CN108578667A - A kind of drug that treating methamphetamine abstinence syndrome and its application - Google Patents

A kind of drug that treating methamphetamine abstinence syndrome and its application Download PDF

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CN108578667A
CN108578667A CN201810789100.5A CN201810789100A CN108578667A CN 108578667 A CN108578667 A CN 108578667A CN 201810789100 A CN201810789100 A CN 201810789100A CN 108578667 A CN108578667 A CN 108578667A
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methamphetamine
drug
treatment
radix
tuber
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邓华亮
张沁园
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Shandong University of Traditional Chinese Medicine
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Abstract

The invention discloses a kind of drugs for treating methamphetamine abstinence syndrome, are made of the bulk pharmaceutical chemicals of following component：30 40 g of radix bupleuri, 15 20 g of keel, 9 15 g of radix scutellariae, 6 12 g of ginger, 12 18g of corydalis tuber, 9 15 g of raddle, 12 18 g of Radix Codonopsis, 9 15 g of cassia twig, 9 15g of Poria cocos, 69 g of the tuber of pinellia, 6 12 g of rheum officinale, 12 21 g of oyster, 6 12 g of jujube.The preparation method and application of the drug are also disclosed, which can significantly improve the Negative Emotional and somatization that methamphetamine dependent gives up, and research will be to playing the multiple curative effect of classical prescription, and abundant and Developing TCM drug rehabilitation theory is of great significance with clinical practice.

Description

A kind of drug that treating methamphetamine abstinence syndrome and its application
Technical field
The invention belongs to drug fields, and in particular to a kind of drug that treating methamphetamine abstinence syndrome and its application.
Background technology
According to the United Nations's drugs and crime problem office《World's drug Use Report in 2016》It has been shown that, the east including China Sub-, south east asia is the main region of methamphetamine abuse, and only in 2009 ~ 2014 years, the methamphetamine of East Asia and south east asia is captured Quantity has almost been turned over twice, and methamphetamine abuse number and Area distribution start to occur gradually spreading in recent years it is widened become Gesture.Latest domestic data show that China was in new discovery drug addict 53.1 ten thousand in 2015, wherein the amphetamines such as abuse methamphetamine The personnel of drugs account for 73.2%.It is more than after heroin abuses group's ratio, in 2015 for the first time that methamphetamine, which abused group's ratio in 2014, Year further widens ratio gap, reflects that profound change occurs for Chinese drug abuse structure.
According to China《Criminal law》Regulation：Drugs refer to opium, heroin, crystal methamphetamine（Methamphetamine）, morphine, hemp, can Cacaine and other narcotics and psychotropic substances that can make one to form addiction of national regulation control.Crystal methamphetamine （Methamphetamine, MATM）It is the main component of methamphetamine, is a kind of central nervous system stimulant of potent, easy habituation Agent has higher lipophilicity, all can well be absorbed by body by different administration routes and be distributed in whole body, especially extensively It is general to be distributed in the tissues such as the higher blood-brain barrier of fat content.Studies have shown that using methamphetamine in short period, feelings can be promoted Thread, vigilance, energy level and concentration, if but long-term or single high dose using methamphetamine often lead to drug addict occur with depression, A series of mental health issues based on the Negative Emotionals such as anxiety.The Negative Emotionals such as these depression and anxiety not only influence drug addict Quality of life, while being also to lead to the one of the major reasons that addict received treatment relapses.
Harm in face of drugs to human health, clinically treatment methamphetamine gives up the negativity feelings such as retarded depression, anxiety at present The method of thread, being summed up mainly has antipsychotic treatment, behavior and psychotherapy, physiotherapy etc..In non-drug therapy, Clinically such as use cognitive-behavioral therapy, intelligence amic therapy method, aerobic exercise therapy, transcranial magnetic stimulation therapy, biofeedback therapy Treat methamphetamine dependent.In drug therapy, clinically Quetiapine, Olanzapine, chlorpromazine, Citalopram is such as used to treat methamphetamine The phrenoblabias such as caused depression and anxiety.Although above-mentioned therapy has a constant current modulation to phrenoblabias such as depression and anxiety caused by methamphetamine Effect, but said medicine belongs to the antipsychotics class drug such as antidepression, antianxiety, tranquilizing and allaying excitement more, also belongs to make one to form addiction Psychopathic Drugs, if patient take for a long time, equally patient can be promoted to form new pharmacological dependence to a certain extent, promote to suffer from Person takes medicine throughout one's life.It is treated compared to said medicine, non-drug therapy there are treatment cycles long, clinical slowly effect, and when curative effect continues Between it is short, it is more difficult to obtain patient approval.
With the profound change of China's drug abuse structure in recent years, novel drug methamphetamine abuse group ratio is passed year by year Increase, is also gradually enriched to the scientific research of methamphetamine about Chinese medicine.It makes a general survey of in recent years, treatment of the Chinese medicine to methamphetamine withrawal symptom It is mainly reflected in acupuncture and tuina-massage treatment and Chinese medicine prescription etc., and there is certain clinical efficacy, is clinically answered extensively With.Seminar is by the observational study to methamphetamine withrawal symptom, outlook on health and " few sun based on Chinese medicine traditional " body and the spirit one " The feelings will of the main catharsis of liver and gall " is theoretical, it is believed that for the main duty of methamphetamine abstinence syndrome in few positive liver and gall, heresy enters few sun, dysfunction of acting as a pivot, few fire It is interior strongly fragrant, thus when with harmonizing Sharyang, Xuan Chang important departments, tranquilizing the mind of purging heat is therapeutic rules.Meanwhile professor Zhang Qinyuan combines《The Treatise on Fevrile Diseases》 " analysing and differentiating of febrile disease in accordance with the theory of the six pair of channels " is theoretical, it is believed that many symptoms and its interpretation of the cause, onset and process of an illness in methamphetamine abstinence syndrome demonstrate,prove phase with Cyclic nucleotide Answer, it is believed that the classical prescription classical prescription Cyclic nucleotide of Zhong Jing can effective prevention methamphetamine abstinence syndrome, however the party is guarding against The modern clinical research in malicious field even blank.
Invention content
This research will be intervened methamphetamine with classical prescription Cyclic nucleotide and give up depression on the basis of project previous work The clinical observation on the therapeutic effect of mood is research target spot, inquires into its mechanism of action.This research will to play the multiple curative effect of classical prescription, enrich and Developing TCM drug rehabilitation theory is of great significance with clinical practice.In described below, Cyclic nucleotide is to treat The drug of methamphetamine abstinence syndrome.
The present invention provides a kind of drug for treating methamphetamine abstinence syndrome, which can significantly improve methamphetamine dependent ring Disconnected depressive emotion.
A kind of drug for treating methamphetamine abstinence syndrome, is made of the bulk pharmaceutical chemicals of following component：Radix bupleuri 30-40 g, keel 15-20 g, radix scutellariae 9-15 g, ginger 6-12 g, corydalis tuber 12-18g, raddle 9-15 g, Radix Codonopsis 12-18 g, cassia twig 9-15 g, Poria cocos 9- 15g, tuber of pinellia 6-9 g, rheum officinale 6-12 g, oyster 12-21 g, jujube 6-12 g.
Preferably, which is made of the bulk pharmaceutical chemicals of following component：Radix bupleuri 36g, keel 12g, radix scutellariae 12g, ginger 12g, Corydalis tuber 15g, raddle 12g, ginseng 15g, cassia twig 12g, Poria cocos 12g, tuber of pinellia 9g, rheum officinale 9g, oyster 18g, jujube 9g.
The preparation method of drug described above, includes the following steps：Each bulk pharmaceutical chemicals are mixed, water 1400ml is added, are heated It to 120 DEG C of temperature, decocts 40 minutes, filtration obtains liquid.
Taking dose：Decocting takes juice, one 400ml, one dose per day, each 200ml, warmly takes for 2 times point sooner or later.
The application of drug described above in improving methamphetamine dependent and giving up depressive emotion.
The drug can add the auxiliary material that can medically add and pill, tablet, powder, capsule, particle is made Agent, injection, microcapsules, syrup or oral solution.
Advantageous effect
For the main duty of methamphetamine abstinence syndrome in few positive liver and gall, heresy enters few sun, and dysfunction of acting as a pivot is strongly fragrant in fire less.Dysfunction of acting as a pivot, hepatic depression Knot can cause the activity of feelings will abnormal, common depressed emotion, depressed；Stagnation of liver qi is too, strongly fragrant in few fire, it is seen that edgy, Excited irritability etc..If strongly fragrant influence temper rises turbid with stomach Qi drop clearly in few fire, clear gas is caused to sink, stomach Qi upward reversal, it is seen that vomiting is disliked The heart, abdominal distension, diarrhea, the diseases such as indigestion and loss of appetite, gastral cavity is swollen, constipation.If strongly fragrant influence choleresis excretion in few fire, then, it is seen that apocleisis, abdominal distension, the side of body Pain etc..If Yu Jiu is high inverse in few fire, catharsis too, can cause bile superinverse, bitter taste occur, general to pour out one's grievances；Meanwhile if few fire Liver and gall of lying across and cause the absurd row of the state of mind free, then, it is seen that the diseases such as insomnia and dreamful sleep, nightmare somniloquy, sleep-walking or illusion；Or cause to lose one's mind, There are the diseases such as frenzied, irritated, uneasy sleeping at night.Therefore Cyclic nucleotide, with Xiao Chaihu Tang harmonizing Sharyang, Xuan Chang important departments make liver Gas bar adds keel, oyster, raddle transquilization with heavy material, adds cassia twig temperature yang transforming qi, Poria cocos is added to allay excitement and diuresis up to unobstructed, increases Huang Qing lets out inner heat, goes Radix Glycyrrhizae, in case its sweet slow stays heresy.All medicine phases are closed, and play and lack sun altogether, smooth important department, let out inner heat, tranquilizing the mind will it Work(.
