Is cocaine addiction a cure? Tester: Endure 3 minutes to get rid of a lifetime of pain

Release date: 2017-09-18

The sound during repetitive transcranial magnetic stimulation is large, and the electromagnetic force behind each pulse generates a squeak that can be heard by the human ear, but the subject does not have to worry because there is a good safety record, of course This does not mean that the treatment process is enjoyable and enjoyable. The pulse caused contraction of the scalp muscle under the coil, and approximately one-third of the subjects expressed pain.

Legend: Donald Baker receives brain circuit magnetic stimulation while watching cocaine images.

In 2012, in the central Italian city of Perugia, Luca Rossi in the bedroom was trying to hang himself. When Rossi, who was hanging on the belt for hanging, began to feel suffocated, his fiancee came in unexpectedly. At the last moment before death, Rossi was saved.

The 35-year-old doctor has all the reasons to live on his own: a medical career, a plan to build a family, and support for his parents. But Rossi was heavily addicted to cocaine, and he got into the habit shortly after he entered the medical school, when he confidently thought he could control himself. Since cocaine was dyed, Rossi was in a passionate and maddening mood. He no longer cried and no longer laughed. Although Rossi realized that his condition would endanger his patients, he could not make a change because he was indifferent to anything other than wanting to get the next cocaine. "This feeling makes people want to commit suicide, because you will feel endless emptiness," Rossi said. In the first few months of suicide, Rossi did not stop using cocaine, which cost $3,500 a month. At the beginning of 2013, Rossi learned that her fiancee was pregnant. Rossi's pressure has increased sharply. He is afraid of his willingness to get his father's identity, so he is more serious - he has not stopped, and can't stop.

Then, in April 2013, Rossi's father, a chemist, accidentally saw an article in the local newspaper introducing the latest research in Nature. A team of neuroscientists led by Antonillo Bunge and Chen Bie of the National Institute on Drug Abuse in Baltimore and Maryland studied mice that were forced to smoke cocaine. The researchers found that the animals were already addicted, and in order to get cocaine, they could endure repeated electric shocks to the feet! These mice have undergone genetic modification so their neurons can be controlled by light. When the researchers are stimulating the brain areas that are responsible for controlling the impulses, these mice will basically quit cocaine addiction. “They almost immediately stop looking for cocaine,” Bonge said.

Bonzi and co-authors of the paper indicated that directional stimulation of similar areas in the human brain (prefrontal cortex in the posterior frontal forehead) can help cocaine compulsive addicts. In the Italian newspaper article, Bonzi explained that transcranial magnetic stimulation (TMS), a non-invasive method of triggering neural activity, may work.

Rossi’s father began to ask for help frantically, and he found Luigi Garinbetti. Garin Betty is an outstanding Italian doctor who studies addiction and runs his own clinic in Pavado. Rossi and his father came to the clinic in Garin Betty, holding the newspaper in their hands. "My son is a drug addict. Can you help him?" Rossi's father pleaded.

Legend: Positioning frame; coil; magnetic field. "Magnetic drugs", electrical pulses generated in coils near the scalp induce changes in the magnetic field to produce electrical current in the cerebral cortex. Changing the frequency and pattern of magnetic pulses delivered to the cortex can modulate neuronal activity. Multiple stimulation strategies are being used to combat cocaine addiction. Cortex; 1 dorsolateral prefrontal cortex; 2 ventral median prefrontal cortex; midbrain; caudate nucleus; nucleus accumbens; (middle brain) ventral tegmental area.

Legend: “Ice” (execution control) loop. In a transcranial magnetic stimulus, the pulse is released many times per second and intermittently lasts for a few minutes. This intermittent stimulation of the dorsolateral prefrontal cortex can be transmitted to the midbrain to strengthen the "ice" (dark pink area on the right) circuit to eliminate the impulse of the drug.

"Fire" circuit (eager to get cocaine, very active). Intermittent stimulation applied to the anterior medial prefrontal cortex is thought to inhibit neurons in the "fire" (light pink) circuit that is connected to the nucleus and ventral tegment of the midbrain. When people are addicted to cocaine, they can make this area extremely active before being exposed to the white powder.

