Acupuncture & Addiction

1. Acupuncture & Addiction By Shahla Modir, MD Addiction Medicine UCLA Neuropsychiatric Institute

2. Traditional Chinese Medicine dates back 2500 years 4 components: Acupuncture Herbal medicine Tui Na Qi gong History of Acupuncture

3. Chinese Medicine Theory • Non-linear/Non-reductionist paradigm • A part can only be understood in relation to the whole: dialectical logic • TCM is based on Yin & Yang theory • Uses the constructs of the 2 polar complements • Neither forces nor material entities • Identify how things function in relationship to each other

4. Yin • Represents the element of water • Associated with cold, rest, passivity, shade, tranquil, downward, decrease, quiescence • The end, completion and fruition • Present in the body and fluids, but also in the natural environment

5. Yang • Represents the element of fire • Associated with bright, heat, stimulation, movement, excitement, vigor, light, up, outward, increase • It is arousal, beginning, and dynamic potential • Present in the body and in the natural environment

6. Yin and Yang Theory • Examples of Yin & Yang • Night/Day, Earth/Heaven, Fall & Winter/ Spring & Summer, Male/Female, Cold/Hot • Acceptance & Responsiveness/Desire &Willfulness • Yin and Yang control each other: if Yin is in excess, yang will be too weak • Yin and Yang transform into each other • Harmonious change as a natural cause of events • Sudden rupture and transformation of extremely disharmonious situations

7. Yin and Yang

8. Balanced Health • People are constantly bombarded in the natural universe with changes in Yin and Yang: • daily cycles, seasonal changes, food and lifestyle choices • all affect the organisms balance of yin/yang • When the amount of Yin and Yang are relatively balanced • a state of health and equanimity • When there are unequal portions of Yin and Yang in the system • leads to disharmony in the body and mind and symptoms or correlates of disease • Extreme disharmony means that the deficiency of one aspect can not continue to support the excess of the other aspect • Extreme high fever leading to shock and hypothermia • Relationship of an extreme passive person with an aggressive person

9. Macrocosmic Qi • Fundamental to TCM and Chinese culture, but difficult to capture the meaning • All in the universe that is organic, inorganic is defined by its qi • Mountains, plants, human emotion • Vital energy, a kind of matter on the verge of becoming energy • The thread connecting all beings, the potential of and actualization of transformation • Does not cause change but is present before, during , and after

10. Microcosmic Qi • Qi in an applied practical setting of the human organism • Means the dynamic of engendering movement, tension, activation (yang aspect) • 3 sources of Qi • Original Qi: (Yuan qi) inherited or ancestral qi • Grain Qi: (Gu-qi) derived from food • Natural Qi: (Kong qi) extracted by lungs from the air

11. 5 functions of Qi Source of all movement & accompanies it Protects the body Source of harmonious transformations Ensures stability and governs retention Warms the body 5 primary types of Qi Organ qi Meridian qi Nutritive qi Protective qi Ancenstral qi Qi in the body

12. Meridians (Jing-luo) • Jing meaning to go through or thread in a fabric • Luo meaning something that connects or attaches • Meridians are the 12 pathways that carry qi and blood through the body; they are not blood vessels or nerves • A subtle energetic lattice that links together the fundamental textures to the organs and unifies all parts of the body • Essential for harmonious flow to occur in order to regulate the flow of the yin and yang, move qi and blood, moisten the tendons and bones, and benefit the joints • Imbalanced (too much or too little) yin or yang in the flow, blocked flow, insufficient/excess qi all create disharmony and disease

13. Acupuncture The Meridian system 12 regular meridians that correspond to each of the 5 Yin and 6 Yang organs and to the Pericardium Insertion of very fine needles into points along the meridian can rebalance the bodies disharmonies

14. Auricular Acupuncture Auricular acupuncture is a variant assumes that the body is like a holograph and is represented entirely on the ear. the map was created based on the experience of 50,000 soldiers in the Nan Jing army the needles are inserted 1-3 millmeters and withdrawn

15. Auricular Acupuncture

16. Neuronal specificity of acupuncture response: an fMRI study with EA Study of 15 healthy volunteers using mock EA (no EA), minimal EA at real acupoints used for analgesia, sham EA (real EA at non-meridian points The limbic system showed significant modulation by EA at analgesic acupoints rather than non-meridian points Correlation between acupoints and corresponding brain cortices on fMRI 12 healthy volunteers stimulated visual acupoints Found correlations between the activation of specific visual cortex and the corresponding acupoint stimulation predicted by the acupuncture literature Landmark Studies

