Summary: Cocaine use disorder (CUD) is quite common in the US, and yet it has received insufficient attention from researchers. There are very few drugs that can help manage CUD. New studies show that ketamine may help achieve CUD remission. A new study using AI went through 90 million EHRs and found that those who received ketamine as an anesthetic were more likely to achieve CUD remission than those who received other anesthetics or antidepressants.

Cocaine addiction and overdose are significant problems in the United States. Millions of individuals struggle with cocaine use disorder (CUD) each year. According to the National Survey on Drug Use and Health, approximately 2 million Americans aged 12 or older had used cocaine in the past month in 2020. Moreover, the number of cocaine overdose deaths in the United States has been increasing steadily over the past decade. In 2022, there were more than 32,000 overdose deaths involving cocaine or other psychostimulants. Over the last decade or so, the number of people living with CUD has increased significantly, and so have overdose-related deaths. Thus, an urgent need is to find an effective treatment for the condition.

Despite years of research, effective treatment options for CUD have remained elusive. The complex nature of cocaine addiction, which affects multiple neurotransmitter systems in the brain, and the lack of research funding for CUD are the main reasons behind the difficulty in developing effective treatments.

Cocaine is a highly addictive stimulant that affects the brain’s reward and motivation pathways. It works by increasing dopamine, norepinephrine, and serotonin levels in the brain, which leads to euphoria and heightened energy. However, the effects of cocaine are short-lived, and individuals who use cocaine frequently develop tolerance, which means they need ever-increasing doses to achieve the same effect. This can lead to dependence, withdrawal symptoms, and compulsive drug-seeking behavior, which are hallmarks of addiction.

Traditional therapies, such as cognitive-behavioral therapy and contingency management, have shown some success in treating CUD. Still, they are often not enough to prevent relapse in the long term. In addition, medications approved for the treatment of drug addiction and other substance use disorders, such as methadone and buprenorphine for opioid use disorder, have not been effective in treating CUD.

The lack of effective treatments for CUD is due in part to the complex nature of the disorder. Cocaine addiction involves changes in multiple neurotransmitter systems in the brain, which can alter reward and motivation pathways. Moreover, cocaine use can have both physical and psychological effects, making it difficult to address through a single approach. Another challenge is the lack of research funding for CUD. Compared to other substance use disorders like opioid addiction, CUD has received relatively little attention from researchers and policymakers. This lack of funding has made conducting large-scale clinical trials and developing new medications and therapies difficult.

However, emerging research suggests that ketamine may be a promising new approach for treating CUD. Ketamine is an anesthetic drug shown to have rapid antidepressant effects in low doses. In addition, studies have suggested that ketamine may also be effective in reducing cocaine cravings and preventing relapse in individuals with CUD. 

With every passing year, evidence is increasing in support of the use of ketamine for treating CUD. In one of the recent studies published in the journal Addiction, researchers used artificial intelligence to understand the role of ketamine in CUD.

Why use artificial intelligence? Well, AI has some distinct benefits, like it is better suited than humans for analyzing massive data sets. For example, researchers used AI in the study to analyze 90 million electronic health records (EHRs). And many of them were given various anesthetics.

In the study, AI found that patients who were given ketamine as an anesthetic and were living with CUD had much higher CUD remission rates compared to patients who were given other anesthetics. For example, the rate of CUD remission was four times higher than patients who received antidepressants or midazolam. Thus, the researchers concluded that ketamine has excellent potential for managing CUD.

Summary: Ketamine is an anesthetic and can also reduce pain sensation. However, its use to treat depression is new. Studies show that few ketamine infusions can provide prolonged relief from depression. However, some doctors have raised concerns regarding the risk of ketamine abuse. Fortunately, a new study in rodents shows that ketamine is not addictive. It does cause an increase in dopamine. However, any such upsurge is short-lived and thus does not appear enough to cause addiction.

Ketamine is an anesthetic, and it is also known to help with pain. However, its use in managing depression is new. There is significant interest in ketamine treatment for depression as the studies show that it may help provide prolonged relief, unlike traditional antidepressants.

However, conversely, it is no secret that ketamine is also a club drug, a substance of abuse. It causes euphoria at higher dosages. Therefore, doctors worry that its frequent use may put their patients at risk, and many might become addicted to it. 

But some experts think that though it is psychotropic, it does not appear addictive. After all, it has been available for a long time, and there are not many people addicted to ketamine. Now, a new study shows that though it may stimulate the reward pathway, it also affects some other brain pathways that help prevent ketamine abuse.

Addiction vs. Dependence

Before discussing the risk of addiction further, it is vital to understand that addiction and dependence are two different things. Addiction is when one seeks a substance despite its negative health consequences. Addiction is a kind of behavioral disorder. For instance, opioid addiction treatment is carried out when abuse of opioids begins to produce negative effects on the body.  

