Zhang Xiu-mei Department of Pharmacology, School of Medicine, SDU E-mail: zhangxm@sdu

1. Zhang Xiu-mei Department of Pharmacology, School of Medicine, SDU E-mail: zhangxm@sdu.edu.cn Tel: 88383146 Drug Dependenceand Abuse

2. Conflict of Interest I have no financial relationships or support from commercial interests to disclose.

3. Case - ecstasy Sarah J, a vivacious 17-year-old, went out with her friend James on a Friday night, to meet other friends, drink and dance, and “have a good time” before the end-of-year examinations. Everything went well until around midnight, when Sarah took two “ecstasy” pills. As short time after that, she started feeling ill and dizzy. The temperature in the club had been high, and Sarah kept drinking alcoholic drink and a lot of water, to compensate for the dehydration caused by hours of dancing. About 3 am, she felt sick and vomited several times, complaining of a terrible headache. James took her to a friend’s house nearby, for a rest, but Sarah’s state deteriorated rapidly. She kept vomiting, and drifted in and out of consciousness. James and his friends took her to hospital around 6 am. and phoned her parents. The doctors immediately suspected intoxication with ecstasy, and her blood Na+ level (123mmol/L) confirmed their suspicion. After a day in hospital, her situation remained critical and the consultant expressed reserved optimism as to her survival. Sarah’s state gradually started improving the next day. James is puzzled, and explained that she only took some ecstasy pills, as usual, and cannot see the harm in it. He argues that it was only ‘a little bit of fun’, and that neither he nor Sarah have done any stuff like cocaine, as some of his old friends do.

4. Questions 1. What has led to Sarah’s critical state after her use of ecstasy摇头丸? 2. Is ecstasy a safe drug and what differentiates it from cocaine? 3. What is the incentive that leads to the use of life-threatening drugs? 4. Is it correct to assume that there are ‘hard’ and unsafe drugs of abuse, in contrast to ‘light’ and generally safe drugs? 5. What treatment saved Sarah’s life after admission to hospital?

5. Drug Dependenceand Abuse Objectives 1. Terms related to the drug dependence and abuse. 2. Classifications of the dependence-potential drugs. 3. The harm and major symptoms of dependence and withdrawal of drug. 4. The main mechanisms of drug dependence. 5. The principles of treatment for drug addiction.

6. 1. Terms Related to Drug Dependence and Abuse. (1)Drug dependence Refers to drug induced adaption in cells and tissues after prolonged use, which lead to the need to continue drug intake. A characteristic of drugs on central nervous system (including inhibitors and stimulants of CNS).

7. WHO Expert Committee(1964) The compulsion of humans to use certain substances in order to get a general feeling of wellbeing and pleasure, to relieve sadness or induce euphoria, or to avoid uncomfortable feeling of withdrawal.

8. Drug dependence 药物依赖性 药物依赖性是药物与机体相互作用所造成的一种精神状态，有时也包括身体状态，它表现出一种强迫要连续或定期用该药的行为和其他反应，为的是要去感受它的精神效应，或是为了避免由于断药所引起的不舒适。可以发生或不发生耐受性。同一个人可以对一种以上药物产生依赖性(WHO)。

9. (2)Physical/physiological dependence An adaptive physiological state produced by repeated use of a drug, which is characterized by occurring abstinence syndromes (withdrawal syndromes) if drug administration is stopped. 大多数具有依赖性特征的药物经过反复使用所造成的一种适应状态，用药者一旦停药，将发生一系列生理功能紊乱。

10. 具有生理依赖性特征的药物停药，发生的生理功能紊乱，称戒断症状(abstinence syndrome) 。 Diarrhea Vomiting Chills Fever Lacrimation Rhinorrhea Tremor Abdominal cramps Pain

11. (3)Psychic (psychological) dependence The feeling of satisfaction and psychic drive that require periodic or continuous administration of the drug to produce a desired effect or to avoid discomfort. 用药后使人产生一种对药物欣快感的渴求(craving)，这种精神上不能自制的强烈欲望驱使滥用者周期性或连续地用药。 Euphoria: rush and high. Some times people have habituation to nicotine and alcohol.

12. (4)Addiction（成瘾性） Refers to a compulsion to take a drug, with loss of control over drug-taking. Dependence to some drugs. Including physical and psychical dependence.

13. (5)Drug abuse (药物滥用) No medical use of dependence-potential drugs. 与医疗目的无关反复大量使用有依赖性的药物, 用药者采用自身给药形式，导致发生精神依赖性和身体依赖性，造成精神混乱和产生一些异常行为。 Stop use  abstinence syndrome compulsive drug-seeking behavior abuse.

14. (6)Tolerance Refers to the necessity to escalate the dose of drug in order to obtain the same effects as those obtained initially.

