Physiology and Behaviour of Withdrawal Syndrome Idrees M, Hussain A, Hyman A, Humphries R & Hughes E. Introduction On administering certain drugs for long term use, a person can develop physical as well psychological dependence; as a result, the body develops tolerance to that particular drug. Abstinence from the drug results in symptoms collectively known as drug withdrawal syndrome. These symptoms are somatic (physical) and affective (behavioural). Somatic symptoms are generally gastrointestinal discomfort, bradycardia and an increase in appetite. Affective symptoms generally include craving, depression, dysphoria, anxiety, aggression and difficulty concentrating (Kenny & Markou, 2001). The duration and severity of withdrawal syndrome vary on the drug in which the subject is dependent on. Withdrawal symptoms of opioid drugs last for 8-10 days, whereas symptoms from nicotine withdrawal last 2-3 weeks and are less severe than opioid withdrawal. Physiology of Withdrawal Physiological effects of withdrawal are in most cases the opposite effects to those which the drug induced. An example being abstinence from the sedative morphine producing restlessness. (Nestler 2004) This is thought to be due to an increase in adenylyl cyclase activity in the nucleus accumbens which compensates for morphine’s inhibitory effect on cyclic AMP formation. Therefore when morphine administration stops there is an’ increase in cAMP production. Chronic adminstration of morphine also increases the number of G Proteins and protein kinases present within the cAMP reaction cascade. This increases cell excitability as cAMP dependent kinases can be responsible for the activity of cell ion channels. Reference: Bateson A Mechanisms of drug tolerance and dependence, lecture notes distributed in bmsc1212 introduction to pharmacology. University of Leeds. Also seen in withdrawal is the decrease/ loss of the reward that constituted the positive reinforcement of the drug taking. Cocaine increases the lifetime of dopamine as it blocks dopamine transporters preventing re-uptake. This creates the positive ‘high’ of the drug. During withdrawal the dopamine lifetime is decreased. This causes the ‘low’ experienced in the initial stages of abstinence which may lead to relapse. Discussion Drug withdrawal syndrome shows symptoms which fall into two categories – Somatic and Affective. These symptoms arise from adaptations in physiology caused by chronic drug intake. Therefore pharmacological treatments are used to maintain these adaptations. For example bupropion is used to prevent nicotine relapse by blocking reuptake of dopamine (Paterson, 2008). Withdrawal from many drugs of abuse, e.g. ethanol, cocaine and opioids, have shown an increase release of corticotropin-releasing factor which is involved in the stress response. Corticotropin-releasing factor receptor antagonists are being developed as treatments for drug withdrawal syndrome. Although treatment can alleviate symptoms of withdrawal syndrome and prevent relapse in subjects the first line of action is at the political level. Governments, advised by health organisations, provide legislation to prevent dependence on medicines or drugs of abuse. This can range from the legal dose morphine to a patient to the penalty for possession of an illegal substance. Without dependence of a drug there will not be drug withdrawal syndrome.