Summary: As opioid use for chronic pain becomes less common in the US, doctors are exploring alternatives. One of the latest studies shows that many physicians are switching to medical cannabis instead. Thus, the use of medical cannabis is increasing, and the use of opioids is decreasing.

There is no doubt that opioids are among the most potent painkillers known to science. That is why they are preferred for severe pain and also to manage chronic pain. Moreover, opioids are not just painkillers, as they help in multiple ways. This explains why they are so effective for chronic pain.

However, now, one of the new studies shows that many doctors might prefer medical cannabis over opioids. Due to ever-changing guidelines, doctors are now more hesitant to prescribe opioids.

In recent years, opioid prescriptions have declined in the US. Opioid prescription guidelines have become more stringent due to safety concerns.

Surely, companies that produce opioids are also working to improve the safety of opioids. There is little chance that doctors will stop using opioids anytime soon. Opioid manufacturers are trying to develop drugs that have better safety profiles and opioids less likely to cause addiction and other health issues.

However, till then, it appears that doctors are actively looking for safer and yet effective options. Hence, many are increasingly prescribing medical cannabis. Although medical cannabis is not as potent for pain relief as opioids, but it might be quite good for certain chronic pain conditions due to its numerous effects, like the ability to reduce stress and modulate other brain pathways.

So, for this study, researchers analyzed data on direct payments from opioid manufacturers to physicians. In the study, they found that such payments are decreasing. Manufacturers of opioids make these payments to doctors to improve the professional skills of physicians and to ensure better prescribing practices. However, now, due to declining prescriptions, such payments have become less common.

Researchers say that this is also because doctors are increasingly viewing medical cannabis as a substitute for opioids for chronic pain treatment. Moreover, doctors are pretty excited about medical cannabis, and they think that, in some instances, it may be even superior to opioids.

Of course, when it comes to medical cannabis, things are still evolving. For several decades, cannabis remained classified as a controlled substance, which prevented research into its health benefits. However, now cannabis and its products are being increasingly used.

Sure, there are many different kinds of cannabis products, from very mild CBD-based products available without prescription to medical cannabis prescribed by doctors.

CBD is now a very popular topic, as health experts realize that cannabis extract has many cannabinoids with different modes of action. Moreover, these cannabinoids may even have opposing actions.

Thus, there are cannabinoids like cannabidiol or CBD with relaxing effects, and then there is THC known to cause intoxication. Although THC may cause intoxication, but it is also more potent for certain medical conditions, and for severe pain, and other health issues. Thus, medical cannabis contains full-spectrum cannabis extract that is high in CBD, THC, and other minor cannabinoids.

Medical cannabis cannot be compared to CBD products solely online since it has a much higher concentration of cannabinoids like CBD, THC, and other cannabinoids. This makes medical cannabis much more potent, but it also means that there are also safety concerns regarding its prolonged use.

To sum up, medical cannabis is slowly emerging as one of the potent treatments for chronic pain. Doctors are now increasingly viewing it as a substitute for opioids.

Source:

Karmakar, B., Mukherjee, G., & Kar, W. (n.d.). Using Penalized Synthetic Controls on Truncated Data: A Case Study on Effect of Marijuana Legalization on Direct Payments to Physicians by Opioid Manufacturers. Journal of the American Statistical Association, 0(0), 1–16. https://doi.org/10.1080/01621459.2024.2406583

Summary: One of the latest studies shows that consuming alcohol, even in small amounts, makes people more tolerant of pain, making them less empathetic to others and more aggressive. Thus, aggression associated with alcohol intake is due to reduced pain sensitivity.

Alcohol is a mind-altering substance and is widely consumed in various parts of the world. If consumed responsibly, it is quite safe. However, alcohol addiction is not rare. Thus, for example, studies report that about 29 million adults are living with alcohol use disorder (AUD) in the US.

High alcohol intake is associated with many harms. It damages the liver, kidneys, brain cells, and more. It also causes a deficiency of certain nutrients. It significantly increases malnutrition risk.

A significant area of concern is that alcohol alters the short-term and long-term behavior of those who consume it frequently. Thus, for example, those who are intoxicated are more likely to behave aggressively. Most of those living with AUD show aggressive behavior. Now, one of the latest studies shows that this issue is due to a reduced pain threshold.

It has been long known that alcohol may reduce pain sensation, but what is new in this study are findings that alcohol may have a long-term impact on pain threshold. This reduced pain sensation makes those living with AUD less empathetic, and they are more likely to be insensitive to others and behave aggressively.

Alcohol inhibits brain neurons. So, at higher dosages, it alters sensations, including pain sensations. In the olden days, alcohol was used as an anesthetic. However, it is no longer used as an anesthetic due to a very narrow safety window.

