Turn off the "switch" of drug addiction

“How old are you starting to take medication (note: heroin)?”

"15 years old. Because of curiosity."

“When did you receive a DBS (brain deep electrical stimulation) clinical trial?”

"Year 2014."

"Do you want to take drugs after receiving the test?"

“I’ll think about it when I’m done, I don’t want it now.”

Nora D. Volkow from the United States is a doctor specializing in drug addiction research. In the face of her question, the 24-year-old Xi'an young man Xiaodong (a pseudonym) calmly described his exposure to the drug and the clinical trial of DBS.

Xiaodong looks strong and runs a landscaping company. In 2014, he accepted the DBS clinical trial at the Tangdu Hospital affiliated to the Fourth Military Medical University (now Tangdu Hospital affiliated to the Air Force Military Medical University, hereinafter referred to as Tangdu Hospital). He has not relapsed so far; he married in 2015 and is now Father of two children.

Drug addiction is a disease

Xiaodong is one of the 11 subjects that was first included in the clinical research of DBS drug rehabilitation technology by Professor Gao Guodong of Tangdu Hospital. At that time, Dr. Chen Lei of Tangdu Hospital was mainly responsible for the first 8 cases. Xiaodong was the subject of Chen Lei.

It is understood that many drug addicts, like Xiaodong, were initially exposed to drugs only because of curiosity. After several exposures, they gradually formed a “euphoria” after taking the drug; in order to pursue this “euphoria”, they repeatedly used drugs and eventually Addiction.

Drug abuse has led to many human tragedies. In order to detoxify, many addicts and their families have made great efforts, but still can not escape the clutch of drug addiction.

"Relapse after withdrawal is the most difficult problem in treatment, and it is also an international problem." According to Chen Lei, the treatment of drug addiction is divided into two stages according to its own characteristics: one is detoxification treatment, and the other is prevention. Suck. Existing treatment methods such as compulsory detoxification, drug replacement therapy, psychological behavior intervention, etc., can significantly reduce the physical dependence of addicts on drugs, that is, the effect of detoxification is significant, but they can not effectively reduce the psychological cravings of addicts for drugs, ie "Heart addiction" persists, resulting in a relapse rate of 97% within half a year of drug detoxification. Addicts often fall into a vicious circle of "drug abuse - detoxification - relapse".

Many people attribute the relapse of addicts to "bad habits", and even academics have regarded drug abuse as a bad habit. In fact, drug addiction is a disease. As early as 2000, McLellan and other scholars published an article entitled "Drug addiction is a chronic disease" on JAMA, suggesting that drug addiction is a chronic disease similar to type 2 diabetes, hypertension, and asthma. Since then, this view has gradually gained recognition from the academic community.

"The first drug abuse is a social problem, and after the addiction is a biomedical problem." Wang Xuelian, director of functional neurosurgery at Tangdu Hospital, said.

Drug addiction is actually a pathological change in the brain, and it is difficult to return to normal in a short time. According to clinical medicine, this addiction should be included in the scope of mental illness. With the change in the understanding of addiction, people began to reflect on whether the measures of drug treatment in the past were appropriate. In 2013, The Lancet magazine published an article entitled “The Deadly Burden of Overdose”, which evaluated the transformation of the US drug treatment policy: I believe that past punitive measures (compulsory detoxification, imprisonment) are ineffective for detoxification and addictive to drugs. It should be treated like other chronic diseases.

Find the pathogenesis of drug addiction

To control the addiction and remove the demons of drug abusers, we must first find out the pathogenesis and find a "switch" to control drug addiction. To this end, the team of Professor Gao Guodong of Tangdu Hospital cooperated with Suzhou Jingyi Medical Devices Co., Ltd. to carry out a series of cooperation research from basic research to industrialization research and development. Xiaodong is one of the subjects in this series of studies.