By the evaluation to SDS, HAMD scale score and HAMD curative effects, result of study shows Cyclic nucleotide Methamphetamine dependent can be effectively improved and give up depressive emotion, and is significant in efficacy.By treating forward and backward intracerebral nerve to two groups of patients The evaluation that mediator measured value compares, result of study show to treat through Cyclic nucleotide, methamphetamine dependent's intracerebral neurotransmitter Tend to normal level, and in addition to neurotransmitter 5-HT, the recovery of GABA, Glu, Ach, NE, DA level is more obvious.Meanwhile Compared to methamphetamine dependent give up taking addictive drugs by force without any remedy measures, Cyclic nucleotide can more effectively improve god It is horizontal through mediator Ach, NE, DA, it is allowed to more tend to normal level.In conclusion Cyclic nucleotide can significantly change Kind methamphetamine dependent gives up depressive emotion, thus it is speculated that its mechanism of action can may effectively promote with Cyclic nucleotide methamphetamine according to Bad person, which gives up neurotransmitter GABA, Glu, Ach, 5-HT, NE, DA levels in hindbrain, tends to balance related, especially passs nerve The improvement of matter Ach, NE, DA level is more obvious.It is closely related because of reward system and above-mentioned intracerebral neurotransmitter, therefore speculate bavin Recklessly plus Os Draconis Concha Ostreae soup has certain improvement result to methamphetamine dependent's intracerebral reward system.
Specific implementation mode
The present embodiment is being implemented down based on the technical solution of the present invention, gives detailed embodiment and specific Operating process, but protection scope of the present invention is not limited to following embodiments.
Embodiment 1
Understanding and research overview of 1.1 western medicines to methamphetamine abstinence syndrome
1.1.1 understanding of the western medicine to methamphetamine habituation mechanism
Methamphetamine habituation is otherwise known as methamphetamine dependence, is a kind of brain function sexual dysfunction, and essence is body after Long Term Contact METH, Itself central nervous system is suitable in the compensatory that the different levels such as molecule, gene, cell, neural circuitry and brain structure occur It answers, which adapts to mostly related to the higher mentals nervous activity such as award, motivation, learning and memory.
Hypothesis at present about methamphetamine habituation mechanism is relatively more, and " award object substitutes theory " of wherein Gaetano is modern Researcher generally receives, and research field of quitting drug abuse mostly explains drug addiction mechanism with this theory." award object substitutes theory " is There is can be to natural reward object in finger central nervous system（Such as food, water, maternal behavior, sexual behaviour）Generate rewarding effect " reward system ".But when body contacts dependence producing drug, these drugs can replace natural reward object induction stimulation maincenter god Rewarding effect is generated through " reward system " in system, and body is made to generate psychological dependence to dependence producing drug." reward system " is main It is related to multiple brain areas such as Ventral Midbrain tegmental region, nucleus accumbens septi, ventral pallidum, corpus straitum.And it is related to including dopamine （Dopamine, DA）, norepinephrine（Norepinephrine, NE）, serotonin（5-hydroxytryptamine, 5-HT）, γ-aminobutyric acid（γ-aminobutyricacid, GABA）, glutamic acid（Glutamate, Glu）And acetyl courage Alkali（Acetylcholine, Ach）Etc. various neurotransmitters including systems.Above-mentioned nerve brain area and neurotransmitter are coordinated mutually Effect, to generate rewarding effect.Wherein most crucial is DA systems, and other systems also play a role to some extent.
1.1.1.1 the relationship of monoamine transmitters and methamphetamine habituation
Monoamine transmitters are mainly including DA, 5-HT, NE etc..Amphetamines is similar to monoamine transmitters structure, therefore phenylpropyl alcohol Amine drug can have an effect after entering neuron with DA transporters, 5-HT transporters and NE transporters, and synaptic vesicle is promoted to release Put monoamine transmitters.
1.1.1.1.1 dopamine
DA is a kind of critical small molecule neurotransmitter in award access, is primarily involved in a variety of including mood, behavior, memory etc. Adjusting including physiological function, and intracerebral reward system can be activated and make the main neurotransmitter of brain generation floaty euphoria.It grinds Study carefully and shows that its related brain areas such as DA and ventral pallidum, corpus straitum and methamphetamine habituation are closely connected.Wherein, middle limbic brain Dopamine system is the key that promote body methamphetamine habituation brain area.The Mesolimbic dopamine system for adjusting dopamine level is main Including interior ventral tegmental area DA projection neurons and its main target nucleus nucleus accumbens septi and prefrontal cortex.
Under normal physiological conditions, DA is stored in the presynaptic vesica of neuronal terminals, is discharged by presynaptic membrane prominent Gap is touched, its receptor is acted on and generates physiological effect, while can presynaptic membrane be taken in by DA transporters again again, make its concentration It is maintained at proper level, in case utilizing again.The release of DA maintains normal equilibrium state with reuptake, is to ensure that DA is participated in respectively Kind physiological activity and the important prerequisite for generating physiological effect.
There is research to think, since methamphetamine keeps smoker's generation additive by the release and intake of interfering DA.Methamphetamine habituation The level of person's intracerebral, presynaptic membrane DA and DA transporter declines.On the one hand, MATM is combined into the presynaptic with DA transporters Film promotes the release of DA, to improve nerve endings DA concentration.On the other hand, the MATM and monoamine for entering presynaptic membrane turn It transports body to combine, and by inhibiting DA reuptakes in synaptic cleft, and indirect activation DA receptors, and then activates in central nervous system " reward system ", generate rewarding effect, to generate psychic dependence.
1.1.1.1.2 serotonin
In addition to DA, 5-HT is also that MATM causes a kind of important neurotransmitter in neurotrosis and habituation forming process.Moreover, 5- HT systems and DA systems intersect in MATM habituation mechanism and respectively play a role, but it is still necessary into one for the interaction of the two Step confirms.
Studies have pointed out that mechanism of action of the 5-HT systems in drug habit may be with it to " the award of intracerebral nerve center The adjusting of system " DA releases is related.MATM promotes raw in 5-HT and release by the reuptake transporter independent mechanism of 5-HT, together When, a large amount of interior raw 5-HT can increase the synthesis and release of DA again.In addition, having foreign scholar the study found that METH can also be to 5- HT transporters, which generate, directly to be acted on, and causes 5-HT to accumulate in the cell, body is made to generate floaty euphoria and tingle, to promotion at The development of addiction.
1.1.1.1.3 norepinephrine
Norepinephrine is that adrenaline removes the substance formed after N- methyl, in chemical constitution with adrenaline （Adrenaline, Ad）, DA belong to catecholamine.
Research points out that the NE that MATM can increase synaptic cleft is horizontal, and speculates that MATM drug habits may be discharged with NE Mediate awakening, cardiovascular activation and stress reaction signal transduction related.In addition, oral MATM can result in peripheral blood The release of the Catecholamines Neurotransmitters in Blood such as methylepinephrine increases, and faces to cardiac muscle cell's hypoxic-ischemic, arrhythmia cordis etc. occur Bed symptom.
1.1.1.2 nervous transmitter
1.1.1.2.1 γ-aminobutyric acid
γ-aminobutyric acid is as the widest inhibitory aminoacid class mediator of distribution, Central nervous system in central nervous system The inhibiting effect of system is extensive and strong.Direct damage of the amphetamines to GABA serotonergic neurons, leads to DA neuronal activities Being suppressed property is adjusted.
More in recent years study thinks that the regulation and control of METH habituation are inseparable with the relationship of GABA neurotransmitter systems.Padgett Deng the study found that being triggered by cynapse on GABA neurons in Ventral Midbrain tegmental region after giving mouse METH mono- day GABABR-GIRK electric currents are substantially reduced, and the presynaptic inhibiting effect mediated by GABA neuron terminals GABABR is weakened.Thus Speculate that METH is altered by GABABR signal pathways, transmitted to increase in mesolimbic system GABA, participate in METH at The regulation and control of addiction.
1.1.1.2.2 glutamic acid
Glutamic acid（Glutamic acid, Glu）As the highest excitatory amino acid of intracerebral content, can promote excitant or Drug sensitization, craving and Induction of neuronal plasticity and sensitization, by with important work(that brain is participated in by Glu acceptor interactions It can adjust.
The study found that the increase of nucleus accumbens septi and prefrontal cortex DA releases, induces with METH and increases Ventral Midbrain tegmental region Glutamatergic neurons activity is closely related.Wooters etc. is studies have shown that block N-methyl-D-aspartate（N-methyl- D-aspartic acid, NMDA）Receptor can be such that METH interoceptor stimulus qualities are enhanced.Studies have shown that nmda receptor Antagonist can inhibit conditioned place preference, self administration behavior and the Motor stimulation effect of METH inductions and " mechanical " row For.