Dependence, on the other hand, causes withdrawal syndrome on discontinuation of the use of the substance. In addition, dependence often causes severe physical signs. Drugs that cause dependence may affect most people who use them regularly.

Although most people may become dependent on some substances after their prolonged use, the same is not true for addiction. Studies show that only some people become addicted. Moreover, addiction only affects a small number of people.

For example, studies show that only one-fifth of cocaine users are really addicted to it. And for opiates, this rate is about 30%. In a recent study, researchers tried to understand the risk of addiction to ketamine.

Ketamine has a short-lived impact on the reward pathway

Generally, people get addicted to substances as they increase the levels of the pleasure molecule dopamine. For example, cocaine can boost the brain’s dopamine level for a long time. However, after some time, it would start falling, and thus a person would seek the drug to increase dopamine level again.

In the new study, researchers used a special device that allowed mice to self-administer ketamine. They found that it increased dopamine levels in mice, so they repeated the self-administration. However, they found dopamine levels elevated due to ketamine also falling quite quickly, unlike many other drugs of abuse.

Ketamine also seems to have the effect that prevents reward pathway stimulation

Researchers wanted to know why, unlike other drugs of abuse, ketamine treatment for depression causes such a short-lived increase in dopamine levels. They found that ketamine increased dopamine by inhibiting NMDA receptors. However, it also modulated other receptors, called the D2 receptors, that act as a brake on the rapidly increasing dopamine. 

Hence, they found that it is this dual mechanism that helps prevent permanent changes in the brain, unlike other drugs. Therefore, ketamine does not cause long-term behavioral changes. The increase in dopamine levels is for such a short time that it is not enough to cause addiction. The researchers concluded that there is almost zero addiction risk of ketamine in rodents.

Of course, these are still early findings. Nonetheless, it provides the basis for further studies. There is a need to find out if this is also true for humans. Considering that quite often, what works in rodents also works in humans, it is likely that it does not cause addiction. Even if it does cause, any such effect is probably quite low.

Summary: PTSD is quite a common problem managed both with the help of medications and cognitive behavioral therapy. Among drugs, doctors mainly use antidepressants to treat the condition. Although most may benefit from treatment, it has a high relapse rate. To reduce treatment duration and prevent disease relapse, researchers need to understand the underlying mechanism of PTSD and find new medications. New studies show that modulating NMDA receptors may help erase traumatizing memories and help achieve spontaneous disease remission. Currently, using ketamine along with cognitive therapy is one way of doing so. In the new study, researchers tested the new molecule NYX-783 with great success.

An estimated 3.6% of US adults are living with PTSD. In addition, it is estimated that about 7% of adults would be affected by PTSD during their lifetime.

PTSD as a diagnosis is not old, and doctors first started using this term to describe mental health issues in Vietnam war veterans. Thus, doctors first defined PTSD in the 1970s. However, it does not mean that PTSD does not exist in olden times.

PTSD has always existed. It is caused by some traumatic experience. Some individuals find it hard to forget those experiences and report trauma symptoms like flashbacks, anxiety, and negative cognitive performance.

One of the issues with mental health disorders is that they are pretty difficult to treat. This is because the researcher still does not fully understand their pathogenesis (how the disease develops and underlying mechanisms). Moreover, modulating specific parts of the brain is even more challenging. Nonetheless, research is ongoing, and we can expect the introduction of safer and more effective therapies in the future.

At present, doctors use a range of drugs to manage post traumatic stress syndrome. They especially use antidepressants like selective serotonin reuptake inhibitors (SSRIs).

A combination of cognitive behavior therapy and drug therapy may help in spontaneous recovery

Along with drug therapy, doctors also use non-pharmacological means to manage the effects of PTSD. People living with PTSD are sane, and thus they can follow the instructions. Hence, cognitive behavior therapy may help desensitize individuals and help erase fearful memories.

Of course, non-pharmacological treatment is better in many ways. In many cases, it has a higher safety profile and may ensure prolonged disease remission or even complete cure. But, non-pharmacological & telehealth treatments like cognitive behavior therapy need much effort and time. Moreover, it fails to help in almost half of the cases. It means that its efficacy can be increased by combining it with some medications.

There are many ways of erasing these fearful memories faster, like using ketamine. However, researchers are looking for more effective and safer drugs.

Studies show that glutamatergic neurons play an important role in PTSD development. Further, studies suggest that the N-methyl-D-aspartate receptor (NMDAR) on these neurons helps control learning, memory, and synaptic plasticity. It means modulating these receptors could be a key to faster PTSD recovery.

Researchers tested a new molecule that may help erase traumatic stress & fearful memories and thus, treat PTSD

In the new study published in the journal Molecular Psychiatry, a team of researchers tested a new molecule called NYX-783 in a mice model. It means that this is still an early study or pre-clinical study. Nevertheless, they found that this particular compound could modulate NMDAR and thus can help modulate memories and early experiences.