Chen Lei introduced that the physiological basis of “euphoria” after using drugs is the massive release of dopamine in the brain of drug users, which makes the body in a high dopamine potency state. Because the body has a regulating function, when the patient becomes addicted, a neurological adaptive change (called a change in neuroplasticity) will occur, resulting in an increased tolerance to drugs. To maintain the same level of euphoria as before, you need to increase the dose of drugs. At this time, the patient's own synthesis of dopamine is reduced, and the number of dopamine receptors that function in combination with dopamine is reduced, the function is decreased, the number of dopamine transporters that re-uptake dopamine back into the cells is reduced, the function is lowered, and the body is in a low dopamine potency state. When a drug user suddenly stops using drugs, the dopamine required to maintain the normal function of the body does not meet the demand, and an withdrawal reaction (physical dependence) occurs. Since then, the patient’s continued use of drugs has gradually shifted from “getting euphoria” to “avoiding the emergence of withdrawal response to physical discomfort” and compulsively and desperately want to acquire drugs in the event of drug addiction. Psychological dependence on drugs. That is, addiction is a process from "occasional drug abuse" to "habitual drug abuse" and finally to "forced drug abuse"--this is the research understanding of the addiction process in the scientific and medical circles in recent years.

Studies on the underlying mechanisms of drug addiction suggest that long-term effects of drugs on the brain can lead to “reward loops” in the midbrain-edge dopamine system and several dysfunctions of brain circuits associated with addiction, such as motivation, memory, and impulsivity. . Based on this, Professor Gao Guodong first proposed the Nucleus accumbens (NAc) in the midbrain-marginal-cortical system reward loop to treat opioid addiction in 2000. The 5-year follow-up results showed ethical rate. (no relapse rate) was 61.5%. The relevant research results were published in the foreign professional functional neurosurgery magazine "Stereotactic and Functional Neurosurgery". Later, many hospitals in China also carried out similar clinical services. However, due to the inaccurate indications and damage to the exact location and scope of the brain, many complications occurred and were stopped by the health department. The former Ministry of Health approved the team of Professor Gao Guodong to continue research on how to reduce the side effects of surgical detoxification and improve its efficacy.

In 2009, under the support of the National “Eleventh Five-Year” Science and Technology Support Program, Professor Gao Guodong led a nationwide multi-center retrospective follow-up study of patients who had been on the surgery for more than 5 years. The results showed that the ethics rate was 61.5%. The incidence of sexual complications (such as personality changes, memory loss, apathy, etc.) was 7%, mental health and quality of life were significantly improved compared with preoperative, and the long-term efficacy of nucleus accumbens detoxification was ideal.

As a result, the nucleus accumbens is locked into an addictive surgical intervention target. In July 2012, the Expert Committee of Functional Neurosurgery of the Chinese Medical Association's Neurosurgical Branch approved and passed the Consensus Expertise on Surgical Treatment of Drug Addiction, and concluded that surgical addiction treatment is one of the important means of anti-relapse, and it is safe and effective. Feasible; nucleus accumbens is an effective target for interventional anti-relapse surgery after withdrawal.

New therapy is expected to close the addiction "switch"

However, the brain core group destruction is a destructive and irreversible operation on the brain tissue, which may lead to permanent brain damage. How can it not damage the patient's nucleus accumbens structure and effectively prevent relapse?

DBS is a new technology developed in the 1980s, also known as brain pacemaker technology. "DBS has opened a new door for the treatment of many neurological and psychiatric diseases." Ning Yihua, chairman of Suzhou Jingyi Medical Devices Co., Ltd. said. Since its inception in 2009, the company has been working on the development of different types of cranial nervous system diseases with DBS and has been successful in treating Parkinson's disease. At present, tens of thousands of people worldwide receive DBS treatment every year, and their safety has been widely verified.

Professor Gao Guodong's team conducted a clinical study of DBS detoxification in 2009, and based on the results of the study, the multi-target joint stimulation based on the nucleus accumbens may bring better curative effect to addicted patients and more. Clinical benefit. Therefore, the combination of nucleus accumbens + internal capsule forefoot dual-target joint stimulation for DBS treatment drug addiction has emerged.