Since Rossi visited the Garinbeti clinic, transcranial magnetic stimulation has attracted the interest of a small group of researchers and doctors who use this technology to treat cocaine addiction, and of course there are doubters who express doubts. Galin Beati had an inspiring result after conducting a preliminary study of 32 cocaine patients. He began offering the therapy in the clinic, and he and his colleagues have now treated more than 300 addicts.

More rigorous testing is being carried out on the control of sputum impulses by transcranial magnetic stimulation. Last year, a research team led by neurobiologist Colleen Hanlon of the University of South Carolina Medical School in Charleston (the capital of West Virginia) launched the first randomized double-blind trial of this therapy. In May of this year, the National Institute of Psychiatry in Mexico City launched a second randomized double-blind trial. In Baltimore, researchers at the National Institute on Drug Abuse are conducting a preliminary study of cocaine addicts in preparation for a large controlled trial to be launched next year.

Transcranial magnetic stimulation is not a new medical tool that has been proven to treat depression. But in the treatment of drug addiction, scientists need to do more research. Although transcranial magnetic stimulation is effective in treating depression, no one knows exactly how to apply this technique to the brains of cocaine addicts, and different patients will respond differently to this therapy. "We still have a lot of things about transcranial magnetic stimulation, so we wouldn't be surprised if the current treatment trials didn't work," said doctor Michael Fox. Fox is a brain imaging specialist at Harvard Medical School (HMS) in Boston. He also uses transcranial magnetic stimulation to treat patients with depression. Fox has great confidence in the treatment of addiction with transcranial magnetic stimulation.

Hanlong and other researchers have confidence in transcranial magnetic stimulation. “In the past three to five years, basic scientific research on drug abuse has taught us that this therapy is very promising,” Hanlon said. About 1 million people in the United States are addicted to cocaine, and there are 13 million addicts in the world, so the demand for effective therapy is widespread and urgent. Common addictions are nicotine, alcohol, and the most significant and most influential heroin and synthetic opioids, so if this therapy only proves to be effective for cocaine addiction, then it will not be used by the US Food and Drug Administration. Approved. Although the regulations of the Food and Drug Administration are harsh, they also have their own considerations. Because many addiction symptoms will recur after the withdrawal without corresponding intervention, the one-year recurrence rate of people trying to quit smoking is around 80%!

"Imagine if transcranial magnetic stimulation became the first neurobiological therapy approved for cocaine addiction. This is a big deal, a game that changes the rules of the game," Bonge said. (After being approved by the National Institute on Drug Abuse, Bunge was able to form a financial partnership with Galin Betty during the trial period. They opened a clinic for the treatment of drug addiction in Milan, which is in line with the trial. )

Anthony Barker, a medical physicist at the University of Sheffield in the United Kingdom, introduced transcranial magnetic stimulation in 1985. This technique was used as a laboratory tool for exploring human neurophysiology. Buck placed an involuntary movement in his hands and legs by placing an electromagnetic induction coil above the sports cortex near the scalp, which then delivered a brief and intense pulsed current. They speculate that this time-varying magnetic field, which is generated by the coil current and acts on the outer layers of the cortex and brain, stimulates neuronal activity.

First, the researchers used transcranial magnetic stimulation to study how the motor cortex controls motion and then examine how the visual cortex of the blind works. In the 1990s, researchers began experimenting with Repetitve Transcranial Magnetic Stimulation (rTMS). They have some understanding of low-frequency stimuli. They use 1 pulse per second (1 Hz) to reduce neuron activity, while high-frequency pulses of 5 to 20 Hz make cells more active. They found that depressors responded to high-frequency repetitive transcranial magnetic stimulation, presumably because high-frequency pulses promoted the activity of dull neurons. In contrast, low-frequency transcranial magnetic stimulation seems to suppress the auditory hallucinations of schizophrenia.

The researchers also used repeated transcranial magnetic stimulation to test patients with obsessive-compulsive disorder, traumatic stress disorder, stroke, Parkinson's disease, epilepsy, tinnitus, and chronic pain. Since 2009, they have been testing other addictive behaviors (mainly nicotine and alcohol). Recently, due to concerns about opioids, many research groups, including Hanlong, have begun to evaluate the therapeutic effects of transcranial magnetic stimulation on such high-risk addicts.