18. Acupuncture and Addiction • Chinese neurosurgeon HL Wen in 1972 discovered benefits on accident • Noticed that acupuncture pain treatments in post-surgical, opiate addicted patients seemed to alleviate withdrawal • Used EA of lung point in 40 patients with opiate addiction found uniform decreases in opiate withdrawal symptoms • Pomeranz et al found EA in rats significantly reduced the signs of morphine withdrawal • Supports work of Ng, Thoa, and Albert that showed auricular EA significantly reduced signs of naloxone-induced withdrawal in morphine dependent rats

19. NADA protocol • Michael Smith, a psychiatrist in the Bronx, N, modified Wen’s protocol by eliminating the EA and abbreviating the prescription to five auricular needles • This prescription was not designed for withdrawal from any particular drug • Instead designed to reduce anxiety, craving, and dysphoria during the early weeks of withdrawal • Meant to make acupuncture more accessible and affordable

20. National Acupuncture Detoxification Association 800 treatment centers use this protocol Many studies use some variant of the protocol which states 3-5 points should be used Uses 5 points in bilateral auricles left in place for 40 minutes and removed Points: Shen Men Sympathetic Lung Liver Kidney NADA protocol

22. Acupuncture Study Design • Problems with designing acupuncture studies • Single blinded • Control points are usually active “unrelated” points • No inert treatments in TCM model; paradigm mismatch • Ulett (1992) from Western perspective argued auricular acupuncture effect due to stimulation of the vagus nerve that innervates the entire concha & thus needles anywhere on the concha will produce an effect

23. Opiate detoxification • Washburn, Keenan, and Nazareno (1990) reported on study 100 subjects with opiate dependence randomly assigned to receive acupuncture or sham acupuncture • Outpatient, 21 day detox program • Exp’tl subjects showed significantly better attendance and remained in treatment for longer periods than controls • However only 7% of exp’tal grp and 4% of the placebo group tested negative for opiates after 2 weeks

24. Clark (1990) N=84 opiate dependent chose either methadone or acupuncture Methadone was gradual decrease over 21 days 42 pairs subjects matched age, race, and sex Results At 90 day f/u: 31% acupuncture subj drug free/ 53% pos U/A 14% methadone subj drug free/ 62% pos U/A Opiate detoxification

25. Greiger 1987 65 incarcerated opiate dependents Randomly assigned Methadone detox with acupuncture Methadone detox without acupuncture Results: Methadone with acupuncture reported significantly less withdrawal symtoms (stomach cramps, diarrhea, h/a, depression) No placebo arm of the study Opiate Detoxification

26. Two placebo-design studies Bullock (1987) studied 54 chronic alcohol abusers and randomly assigned to receive acupoints or near by acupoints (non detox oriented) Inpatient setting, free to leave each day, alcohol consumption not excluded 2 ½ months of treatment Results Throughout study experimental subjects showed better attendance and decreased self report need for alcohol After 2nd week of tx, exp’tal group reported decreased number of drinking episodes, decreased number of subjects admitted to a local detox unit for alcohol tx Alcohol detoxification

27. Bullock et al (1987) replicated using a larger sample N=80 with subject interviews at 1,3, and 6 months post treatment 2 months of treatment Results Acupuncture group showed greater retention in treatment During the 1,3, and 6 month f/u interviews, exp’tal subjects expressed Less need for alcohol Less self reported drinking episodes Greater self reported abstinence Alcohol detoxification

28. Lipton, Brewington, and Smith (1990) conducted a placebo designed study 150 cocaine/crack abusers entering a substance abuse program randomly assigned to receive auricular acupuncture at correct sites or nearby points not related to detoxification Treatments provided for 1 month and urine tox were provided after each session Interviews at 30 and 90 days after treatment were conducted Results Self report measures and U/A profiles showed a significant tendency with both groups toward decreased cocaine consumption Pre-tx cocaine/crack usage ave at 20 days/month with all subjects. During tx period and at 3 mos post tx self report use was reduced to 5 days/month with both grps Tx retention throughout the experiment did not differ U/A profiles indicated superior outcomes with the exp’tl grp during tx & showed more cocaine negative urines over the course of tx (24% vs 21). Cocaine detoxification