1.1.1.3 other neurotransmitters
The Ach of cholinergic neuron release is excitatory neurotransmitter important in nervous system, function mainly with maintain to anticipate Knowledge is awake closely related with ability of learning and memory, is one of the neurotransmitter for promoting body drug addiction.
Taguchi etc. the study found that after the emission levels of Ach can be taken in METH in corpus straitum the change of DA systems and be in Dependent change.Meanwhile METH can also cause Glu concentration in corpus straitum to increase, and further cholinergic neuron be promoted to discharge Ach, therefore speculate that Glu neurotransmitter systems have certain adjustment effect to Ach releases.
1.1.2 therapeutic profile of the western medicine to methamphetamine abstinence syndrome
1.1.2.1 non-drug therapy
1.1.2.1.1 psychotherapy
Cognitive-behavioral therapy, intelligence amic therapy method and biofeedback therapy belong to psychotherapy scope.As Wang Wei by methamphetamine at Addiction patient is randomly divided into test group and control group.Control group gives conventional Drug Abuse Resistance Education intervention, and test group is in conventional Drug Abuse Resistance Education On the basis of give cognitive-behavioral therapy intervention, intelligence amic therapy method treatment.Result of study shows cognitive-behavioral therapy, intelligence chemotherapy Method has certain clinical efficacy to improving the Negative Emotionals such as methamphetamine addict anxiety, depression, and can correct its re-addiction tendency, effectively Mitigate chronic craving situation of the methamphetamine addict to drugs.Palace uncut jade etc. the study found that methamphetamine addict in negativity such as anxiety, depressions It is more apparent in terms of mood.Methamphetamine addict's anxiety anxiety and angry hostility can be effectively relieved in biofeedback therapy, and The clinical value in terms of psychotherapy.
1.1.2.1.2 transcranial magnetic stimulation
Transcranial magnetic stimulation technical principle is according to electromagnetic induction principle, by frequency of stimulation difference and the undamped magnetic letter through skull Cerebral cortex number is acted on, cerebral cortex specific region electric current is changed, to play excited or inhibit target brain tissue region Effect.It is generally believed that high frequency（>1Hz）The effect of excited target brain tissue region, low frequency can be played（≤1Hz）It can then send out Wave the effect for inhibiting target brain tissue region.Studies have reported that claiming, rTMS can be effectively improved methamphetamine dependent patient anxiety symptom With drug craving situation, and clinical efficacy is notable.
1.1.2.1.3 aerobic exercise
The aerobic exercise of rule and body movement are one of the effective ways for promoting mental health, preventing or slowing down mental disease. Wang Dongshi etc. the study found that moderate strength aerobic exercise in 12 weeks it is suitable to enhancing MATM dependent's bodies can act on it is notable, and can be effective Methamphetamine dependent is reduced to MATM cravings degree and improves its depression and anxiety impairment property.
1.1.2.2 drug therapy
Currently, the treatment relied on for methamphetamine is mainly based on symptomatic treatment.It is therefore more difficult to fundamentally control the state of an illness, recur Rate is higher.But there is clinical research to show that the drug therapy craved for methamphetamine and recurred in recent years also achieves certain progress.
1.1.2.2.1 Quetiapine
Quetiapine is played anti-as a kind of second generation antipsychotics bys blocking II receptors of DA and 5-HT2A receptors etc. The effects that mental disease, calmness, antianxiety, antidepression, can be effectively improved mental disorders symptom.There are clinical research discovery, quinoline Sulphur is flat to can effectively improve methamphetamine caused by mental disorder, the two therapeutic equivalence with Risperidone.But reducing adverse drug reaction side Face, Quetiapine are substantially better than Risperidone.
1.1.2.2.2 Olanzapine, Risperidone
Olanzapine, with Risperidone as a kind of novel atypical antipsychotic, can by with d2 dopamine receptor and 5-HTA2 receptors in conjunction with and generate blocking effect and the effect of play antipsychotic.There are clinical research report, Zhou Yongbin research hairs Existing, Olanzapine can effectively treat methamphetamine caused by mental disorder, improve patient mental's disease symptoms, and clinical efficacy is notable.It grinds simultaneously Study carefully discovery, in terms for the treatment of methamphetamine caused by mental disorder, significant curative effect can be played by giving the oral Olanzapine of patient and Risperidone, And carry out therapeutic equivalence.But Risperidone is compared, the adverse reaction rate of Olanzapine is lower, and clinical application is safer.
1.1.2.2.3 chlorpromazine
Chlorpromazine has the symptoms such as restless, the nervous, illusion of excitement of control schizophrenia or other mental diseases, vain hope Preferable sedation effect can be effectively improved patient's positive symptom.Zhou Fangzhen etc. is the study found that in treatment methamphetamine caused by mental disorder The clinical efficacy of aspect, chlorpromazine is better than Risperidone, and the two adverse reaction is suitable.Meanwhile also having clinical research discovery, nitrogen difficult to understand It is flat suitable to psychotic disorders clinical efficacy caused by treatment methamphetamine with chlorpromazine, and Olanzapine is to improving anxiety-depression Clinical efficacy is substantially better than chlorpromazine.
1.1.2.2.4 Citalopram
Citalopram can block presynaptic membrane to the reuptake of 5-HT by selective depression 5-HT transporters, to extending and Increase the effect of 5-HT, generates antidepressant effect.It is low dose of new that Xu Tao etc. gives two groups of methamphetamine abuse caused by mental disorder patients It is treated based on type antipsychotics, and observation group adds use citalopram treatment on this basis.Result of study discovery, It treats caused by methamphetamine abuse in terms of depression and anxiety, takes Citalopram compared to individually taking New antipsychotics curative effect more Significantly, it is believed that Citalopram can be used as the active drug of depression and anxiety caused by treatment methamphetamine class.
1.1.2.2.5 combination therapy
Qin Chunli etc. is the study found that Olanzapine joint Trazodone treatment can effectively improve methamphetamine and cause patient with phychlogical problems's clinical condition Shape, and the two combination therapy does not increase adverse drug reaction.Text is defended the study found that Risperidone merging Paxil can significantly change The psychotic disease state and depression and anxiety mood of kind methamphetamine caused by mental disorder patient.Pass through netted Meta assays drug Treat the validity of methamphetamine caused by mental disorder, the results showed that, for the medicine of methamphetamine caused by mental disorder, answer preferred quinoline Sulphur is flat, secondly can select chlorpromazine, Olanzapine, Risperidone etc. successively.
Understanding and research overview of 1.2 traditional Chinese medicine to methamphetamine abstinence syndrome
1.2.1 understanding of the traditional Chinese medicine to drug addiction mechanism
From after opium is passed to China, all doctors deepen continuously to the drugs such as opium and its addicted understanding.According to statistics, China Modern age（1840 ~ 1949 years）Chinese medicine book up to 800 remaining parts about drug rehabilitation, wherein with《Rescue fan's good recipe》《It gives up smoking full method》《It picks out Addiction superficial remards》《Opiumism gives up method》《It gives up smoking happy remarkable book》Equal influences are the most extensive.
It is what big to answer Lin Zexu's smoking ban demand and write《Rescue fan's good recipe》（1833）, and " internal organs are proposed in book It is said by addiction ".Chen Gongmin, in conjunction with personal clinical experience, writes in the theoretical foundation of Lin Zexu《It gives up smoking full method》（1854）One Book, and " vital organs of the human body are by addiction " theory of pathogenesis is proposed in book, so that the cigarette poison habituation interpretation of the cause, onset and process of an illness is further improved development.Meanwhile Wang Yanchang exists《Wang Shi doctors deposit》（1875）Middle proposition " film original is said by addiction ", " qi-blood-body fluid is impaired to be said ", " phlegm accumulates cold-dampness internal injury Say " etc. Pathogenesis Theories.Du Zhongjun exists《Pick out addiction superficial remards》（1909）In for paregorism card propose that " qi-blood-body fluid impaired says " is sick Mechanism opinion.The all doctors of Republic focus more on the etiology and pathogenesis of all diseases after drug addict's detoxification, while to supporting after detoxification It is raw to have carried out correlative study with protection.In this theoretical foundation, later age doctor lets a hundred schools contend, and has preferably to drug addiction theory Succession and development.Gao Xuemin etc. think the interpretation of the cause, onset and process of an illness of opium drug habituation be mainly " qi-blood-body fluid impaired says " and " internal organs by Addiction is said ".Yang Chaoyang etc. thinks drug addiction disease position mainly in liver, kidney, and the cause of disease is mainly related with liver,kidney,spleen functional disturbance, characteristic of disease Simulataneous insufficiency and excessive.Song Yuehan etc. is from the differentiation of qi-blood-body fluid, it is believed that the pungent perfume of opium is dry strong, and easy consumption hinders vitality of human body, to cause Make visceral dysfunction, water-damp not being transformed is poly- and is " phlegm ", becomes the Etiological for leading to opioid addiction.