In 2008, repetitive transcranial magnetic stimulation for refractory depression was approved in the United States, the only approved clinical application to date. Regulators in Europe, Canada and elsewhere have also approved the use of this technology in depression. But skeptics say support for the lack of data, they also believe that in the United States alone, more than 700 repetitive transcranial magnetic stimulation devices are the result of exaggerated efficacy of device manufacturers. "My distinguished colleagues, I think they are honest people, they will swear by the efficacy of these devices. And I will not," said Walter Brown, a psychiatrist at Brown University in the United States. Brown mainly studies the placebo effect, and he believes that most successful cases of repetitive transcranial magnetic stimulation for depression are placebos at work.

Brown also suspects that transcranial magnetic stimulation can counter drug abuse. “Some cocaine addicts who have been treated with transcranial magnetic stimulation will get better, and I have no doubt about it. But in my opinion, this is not the effect of the therapy itself.”

"A Song of Ice and Fire

One morning in May, in a windowless room in the National Institute of Drug Abuse, Baltimore, 45-year-old unemployed Donald Baker, who had a weather-beaten face and wore an open-collar shirt, was finishing a Computer questionnaire. “I am trying to get cocaine,” I gave a sample on the computer screen. The title options are “1” to “7”. The higher the number, the stronger the desire, and the “7” stands for strong agreement. Baker chose "4". "If I have cocaine in front of me, then I can hardly control myself." Baker chose "5" in another question about the amount of cocaine used. "I can't control how much cocaine I use."

Baker was the second person to participate in the preparatory trial, which was conducted by the postdoctoral student Vaughne Steele in the laboratory of Elliott Stein. Elliot is a neuroscientist at the National Institute on Drug Abuse. This preliminary trial was designed to evaluate repetitive transcranial magnetic stimulation therapy. “The addict will say? 'I want to get treatment, but what useful treatments are there now?', I hope that we can say that transcranial magnetic stimulation can be done soon,” Steele said.

Baker has just completed a two-day preliminary test. The first phase of the trial was to determine the safety and tolerability of the therapy for cocaine addicts, not to determine whether the therapy would reduce the patient's desire for drugs. In fact, this morning, Baker said to Steele: "I used cocaine when you were not in front of you." Baker's statement was also confirmed in the subsequent urine test. Despite this, Baker said that he has made some progress. During his repeated symptoms, he earned $150 for his uncle trimming the bushes, and now he still has $120 in his pocket. "I took $30 of cocaine, and then I asked myself what I did just now. I have some regrets. I have never had this kind of remorse for the past 25 years. Once I open it, I can't do it. But then I do Arrived."

During the 25-year drug abuse period, Baker lost a marriage, a house and many jobs. Baker has no car, no fixed job, and has not contacted his three grown-up children. Although Baker knew that the study was not intended to show efficacy, he still hoped that the therapy would help him quit his addiction. He met someone he wanted to marry. Of course, this is not the only reason he wants to get rid of addiction.

In a room in the hall, Baker sat in a large chair, and he placed his chin on a slinging device with a tight "hat" on his head. The researchers marked the target area on the Baker head. Not far from the hairline, the left side of the skull is the left frontal lateral prefrontal cortex, which is a key part of this brain area responsible for suppressing impulse stimuli, often referred to as the executive control network, for ease of understanding, we call it here "Ice" means that the activity of "suppressing impulse" is not enough. Because the left dorsolateral prefrontal cortex is extensively associated with deeper brain regions, imaging studies have shown that the deeper brain regions of those who are addicted to cocaine are not active. The researchers used a repetitive transcranial magnetic stimulus called "short-array fast pulse stimulation," which, when pulsed, was like a machine gun. This therapy takes 10 days, 3 times a day, 3 minutes each time.

"Through the pain of 3 minutes, you can get rid of the pain of your life."

- Test participant Donald Baker

The sound during repetitive transcranial magnetic stimulation is large, and the electromagnetic force behind each pulse generates a squeak that can be heard by the human ear, but the subject does not have to worry because there is a good safety record, of course This does not mean that the treatment process is enjoyable and enjoyable. The pulse caused contraction of the scalp muscle under the coil, and approximately one-third of the subjects expressed pain. "If someone pulls on the rubber band and then pulls you out, you definitely don't want him to do this," Stein said. "Your brain doesn't feel pain, but your scalp and skull will feel it." Transient scalp pain is the only common side effect, and half of the subjects have this feeling. During the course of treatment, there is very little convulsion in the subject.