It is vital to realize that most alcohol benefits are at very small dosages. However, at higher dosages, it is mostly harmful. Alcohol overdose is also life-threatening. Alcohol causes both acute and chronic adverse effects. Thus, for example, acute intoxication may alter a person’s ability to make decisions and have a negative impact on motor function. However, in the long run, chronic alcohol consumption may even alter the working of the brain.

 

Thus, for example, the present study was done on individuals who were not essentially living with AUD. These were people who consumed alcohol casually, drinking 3-4 alcoholic beverages a month. Even these individuals showed changes in the working of their brains.

These were the results of two independent studies with 543 and 327 participants. In both studies, participants were divided into two groups, with one group given an alcoholic drink and another placebo that resembled alcoholic drinks due to their low alcohol content. Then, both groups were exposed to painful stimuli. Researchers found that alcohol-drinking groups were more resilient to pain or less sensitive. Moreover, alcohol also made individuals more aggressive, and they were more ready to tolerate pain.

So, researchers say that this also makes such individuals who drink alcohol insensitive to the pains of others. On the other hand, those who do not consume alcohol can feel greater pain, and they would not like to inflict pain on others.

Here, it is essential to note that those who participated in the study had blood alcohol levels between 0.095% and 0.11%. This is marginally above the legal limit in most states, which is 0.08%. So, this shows that even small amounts of alcohol can suppress pain sensations and make individuals more aggressive.

Thus, it is also logical to conclude that this effect would be even more pronounced in those who drink alcohol heavily and frequently. Therefore, those living with AUD become more aggressive towards others in the long run. For those struggling with alcohol addiction and its consequences, online alcohol addiction treatment offers a promising solution for recovery and long-term health.

Source:
DeWall, C. N., Giancola, P. R., & Bushman, B. J. (2024). Too Insensitive to Care: Alcohol Increases Human Aggression by Increasing Pain Threshold. Journal of Studies on Alcohol and Drugs, jsad.24-00144. https://doi.org/10.15288/jsad.24-00144

Summary: Many patients experiencing severe pain are not administered opioids even when other medications fail to help. One of the new studies shows that when opioids are administered in an emergency care setting to opioid naïve patients, it does not pose an addiction risk.

Not every kind of opioid use poses an addiction risk. This is especially important to understand, as an increasing number of voices are being raised to reduce opioid use in clinical practice. However, reducing opioid use or discontinuing opioids in all clinical scenarios may do more harm than good.

Opioids are among the most potent pain relievers. They are exceptionally good for managing moderate to severe pain. Opioids are equally suitable for managing acute and chronic pain.

Unlike in chronic health issues, when opioids are used for managing acute pain, they are less likely to cause addiction or even other harm. This is because, when they are used to manage acute pain, their use is not prolonged.

For example, opioids may provide excellent relief to a person with a broken leg or arm or in other kinds of traumas. These drugs are really good for use in emergency medicine. Moreover, in emergency medicine, these drugs are injected under medical supervision, and thus, they rarely cause any severe side effects.

However, in the last few years, opioid use in various clinical scenarios has declined. This is because many believe that even short-term use of opioids may cause addiction and other harms. However, one of the new studies shows that these concerns are ill-founded. The use of opioids in emergency rooms is unlikely to cause addiction.

 

This new study was published in The Journal of Emergency Medicine. In the study, researchers screened 1555 patients. In the final study, 506 patients were included. These were patients who were administered opioids in the emergency room. Some of the commonly used opioids were hydromorphone and morphine.

In the study, researchers followed these patients for 6 months after their last visit to the emergency department or opioid use. They found that at 6 months, just one of those patients was persistently using opioids. Hence, it would be right to say that the risk of addiction to opioids when they are used in an emergency room is close to 0% or nil.

Here, it is also worth noticing that these were opioid naïve patients. It means that they had no prior experience of opioid use. They received their first opioid injection in an emergency care setting. This study confirms that when opioids are administered in such settings, they do not pose any risk of addiction.

Moreover, researchers further noticed that after treatment in the emergency room, 63 of the patients were even given opioid prescriptions on discharge. However, all of them discontinued opioid use after their recovery,  and only one of the patients continued opioid use at 6 months. This highlights that Opioid Addiction treatment is rarely needed when opioids are used responsibly in emergency settings, as the risk of addiction is minimal.

Researchers say that one should still use opioids with extreme care and only when there are strong clinical indications, like severe pain uncontrolled by other painkillers like acetaminophen. However, they also say that their study shows that when opioids are used carefully, they are safe, helpful, and do not cause addiction.