1.2.2 therapeutic profile of the traditional Chinese medicine to methamphetamine abstinence syndrome
According to the sorting technique of World Health Organization, methamphetamine belongs to central nervous excitation class drug, has to drug addict The psychic dependence of severe and slight physical dependence are reported, it is known that ice according to the previous work of this seminar and pertinent literature Malicious dependent Yi Dan stop suck methamphetamine after, a series of methamphetamine withdrawal symptoms will occur, mainly with depression and anxiety, The psychology such as irritability, irritability, the mental symptom of feelings will variation fluctuation greatly are the most prominent.It is many studies have shown that acupuncture treatment, massage are controlled It treats and is improved significantly with tcm therapies such as Chinese medicine treatments to alleviating the symptoms such as anxiety, depression.
1.2.2.1 acupuncture and tuina-massage is treated
Acupuncture and tuina-massage therapy belongs to external treatment with Chinese medicine therapy scope, is an important component of traditional Chinese medicine, in drug rehabilitation field Correlative study compared to Traditional chinese medicine medicament drug rehabilitation starting evening, found for the first time in the last century 70's.Henceforth, studies in China people Member has carried out a large amount of clinical research, especially Abstinence from Narcotin Drugs by Acupuncture therapy to acupuncture and tuina-massage drug rehabilitation therapy and has been widely used in drug rehabilitation neck Domain, development trend compared to massage treatment more extensively with deeply.
There is clinical research discovery, by " the terrible cave " of methamphetamine dependent or Baihui, interior pass, Shenmen, point st 36, or The ear acupuncture point is pierced into the hand-manipulating of needle, and discovery can be effectively improved the MATM withrawal symptom symptoms such as MATM dependents anxiety, depressive emotion.Meanwhile Also studies have found that, as treatment time extends, ear acupuncture more remarkable treatment effect is compared in acusector body cave.Chen Ling is the study found that needle thorn knot The depression and anxiety of MATM habituation patients can be significantly improved by closing psychological counseling treatment, and needle thorn combines psychological counseling treatment pair In the treatment of depression, it is more effective to dredge treatment compared to simple acceptable learning.Compared with Abstinence from Narcotin Drugs by Acupuncture, though Chinese traditional massage drug rehabilitation has It is of low cost, safe and reliable, without advantages such as new pharmacological dependences, but at present for traditional Chinese massage massage drug rehabilitation document report phase To less, 1 drug addiction person of Jin Huangding states pair carries out reflexotherapy massage therapy, finds the patient after treating three months not Drug addiction is broken out again.
1.2.2.2 Chinese medicine is treated
Although China is to the understanding and treatment long history of drug addiction, its research mainly to traditional drugs such as opium. Since methamphetamine is just gradual popular novel drug in recent years, therefore the Chinese medicine of novel drug methamphetamine treatment document is even lacked It is weary.
Nobleness etc. with Chai Hu Shu Gan San plus-minus with buspirone hydrochloride respectively to by amphetamine substance depilatory patient into Row treatment, as a result, it has been found that Chai Hu Shu Gan San plus-minus is notable to anxiety disorder clinical effectiveness caused by treatment amphetamine substance.Zhu Qian Secondary make Deng the study found that FUKANG PIAN can effectively improve male methamphetamine dependent withrawal symptom, depression and anxiety, and without apparent With.Meanwhile the influence with FUKANG PIAN joint antidepressant Paxil to methamphetamine dependent patient relapse rate such as common vetch carries out Research finds that drug combination has significant curative effect, and non-evident effect to reducing methamphetamine dependent patient relapse rate.
2 clinical researches
2.1 research object
2.1.1 case source
63 cases selected by this research derive from March, 2017 to during in August, 2017 Shandong Province quit drug abuse monitoring treatment institute, Middle areas in Shandong Province forced quarantine narcotic house of Shandong Province and woman's forced quarantine narcotic house of Shandong Province carry out isolation drug rehabilitation meet methamphetamine according to Rely the patient that depressive emotion diagnoses during person's acute withdrawal.
2.1.2 diagnostic criteria
With reference to the U.S.《Phrenoblabia diagnostic ＆ statistical manual the 5th edition》（DSM-V）Amphetamines addict's diagnostic criteria is quasi- It is fixed.Subject at least occurred within past 12 months following two symptoms then meet the diagnosis of methamphetamine addict in this research according to According to：
1. being difficult to usage time, frequency and dosage of the autonomous control to methamphetamine.
2. continuing the existing wish stopped or control methamphetamine uses, or has and repeatedly make great efforts and the experience of failure.
3. taking a substantial amount of time for obtaining, using and from restoring in the effect of methamphetamine.
4. to using methamphetamine to have strong craving, desire or impulsion.
5. cannot often fulfil the responsibility in work, school or family because using methamphetamine.
6. although often occurring because using methamphetamine or aggravating society or relationship problems, but still being continuing with.
7. important society, occupation or amusement behavior are abandoned or reduced because using methamphetamine.
8. although body or psychological problems that understanding often occurs are caused by using methamphetamine, but still being continuing with.
9. the dosage for increasing methamphetamine is needed to can be only achieved enjoyable or wish the effect reached；Or it is continuing with one The effect that the methamphetamine of amount generates is decreased obviously.
10. then there is the withrawal symptom of individual features when reducing or terminating the use to methamphetamine；Or it needs to use Methamphetamine is to mitigate or avoid the occurrence of withrawal symptom.
With reference to《Chinese Spirit Obstacles classification and diagnostic criteria the 3rd edition》（CCMD-3）Paralepsy diagnostic criteria is drafted.By Examination person is for 2 weeks above low for main feature with mental state, and at least occur following four symptoms then meet it is tested in this research The diagnosis basis of person's depression：
1. hebetude is felt without happiness.
2. decreased energy or tired sense.
3. psychomotor activity is sluggish or intense.
4. self-assessment is too low, self-accusation, or has feeling of guilt.
5. association's difficulty or conscious elaborative faculty decline.
6. occurring the thought wanted to die repeatedly or having suicide, autolesionism.
7. sleep disturbance, such as insomnia, early awakening or hypersomnia.
8. appetite reduces or weight is substantially reduced.
9. sexual hypoesthesia.
2.1.3 inclusion criteria
1. meeting above-mentioned diagnostic criteria and age person between 18 ~ 60 one full year of life.
2. detoxification treatment 7 days or more（It is detached from physiology During Detoxification）, urine examination crystal methamphetamine feminine gender.
3. before clinical test in 15 days, not taking any therapy and drug that may influence the judge of this therapy.
4. this research of patient's voluntary participation, and sign informed consent form.
5. having good compliance to the treatment of researcher.
2.1.4 exclusion criteria
1. not meeting above-mentioned inclusion criteria person.
2. there is previously or now serious hepatorenal damage or cardiovascular patient.
3. organic mental disorders or non-methamphetamine caused depressive emotion patient after giving up.
4. gestation or nursing period patient.
5. serious aphasia, mistake are known or can not the persons of communication.
6. there is similar medicine allergies patient.
6. participating in the patient of other clinical tests in nearly one month.
5. can not judge the not congruent person of affecting the treatment of curative effect or data by regulation medication.
2.1.5 standard is rejected
1. finding not meeting inclusion criteria and be not accidentally included in person after being included in, rejected.
2. being rejected after being included in because the patient of any treatment is not carried out in a variety of causes.
2. voluntarily taking other drugs person influential on this research to be rejected.
2.1.6 fall off standard
1. the person of automatically exiting from during clinical research.
2. serious adverse events or adverse reaction occur during clinical research, there is other serious complications or disease Feelings deterioration person and other persons that should not continue reception test.
3. because other a variety of causes fail to complete treatment and observer in strict accordance with research approach.
2.2 research method
2.2.1 it is grouped situation
According to patient assessment's sequencing, using random digits table, by 63 standard compliant methamphetamine dependent acute withdrawals Phase, depressive emotion patient was according to treatment group and control group 2:1 ratio is randomly assigned, and according to《Chinese drugs shape in 2016 Gesture is reported》It has been shown that, the existing drug abuse male to female ratio in China is about 6:1, therefore treatment group 42, wherein male 36, women 6； Control group 21, wherein male 18, women 3.
2.2.2 medicine
Prescription title：Cyclic nucleotide side.
Prescription forms：Radix bupleuri 36g, keel 12g, radix scutellariae 12g, ginger（It cuts）12g, corydalis tuber 15g, raddle 12g, ginseng 15g, cassia twig（Peeling）12g, Poria cocos 12g, the tuber of pinellia（It washes）9g, rheum officinale 9g, oyster（It endures）18g, jujube（Thumb）9g.Above-mentioned medicinal material is equal It purchases in medicinal material company of Shandong Province.
It is prepared by decoction：It is quit drug abuse by Shandong Province and monitors treatment institute（Eight or three hospitals are built in Shandong Province's life）It is prepared by department of traditional Chinese medicine decoction room.
2.2.3 therapeutic scheme
Treatment group：The treatment of patient Cyclic nucleotide side is given, daily 1 dose, decocting takes juice 400ml, each 200ml, point Sooner or later it warmly takes for 2 times, continuously takes 12 days.
Control group：Patient does not give any treatment.
Other antidepressants must not be used during two groups of treatments, and conventional drop blood can be given to diabetes, hypertensive patient Sugar and blood-pressure drug treatment.