"Imagine the dual-target joint stimulation for the basis of DBS treatment drug addiction. First, addiction involves the abnormal function of the reward loop in the brain. The reward loop is to survive and multiply, for example, when people are very hungry When you get to the food you want to eat, you will feel very satisfied. When the drug is addicted, the drug abducts this loop. The nucleus accumbens is the core structure of the loop and can be regarded as important for information transmission (such as satisfaction). Nodes, at the same time, the nucleus accumbens and switches, the functions of the edge system (mainly responsible for emotions, ideas), the movement system (mainly responsible for the implementation of the exercise) interface, so the nucleus accumbens is the basis of DBS treatment addiction." The reporter explained.

Secondly, the forelimb of the internal capsule (ALIC, another important structure related to the treatment of addiction in the brain) is a classic target for surgical treatment of obsessive-compulsive disorder and depression. The real structure of the internal capsule is to connect the brain decision-making department (prefrontal lobe) and The white matter fiber bundle of the deep executive department (important nuclei) of the brain can be regarded as the wire that transmits information. These wires transmit information such as memory, impulsivity, and control related to addiction to the brain's decision-making department (prefrontal cortex), and transmit information that has been integrated and processed by the decision-making department to drive human actions. Intervention of the forelimb of the internal capsule, that is, the white matter fiber bundle, can interrupt the transmission of related morbid information (such as the strong and unstoppable urge to take drugs) when it is kidnapped in addiction, and has a coordinated effect on the treatment of addictive diseases. In addition, in the anatomical structure, the nucleus accumbens and the forelimbs of the internal capsule are "neighbors", and joint stimulation can be technically achieved.

However, how to technically achieve the joint stimulation of the nucleus accumbens and the forelimb of the internal capsule is another problem encountered by researchers. After learning about the situation, Ning Yihua, who has cooperated with Professor Gao Guodong, led his multidisciplinary and high-level research team to develop a new DBS system and dual-function zone joint stimulation electrode according to clinical needs. Different stimuli are used in different nucleus sites of the brain to achieve a combined stimulation of the nucleus accumbens and the bifunctional region of the forelimb of the internal capsule.

"Detoxification DBS is based on the integration of various addictive mechanisms in recent years, combined with the research results of the team of Professor Gao Guodong, who has a large sample and experienced clinical research on addiction surgery in China and even around the world. This is Our original technology is at the world's leading level." Ning Yihua introduced.

"In 2014, 8 patients underwent clinical trials of nucleus accumbens + internal forelimb combined with electrical stimulation for anti-relapse after heroin withdrawal. As of 2018, 5 of 8 patients had no relapse, 2 had relapse 1 case lost follow-up." Chen Lei published a paper in SCI in 2018 to discuss the results of this research. To date, 5 patients who have not relapsed have been maintained for 5 years.

Xiaodong is benefiting from this research.

"In the past, if you didn't smoke (heroin), you wanted to smoke all day; you didn't want to go after the test, and occasionally thought like a piece, and it quickly passed." Xiaodong told Nora D. Volkow.

China's research has drawn the attention of the world, especially the United States, which has suffered huge losses due to the abuse of opioids.

"Western countries have failed to promote clinical trials of DBS treatment drug addiction, and China is gradually becoming the center of this research." On May 8, the Associated Press reported that Shanghai Ruijin Hospital also used the nucleus accumbens + internal capsule forelimb joint Stimulate clinical research for detoxification. The report also said, "In February of this year, the US Food and Drug Administration (FDA) approved a clinical trial on DBS treatment of opioid addiction in West Virginia."

The multi-center DBS treatment of opioid withdrawal prevention and relapse in China has been initiated in 2018. It is led by Tangdu Hospital and China Institute of Drug Dependence, and is also in Tangdu Hospital, China Institute of Drug Dependence, Shanghai Transportation. University Ruijin Hospital, West China Hospital of Sichuan University, and Southern Hospital of Southern Medical University. The DBS equipment used by Suzhou Jingyi Medical for the treatment of opioid addiction has also been included in the special approval channel for innovative medical devices.

In the Associated Press report, Adrian Carter, head of the Neuroscience and Social Group at Monash University in Melbourne, said: "If you pull the switch (can detoxify), that would be great, but now At the stage, this may be a fantasy."

In China, this fantasy is becoming a reality. (Reporter Wang Zexuan)

Source: China Food and Drug Network

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