If 10 subjects were able to endure treatment and there were no safety issues, the Steele team would conduct a double-blind, phase 2 trial of 60 cocaine addicts, and the team was particularly concerned about the seizures. Subjects will be randomly assigned to receive actual treatment or false treatment. In order to ensure that neither the subject nor the researcher knew who received the treatment, the trial determined that the coils used by the subjects looked the same, while replicating the sound and scalp sensation produced by the repetitive transcranial magnetic stimulation to the false treatment group. . Researchers will receive a random code before the trial to tell them which subjects to record. To test whether the therapy works for cocaine addicts, the team plans to use magnetic resonance imaging to detect whether repetitive transcranial magnetic stimulation enhances the activity of the control network region.

Baker’s 10-day treatment has now progressed to half. Betty Samoan, a doctor at the National Institute on Drug Abuse, is responsible for the treatment of Baker. Samo Wing put this coil "hat" on Baker's scalp, her eyes fixed on the display screen that tracks the position of the coil, and the red dot on the display that is related to the position of the coil is the target of the target, that is, the dorsolateral forehead Leaf area.

"Are you all ready?" Steele asked Baker. "Yes."

"It is now 10:02," Samo Rong said. "Start!"

In addition to the intermittent ticking, the room was silent. Baker's attention is focused on a screen that shows cocaine and pictures of a lot of cash. At the same time, the coil on Baker's head outputs 600 pulses in a 50 Hz mode - pause for 2 seconds and then continue for 10 seconds - this process takes about 3 minutes.

Baker's eyes squinted and shimmered, and his mouth turned into a tight purple line. Then the treatment is over. "Through the pain of 3 minutes, it is possible to get rid of the pain of a lifetime," Baker said.

Define parameters for effective repetitive transcranial magnetic stimulation—how many pulses, at what frequency, how long, and which area of ​​the brain to act—for research seeking to combat cocaine and other addictions For personnel, this is still a fundamental challenge. Most of the effort is directed at "ice", and the dorsolateral prefrontal lobe is a key part of the pulse control zone. But Hanlong, who had been trained at Stan, had a different thinking. Hanlon chose a different target before the South Carolina Medical University set up its own laboratory: the "fire" circuit - this area will launch an impulse about rewards and desires. Non-drug users become active in the brain when they see photos such as delicious food. But cocaine addicts appear to be too active in this area of ​​the brain when they see items related to cocaine or drugs themselves. Unlike intermittent pulse stimulation, Hanlong hopes to suppress the activity of the "fire" loop region through continuous stimulation.

In a study published in the September 1 issue of the journal Drug and Alcohol Dependence, the Hanlong team found 25 cocaine addicts in a circuit after repeated transcranial magnetic stimulation. Neuronal activity was significantly reduced at key locations. This treatment also seems to inhibit the activity of functionally relevant areas (areas about drug activation and stimulation), which can be very active if not inhibited, meaning that drug addicts are more susceptible to drugs or drugs. Related items are shaken.

Because Hanlong’s sister is fighting heroin addiction, she has a more intuitive and close-up experience of addiction. Hanlong admits that his team's research is preliminary. Her team studied theta burst stimulation (TBS) six times a day, and they thought it might take weeks of treatment to change the brain circuit. But with the support of the National Institute on Drug Abuse, in August last year Hanlong began recruiting volunteers who participated in a longer double-blind trial to test whether the therapy could reduce the activity of the brain's “fire” area. “We are optimistic,” said Hanlong. “I believe we can change the people who use cocaine.”

Eliminate the memory of cocaine "pleasure"

The word "optimistic" can no longer describe Garry Betty, because he is almost convinced of the efficacy. When Rossi and his father appeared in the clinic in Petitpa, Garin in 2013, he had treated patients who had been dependent on cocaine for 20 years. Garin Betty has tried psychotherapy, medication, and hospitalization to treat addicts, but unfortunately these treatments have had little effect. "Cocaine addiction is a brain circuit disease," Garin Betty said. "But none of the treatments we used before were correcting these circuits, so the results can be imagined."

