1. Physiology and Behaviour of Withdrawal Syndrome Idrees M, Hussain A, Hyman A, Humphries R & Hughes E. Introduction: Chronic administration of certain drugs physical as well psychological dependence for the drug can develop. Abstinence from the drug leads to a series of symptoms, collectively known as drug withdrawal syndrome. These symptoms fall into two categories – Somatic (physical) and Affective (behaviroual). Typical symptoms of withdrawal syndrome include Restlessness, aggression, depression, tremor, piloerection and strong craving for the drug. The duration and severity of the symptoms depends on the drug administered. Physiology of Withdrawal Syndrome: Chronic administration of a drug may lead to adaptations of physiology in a system. When the drugs are withdrawn the symptoms of drug withdrawal syndrome occur. Many drugs of abuse change the cell signalling pathways of the Nucleus Accumbens and the Ventral Tegmental Pathway (Nestler, 1993). Morphine inhibits cAMP formation in the Nucleus Accumbens. This results in increased excitability of cells during withdrawal. Reference: Nestler E, (1993), Molecular mechanisms of drug addiction in the mesolimbic dopamine pathway, Sem. in Neuro. 5; 369-376 Philip Morris. International Presentation. 1984, 20 th March. Cocaine blocks reuptake of dopamine in the mesolimbic reward system. This increase reward feeling from administration. Withdrawal can result in depression A common response to withdrawal is an increase in the release of corticotropin-releasing factor (CRF). CRF is involved in the stress response and causes the release of ACTH from the anterior pituitary. Behaviour of Withdrawal Syndrome: As a result of the physiological adaptations changes in behaviour occur at withdrawal from a drug. General affective symtptoms of withdrawal are aggression, depressed mood, difficulty concentrating, dysphoria, anxiety and social isolation. Often these symptoms are the cause of relapse when someone attempts to quit. “... For the most part, people continue to smoke because they find it too uncomfortable to quit” (Philip Morris, 1984) 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. Figure 1. Inhibition of cAMP formation by morphine.