There is some sound data that many patients are being refused parental opioids, even when they are experiencing severe pain, a pain that other drugs could not control, which means that excessive precaution or worries regarding the side effects of opioids are causing more harm than good.

Of course, this is not the first study in this direction. Previous studies have also shown that the chances of opioid addiction are really low when they are used in emergency settings and in patients.

Source:

Irizarry, E., Cho, R., Williams, A., Davitt, M., Baer, J., Campbell, C., Cortijo-Brown, A., & Friedman, B. W. (2024). Frequency of Persistent Opioid Use 6 Months After Exposure to IV Opioids in the Emergency Department: A Prospective Cohort Study. The Journal of Emergency Medicine, 67(2), e119–e127. https://doi.org/10.1016/j.jemermed.2024.03.018

Summary: New reports show that opioids are in short supply, and things are unlikely to improve. DEA has been cutting down production quotas, and manufacturers have also been hesitant to produce these drugs due to rising litigation costs.

The US has been going through an era of drug shortages for quite some time. This problem has been especially acute during the last few years. However, as the COVID-19 problems eased, so did the drug supply. But, this did not change things for patients living with chronic pain, as the shortage of opioids persists. Thus, drugs like oxycodone, hydrocodone, and many other painkillers or opioids are in tight supply.

Surely, the latest report by the American Society of Health-System Pharmacists (ASHP) shows that things are improving, and thus, drug shortages have declined from a peak of 323 to 277. However, as one can see, there is still not much improvement.

These shortages are affecting many essential medications, and not just opioids or painkillers. Thus, there is a significant shortage of various IV fluids, dialysis fluids, or sterile fluids. Such acute is this shortage that the American College of Emergency Physicians is asking specialists to use tap water for cleaning wounds instead of sterile irrigation fluid.

There are some other worrisome facts. Despite the information, it appears that not enough is being done. Thus, for example, industry stakeholders have not been able to explain the reason for the deficit of many drugs. However, they do say that it is due to multiple reasons like increased demand, manufacturing problems, raw material shortages, and business decisions.

When it comes to opioids, surely, regulatory changes are among the significant reasons. DEA production quota is insufficient to meet the requirements of opioids, leading to rationing of these drugs. Therefore, surveys show that 90% of patients have difficulty getting their opioid prescriptions filled by the pharmacy.

In fact, some of the drugs, like Transmucosal Immediate-Release Fentanyl Medicines (TIRF), have been discontinued by the manufacturer. This drug is used in a small number of patients to manage severe pain in cancer patients, and those patients have now been left without any options.

Although manufacturers are not saying why they have discontinued producing certain opioids, industry experts think that it is not difficult to understand. Many of the manufacturers have been experiencing losses and legal issues, so they decided to discontinue producing certain opioids.

As per ASHP, oxycodone, hydrocodone, hydromorphone, fentanyl patches and solutions, and morphine solutions are some of the opioids that are in short supply. These are some of the most potent painkillers and widely used opioids, and their short supply means that a significant number of patients have to seek other options.

 

Some industry experts warn that things are unlikely to get better since, in 2025, the DEA would further reduce the quota for producing opioids. If the quota is implemented, it will only make things worse.

These shortages are not only making it difficult to manage severe and chronic pain but also causing other health issues. Thus, many patients are experiencing higher levels of anxiety, and they have to struggle a lot to get their prescriptions filled.

Doctors are already raising the alarm, and some of them have written to the regulatory agencies that any cut down in the production of opioids will cause significant harm to their patients. In fact, these shortages are also causing stress and burnout in physicians, as they feel helpless and unable to help their patients. Doctors say it is regretful to see that patients must call 10-20 pharmacies and often travel hundreds of miles to get their medications.

Further, if those living with chronic pain do not get these medications, they are more likely to consider other ways to manage their pain, which may include using illicit drugs, which may further make things worse. This creates an added concern for doctors specialising in opioid addiction treatment, as it may lead to a rise in illicit drug use and related complications.

 

Summarize: One of the new studies analyzed gene expression in brain cells of those living with Alzheimer’s and alcohol use disorder (AUD), and they found many similarities. Thus, this study suggests that AUD may increase Alzheimer’s risk and also fasten its progression.

It would be right to say that alcohol is the most widely consumed legal, mind-altering substance in the US. Sure, caffeine is also classified as a mind-altering substance, but it does not cause euphoria or intoxication like alcohol does. Alcohol consumption also causes behavior changes.

When consumed responsibly, alcohol is safe, but at higher dosages, it is harmful. There have been many studies regarding the use of alcohol. Studies show that about 10% of US adults consume alcohol in dosages greater than recommended, or about 29 million adults in the US are living with alcohol use disorder (AUD). Those are massive numbers.