Garin Betty tried to help Rossi through antidepressants, anti-anxiety drugs and psychotherapy. Because it had no effect, Rossi later chose to leave the clinic of Garin Betty, and he became more addicted to cocaine. After spending four months researching the article published in Nature, Garry Betty bought a transcranial magnetic stimulation device that he and his employees used to treat the device after learning how to use it. Two cocaine addicts. The Rossi, who was about to be his father, was swaying and ruining. At this time, Garin Betty contacted him and asked if he wanted to be the third person to receive transcranial magnetic stimulation.

Rossi vividly recalled his first use of repetitive transcranial magnetic stimulation after treatment. "It was a hot August. When I walked out of the clinic, I found the street, the pebbles so beautiful, everything is so beautiful. I feel like I have never used drugs in my life."

But Rossi's fiancée thought that repeated transcranial magnetic stimulation was a trick, and Rossi's fiancee was also a doctor who questioned Garin Betty and his employees. Later, Rossi's fiancée made it clear that she did not believe that the first treatment would help Rossi, so Rossi withdrew from Garin Betty's treatment program. However, after the withdrawal, Rossi relapsed. Two days after his daughter was born in late September 2013, he came to Padua again. Here, he participated in a six-month repetitive transcranial magnetic stimulation course. Rossi said that he has never used cocaine since then.

Galin Beatty and his colleague, psychologist Alberto Treneo, soon began to include patients in non-blind funding funded by several Italian organizations and the National Institutes of Health (NIH). Treatment research. As with Rosie, the clinic treated 16 cocaine addicts with high-frequency repetitive transcranial magnetic stimulation aimed at enhancing the activity of the “ice” circuit by stimulating the dorsolateral prefrontal cortex. The other 16 cocaine addicts in the control group will receive conventional medication. In the 29-day study, the desire to use cocaine was significantly lower in the treatment group receiving transcranial magnetic stimulation and significantly higher in those who passed the cocaine-free urine test than in the control group receiving conventional drug treatment. Researchers, including Bunge of the National Institute on Drug Abuse, reported the study in the December issue of the journal European Neuropsychopharmacology. (The cocaine addicts in the control group were later treated with repeated transcranial magnetic stimulation; the authors reported that the symptoms of the control group were also significantly improved.)

Garin Betty and Trinán do not feel the need to wait for larger and more rigorous tests, such as the National Drug Abuse Research Institute, which takes years to complete. When Garin Betty’s research was published, they had treated 220 cocaine addicts in their clinic in Padua – the 220 addicts are now “believers”. By July 31 this year, this number had reached 342. (On average, the clinic costs £100 per treatment, but the clinic says people who have no money to see a doctor can receive free treatment.) “Although we didn’t discuss the details before the paper was published, the results were encouraging,” said the Padova team. Said. For Trinault, the effect of repetitive transcranial magnetic stimulation on cocaine addicts is straightforward, as simple as a patient who has received treatment loses cocaine "pleasure."

Four years later, I finally had a complete repetitive transcranial magnetic stimulation treatment program. According to everyone, Rossi has not used cocaine until now. Although Rossi and his fiancée broke up in 2015, he said that he now has a happier relationship. His daughter is almost 4 years old. He and his daughter will go to the local park. He pretends to eat insects to tease his daughter. Happy laughing. Rossi is about to complete the internship training for comprehensive internal medicine, and he is also preparing to study angiology. Rossi said that he no longer wants to use cocaine, "because there are more important things in life."

In an interview in early August, Baker also said that he no longer uses cocaine. Baker spent a few days writing a proposal urging policymakers to take more steps to help the transitioning patient transition to an independent, normal life. Baker was still thinking about cocaine for some time. "But I didn't take action. I will think more about the consequences of the action than before." Perhaps Baker's "ice" circuit became active due to transcranial magnetic stimulation.

The National Drug Abuse Research team is ambitious for follow-up trials that may be launched next year, and they hope that the trial will produce more such promising results. "This story of transcranial magnetic stimulation shows that we have the opportunity to directly interfere with the brain circuit, which is quite exciting," Stein said. "The question is: Will transcranial magnetic stimulation be the last laugh?"

Note: Luca Rossi is a pseudonym.

Source: Netease Science

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