The researchers carried out a test by exposing mice to severe and prolonged stress to induce PTSD-like conditions in them. Next, they started treatment procedures aimed at erasing those traumatic memories.

They tested the NYX-783 drug along with ketamine. The researchers found that injecting the new substance about an hour before starting fear extinction therapy could help quite well. The new drug was especially good at inducing spontaneous recovery. It also helped prevent treatment relapse, thus the return of PTSD.

The researchers further studied how this particular molecule works and found that it helps in multiple ways. First, it modulates NMDA receptors by action on the so-called GluN2B subunit. However, their drug activity diminished if they used the Grin2b knockdown model.

Researchers found that although this molecule helped erase traumatic memories, it was dependent on a brain-derived neurotrophic factor (BDNF) to work. Thus, the molecule was less effective in those with suppressed BDNF activity.

Summary: Chronic groin pain is a significant issue in those who have undergone surgery for an inguinal hernia. This often leads to patients blaming the mesh companies. It also causes prolonged distress and trauma to the patients. However, doctors often fail to treat such pains. Studies suggest that in many such instances, pain is due to some other underlying cause like low back pain or trauma, and only in small cases is it secondary to surgical intervention. Thus, doctors recommend careful history taking to identify the cause of this pain and suggest various treatments like Suboxone treatment. Additionally, experts also recommend exploring nontraditional treatments for chronic pain, like psychedelic-assisted psychotherapy.

 

In the annual meeting of the American Hernia Society, 2021, Doctor Brian P. Jacob discussed the significance of understanding chronic groin pain and finding its solution using innovative treatment methods.

 

Groin pain is a pretty common complaint among those living with inguinal hernia. Quite often, this hernia is treated using mesh repair. It is a relatively simple surgical procedure that provides instant relief in 70% of cases. However, experience shows that one-third of patients continue to experience pain. Quite often, they blame mesh for their continued pain, and doctors fail to understand the cause of such pain.

 

Dr. Jacob has multiple recommendations for surgeons and pain clinics for managing such pain. He also underlined the importance of understanding this pain. Since this continued pain after surgery is a source of significant distress. It makes patients quite angry, and they also go on blaming the mesh companies for their pain. Not only that, untreated patients undergo significant trauma, resulting in PTSD.

 

Surgeons must identify the cause of chronic pain

Dr. Jacob says that there are two sources of these chronic pain in those who had hernia surgery. The first and often overlooked cause of this chronic pain is some pre-existing condition in the patient, like a back issue or some other trauma. Unfortunately, doctors often fail to notice or identify these causes, and the patient continues to associate this pain with the surgery.

 

The second reason for such chronic pains is naturally the surgery itself, which means unintentional fault. Unfortunately, however, surgeons are often hesitant to accept that something has occurred due to the surgical procedure, and this negation only adds to the patient’s frustration.

 

There cannot be more frustrating for the patient than doctors failing to recognize the cause of pain. Thus, such patients have to tolerate this continuous chronic pain, and at the same time, they undergo severe emotional trauma. Worst in this situation is the fact that these patients largely remain untreated.

 

Thus, Dr. Jacob recommends that doctors accept that their patient is going through severe and chronic pain and focus on finding the solution. It is true that identifying the cause of such chronic pain is challenging. Nevertheless, they need to treat such patients. He particularly recommends focusing on alternative therapies

Alternative therapy for chronic groin pain

Dr. Jacob advocates exploring alternative treatments for chronic pain. This does not essentially mean supplements. It also means exploring uncommon approaches to pain management. The traditional way of pain management appears to mask the pain origins and provide temporary relief.

 

Unlike traditional painkillers or opioids, doctors must explore non-pharmacological therapies like meditation, mindfulness, yoga, pilates, and even psychotherapy. Dr. Jacob is also a proponent of psychedelic-assisted psychotherapy.

 

When it comes to psychedelic-assisted psychotherapy, this therapy mainly uses ketamine these days. Ketamine is proven to work, safe, and supported by many clinical studies. The results of ketamine-assisted psychotherapy are pretty promising.

 

However, Dr. Jacobs also favors exploring other ways of psychedelic-assisted psychotherapy. Among the other agents, psilocybin and MDMA are pretty promising. These medicines have excellent safety profiles and maybe even better than ketamine. Moreover, these therapies not only treat pain but also help overcome anxiety, depression, PTSD, and other severe mental health issues.

 

In short, Dr. Jacob strongly recommends taking a thorough history of patients with groin pains. The doctor should not assume that this pain is only due to an inguinal hernia. In many cases, other unidentified causes of groin pain remain undiagnosed. Additionally, in some cases, the cause of chronic pain could be a surgical procedure. In all these conditions, doctors must understand the patient’s pain and focus on treating chronic pain using various methods.