Similarly, Alzheimer’s is also one of the most common diseases. It is among the top 5 leading causes of mortality in the US. At any given time, more than 7 million adults are living with Alzheimer’s in the US.

So, it would be right to explore the association between AUD and Alzheimer’s. Moreover, it is no secret that people drink alcohol because it modulates brain activity. This also means that not all alcohol use-related modulations in brain physiology are good. At higher dosages, alcohol may damage brain cells and alter brain chemistry. Chronic alcohol use, like that by people living with AUD, may result in some irreversible brain changes.

Now, one of the new studies shows that AUD may accelerate Alzheimer’s progression in some individuals living with specific kinds of genes. The study found that many of those living with AUD or Alzheimer’s have similar types of gene expression patterns in the brain.

The findings of this study were published in the journal eNeuro. Researchers say that they found that those living with Alzheimer’s have similar kinds of genes and pathways dysregulated as those living with AUD. This suggests a link between the ailments, and it also suggests that chronic alcohol use or abuse may fasten Alzheimer’s progress. For individuals looking to address alcohol use issues, exploring alcohol addiction treatment online may provide accessible and effective options.

What makes this research different is that it did not focus on DNA but rather on RNA and, thus, on the gene expression within the brain cells. So, they wanted to understand if there are similarities between the gene expression in those living with AUD and Alzheimer’s.

This study built on one of the previous studies showing that there are certain similarities in gene expression of those living with AUD and Alzheimer’s. So, for this study, researchers analyzed RNA sequences of hundreds of thousands of brain cells from 75 patients living with different Alzheimer’s stages and also compared the results with brain cells of 10 individuals without Alzheimer’s.

They found that gene expression was far more similar between those living with AUD and Alzheimer’s compared to healthy adults (not living with Alzheimer’s or abusing alcohol).

Researchers say that this deepens our understanding of Alzheimer’s. This study shows that alcohol must be included in the Alzheimer’s risk factors.

Of course, there is still a need for more extensive studies in this direction. Nonetheless, this study brings some new insights. Moreover, it shows how analyzing a single cell may help better understand certain complex diseases like Alzheimer’s. For those struggling with AUD, options such as alcohol addiction treatment online can make help more accessible, potentially mitigating these risks early.

Source:

Joshi, A., Giorgi, F. M., & Sanna, P. P. (2024). Transcriptional Patterns in Stages of Alzheimer’s Disease Are Cell-Type–Specific and Partially Converge with the Effects of Alcohol Use Disorder in Humans. eNeuro, 11(10). https://doi.org/10.1523/ENEURO.0118-24.2024

Summary: One of the most extensive studies to date shows that methadone has much lower dropout rates when used to treat opioid use disorder than buprenorphine, making it a better choice. Moreover, both methadone and buprenorphine are equally safe in real-world conditions.

When treating opioid use disorder (OUD), dropout rates remain a significant issue. A new study done in British Columbia shows that dropout rates with methadone are 37-40 lower than those with buprenorphine.

The new study was published in the JAMA Network, and it was one of the most extensive studies to date that analyzed more than 30,000 patients treated for opioid use disorder between January 1, 2010, and March 17, 2020.

Despite the best efforts, OUD remains a significant issue in the US. Although in recent years, opioid prescriptions have declined, OUD cases have not declined as expected. This is due to the widespread use of opioids for chronic pain. Further, many people continue to use illicit opioids for their pain.

However, as the awareness about the health risks of OUD increases, much has changed. In the US, now it is easier to get certain prescription drugs for OUD, and some of them even through telemedicine, thus helping enhance treatment accessibility and helping overcome the social stigma associated with the condition.

At present, there are three options for managing OUD that is methadone, buprenorphine, and naltrexone. Among them, methadone and buprenorphine are the most commonly prescribed drugs for OUD. Despite their widespread use, some knowledge gaps remain, like which one is better for initiating therapy and which of these two most popular drugs is associated with lower treatment discontinuation rates.

Methadone works amazingly well since it is also an opioid but a much safer opioid. Thus, it is excellent for overcoming withdrawal symptoms. However, methadone can only be dispensed by federally registered Opioid Treatment Programs (OTPs), which is its significant downside.

 

On the other hand, buprenorphine is less stringently controlled. Commonly called “bupe,” it also helps reduce carving and is a partial opioid. Since December 2022, certain regulations have changed, making it easier for qualified clinicians to prescribe this drug. This means that, over the years, buprenorphine has become more popular for opioid addiction treatment.

There are reasons for more strict regulations regarding methadone, as there are greater chances of people living with OUD abusing this drug.

