the various dopamine receptor subtypes on brain cells has been difficult to precisely delineate.
     And then, of course there are two important questions:
1. Are the receptors for the 'reward neurotransmitter' (ie dopamine) different in the addict as compared to the non-addicted individual?
2. Is there a genetic 'predisposition' (a marker? a subtle difference in the gene(s) that codes for these receptors?) in the 'addictively-predisposed' individual?
Chemical Structure of Dopamine

     A great deal of research has looked at the genetics of addiction, mostly focusing on the differences in the genes that code for dopamine receptors in the brain. These studies, which examined families, identical and non-identical twin subjects and control subjects who differed in their drug use habits suggest that there is indeed a significant difference in the make-up of specific dopamine receptors, most markedly at the specific 'DRD2' gene site that codes for dopamine receptors.
Neurotransmitter at Nerve Ending (Synapse)

     Unfortunately, nothing in science is ever quite this simple and these research findings do not hold true in all studies. It seems evident that drug addiction certainly has a genetic component but environment as well as social factors also play important roles.
     One key aspect to addiction however seems to be that it is the neurotransmitter, dopamine that plays a central role in addiction, this scourge of many in today's society.

     An interesting 'mouse party' that demonstrates the brain's activity in drug use has been produced by the Department of genetics at the University of Utah. Click on the link below:
     *The genetics of drug addiction: subject of research for the novel Whip the Dogs - Amazon Kindle

Monday, December 12, 2011

Your Personal Narcotic

     All human beings (and probably all mammals) use 'narcotics' on a daily basis. We are not all drug abusers. We are not all drug addicts. The 'narcotics' that we use are our own, made by our bodies (endogenous) for normal daily function.
The Pituitary Gland and Hypothalamus

     These endogenous narcotics are called endorphins and are produced by the pituitary gland (at the base of the brain) and by the hypothalamus (a deep brain structure). These 'morphine-like' substances are released when we are excited, when we are in pain, when we are in love, during orgasm and even during exercise. Release of endorphins provides the body with a sense of well-being and can dull pain that could otherwise be disabling.
    Endorphins are neurotransmitters (see post: The Genetics of Drug Addiction) and the most important endorphin (or at least the one most studied) is called 'ß-endorphin'. The importance of this particular endorphin comes from the fact that it reacts mostly with specific receptors on the nerve cell (called μ1-opioid receptors). These μ1-opioid receptors are the same receptors that narcotics such as morphine react with. When ß-endorphin (or morphine) attaches to the μ1, certain neurotransmitters are blocked (GABA) and others are enhanced. The enhancement is especially pronounced with dopamine, the 'brain-reward' transmitter (see post: The Genetics of  Drug Addiction).
The Runner's 'High'

     The pleasure or 'brain reward' experienced with endorphin or morphine stimulation at these μ1 receptor sites, leads to the desire and 'need' to seek out this same stimulus - endorphin release from a 'runner's high' or (often intravenous) narcotic administration. When narcotic abuse is the case, these μ1 receptors are essentially 'high-jacked', triggering dopamine release and creating dependency.
     But why do human beings have this 'natural morphine' release? What use could it be or could it have been in the past? One theory to explain this phenomenon is based on the statistics of running speed and endurance. Animals, such as human beings, are not fast runners but do have the ability to run for long distances.

Masai Hunters
     In prehistoric times, catching a fast-moving meal may have been impossible for these relatively slow-moving humans but eventually, if chased far enough and for a long enough period of time, the meal-to-be would tire, slow down and fall into the hands of the pursuer. 
     Endorphin release in the man chasing the prey enabled the hunter to ignore the pains of twists and bumps, the aches of exhaustion and reach his goal. This may explain why some of the best long-distance runners in the world originate from regions where long distance hunts are common and have been for thousands of years.

Isolation/Flotation Tank
     Certain studies have suggested that endorphin release also occurs when floating in 'isolation/flotation tanks' as well as during acupuncture.

     The placenta secretes endorphins during pregnancy into the mother's blood stream. Why this occurs is unclear but some suggest that this ß-endorphin production creates dependency in the mother and forces her metabolism to direct nutrients to the growing fetus (the child addicts the mother!).

Acupuncture and Endorphin Release

     Post-partum depression may therefore be a type of 'narcotic withdrawal' that sometimes can be countered by the mother's own endorphin release when breast-feeding.
Placental Secretion of Endorphins

     The 'runner's high' is probably not entirely due to these morphine-like substances our bodies produce. There are many other natural chemicals that have been suggested as important in feeling the euphoria of victory or extreme exertion and in dulling the pain of a severe injury.

     Naturally occurring cannabinoids (endocannabinoids) such as anandamide are thought to play such a role.
     Other neurotransmitters such as epinephrine, serotonin and dopamine (that wonderful reward neurotransmitter) have also been shown to be important.

      * The genetics of drug addiction: subject of research for the novel Whip the Dogs -Amazon Kindle