29. Further results • Subjects in the study did not routinely get counseling. Each morning, the clinic accepted into tx the first 3 people and they were put in therapy and acupuncture. Later walk ins received acupuncture alone. • Urine profiles of the 73 subjs who received correct site acupuncture were compared with 42 clinic pts who received counseling and acupuncture • Results showed drop out/retention rates were the same but 50% of counseling/acu pts had neg cocaine urines vs. 24% for acu only pts

30. Cocaine Addiction • Margolin 2000 • 82 cocaine dependent, methadone maintained patients/ oupt program • Random assignment • Auricular acupuncture 4 points • Auricular control 4 points • Relaxation control: videos and relaxation training • 5x/ week for 8 weeks • No financial incentive • 40 min of each tx, after methadone dose

31. Results • Patients assigned to acupuncture group significantly more likely to provide cocaine negative urines compared to both the needle control and relaxation training. • P=.01 • odds ratio 3.41 • confidence interval 1.33-8.72

32. Cocaine/Opiate Addiction • Margolin (2002) • RCT single blind/ outpatient study • 6 community based clinics : • 3 hospital affiliated/3 methadone maintenance • N=620 Adults, ave. age= 38.8 • 412=cocaine only 208=opiate & cocaine

33. Cocaine and Opiate • Random assignment to 3 arms • Auricular acupuncture = 222 • Needle control auricular = 203 • Relaxation training = 195 • Treatments 5X/week for 8 weeks • Paid 2$/session and 10$/week • Drug counseling “N.A.” provided not required

34. Results • Intent to tx analysis of U/A showed decreased cocaine use in all 3 groups p=.002 • No between group differences • No differences in treatment retention 44%-46% for 8 weeks • Counseling ie, NA was poorly attended for all • Authors state that a model of just acupuncture without more intensive psychosocial tx led to poor outcome; subj population also very difficult

35. Methamphetamine and Acupuncture • No single study reports in the literature • Only one found uses data collected on patients with chronic arrest history and drug abuse: non-randomized, no placebo acupuncture • 37 patients received acupuncture during early weeks of tx and were followed for 180 days post admission • These data were compared to archived information from 49 no acupuncture patients who entered tx the 5 mos before it was available • Total of 86 subjects completed: MA drug of choice for 44/86 subjects

36. Protocol • Acupuncture protocol: • NADA auricular protocol daily for 3 weeks then M,W,F for 4 weeks, then M, T for 2 weeks • During tx, no talking, sitting in recline chairs with soft music for 45 minutes • Non-AC protocol: Tx as usual

37. AC patients significantly higher program retention than NA patients at day #: 30 (p>0.0001) 60 (p>.002), 90 (p>.001), 120 (p>.007), 150 (p>.031) At 180 days a higher % AC than NA pts remained in tx, not significant In AC pts: decreased # of new arrests, drug positive U/A, but not significant Regardless of tx condition MA pts had lower program retention overall AC improved the retention only up to 30 days (p>.021) Does AC not work in this population or is more tx rqr’d? Results

38. Acupuncture Mechanism • Clement-Jones et al (1979) • Examined EOP levels in 5 grps of subjs • 6 heroin dep with mild withdrawal who rcv’d EA and gave bld and CSF • 6 heroin dep with severe withdrawal; No EA but gave bld • 7 hospitalized pts (unspecified conditions) –provided CSf • 25 healthy volunteers; gave blood • 18 hospitalized pts with non-endocrine dz; gave blood

39. Results • Heroin dep subj basal B-endorphin levels higher in both blood and CSF vs. non-addicted pts • Addicted subj’s bld and CSF B-endorphin levels not change significantly with EA • Basal met-enkephalin level of heroin addicted pts not differ from non-addicted • EA tx of heroin addicts led to rise in CSF met enkephalin level but no change in blood met-enkephalin levels

40. Acupuncture Mechanism • Wen et al 1978a • 8 heroin dependent females undergoing detox • 6 non-abusing controls • Measured blood levels of: ACTH, cortisol, c-AMP and urine aldosterone, catecholamines, VMA, cortisol, and cAMP

41. Design • Heroin abusing subjects received methadone decreasing over 10 day period (30 mg-10 mg) • On days 4-10 no additional medication given, but subj received EA 3x/day • Non-abusing controls received EA on days 4-10 3x/day