However, there are also worries that these stringent regulations might be having a negative impact on OUD treatment. But, to date, evidence has been mostly missing.

However, this new study shows that methadone may be better due to much lower discontinuation rates. Considering the study duration and massive sample size, the study results are generalizable to various parts of the North American continent.

The study also analyzed the incidence of adverse events in both groups, and it found that both drugs were equally well tolerated. Though methadone was slightly more likely to cause side effects compared to buprenorphine, there wasn’t any statistically significant difference between the groups.

One of the reasons for the more widespread use of buprenorphine in the US and less stringent regulations is the belief that it has a better safety profile. However, when it comes to analyzing the safety profile of any drug, it is also vital to consider its overall efficacy.

At least, this study shows that methadone, in real-life conditions, is not likely to cause significantly more side effects than buprenorphine, though it is much more effective. Hence, these findings must be taken into consideration by policymakers to ensure better methadone availability for opioid addiction treatment.

Source:

Nosyk, B., Min, J. E., Homayra, F., Kurz, M., Guerra-Alejos, B. C., Yan, R., Piske, M., Seaman, S. R., Bach, P., Greenland, S., Karim, M. E., Siebert, U., Bruneau, J., Gustafson, P., Kampman, K., Korthuis, P. T., Loughin, T., McCandless, L. C., Platt, R. W., … Socías, M. E. (2024). Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder. JAMA. https://doi.org/10.1001/jama.2024.16954

 

Summary: One of the new studies shows that alcohol may increase the chances of developing chronic pain. It found that prolonged alcohol abuse may even cause permanent chronic pain, and this risk is relatively greater in females.

Chronic pain is one of the most common complaints these days, and yet science has been struggling to understand its cause. Of course, it is evident that it occurs for many reasons, making pinpointing its cause challenging. Moreover, due to its different causes, its treatment also remains challenging.

Studies show that more than 20% of US adults experience chronic pains. Further, about 7-8% experience high-impact pain. Thus, these are individuals who are also more likely to abuse medications, opioids, or even alcohol.

Although alcohol may provide some short-term relief, however,  a new study shows that in the longrun, it may make things much worse or even make chronic pain a permanent issue.

The risk of developing chronic pain after alcohol withdrawal depends on how frequently a person drinks and how much. Those who abuse alcohol at higher dosages for a long are much more likely to develop chronic pains.

These findings are vital considering that alcohol use disorder (AUD) is not a rare problem among US adults. Studies show that more than 10% of US adults abuse alcohol. In the US, about 29 million adults are living with alcohol use disorder. Accessible options like alcohol addiction treatment online may play a crucial role in managing this widespread issue and reducing its long-term impact.

This new study published in Pharmacological Research was done in mice models. In the study, researchers divided into three groups. The first group of mice consumed alcohol for 5 weeks in moderate amounts. Researchers found that on discontinuing alcohol exposure, these mice showed high pain sensitivity or heightened allodynia for five days.

However, things were worse in the second group, given a greater amount of alcohol. These mice showed heightened pain sensitivity for several days. There was one more interesting finding, which is the difference between the genders. Researchers found that female mice took almost twice as long to recover from this increased pain sensitivity or allodynia compared to male mice.

 

Things were quite different for the group of mice fed with higher alcohol dosages for longer. These mice did not show any sign of recovery even after 26 days of abstinence. Researchers say that 26 days in their mice model is equal to 30 months in humans. So this suggests that heavy drinking for longer causes some permanent changes in the body, resulting in permanent chronic pain.

To understand the cause of these permanent changes, researchers examined the dorsal root ganglia of heavy-drinking mice. They found that prolonged duration of heavy drinking led to permanently reduced levels of endocannabinoid 2-AG in the ganglia. Hence, researchers think that treatment targeting 2-AG may be one of the ways of managing allodynia.

The researchers also found altered levels of eicosanoids, a type of immune signaling molecule, especially in the dorsal root ganglia of female mice, explaining sex differences between the groups.

So, researchers say that the next logical step would be finding out if normalizing 2-AG levels using various modulators or some medications can help prevent or reverse allodynia due to alcohol drinking. Further, it is also vital to see how males and females may respond differently to various treatments.

To sum up, this study found that chronic alcohol use, especially at higher dosages, may cause some permanent changes in the nervous system, causing persistent pain. Further, this risk is much greater in females than in males.

Considering that AUD is not a rare issue in the US, it may be one of the significant causes of increasing reports of chronic pain. Understanding the mechanism behind chronic pain in various population groups is essential for finding its safe and effective treatment.