2.2.4 observation index
2.2.4.1 instrument
ML-2001 type Encephalofluctuograph technology instrument, Beijing colleague photoelectricity technology corporation, Ltd.；
TR-09A/B types psychological assessment-portable machine, Beijing colleague photoelectricity technology corporation, Ltd..
2.2.4.2 neurotransmitter levels observation index
The measured value of intracerebral neurotransmitter Glu, GABA, 5-HT, Ach, NE, DA.
By analyzing the super slow fluctuation of different frequency brain wave, professor Mei Lei establishes brain wave S line spectrums in Correspondence in pivot nervous system between neurotransmitter GABA, Glu, Ach, DA, NE, 5-HT etc., and it is super slow to develop brain electricity Fluctuation map analysis instrument（Encephalofluctuogram technology, ET）.ET technologies are originally used for the brain of China astronaut Changes of function is analyzed, and is promoted by clinical research for many years, has been widely used in the phase caused by neurotransmitter motility disorder The research field of related disorders.
This research is analyzed by carrying out the super slow fluctuation of brain wave to subject, when the review time is the morning 9 ~ 11 or afternoon When 3 ~ 5.Patient affected by inspection is advised to keep awake, seat, close mesh, rest state when inspection, by international standard lead（10~20）System is pacified Electrode is set, selecting F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, T6, totally 14 electrodes retouched with reference to lead Note, with ears line（A1+A2）For reference electrode, forehead center（PF2）Ground protection.Entire detection process in screened room into Row is responsible for operation, unified inspection parameter when detection by fixed personnel：50Hz is not filtered, cutoff frequency 30Hz, time constant 0.1s records 1024s per 100 μ V of lattice.The brain electricity spectral line signal of acquisition, through analog-to-digital conversion（A/D）Encephalofluctuograph is applied afterwards The analyzing processing of analyzer program is simultaneously stored for post analysis.Instrument Automatic analysis and provide intracerebral neurotransmitter GABA, The normal value of Glu, Ach, DA, NE, 5-HT（Normal person's detected value that apparatus manufacturer provides）And measured value.
2.2.4.3 emotional state observation index
Depression self-rating scale（Seu-Rating Depression Scale, SDS）Integral；Hamilton depressive scale （Hamilton Depression Scale, HAMD）Integral.
The Depression Scale that SDS is worked out by W.K.Zung in nineteen sixty-five develops, and is to weigh testee's depressive state weight Degree and its over the course for the treatment of most common Self-assessment Scale of symptom situation of change.HAMD（24 versions）By Hamilton in Nineteen sixty is worked out, and is most common his evaluation table of depression when clinically evaluating depressive state, often by the work Jing Guo formal training Personnel are completed using talk and view mode inspection evaluation.
Psychological assessment is the specific purpose tool for measuring and assessing subject's mental health state, and mental measurement tool includes SDS, HAMD isodose chart are suitable for one, group mind and test and assess.The instrument is by a laptop, a signal receiver It is formed with a set of Digiplex.Psychological Evaluation uses wireless remote control information acquiring technology, subject's employing wireless remote controler to return Question and answer is inscribed, test result can immediate feedback, be efficient easily Psychological Evaluation tool.Subject per completes neurotransmitter levels After detection, this purpose and content for evaluating is introduced from the staff Jing Guo formal training to evaluation patient, in patient affected by inspection After obtaining informed consent, Psychological Evaluation work can be started.
2.2.5 efficacy assessment standard
Using psychological assessment-portable machine TR-09A/B（The old colleague photoelectricity technology corporation, Ltd. in Beijing）Middle HAMD（24 versions） Scoring, and efficacy evaluation is carried out according to its deduction rate standard that scores.
Recovery from illness：HAMD deductions rate >=75% after treatment, symptom disappear；
It is effective：HAMD deductions rate section 50% ~ 74% after treatment, symptom is obviously improved or disappears；
Effectively：HAMD deductions rate section 25% ~ 49% after treatment, partial symptoms improve；
In vain：HAMD deductions rate ＜ 25% after treatment, symptom are most of without improvement；
Total effective rate=（Recovery from illness+effective+effective number of cases）/ complete case load × 100%.
2.2.6 statistical procedures
It is handled and is analyzed using 5.0 statistical softwares of GraphPad Prism, test data measurement data is examined using t, meter Number data uses Chi-square Test, and all data are with mean ± standard deviation（`x±s）It indicates, indicates that difference has system with P ＜ 0.05 Meter learns meaning.
2.3 results of study and analysis
2.3.1 general information
Known by table 1：Control group average age 33.62 years old, 69.81 kilograms of average weight, 0.36 gram of daily drug abuse amount are taken drugs the time 67.952 months；Treatment group's average age 32.83 years old, 69.64 kilograms of average weight, 0.36 gram of daily drug abuse amount are taken drugs the time 79.64 months.The basic documents such as gender, age, the weight composition of two groups of patients compare, and difference is not statistically significant（P ＞ 0.05）, it is comparable between showing two groups.
1 two groups of general information of table compare（`x±s）
2.3.2 treatment results and analysis
2.3.2.1 pretherapy and post-treatment SDS, HAMD scale score of two groups of patients compares and analyzes
Known by table 2：Before treatment, two groups of SDS, HAMD scorings are compared, and difference is not statistically significant（P ＞ 0.05）.
Through treatment, two groups of SDS, HAMD scorings reduce before comparing treatment, and treatment group's SDS, HAMD scoring is compared to treatment It is preceding that there were significant differences（P ＜ 0.01）, and control group SDS, HAMD scoring are compared to no significant difference before treatment（P ＞ 0.05）.
Through treatment, treatment group's SDS, HAMD scoring is below control group, and wherein treatment group SDS scorings have bright compared to the control group Significant difference is different（P ＜ 0.05）, there were significant differences compared to the control group for HAMD scorings（P ＜ 0.01）.
Show that Cyclic nucleotide can significantly improve methamphetamine dependent and give up depressive emotion.
2 two groups of SDS, HAMD scale scores of table compare（`x ± s, point）
Note：Compared with before same group for the treatment of*P<0.05,**P<0.01；Compared with after control group treatment△P<0.05,△△P<0.01。
2.3.2.2 Clinical efficacy comparison and analysis after two groups of patient's treatments
Known by table 3：Control group is fully recovered 0, effective 1, effective 3, invalid 17, total effective rate 19.05%；Treatment group's recovery from illness 8 Example, effective 14, effective 10, invalid 10, total effective rate 76.19%.Treatment group's total effective rate has significantly compared to the control group Difference（P<0.01）.
Show that Cyclic nucleotide can be effectively improved methamphetamine dependent and give up depressive emotion, and significant in efficacy.
3 two groups of curative effects of table compare（Example）
Note：Compared with after control group treatment△P<0.05,△△P<0.01。
2.3.2.3 two groups of pretherapy and post-treatment brain neurotransmitter levels of patient compare and analyze
2.3.2.3.1 two groups of patients treat in forebrains neurotransmitter measured value comparison among groups and its compared with normal value and analyze
Known by table 4：Before treatment, comparison among groups are carried out to two groups of patient's intracerebral neurotransmitter measured values, difference is not statistically significant （P>0.05）.
Before treatment, two groups of patient's intracerebral neurotransmitter measured values are compared with normal value, two groups of patients GABA, Glu are surveyed Value is above normal value, and has notable difference（P<0.05）, and Ach, 5-HT, NE, DA measured value are below normal value, wherein 5- HT, control group A ch measured values have notable difference compared with normal value（P<0.05）, NE, DA, treatment group's Ach measured values and normal value phase Than there were significant differences（P<0.01）.
Show that methamphetamine can change intracerebral neurotransmitter levels, is embodied in GABA, Glu measured value and rises, Ach, 5-HT, NE, DA measured value decline, and the decline of NE, DA measured value level is more obvious.
2.3.2.3.2 two groups of patients, which treat, compares and is analyzed in forward and backward intracerebral neurotransmitter measured value group
Known by table 4：Through treatment, control group GABA, Glu measured value declines, and 5-HT, DA measured value increase, and four compared to difference before treatment It is not statistically significant（P>0.05）, and treat after Ach, NE measured value increase, compared to treatment before have notable difference（P< 0.05）.
Through treatment, treatment group's GABA, Glu measured value declines, and there were significant differences compared with pre-treatment（P<0.01）.Treatment Ach, 5-HT, NE, DA measured value rise afterwards, and wherein 5-HT measured values have notable difference compared with pre-treatment（P<0.05）, and Ach, There were significant differences compared with pre-treatment for NE, DA measured value（P<0.01）.
Show methamphetamine dependent during giving up taking addictive drugs by force, intracerebral neurotransmitter Ach, NE is compared without any remedy measures Variation is big before treatment, and there are the trend of self-recovery normal level, though other neurotransmitters change unobvious.Through radix bupleuri plus Os Draconis Concha Ostreae soup is treated, and methamphetamine dependent's intracerebral neurotransmitter tends to normal level, and in addition to neurotransmitter 5-HT, GABA, The recovery of Glu, Ach, NE, DA level is more obvious.
2.3.2.3.3 two groups of patients treat neurotransmitter measured value comparison among groups and analysis in hindbrain
Known by table 4：Through treatment, treatment group's GABA, Glu measured value is high compared to the control group, and 5-HT measured values are low compared to the control group, but difference It is not statistically significant（P>0.05）.Treatment group's Ach, NE, DA measured value is low compared to the control group, and has notable difference compared with the control group （P<0.05）.