15. 2.The Harm of Drug Abuse • (1)Death by acute poising. 依赖形成之后，一旦中断用药便会产生一系列戒断症状，使人难以忍受。最终想方设法寻求药物，使瘾癖不得矫正。吸毒人群的死亡率通常高于一般居民人群的15倍。

16. Drug taking吸毒 吸毒指凡采取各种方式，反复大量地使用一些具有依赖性潜力的物质，这种使用与医疗目的无关，其结果是滥用者对该物质产生依赖状态，迫使他们无止境地追求使用，由此造成健康损害并带来严重的社会、经济甚至政治问题。 吸毒是中国的习惯讲法，多用在社会、法学等领域，在医学上多称药物依赖和药物滥用，国际上通用术语则为麻醉品的滥用或药物滥用。

17. (2)Infections by pathogens 吸毒者自行注射毒品，往往由于注射器、针头、溶液以及药品的污染造成一系列病原体的感染。最常见的是细菌感染，如金黄色葡萄球菌造成的皮肤感染和深层感染、细菌性心内膜炎或骨髓炎等， 最终形成败血症或神经系统与肾脏 并发症。有时病人则由于注射时的 细菌污染，直接发生破伤风。 Bacteria tetanus.

18. (3) Acquired immune deficiency syndrome, AIDS 艾滋病疫情蔓延，被视为当今人类的重大灾难。据流行学研究显示，艾滋病的传播途径主要为同性恋或性乱、静脉滥用药物以及输血或血液制品这三大方面。 据我国卫生部对30万重点人群进行HIV监测的资料，发现HIV阳性者1526例。其中978例为大陆公民，而978例中877例为吸毒者。吸毒人群之所以容易播散艾滋病，在于他们交叉使用已污染的注射器，使HIV迅速传播。

19. （4）On production of woman and newborn 吸毒使人的社会生活衰退，道德沦丧，众多的女性吸毒者最终走向卖淫的歧途。生理上，女性吸毒者常有闭经、不排卵或不能生育。吸毒的孕妇胎儿发育迟缓，娩出的新生儿体重甚低。

20. Newborn 受母体毒害的新生儿，一出生就表现出类似成年冷火鸡(cold turkey)般的戒断症状: 震颤、不安、多动、肌张力增高、号哭、呼吸增快、吮奶不佳、抽搐。 新生儿发烧、打哈欠、吐、泻，流鼻涕。新陈代谢也发生障碍，出现呼吸性碱中毒，过度钠丢失，血浆5-HT含量改变等。必须立即救治，以挽救生命。

21. (5)On family and children 长期滥用麻醉药品成瘾，影响家庭生活和家庭关系。吸毒成瘾导致钱财耗尽，一贫如洗，家庭成员特别是夫妻情感失和，妻子因而产生焦虑、抑郁绝望，离婚率高，最终造成妻离子散家破人亡。

22. On family and children 生活在这类家庭中的未成年子女心理的发展与成长受到严重影响，出现行为问题或精神症状，在学校的学习成绩低，升学率和就业率低，犯罪率高。

23. (6)On the society 吸毒与犯罪是直接联系与相互影响。即吸毒酗酒导致犯罪，犯罪者更易沾染吸毒、酗酒。长期吸毒或酗酒者惯用诈骗的方式获得药物。药物滥用者中有许多人走上卖淫的歧途，有的在群体吸毒中鬼混，进行性交易犯罪。

24. 有些滥用药物者为了追逐毒品的满足不惜铤而走险，非盗即抢，吸毒、贩毒、制毒密不可分，严重触犯国家法律刑律，最终以身陷囹圄而了结余生。而人群间的药物滥用乃致全局性流行终使一个国家在禁毒和戒毒的防、治管理工作中， 消耗大量人、 财、物和社会财富，久而 久之，会引发社会与民 族 的灾难。

25. 3.Classifications of Dependence-potential Drugs (1) Narcotic drugs a. Opioids (a)Natural opium and its phenanthrenescomponents: morphine codeine

26. Papaver somniferum Powdered dried exudate of the fruit capsule (opium)

27. Is it a beautiful flower or a poison ? Papaver somniferum (罂 粟)

28. 美丽的罂粟花

29. 美丽的罂粟花

30. 美丽的罂粟花

31. 在某个国家的田野、山川、小溪里生长着许多植高花大，色彩艳丽的花朵，有白色、红色，还有紫色等。一眼望去似牡丹又像芍药，一望无际，灿若云霞，它就是罂粟。在某个国家的田野、山川、小溪里生长着许多植高花大，色彩艳丽的花朵，有白色、红色，还有紫色等。一眼望去似牡丹又像芍药，一望无际，灿若云霞，它就是罂粟。 美丽的罂粟花