Source:

Borgonetti, V., Vozella, V., Ware, T., Cruz, B., Bullard, R., Cravatt, B. F., Galeotti, N., & Roberto, M. (2024). Excessive alcohol intake produces persistent mechanical allodynia and dysregulates the endocannabinoid system in the lumbar dorsal root ganglia of genetically-selected Marchigian Sardinian alcohol-preferring rats. Pharmacological Research, 209, 107462. https://doi.org/10.1016/j.phrs.2024.107462

Summary: One of the new studies showed that one of the anti-epilepsy medications can be of significant help in preventing the progress of mild cognitive decline to full-blown Alzheimer’s disease. This drug may slow down cognitive decline by as much as 40%. This drug seems to only work for those not carrying the ApoE-4 gene variant.

Repurposing existing drugs always comes with certain benefits, such as their clinical safety, which has already been proven. Now, one of the safe and relatively readily available anti-epileptic drugs seems to help treat Alzheimer’s significantly.

This drug has been given the name AGB101, which is slow-releasing levetiracetam. This drug has been in clinical use for quite a long. It is inexpensive, is known to boost brain cell metabolism, and has other benefits. Now, studies show that if this drug is given early enough, it may help prevent or even manage Alzheimer’s. These were the findings of the HOPE4MCI study.

It is known that Alzheimer’s develops slowly over the years. Thus, early treatment is always a great time to slow down its progress or treat the condition. One of the early signs of the condition is mild cognitive impairment.

Of course, not all people with mild cognitive impairment progress to Alzheimer’s. However, studies show that about one-third of those with mild cognitive impairment would ultimately be diagnosed with Alzheimer’s.

This new study shows that this drug is only effective for those not carrying the ApoE-4 genetic variant. This is probably because this genetic variant significantly increases the risk of developing Alzheimer’s. However, this does not reduce the relevance of the study since more than half of all those diagnosed with Alzheimer’s do not carry this genetic variant. This means that repurposing this anti-epileptic drug may help numerous people.

Studies have shown that even in mild cognitive decline, one can see amyloid and tau pathology and hyperactivity of certain brain parts like the hypothalamus. It is a stage when memory impairment is still mild. Nonetheless, it shows that brain cells are fast dying, and a person is quite likely to be diagnosed with Alzheimer’s.

This new investigational drug, with a known safety profile and once-daily dosing, may help slow down the death of brain cells (brain atrophy). Hence, it may either help prevent the progression of mild cognitive decline to Alzheimer’s or slowdown the process. However, researchers noticed that this benefit was only seen in those not carrying the ApoE-4 gene variant.

 

Investigators say that they noticed that this drug helped reduce hyperactivity of certain brain parts like the hypothalamus, known to cause mild memory issues in early dementia cases. Thus, this drug could help prevent cognitive decline in many cases, and many of the patients became close to normal, making it an area of interest in opioid addiction treatment.

These results are significant. The study found an almost 40% reduction in cognitive impairment, which is massive. The participants were given this experimental drug for 18 months, and this improvement was compared to placebo. Hence, it shows a significant and meaningful benefit.

Investigators are really excited about their findings since slowing down mild cognitive impairment in its early phase would allow individuals to live independently for longer, and it would significantly delay the onset of dementia.

What is good is that researchers noticed that this drug also reduced atrophy or death of cells in other brain parts. So, it is not just about a slowdown in cognitive decline. It is about the slower loss of brain cells.

At present, there is no cure for Alzheimer’s. However, researchers are looking for ways to prevent or slow down its progress so that people may be treated like they are treated for conditions like diabetes and hypertension. It would be great if science is able to find medications that can significantly slow down the disease’s progress.

When repurposed drugs like levetiracetam show efficacy, it is heartening since such drugs can be quickly introduced for treatment. Further,  unlike some of the novel biologics, such drugs are relatively inexpensive.

Source:

Mohs, R., Bakker, A., Rosenzweig-Lipson, S., Rosenblum, M., Barton, R. L., Albert, M. S., Cohen, S., Zeger, S., & Gallagher, M. (2024). The HOPE4MCI study: A randomized double-blind assessment of AGB101 for the treatment of MCI due to AD. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 10(1), e12446. https://doi.org/10.1002/trc2.12446

Summary: Depression is on the rise. Major depression needs medical care, as it considerably increases the risk of self-harm. Although many medications help treat the condition, they work very slowly, generally taking weeks to start working. This is quite unlike psychedelic substances that alter mental state almost instantly. It appears that many of these illicit drugs can even help treat depression, especially psychedelic substances like magic mushroom, Ecstasy, or MDMA. However, the problem with these drugs is that they cause a prolonged trip or euphoria. Researchers think that for managing depression, the much shorter and controlled trip may work. Thus, they need to develop drugs that act only for about a couple of hours. Additionally, some researchers believe that these drugs may work even without causing euphoria or trip. Thus, some are trying to develop psychedelic analogs that would help treat depression but not cause euphoria or addiction. These agents may also help treat PTSD effectively, providing alternative approaches that could benefit those in opioid addiction treatment as well.