Show compared to methamphetamine dependent give up taking addictive drugs by force without any remedy measures, Cyclic nucleotide can More effective neurotransmitter Ach, NE, DA of improving is horizontal, is allowed to more tend to normal level.
4 two groups of patient's intracerebral neurotransmitter comparision contents of table（`x ± s, mHz）
Note：Compared with normal value#P<0.05,##P<0.01；Compared with before same group for the treatment of*P<0.05,**P<0.01；It is controlled with control group Compare after treatment△P<0.05,△△P<0.01。
In conclusion Cyclic nucleotide, which can effectively improve methamphetamine dependent, gives up depressive emotion, and it is significant in efficacy.
3 discuss
Understanding of 3.1 traditional Chinese medicine to Cyclic nucleotide
3.1.1 the document of Cyclic nucleotide is traced to the source
Original text：Come from《The Treatise on Fevrile Diseases distinguishes that shaoyang disease arteries and veins is demonstrate,proved and controlled》107:" typhoid fever eight or nine days descends it, and fullness sensation in chest is tired frightened, and urine is not Profit, delirious speech, heavy feeling all over the body, can not the person of changing one's position, Cyclic nucleotide master it.”
Composition：" four liang of keel radix scutellariae gingers of radix bupleuri（It cuts）Red lead ginseng cassia twig（Peeling）Each two halves tuber of pinellia of Poria cocos Two close half（It washes）Two liang of mono- two halves of male Tochigi of rheum officinale（It endures）Six pieces of jujube（Thumb）.”
Usage：" upper 12 taste is boiled with eight liters of water and is taken four liters, interior rheum officinale, is cut such as chess piece, is more boiled one or two boiling, go dregs.Warmly take one It rises.”
Original text cures mainly typhoid fever eight or nine, misapplies laxative remedy, damages healthy tendency so that heat symptoms caused by an exopathgen are invaginated, and disease involving both the exterior and the interior is formed, deficient and excessive syndromes appearing together Deterioration of a case.Therefore the party can dissipate receipts and be used in combination, adopting both clearing heat method and tonification method, have harmonizing Sharyang, Xuan Chang important departments, expel the heat-evil the benefits of calming the nerves.
3.1.2 to the understanding of the Cyclic nucleotide interpretation of the cause, onset and process of an illness, prescription
Ancient physician illustrates the Cyclic nucleotide card interpretation of the cause, onset and process of an illness rich.Golden Cheng Wuji《Treatise on Febrile Disease with Notes》：" typhoid fever eight or nine Day, perverse trend has become heat, and when passing yang channel again, and lower void is hot in it not to be removed.Fullness sensation in chest and tired person, sun heat visitor is in the heart；It is frightened Person, the heart being averse to heat and god do not keep；Difficult urination person, interior deficiency body fluid are not all right；Delirious speech person, stomach energy；Heavy feeling all over the body can not change one's position Person, yang-energy expert do not seek in table in inner." bright Wang's machine《Medicine principle》：" the cold-evil's gas that cures the wound multiplies under heat it, its empty stomach.It is evil Multiply because in, so that fullness sensation in chest, is tired of frightened, difficult urination, body weight, delirious speech.Husband fullness sensation in chest person, heat symptoms caused by an exopathgen visitor is in the heart；Frightened person, is because in the heart The smoked bright mind of excess heat is without rather；Difficult urination, the heat body fluid that dries up are not all right；Delirious speech person, the bright accumulation of heat of sun；Body severe one, in yang-energy Row is without honor in outside." clear Ke Qin《The Treatise on Fevrile Diseases is noted》：" absurd lower rear heat evil inside fire attack, is tired of frightened delirious speech person, monarch is unknown, and gods Civil strike.Difficult urination person, fire is contained and water loses；Heavy feeling all over the body person, Yang Nei and it is cloudy anti-outer；It is difficult to the person of changing one's position, the pivot of few sun Machine is unfavorable.More yin depletions under this, it is different from the inverse yang depletion of fire." clear You Zaijing《Typhoid fever string of pearls collection》：" fullness sensation in chest after under typhoid fever ... Person, evil numbness is in upper；Difficult urination person, evil numbness is under；Tired frightened person, heresy are moved in the heart；Delirious speech person, heresy knot in stomach, this disease in inner person ；Heavy feeling all over the body, can not the person of changing one's position, tendon and vessel bone and flesh, and by its heresy, this disease in table person.It is patient up and down in husband's conjunction table, Must and negative and positive close and dissipate with to control." in conclusion all doctors think to be that taiyang superficies-syndrome misses described in Cyclic nucleotide side's disease more The case where lower mutagens, the zang-fu differentiation range involved are wider.
Ancient physician demonstrate,proves the interpretation of the cause, onset and process of an illness in conjunction with Cyclic nucleotide and illustrates the content of prescription also compared with horn of plenty.Jin Chengwu Oneself《Treatise on Febrile Disease with Notes》：" be tired of with removing fullness sensation in chest with bupleurum root decoction, add keel, oyster, red lead, astringing vital QI and it is relieving convulsion；Add Poria cocos with Promoting circulation of body fluid, diuresis；Increase it is yellow with by stomach energy, only delirious speech；Add cassia twig with row yang-energy Xie Shenchong.Mixed heresy, this is known more ." bright Wang's machine《Medicine principle》：" it is so that with cassia twig, ginger, row yang-energy is in outer；Ginseng, Poria cocos, jujube, it is big to mend gas in support, Do not make to multiply in perverse trend；The tuber of pinellia is to dissipate fullness sensation in chest；Radix bupleuri heat-clearing；Keel, oyster, red lead astringing vital QI is relieving convulsion；Real heat under rheum officinale and just Delirious speech." bright Fang Youzhi《The detailed analysis of treatise on febrile disease》：" therefore it is sweet light with ginseng poria, entering the heart, it is empty with benefit；The weight in Os Draconis Concha Ostreae red lead Puckery, it is frightened in the towns Lian Xinyi；Tuber of pinellia pungent-warm, to dissipate expiring for chest diaphragm；Radix bupleuri bitter cold, it is hot and suffocating tired to remove；Depletion of body fluid and difficult urination, Ginseng Siberian cocklebur is enough to moisten it；Dry and delirious speech in stomach, ginger jujube have to adjust；Completely in diaphragm, the tuber of pinellia opens it；Non- rheum officinale cannot be washed；Focus on one Body, ginseng grow it, and non-cassia twig cannot be with." clear Ke Qin《The Treatise on Fevrile Diseases is noted》：" this side takes bupleurum root decoction half, with remove fullness sensation in chest it is vexed it Half lining.Leading pellet, dragon, oyster, frightened with relieving palpitation, Poria cocos is with diuresis, and rheum officinale is to stop delirious speech.Cassia twig person, the mistake of Radix Glycyrrhizae.Body is without warm Without exterior syndrome, not handy cassia twig.Go Radix Glycyrrhizae then not at agent.Vexed delirious speech without the person that goes to ginseng, with frightened therefore." clear You Zaijing 《Typhoid fever string of pearls collection》：" side's radix bupleuri, cassia twig.Body weight is removed to solve outside it.Dragon, oyster, red lead.With town, it is interior and only tired frightened.Rheum officinale Stop delirious speech with easing stomach-QI.Poria cocos is to let out bladder diuresis.Ginseng, ginger, jujube.QI invigorating is supported battalion and is defended.Think the evil the dominator of QI of expeling.Such as It is the interior deficiency reality of table.General Ying Qu works as and mixed heresy.Ear is maybe solved to the greatest extent.”
3.1.3 in Cyclic nucleotide side red lead going or staying problem
One medicine of red lead in side is toxic product, and the successive dynasties make external application more, takes that person is few, and main component is lead orthoplumbate orally （Pb3O4）.Ancient medical book is documented red lead.《Tang materia medica》Cloud：" acrid flavour is slightly cold.Main cough is inverse, regurgitation, and frightened epilepsy is insane Disease, except heat, lower gas.Only small facility removes scorchingly hot navel contraction, metal-inflicted wound hemorrhage.”《Book on Chinese herbal medicine plays》" acrid flavour is slightly cold, toxic.It is main to spit against frightened Epilepsy, metal-inflicted wound dissipate blood.”《Sheng Nong's herbal classic is dredged》Cloud：" stasis eliminatings of putting on flesh controlled malignant sore swollen drug, and entered cream again to dismiss heat toxin this life Medicine, be surgery must with object.”《Compendium of Materia Medica》：" weight and property are heavy, and taste and salt, alum walk blood system.Phlegm can be fallen and go timid, therefore controlled frightened Epilepsy is demented, spits converse stomach outstanding service.”《The new compilation of materia medica》Cloud：" salty-cold, heavy, taste and salt, alum.It is interior to fall phlegm with relieving palpitation peace soul, disappear Product desinsection, controls frightened infantile malnutrition due to digestive disturbances or intestinalparasites malaria dysentery.External application is antipyretic, and detoxification analgesic, stasis eliminatings are put on flesh.The heavy the moon of nature and flavor, damages yang-energy.”《Changsha medicine solution》Cloud： " acrid flavour enters foot-shaoyang gallbladder, the liver channel of foot-Jueyin.Drop takes the photograph the state of mind, Zhenan County's palpitation with fear." modern study discovery, lead is polyaffinity poisonous substance, It may act on each system of whole body, major determinant nerve, hematopoiesis, digestion and cardiovascular system.Micro long period application, can also make At chronic lead poisoning.Therefore this side person of modern age clinical application or abandon red lead and do not have to, or with raddle, wherein《Book on Chinese herbal medicine plays》Think " it is raddle bitter, sweet, it trembles with fear, it is nontoxic.Except heat, frightened gas enter abdomen in the five internal organs blood vessels.”《Compendium of Materia Medica》Record raddle " bitter, cold, nothing Poison ", " main wind-heat sputum epilepsy ", " suppressing liver-wind, epilepsy of calming the frightened ".《Book on Chinese herbal medicine is looked for the truth》Record raddle " cool liver blood ", " purging the liver of pathogenic fire heat ".And It is studied and is reported according to relevant clinical, raddle is same as clinical efficacy of the red lead in Cyclic nucleotide side notable.Cause This, this research replaces red lead using raddle.
