Neurochemistry
The basic unit of the nervous system is the nerve cell (neuron). Of the100 billion plus neurons in humans, half are in the brain. The neuron does not have a simple cell structure. It consists of a cell body (soma), containing the cell nucleus; dendrites that branch out from the cell, (extensions that receive incoming signals) and the axon, (a long cell extension that carries long distance signals).
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The effects of any drug (including crack, cocaine or heroin) vary from one person to the next. It depends on many factors including a persons size, weight and health, how the drug is administered, how much of it is actually taken, whether the individual is used to taking it, the person's frame of mind at that time and whether other drugs have been used in combination. The effects also depend on the environment in which the drug is used or whether the person is by themselves or with others.
To understand the effects of drugs on the human body we must first understand how the nervous system functions. The nervous system is a complex network of tissue that branches out from the brain and spinal cord. It controls all our actions and reactions. It allows us to adjust to our changing environment. The nervous system operates by receiving signals from all parts of the body, relaying them to the brain and spinal cord, and then sending the signals out again to muscles and body organs.
The nervous system has two divisions: the central nervous system and peripheral nervous system.
The central nervous system, consists of the brain and spinal cord. The peripheral nervous system comprises cranial nerves, controlling face and neck; spinal nerves, radiating to other parts of the body; and autonomic nerves, which form a subsystem regulating the muscles of heart, glands, lungs, stomach,etc. Stimulant and sedative drugs will affect the nervous system in different ways but suffice to say that stimulant drugs will stimulate the central nervous system and narcotic drugs will depress or sedate the central nervous system.
Cocaine works by stimulating pleasure giving neurotransmitters. One of the main neurotransmitters affected by cocaine is dopamine. It stimulates the neurons to release dopamine in the limbic system, this is the part of the brain that controls among other things, feelings of pleasure. When dopamine has been released it will attach itself to the corresponding nerve cells receptor stimulating a pleasurable response. It is then normally taken back to the neuron that released it. Cocaine blocks this re-uptake causing dopamine to continue stimulating the receptor, which in turn leads to a higher, more pronounced feeling of pleasure. In the long term this depletes dopamine, causing changes in brain function such as depression and mood swings
Methamphetamine (like many psychoactive drugs) acts on the pleasure circuit in the brain by altering the levels of certain neurotransmitters within the synapse. It produces its effects by causing dopamine and noradrenaline to be released into the synapse in several areas of the brain, including the nucleus accumbens, prefrontal cortex, and the striatum, a brain area involved in movement. Specifically, methamphetamine enters nerve terminals by passing directly through nerve cell membranes. It is also carried into the nerve terminals by transporter molecules that normally carry dopamine or noradrenaline from the synapse back into the nerve terminal. 'Once in the nerve terminal, methamphetamine enters dopamine and noradrenaline containing vesicles and causes the release of these neurotransmitters. Enzymes in the cell normally chew up excess dopamine and noradrenaline, however methamphetamine blocks this breakdown' (NIDA 2004)
Ketamine, acts on many systems and chemical pathways in the brain depending on the dose. Its mechanism of action is complex. Ketamine binds to receptors inside the brain and causes a blockage within channels or 'tunnels'. The outer end of the tunnel is attached to a glutamate receptor (called an NMDA receptor) on the cell surface. The whole complex is known as an NMDA-PCP, or N-P receptor. The "N" part is on the outside and locks onto glutamate, and the "P" part is on the inside of the tunnel and locks onto Ketamine. Like Phencyclidine, Ketamine is primarily a non-competitive antagonist of the NMDA receptor which opens in response to binding of the neurotransmitter glutamate. This NMDA receptor mediates the analgesic effects (painkilling effects) of ketamine at low doses. Evidence for this is reinforced by the fact that naloxone, an opioid antagonist, does not reverse the analgesia. Studies also seem to indicate that Ketamine is "use dependent" meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor.
Tetrahydrocannabinol (delta-9- tetrahydrocannabinol),, also known as THC, is the main psychoactive substance found in the Cannabis plant.. It was isolated by Raphael Mechoulam and Yechiel Gaoni from the Weizmann Institute in Rehovot, Israel in 1964. THC acts on "cannabinoid" receptors which are found on neurons in many places in the brain. These brain areas are involved in memory (the hippocampus), concentration (cerebral cortex), perception (sensory portions of the cerebral cortex) and movement (the cerebellum). When THC activates cannabinoid receptors, it interferes with the normal functioning of these brain areas.
Scientists have known for a long time that THC interacted with cannabinoid receptors in the brain, but did not know why the brain would have such receptors. They thought that the brain must make some kind of substance that naturally acted on these receptors. In 1992, they discovered anandamide. Anandamide is the brain's own THC (just like "endorphin" is the brain's own morphine). Still, scientists are not sure what the function of anandamide is in the normal brain but there is currently much research in this area.
MDMA predominately works on the serotonergic system. The chemical structure of MDMA allows it to reach the brain quickly after ingestion. First, the pill is ingested and it disintegrates quickly in the stomach contents. Once dissolved, some MDMA molecules are absorbed from the stomach into the bloodstream, but most of the Ecstasy molecules move from the stomach into the small intestine. There, they are absorbed into the bloodstream very easily. Some studies have suggested that ecstasy has no long-term impact on the levels of the neurotransmitter serotonin in the brain, while others have suggested that it leaves clubbers feeling depressed and unable to concentrate. Studies on animals show damage to neurons but how it exactly does this is not fully explained.
In recent years, there has been a lot of research carried out to understand how Ecstasy affects the brain. Scientists have made a lot of progress in identifying how Ecstasy changes mood and behavior. The long-term effects include changes in brain structure (based mainly on animal studies) and behavior. The nerve pathway that is predominantly affected by Ecstasy is called the serotonin pathway. Serotonin is a neurotransmitter that is synthesized, stored, and released by specific neurons in this pathway. It is involved in the regulation of several processes within the brain, including mood, emotions, aggression, sleep, appetite, anxiety, memory, and perceptions.
With all the above one must consider that the brain is 'plastic' and can mold itself to the environment.. Brain cells (neurons) continually develop throughout ones life and environments play a major factor in conditioning our brains. The inter-play between chemicals that regulate emotion and impulses is complex and forever changing. As our understanding and the technology to study our brain develops there are many findings that have a direct impact on how we work with drug users. For instance, how Brain Derived Neurotrophic Factor (BDNF), a protein implicit in behaviour and learning, may have a major function in addiction and recovery. These finding are by no means controversial, the only controversial thing is that neurology does not get taught within the drugs field or the medical profession in general.
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