The psychedelic effect is experienced by consuming a prodrug called psilocybin, a substance found in many mushrooms. However, it is incredibly high in mushrooms of the genus Psilocybe, and these mushrooms are also called magic mushrooms.

However, psilocybin is relatively common and is present in more than 200 mushrooms varieties. When consumed, it changes to psilocin, causing a mild-altering effect, or euphoria. Many people report having a wonderful spiritual experience by ingesting psilocybin; they call it “a trip.” Thus, little doubt that it may help get rid of depression and PTSD.

Depression and PTSD are significant mental health problems in the US and globally. What is worrisome is their rising prevalence. Though severe cases of depression are treated well with some existing drugs, but there are some issues like low efficacy and a relatively long time needed to experience benefits. In addition, some of these drugs take weeks before the mental state of patients improves.

At present, psychedelic substances are illegal to use, and even possession of psychedelic mushrooms is unlawful in most nations. However, their use is allowed for medicinal reasons or in clinical studies.

Unlike anti-depressants, psilocybin works almost immediately. However, one of the significant hurdles in using commonly available psychedelic drugs like LSD is that they have a prolonged duration of action, with the so-called trip lasting as much as 12 hours. Researchers think that such a long duration of action or trip is unnecessary and even poses a health threat. Thus, there is a need to develop psychedelic drugs with a shorter period of action¹.

 

Of course, there are some substances with quite a short duration of action and excellent safety profile like 5-MeO-DMT, and its action lasts only about 15-minutes. But researchers think that such a duration is too short. So what they are aiming for is something in between. They believe that the sweet spot is about two hours.

The idea of using such substances to manage depression or PTSD is not new. People have used tranquilizers like ketamine to manage depression for a long time, though not legally. However, in 2019, US FDA approved ketamine-based nasal spray for faster depression management. It is safe, acts fast, and is also suitable for resistant depression. So, why not consider psilocybin, which is even more potent².

There is some sound science behind the use of psilocybin for managing depression. Studies show that it acts on 5-HT-2A receptors in the brain, boosting neuroplasticity. Thus, it promotes faster rewiring of the brain, causing rapid and prolonged benefits in depression.

Researchers think that one does not need such a prolonged action as that caused by LSD. Just a couple of hours of trip is enough to cause massive neural changes. However, they expect any such therapy to be done strictly under medical supervision requiring pre and post-psychotherapy.

On the other hand, some researchers believe that this mild altering action of psilocybin is not needed at all. They think that it would work without such an effect or a trip. Thus, some manufacturers are trying to develop drugs that do not cause euphoria or trip and yet help relieve depression. Such a medication would not lead to substance abuse and have a much safer safety profile.

There is a real chance that we may see such a drug approved in the coming years. Thus, Defense Advanced Research Projects Agency (DARPA) has even given a research grant of $26.9 million for research into the subject³. DARPA wants to see the development of a quick and powerful drug for treating psychiatric conditions but a drug that does not cause hallucinogenic ride.

Recently, even a study has been published showing that Ecstasy or MDMA may help manage PTSD. The so-called MDMA-assisted therapy was twice more effective as a placebo for relieving PTSD symptoms. Furthermore, it was effective for 67% of participants. These results are definitely encouraging, showing that psychedelic drugs could prove as a quick fix for many psychiatric disorders⁴.

References

1. Yakowicz W. The Future Of Psychedelic Medicine Might Skip The Trip. Forbes. Accessed February 12, 2022. https://www.forbes.com/sites/willyakowicz/2021/06/23/the-future-of-psychedelic-medicine-might-skip-the-trip-rick-doblin-bryan-roth-mindmed-darpa-maps/
2. Yakowicz W. Why Ketamine-Assisted Therapy Has Gone Mainstream. Forbes. Accessed February 12, 2022. https://www.forbes.com/sites/willyakowicz/2021/10/18/why-ketamine-assisted-therapy-has-gone-mainstream/
3. Roth Leads $26.9 Million Project to Create Better Psychiatric Medications. Newsroom. Published June 15, 2020. Accessed February 12, 2022. https://news.unchealthcare.org/2020/06/roth-leads-26-9-million-project-to-create-better-psychiatric-medications/
4. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. doi:10.1038/s41591-021-01336-3

Alcohol is a mind-altering substance that is in considerable amounts in some of the commonly consumed beverages. Nevertheless, humans have long consumed alcohol to improve mood and social interaction. It may even be good for health in small amounts, though very few people are likely to stick to the recommended limits of a drink or two a day.

