Substances of abuse

42 Substances of abuse





Questions



image What are the pathways involved in drug addiction?

image What substances cause drug addiction and how are they treated?

A number of substances repeatedly taken either legally (nicotine, alcohol) or illegally (amphetamine, cocaine, heroin) can give rise to substance dependence. Substances of abuse increase the mesocortical and mesolimbic dopaminergic pathways associated with salience and reward for natural drives (e.g. food, water and sex) that originate in the ventral tegmental area (VTA) and project to the prefrontal cortex and limbic system. Neuroadaptive changes promote craving, compulsion for drug taking, conditioned response (i.e. cues) linked to craving (e.g. desire to smoke in a social setting), tolerance and withdrawal symptoms (Fig. 3.42.1).


image

Fig. 3.42.1 Substances of abuse. (A) Neural circuitry involved in reward; (B) development of hedonic effects; (C) withdrawal effects.



Opiates


Opioids (heroin, morphine) disinhibit dopaminergic activity in the VTA by stimulating opioid μ receptors on GABAergic interneurons, increasing dopamine levels within nucleus accumbens and VTA. They produce euphoria, sedation and tranquillity when administered acutely. Chronic uncontrolled use gives rise to craving (psychological dependence), tolerance and withdrawal symptoms, which include irritability, aggression, sweating, restlessness, pupil dilatation and piloerection (giving rise to the euphemism ‘cold turkey’). In overdose, they cause lethal respiratory depression. Methadone is a weak agonist of the opioid m receptor and is used to treat heroin addiction as it reduces the severity and manifestation of withdrawal symptoms and craving. Extended exposure to methadone produces cross-tolerance (desensitization) and this, in a sense, antagonizes the pharmacological action of heroin. Furthermore, its longer plasma half-life also accounts for a reduction of the symptoms associated with withdrawal. Buprenorphine is a partial opioid μ receptor agonist that has a slower onset of action and longer duration of action than heroin. Like methadone, it provides cross-tolerance to the actions of heroin and has the added advantage that unintentional overdose is avoided. Naltrexone is a opioid μ receptor antagonist that directly blocks the actions of opiates. This distinct mechanism of action makes the drug useful in the treatment of heroin addiction, particularly when accompanied with behavioural treatment.

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Jul 18, 2016 | Posted by in PHARMACY | Comments Off on Substances of abuse

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