32. 美丽之花 罂粟 灾难之花 在古埃及，罂粟被人称之为“神花”。古希腊人为了表示对罂粟的赞美，让执掌农业的司谷女神手拿一枝罂粟花。古希腊神话中也流传着罂粟的故事，有一个统管死亡的魔鬼之神叫做许普诺斯，其儿子玛菲斯手里拿着罂粟果，守护着酣睡的父亲，以免他被惊醒。 在它美丽的花朵下却蕴藏了给人类带来巨大灾难的鸦片。割开罂粟果，从中流出的白色浆液在空气中氧化风干，变成棕褐色的粘稠状物，就是鸦片。中国人民曾深受鸦片之苦。鸦片中含有20多种生物碱，其中吗啡的含量约10%。吗啡是应用广泛的镇痛药。但应用不当极易成瘾。目前，以吗啡及其衍生物为毒品的危害极大。 Sleepiness Greek mythology

33. Dried juice of the unripe seed capsule of the poppy:opium

34. Opium

35. Morphus 1803年德国化学家F.W. Serturner首次从鸦片中分离出吗啡，他用吗啡在狗和自己身上进行实验，狗用后很快昏睡，用强刺激法也无法使其苏醒；他本人用后也长眠不醒。因此他用希腊神话中的睡眠之神玛菲斯（Morphus）的名字将这种物质命名为“吗啡”。

36. Opium Poppy latex exuding Opioid alkaloids Opioid analgesics Poppy Brown poultices Opium • Natural Compounds • Morphine, Codeine • Synthetic Compounds Pethidine, fentanyl

37. Opioids structure Codeine 可待因 (1832, methyl-morphine) CH3CO CH3 Antitussive, euphoria Heroin 海洛因 (1874, acetomorphine) CH2CH=CH2 More hydrophobic Drug abuse, addiction CH3CO Morphine 吗啡 Nalorphine 纳洛芬 More hydroxyl groups, more hydrophilic Opioid receptor antagonist

38. morphine 2 HO 3 1 A 4 11 10 12 O B 9 13 17 14 D N-CH3 N-CH3 5 16 15 C pethidine 6 8 HO 7 Phenanthrene alkaloid

40. Opioids (b)Artificial synthetic and semi-synthetics Heroine(海洛因) Pethidine(哌替啶，度冷丁) Methadone(美沙酮) Fentanyl(芬太尼) Dihydroetophine(二氢埃托啡, DHE)

41. Heroin 二乙酰吗啡—海洛因。海洛因呈白色粉状，俗称白粉。人一旦吸上，就想再吸，连续数日即成瘾。即使强行戒毒也很难脱瘾，因为心理上毒瘾如魔鬼一般，使其经常复发。

43. Narcotic drugs b. Cocaines：Cocaine base(可卡因碱), cocaine hydrochloride(盐酸可卡因), coca leaf(古柯叶)，coca paste(古柯糊). leaf

44. Narcotic drugs c. Cannabis(大麻类)：Preparation of cannabis from India are called marihuana，the effective component is Δ9-tetrahydrocannabinol(△9-四氢大麻酚，Δ9-THC).

45. （2）Psychotropic substances a. Sedative-hypnotics and antianxiety drugs Barbiturates Benzodiazepines Refers to acting on CNS, exciting or inhibiting, dependence may induced by repeated use.

46. b. Psychostimulants Amphetamine Methamphetamine 甲基苯丙胺, 冰毒 3,4-methylenedioxymethamphetamine 亚甲基二氧甲基苯丙胺, 摇头丸, ecstasy c. Hallucinogens Lysergic acid diethylamide, LSD 麦角酸二乙胺

47. d. Others Tobacco烟草 Alcohol酒精 Volatile organic solvents挥发性有机溶剂 Phencyclidine, PCP苯环己哌啶，NMDA agonist. Ketamine(氯胺酮，K粉)

48. (3)New trends for drugs Since 80th last century, designer drugs were occurred from narcotic derivatives by changing structure, more effective and toxic. Pethidine Fentanyl Amphetamine analogues

49. Examples of drugs abuse Drugs Molecular targets • Opiates µ and δ receptors • BZs and barbiturates GABAA receptor • Cocaine and amphetamine monoamine transporter • Marijuana(cannabis) CB1 receptor • Nicotine N receptor • Ethanol GABAA and NMDA receptor • Phencyclidine NMDA receptor • Inhalants not known • MDMA(ecstasy) 5-HT transporter

50. 4. Manifestations of Drug Dependence (1)Craving and compulsive drug-seeking behavior 药物在人应用后，出现愉悦欣快的精神效应，飘飘欲仙的感觉，即“rush and high”的感受。这种感受会留下极其强烈而牢固的记忆。 出现渴求不断得到这种精神感受的用药欲望和强迫性用药行为，形成感受欣快效应是生活唯一追求的特殊精神状态。 “没有人能够抵御吗啡产生的欣快感带来的诱惑”。