On the contrary, a significant number of people abuse alcohol regularly. Moreover, many people are dependent on alcohol. But,  not only that, it is not rare for some people to combine alcohol with various mind-altering substances. 

Understanding alcohol and its influence on the brain

Alcohol is relatively safe and causes severe side effects only when consumed in large amounts and too frequently. However, mixing alcohol with some synthetic drugs is not a good idea. After all, humans might have traditionally consumed alcohol, but they have not mixed it with synthetic drugs.

One of the reasons why it is so dangerous to mix alcohol with other mind or mood-altering drugs is that they might have opposite and often unpredictable effects.

 

Alcohol is a sedative quite like other commonly used medications. But it does not cause sedation in small amounts because it tends to suppress inhibitory neurons first, which may ultimately cause hyperexcitation. Nevertheless, its sedative effect becomes quite evident when alcohol is consumed in more significant amounts.

Understanding phentermine and its influence on the brain

To begin with, phentermine works in quite the opposite way to alcohol, as it is a stimulant and not a suppressant. It is pretty like amphetamines. In small doses, it improves mood, focus and reduces sleep. However, more importantly, it reduces appetite. 

Phentermine is a medical drug that is primarily approved to treat obesity. It is especially good for those living with severe obesity along with diabetes, hypertension, and other severe metabolic changes in the body.

When used alone, it is relatively safe but not free from side effects. It may cause agitation, glaucoma, and worsening heart disease in many people. It is also a bit addictive due to its impact on the mood. 

However, its primary contraindications are the presence or risk of heart disease, poorly uncontrolled blood pressure, glaucoma, agitation, and history of drug abuse.

Why not mix alcohol and phentermine?

As one can guess, these two substances work quite differently and influence different brain centers. Of the two, one is a suppressant and another stimulator. Thus, the final effect of combining them would remain unpredictable. Therefore, it is not a good idea to combine such diverse substances.

Of course, combining them at lower dosages may not cause significant issues as both may increase excitement and energy levels. However, with higher dosages of alcohol, things may become quite different, resulting in a very unpleasant experience.

But, it is not just about an unpleasant experience. Combining medications with alcohol is never a good idea. Alcohol is terrible for the liver, and it can alter the metabolism of the drugs, too. 

At higher doses, both these substances try to neutralize the effect of each other, resulting in an unpredictable influence on the brain. Moreover, undoubtedly, it results in increased toxicity.

Besides, drinking alcohol when trying to lose weight is never a good idea. In many, alcohol increases appetite, and thus phentermine may fail to help them lose body weight. Additionally, some of the commonly consumed alcoholic drinks are high in sugar content. Alcohol addiction treatment can be essential for those who struggle with alcohol dependency, helping them achieve a healthier lifestyle and improve their chances of successful weight management.

Mixing them is bad for the heart

However, the most significant reason not to mix them is their adverse effects on the heart. It is true that a small amount of alcohol is not harmful to the heart, but then it is a double-edged sword. Having more than two drinks is quite bad for heart health. 

Thus, combining alcohol and phentermine may make blood pressure worse. It may also increase stress on heart muscles. All this considerably increases the risk of a heart attack. Moreover, obese individuals are less likely to have a healthy heart. Additionally, combining them also increases the risk of stroke^1,2.

Prevents weight loss

Phentermine is mainly a weight loss remedy. Thus, it is quite likely that a person taking it regularly on a doctor’s prescription is using it for weight loss. However, alcohol has just the opposite effect. It may stimulate appetite. Thus, it inhibits phentermine’s action, making it almost ineffective.

Of course, there are other factors to be taken into consideration. For example, some people may like the effect of using these substances together. However, using phentermine and alcohol increases the risk of addiction to both these substances, thus the risk of side effects. 

As a stimulant, phentermine can cause high at higher doses. It may mix well with some amount of alcohol. However, mixing phentermine with high alcohol will cause an unpleasant sensation and prevent the high.

To conclude, phentermine is a weight loss remedy that is also a brain or mood stimulant. Thus, using it with alcohol may be addictive. However, combining the two is bad in every way due to their opposing actions at higher dosages. Moreover, such a combination considerably increases the risk of cardiovascular complications.

References

1. Jordan J, Astrup A, Engeli S, Narkiewicz K, Day WW, Finer N. Cardiovascular effects of phentermine and topiramate: a new drug combination for the treatment of obesity. J Hypertens. 2014;32(6):1178-1188. doi:10.1097/HJH.0000000000000145

2. Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke. 1993;24(2):310-313. doi:10.1161/01.STR.24.2.310