42. Results • Heroin addicted subjects showed significant reduction post EA in plasma cortisol, ACTH, c-AMP • Normal control subjects post EA showed decreased ACTH, cortisol • Previous research has shown that heroin abusing subjects in withdrawal normally have increased plasma cortisol-not decreased

43. Acupuncture Mechanism • Wen et al 1978b • Replicated study • N=40 heroin dep subjs/ N=31 non-dependant • Measured changes in cortisol, ACTH, c-AMP pre versus post EA • Found significant decrease in cortisol/ACTH levels post EA in heroin dep subj during detox • No changes were found in the non-dependent controls post EA

44. Acupuncture Mechanism: c-Fos • Purpose of the study to evaluate whether AC could affect the fxn’al alterations of the meso-limbic dopaminergic system involved in the nicotine –induced behavioral sensitization in rats and if AC would decrease the expected increase in nicotine-induced locomotor activity • 35 male rats randomly divided 8 days prior to procedure • Repeat nicotine grps were pre-tx’ed with nicotine 2x/day X 7 days and then were systemically challenged with nicotine on day 11 • Drugs were not injected on days 8-10

45. Protocol • The saline tx’d grp rcv’d saline for 7 days and was challenged with saline • The expt’al grp rcv’d acupuncture at St 36, HT 7, or LU 9 during the withdrawal period • The control grp did not rcv any tx other than a slight grab during the withdrawal • All groups were challenged with systemic nicotine at day 11

46. Behavioral analysis: rats given repeat nicotine showed increased beh response when given nicotine challenge compared to saline rats During the nicotine w/d period, AC at ST 36 , but not the other AC points attenuated the expected increase in nicotine induced locomotor activity to subsequent nicotine challenges Beh response to the nicotine challenge in the repeat nicotine grp was higher than in the acute nicotine grp(p>.01) Stimulation of ST 36 just before nicotine challenge, as well as during the 3 day w/d period, completely blocked the effects of nicotine on locomotor activity duringthe 60 minute test period versus control (p>.05) Results

47. Results • Fos-like immunoreactivity (FLI) measurement found the a massive amt of FLI was present in the nucleus accumbans and striatum of repeat nicotine tx-d grp vs. the acute nicotine tx’d grp • Repeat nicotine grp had sig’ly increase FLI in the shell of the NA but not in the core • AC at ST 36 significantly decreased FLI in the shell and the core compared to controls during subsequent nicotine challenge • Repeat nicotine significantly increased the FLI compared to acute nicotine tx in the DL and VM stiatum • AC at ST 36, HT 7, or LU 9 significantly decreased FLI compared to control in the VM but not DL striatum

48. Acupuncture & Nitric Oxide • NO is one of the most important messenger molecules and has been shown to function much like a neurotransmitter with widespread signaling and function • NO stimulates NE release from the central and peripheral nervous system which can increase sympathetic nervous system activity • NO in the gracile nucleus has been shown to mediate acupuncture signals through the dorsal medulla thalamic pathways in rats

49. NO and Acupuncture • Recent studies by Ma et al showed EA stimulation of ST 36 in rats induces an upregulation of neuronal NO synthase/ NADPH diaphorase expression in the gracile nucleus in the spinal chord • Further study by Ma 2003, showed that the skin underlying real acupuncture points has higher NO and nNOS expression than non-points when given EA in rats • However, EA-induced nNOS expressions may vary in different parts of the brain • Jang et al (2003) showed that nNOS expression was increased in the peri-aqueductal grey in rats with strepozotocin induced diabetes and that EA of ST 36 suppressed this DM enhancement of nNOS

50. Acupuncture for Tx MA Detox: NO Mechanisms • Purpose is to examine the effect of acupuncture on the symptoms of MA withdrawal and to evaluate any related NO changes • Primary hypothesis is that AC increases skin NO, serum nitrate, nitrite, NE during MA withdrawal • MA use depletes CNS neurons of dopamine, NE, and epinephrine thru hyperthermia and hyper-excitation • This depletion leads to characteristic MA withdrawal sx of irritability, apathy, difficulty sleeping, fatigue, and decreased mood. • Acupuncture, through raising NO and central nNOS, will increase NE and epinephrine, and correct for the deficit, yielding sx improvement