3.1.4 the clinical application at all times of Cyclic nucleotide
3.1.4.1 ancient physician is to Cyclic nucleotide clinical application
Classics side of the Cyclic nucleotide as sedative drugs prescriptions is the first choice side that later age doctor treats that emotional disorder becomes.Yin Qili Method is ingenious, applied widely, and ancient physician is for example insane card of Chinese medicine, manic psychosis, strongly fragrant mostly by we for treating various difficult miscellaneous diseases It demonstrate,proves, be insomnia, hysteria etc..
As Xu Ling tires exist《Classified prescritptions from "Treatise on Exogenous Febrile Diseases"》Described in " this can descend the frightened phlegm of liver and gall, control insane pain with it, must imitate.”《Meal It treats and controls miscellaneous words in English shop》Described in " this side's Yong Yu Guang Epilepsy disease and demented must imitate repeatedly.Current patient, the obstruction of the circulation of vital energy have with liver depression person ten Seven or eight.Liver depression person, be epilepsy disease gradually, married woman's liver depression Yu Epilepsy diseases are especially more.”《Experience is collected and compile》Described in " children's high fever day after day is controlled, it is real It is stagnant not go, fevers and chills alternate, palpitation with fear." Yoshimasu Todo exists《Square machine》Described in " syndrome of decoction XIAO CHAI HU and chest and abdomen have person, lose essence person, chest Full tired frightened person, Cyclic nucleotide master it.”《Xu Mingyi Lei》Described in " Zhang Yitian controls a people, between penta March in the third of the twelve Earthly Branches, hair Heat it is uncomfortable in chest does not eat, constipation, difficult urination, body weight sweat it is few, palpitaition and shy.Give evacuation digestants, disease does not subtract, more delirious speech It cries out.It is slow to examine its veins string, row diseases caused by external factors when being are worth the order in few sun department day, though few sun disease is few, machine is obvious.Stringy pulse with fever person, few sun is originally As.Not trencherman uncomfortable in chest, the inverse pivot in few sun point.Close pericardium in few sun three is burnt, puzzled then be tired of and shy, very then positive bright stomach Qi is not With and delirious speech.Few sun follows the side of body, dysfunction of acting as a pivot, then body weight and cannot change one's position.Three cokes are neglected one's duty, then difficult urination.Body fluid not under, Then constipation.This disease is preferably with typhoid fever example, and eight or nine, lower fullness sensation in chest was tired frightened, difficult urination, delirious speech, and heavy feeling all over the body can not change one's position Person, Cyclic nucleotide master it.If ruled it by law, takes consequence and be cured.”《Chinese paediatrics doctor mirror》Described in " children's early teens Between, it sleeps middle soldier and so starts up or rise or such as see that heresy is haunt and plague, popular name is in a trance, very has originator every night, Cyclic nucleotide to have very It tests.”
3.1.4.2 clinical application of the modern doctor to Cyclic nucleotide
Ancient physician mostly using Cyclic nucleotide as treatment emotional disorder become first choice side, and modern medicine then pushes away and it is wide It, is applied to multisystem disease by this side, such as the post-stroke depression of Mental disease, tumour, Parkinson, insomnia, insane Epilepsy etc.；Angina pectoris, arrhythmia cordis of circulation system disease etc.；Chronic gastritis, the Non-erosive stomach oesophagus of disease of digestive system are anti- Flow disease etc.；Amenorrhoea, menopausal syndrome of gynecologic tract disease etc.；Premature ejaculation of andrology's systemic disease etc. and other such as kneecap Arthritis, dependence facial dermatitis etc..
The interpretation of the cause, onset and process of an illness that Cyclic nucleotide card is grasped when it can be found that facing card, in conjunction with clinical concrete condition, in original side On the basis of, addition or subtraction of changes flexibly uses, and proper use of we can then play good therapeutic effect.
3.2 Cyclic nucleotides intervene the Mechanism Discussion that methamphetamine dependent gives up depressive emotion
Classification according to World Health Organization to drugs, methamphetamine belong to central nervous excitation class drug, have to drug addict There are the psychic dependence of severe and slight physical dependence.It is reported according to this seminar observational study early period and pertinent literature, Understand that methamphetamine dependent after stopping sucking methamphetamine, a series of methamphetamine withrawal symptom will occur, i.e. methamphetamine gives up synthesis Sign.Methamphetamine abstinence syndrome includes mainly the Breast bilges frowsty to vomit nausea, malaise, palpitaition of having palpitation, indigestion and loss of appetite, bitter taste in the mouth and dry throat, Pharynx such as object stalk, dysphagia, insomnia and dreamful sleep, nightmare somniloquy, the body class syndrome based on urine short number etc.；And with depression, Anxiety, being irritable and getting angry easily are apt to probably easily shy the mental syndrome based on waiting；And with red tongue with thin and yellowish fur, the sign based on wiry and frequent pulse etc..
Seminar is by the observational study to above-mentioned methamphetamine withrawal symptom, the health based on Chinese medicine traditional " body and the spirit one " It sees and the feelings will of " the main catharsis of few sun liver and gall " is theoretical, it is believed that the main duty of methamphetamine abstinence syndrome enters few sun, important department in few positive liver and gall, heresy It is unfavorable, it is strongly fragrant in few fire, thus when with harmonizing Sharyang, Xuan Chang important departments, tranquilizing the mind of purging heat is therapeutic rules.Meanwhile professor Zhang Qinyuan ties It closes《The Treatise on Fevrile Diseases》" analysing and differentiating of febrile disease in accordance with the theory of the six pair of channels " is theoretical, it is believed that many symptoms and its interpretation of the cause, onset and process of an illness in methamphetamine abstinence syndrome add keel male with radix bupleuri Oyster soup card is corresponding, it is believed that the classical prescription classical prescription Cyclic nucleotide of Zhong Jing being capable of effective prevention methamphetamine abstinence syndrome.
Therefore, this research, which with classical prescription Cyclic nucleotide intervenes methamphetamine and gives up the clinical observation on the therapeutic effect of depressive emotion, is Target spot is studied, the work for intervening Cyclic nucleotide methamphetamine abstinence syndrome from two angles of traditional Chinese medicine and modern medicine is tried Primary Study is carried out with mechanism.
3.2.1 traditional Chinese medicine Study of pathogenesis
For the main duty of methamphetamine abstinence syndrome in few positive liver and gall, heresy enters few sun, and dysfunction of acting as a pivot is strongly fragrant in fire less.Dysfunction of acting as a pivot, hepatic depression Knot can cause the activity of feelings will abnormal, common depressed emotion, depressed；Stagnation of liver qi is too, strongly fragrant in few fire, it is seen that edgy, Excited irritability etc..If strongly fragrant influence temper rises turbid with stomach Qi drop clearly in few fire, clear gas is caused to sink, stomach Qi upward reversal, it is seen that vomiting is disliked The heart, abdominal distension, diarrhea, the diseases such as indigestion and loss of appetite, gastral cavity is swollen, constipation.If strongly fragrant influence choleresis excretion in few fire, then, it is seen that apocleisis, abdominal distension, the side of body Pain etc..If Yu Jiu is high inverse in few fire, catharsis too, can cause bile superinverse, bitter taste occur, general to pour out one's grievances；Meanwhile if few fire Liver and gall of lying across and cause the absurd row of the state of mind free, then, it is seen that the diseases such as insomnia and dreamful sleep, nightmare somniloquy, sleep-walking or illusion；Or cause to lose one's mind, There are the diseases such as frenzied, irritated, uneasy sleeping at night.
Therefore Cyclic nucleotide is with Xiao Chaihu Tang harmonizing Sharyang, Xuan Chang important departments, makes irritability item up to unobstructed, add keel, Oyster, raddle are transquilization with heavy material, add cassia twig temperature yang transforming qi, Poria cocos is added to allay excitement and diuresis, increase Huang and let out inner heat clearly, go Radix Glycyrrhizae, In order to avoid its sweet slow stays heresy.All medicine phases are closed, and play and lack sun altogether, inner heat, the work(of tranquilizing the mind will are let out by smooth important department.
