The End of addiction. Dr Volker Hitzeroth
there is a feeling of pleasure and reward.
Amphetamines
The amphetamine group of drugs has a more direct effect on dopamine in the VTA and nucleus accumbens. They cause dopamine to be released from specific neurons in the pleasure pathway, resulting in an increase in the dopamine levels with subsequent feelings of pleasure and reward. (It should, however, be remembered that some amphetamines have effects on other neurotransmitter systems in the brain, including the serotonergic, noradrenergic and GABA systems. You will also recall that ecstasy has some serotonergic/hallucinogenic effects as well.)
Figure 3.2 Natural and drug influences on the pleasure pathway
Cocaine
Cocaine also has a more direct effect on dopamine release in the mesolimbic pathway. While amphetamines release dopamine directly, cocaine generally inhibits the reuptake of dopamine once it has been released. Due to this inhibition, dopamine cannot be removed from the particular neural space and the levels of dopamine rise, causing a pleasurable and rewarding experience. Like amphetamines, cocaine also affects other neurotransmitter systems in our brain, such as the serotonergic, noradrenergic and GABA systems.
Nicotine
The nicotine inhaled when smoking cigarettes affects the acetylcholinergic system through specific nicotinergic receptors. Nicotine specifically interacts with two important cholinergic receptors. These are the alpha-4-beta-2-nicotinic acetylcholine receptor and the alpha-7-nicotinic acetylcholine receptor. When external nicotine enters the body, it finds its way to these receptors and through a process of chemical reactions leads to dopamine release in the nucleus accumbens, and consequently a feeling of pleasure and reward.
Alcohol
Despite having been consumed by humans across the globe for thousands of years, the effect of alcohol on the brain is the least understood. Alcohol affects numerous different chemical systems in a variety of ways, most of which finally also have an effect on the VTA and the nucleus accumbens, with a subsequent increase in levels of dopamine in the pleasure pathway.
Cannabis
When cannabis is inhaled, it binds with the cannabinoid receptors which occur naturally in our bodies. There are two types of cannabinoid receptors, namely type I and type II receptors. The cannabinoid type I receptor is primarily situated in the brain, while the cannabinoid type II receptor is found mostly in the spleen, thymus and immune system. The active ingredient in cannabis is called delta-9-tetrahydrocannabinol, commonly abbreviated as THC. This chemical is metabolised to another chemically active metabolite, 11-hydroxy-THC. Through a process of chemical reactions this metabolite finally leads to a release of dopamine in the nucleus accumbens and a pleasurable sensation. You will recall that cannabis also has other effects, including stimulant and depressant effects.
Hallucinogens
The group of hallucinogen drugs affects numerous neurotransmitters in the brain, including serotonin, noradrenalin and dopamine. Hallucinogens seem to specifically target the serotonin type 2a receptor, but also have an effect on dopamine release in the pleasure pathway.
Phencyclidine (PCP)
Phencyclidine has a relatively direct effect on dopamine. It stimulates dopamine release and inhibits its reuptake in the pleasure pathway. Phencyclidine seems to do this via a sequence of chemical reactions, including in the glutaminergic and serotonergic systems.
Inhalant drugs
The inhalant group of drugs also releases dopamine in the nucleus accumbens with subsequent feelings of pleasure and reward.
So far we have learnt that there are three components of the pleasure pathway, namely the VTA, mesolimbic pathway and nucleus accumbens. The majority of pleasurable experiences (whether induced by drugs or natural events) result from dopamine release in the common pleasure pathway. This explains why some people cross over from one substance to another once they stop their initial primary drug of abuse. Such examples include an alcohol-dependent person who increases his smoking habit during the alcohol withdrawal phase. A heroin addict is likely to request more benzodiazepine tablets when detoxing from heroin, and a benzodiazepine-dependent patient might use more alcohol when he is weaned off the benzodiazepine medicine. A person who stops smoking cigarettes may increase his coffee intake.
The reason for such crossover behaviour is that the original primary drug of abuse has now been either reduced or stopped, the feelings of pleasure and reward have subsided and there is an urge to re-establish them. By taking a different chemical substance which also acts on the common pleasure pathway, this can be rectified. Various drugs therefore have a similar biochemical effect at the common pleasure pathway (that is, an increase in dopamine levels) and can be partially or wholly substituted.
CHAPTER 4
THE SCOPE OF THE PROBLEM
To be able to address the challenges posed by drugs and alcohol, we have to clarify the nature and extent of drug and alcohol use. Basic data about the scope of the problem are therefore critical to our ability to intervene and assist drug- and alcohol-using clients and their families. Although it is clear that there is a need for further research and collection of data on drugs and alcohol, collecting data alone poses many problems. It is extremely difficult to ascertain exact figures regarding drug and alcohol use across populations. This is because very few people work within the drug and alcohol addiction field and are able to report such data.
Furthermore, alcohol and drug use can present to the authorities in a number of different ways. We know that drug- and alcohol-related problems could present in a medical setting with infections, bleeding tendencies and neurological problems; in a mental health setting with associated depression, anxiety, psychosis and threats or attempts at suicide; in an emergency setting with seizures, cardiac problems, intoxication syndromes and withdrawal symptoms; as a chronic illness with HIV, hepatitis, liver problems and stomach ulcers; in a non-medical setting such as a criminal court due to drunken driving, assault or theft; or at the place of employment with workers arriving intoxicated and unable to do their work. The variety of drug and alcohol presentations makes it extremely difficult to gather useful information on drug and alcohol use.
In addition, a large part of the drug and alcohol world remains illegal and underground and virtually impossible to monitor. Lastly, those using drugs and alcohol often do not disclose the exact volume consumed. In fact, they spend a large amount of time and effort hiding their drug or alcohol use from their family and friends. When questioned, they are likely to underreport their drug and alcohol use due to fear of stigma and blame.
Traditionally, a number of sources of drug and alcohol information are accessed when clinicians, epidemiologists or policy-makers attempt to estimate the drug and alcohol use within a community:
1 One method of accessing information regarding drug and alcohol use is to have individual interviews with users or their families. Although these are very useful, they are also hampered by the problems of self-reporting, such as honesty, fear, shame and ignorance, which could all result in under- or overreporting.
2 Governments or large organisations also attempt to do general population surveys in which large population groups are surveyed using questionnaires or interviews to assess the drug and alcohol use within that specific population. Such surveys usually provide reasonably accurate information, but are costly and time consuming. Furthermore, they would have to include large numbers of individuals within the population in order to give accurate results because the problem of drug and alcohol use remains relatively rare within the general population. Of course, a general population survey is also likely to neglect marginalised groups, who may actually have high levels of drug and alcohol use and who are thus underrepresented in the general survey. Examples of such groups might include the homeless, the unemployed, commercial sex workers, or gays and lesbians.
3 Another method of acquiring valuable information on drug and alcohol use involves using indirect drug and alcohol indicators.