3.2.2 western medicine Mechanism Discussion
By the evaluation to SDS, HAMD scale score and HAMD curative effects, result of study shows that Cyclic nucleotide can It is effectively improved methamphetamine dependent and gives up depressive emotion, and is significant in efficacy.
By treating the evaluation that forward and backward intracerebral neurotransmitter measured value compares to two groups of patients, result of study shows through radix bupleuri Os Draconis Concha Ostreae soup is added to treat, methamphetamine dependent's intracerebral neurotransmitter tends to normal level, and in addition to neurotransmitter 5-HT, The recovery of GABA, Glu, Ach, NE, DA level is more obvious.Meanwhile it being carried out without any remedy measures compared to methamphetamine dependent Give up taking addictive drugs by force, it is horizontal that Cyclic nucleotide can more effectively improve neurotransmitter Ach, NE, DA, is allowed to more tend to just Ordinary water is flat.
In conclusion Cyclic nucleotide, which can significantly improve methamphetamine dependent, gives up depressive emotion, thus it is speculated that it is made With mechanism can may effectively promote with Cyclic nucleotide methamphetamine dependent give up neurotransmitter GABA, Glu in hindbrain, Ach, 5-HT, NE, DA level tend to balance it is related, it is especially more obvious to the improvement of neurotransmitter Ach, NE, DA level.Cause Reward system is closely related with above-mentioned intracerebral neurotransmitter, therefore speculates that Cyclic nucleotide encourages methamphetamine dependent's intracerebral Reward system has certain improvement result.
3.3 model case
June 26 2017 first visit time.Patient Zhang（Docket No.：xxx）, man, in May, 1972 birth（45 years old）, Han nationality, Shandong Zhang Dian people, weight 67Kg, divorce, primary school's educational level are had no property.Private prosecution starts to suck methamphetamine at the beginning of 2013, first to inhale Appetite about 0.1g sucks on June 2017 time 24 for the last time, the amount of sucking about 0.5g.It takes drugs 50 months time, it is average daily Drug abuse amount 0.3g.Physical examination:In a certain state of delirium, answer is slow, and the circle such as bilateral isocoria, sensitive to light reflection, heart and lung auscultation has no different Often, physiological reflex exists, and pathologic reflex is not drawn.It is indigestion and loss of appetite, evil of vomitting, loss of appetite, Breast bilges frowsty, insomnia and dreamful sleep, urine frequency, color Huang, stool are dry.Red tongue with thin and yellowish fur, wiry and frequent pulse.Spirit inspection：Talk is still cooperated, and depressed, eye contact is poor.While with Depressive symptom, show as depressed, being irritable and getting angry easily, be on tenterhooks etc..Bulesis slightly declines, and insight owes complete.In the presence of Phonism, the positive symptoms such as beziehungswahn, persecutory delusion.SDS scores 64 points, and HAMD scores 45 points.Laboratory examination:Methylbenzene third Aminuria inspection is positive, and hepatic and renal function is normal.Past medical history：Patient's the past listless medical history and brain organic disease history.There is self inflicted injury Behavior, double upper limbs have many places knife wound, cigarette butt scald scar.Deny suffering from other diseases.Deny allergies.Deny familial inheritance disease History.Enter to be diagnosed：Doctor trained in Western medicine is diagnosed as methamphetamine habituation（Moderate）, methamphetamine gives up caused depressive emotion；The Chinese medicine analysing and differentiating of febrile disease in accordance with the theory of the six pair of channels is few sun Radix bupleuri through illness adds imperial oyster soup to demonstrate,prove.The main duty of above-mentioned symptom is in few positive liver and gall, and heresy enters few sun, and dysfunction of acting as a pivot is strongly fragrant in fire less, when With harmonizing Sharyang, Xuan Chang important departments, tranquilizing the mind of purging heat is therapy.It controls with Cyclic nucleotide side, is decocted in water for oral dose, daily l agent divides early Evening warmly takes twice.June 27 started to take medicine, and continuously took the party 12 days.Through treatment, many symptoms of patient are changed after 12 days Kind, SDS scorings are 32 points, and HAMD scorings are 16 points.
Conclusion
The clinical observation on the therapeutic effect of depressive emotion is given up it can be found that bavin by intervening methamphetamine dependent to Cyclic nucleotide Recklessly plus Os Draconis Concha Ostreae soup energy effective prevention methamphetamine dependent gives up retarded depression mood, and mechanism of action may add keel male with radix bupleuri Oyster soup can effectively promote methamphetamine dependent give up neurotransmitter levels in hindbrain tend to balance it is related.Because of reward system and intracerebral god Through the closely related of mediator, therefore speculate that Cyclic nucleotide has certain improve to make methamphetamine dependent's intracerebral reward system With.
1 research and innovation point
1.1 Chinese medicine classical prescription new opplications
It is put forward for the first time to add and subtract with Chinese medicine classical prescription Cyclic nucleotide and intervenes methamphetamine dependent's acute withdrawal phase depressive emotion Thinking, and further investigated is carried out to its possible mechanism of action, to playing the multiple curative effect of classical prescription, enriches and Developing TCM is quit drug abuse Theory is of great significance with clinical practice.
1.2 brain ET detector Non-invasive detection intracerebral neurotransmitter levels
Method about detection intracerebral neurotransmitter levels has very much, but more belongs to and have traumatic detection means to subject, And tester is more demanding with auxiliary facility to detection environment, and detection reagent is at high price, the confidence level of testing result It cannot be guaranteed.And brain ET detectors used by this research can carry out intracerebral main neurotransmitter activity objective record, And brain fluctuation map detection is woundless testing, is not injured to patient, it is simple to operate.If by the detection of brain ET detectors As a result one of the objective indicator of depression diagnosis, treatment observation and efficacy determination is given up as non-organic methamphetamine dependent, then Accurately and reliably comprehensive analysis can be carried out to cerebral functional lateralitv.Detection methamphetamine dependent gives up intracerebral brain neurotransmitter activity change Situation, and diagnosis, the treatment of methamphetamine abstinence syndrome are inquired into from neuro-physiology basis emphatically, it will methamphetamine is given up The clinic of syndrome, theory, experimental study are more helpful.
Obviously, various changes and modifications can be made to the invention without departing from essence of the invention by those skilled in the art God and range.In this way, if these modifications and changes of the present invention belongs to the range of the claims in the present invention and its equivalent technologies Within, then the present invention is also intended to include these modifications and variations.

Claims (6)

1. a kind of drug for treating methamphetamine abstinence syndrome, which is characterized in that be made of the bulk pharmaceutical chemicals of following component：Radix bupleuri 30- 40 g, keel 15-20 g, radix scutellariae 9-15 g, ginger 6-12 g, corydalis tuber 12-18g, raddle 9-15 g, Radix Codonopsis 12-18 g, osmanthus Branch 9-15 g, Poria cocos 9- 15g, tuber of pinellia 6-9 g, rheum officinale 6-12 g, oyster 12-21 g, jujube 6-12 g.
2. drug according to claim 1, which is characterized in that be made of the bulk pharmaceutical chemicals of following component：Radix bupleuri 36g, keel 12g, radix scutellariae 12g, ginger 12g, corydalis tuber 15g, raddle 12g, ginseng 15g, cassia twig 12g, Poria cocos 12g, tuber of pinellia 9g, rheum officinale 9g, Oyster 18g, jujube 9g.
3. the preparation method of the drug described in a kind of one of claim 1-2, which is characterized in that include the following steps：By each original Expect medicine mixing, add water 1400ml, be heated to 120 DEG C of temperature, decoct 40 minutes, filtration obtains liquid.
4. according to the drug described in one of claim 1-2, which is characterized in that decocting takes juice, one 400ml, one dose per day, often Secondary 200ml, point warmly takes for 2 times sooner or later.
5. the drug described in a kind of one of claim 1-2 gives up the not moderate application of body and mind in improvement methamphetamine dependent.
6. application according to claim 5, which is characterized in that the drug can add the auxiliary material that can medically add Pill, tablet, powder, capsule, granule, injection, microcapsules, syrup or oral solution is made.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109876123A (en) * 2019-03-08 2019-06-14 山东中医药大学 A kind of drug for recuperating under medical treatment protracted abstinence symptom (psa) irregular menstruation
CN110559414A (en) * 2019-09-23 2019-12-13 北京高新医院有限公司 ice-removing powder

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106890223A (en) * 2017-03-24 2017-06-27 珠海康德瑞戒毒中药研发有限公司 A kind of Chinese medicinal composition for detoxification and preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106890223A (en) * 2017-03-24 2017-06-27 珠海康德瑞戒毒中药研发有限公司 A kind of Chinese medicinal composition for detoxification and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
中医缘的图书馆: "能治失眠的柴胡加龙骨牡蛎汤", 《HTTP://WWW.360DOC.COM/CONTENT/17/1031/13/164406_699702803.SHTML》 *
李巨奇等: "阿片类药物戒断综合征继发顽固性失眠六经辨证特色探讨", 《山西中医》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109876123A (en) * 2019-03-08 2019-06-14 山东中医药大学 A kind of drug for recuperating under medical treatment protracted abstinence symptom (psa) irregular menstruation
CN110559414A (en) * 2019-09-23 2019-12-13 北京高新医院有限公司 ice-removing powder

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