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Non-hallucinogenic Neuroplastogens Enter First-in-Human Trials 

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For years, researchers have been looking for ways to harness the medical benefits of psychedelics, but without the hallucinations. Some neuroscientists even believe that the drugs’ mental-health benefits don’t come from tripping at all. Now, for the first time, researchers have developed psychedelic-inspired drugs that to bring on neuroplastic effects without producing a trip – a new breed of neuroplastogens. 

Neuroplasticity explained 

Neural plasticity describes the brain’s ability to change, adapt, and form new connections in response to various stimuli. It’s a vital aspect of healthy brain function, and as such, essential to the way we humans function in our day-to-day lives. Situations in which the brain demonstrates neuroplasticity include learning a new skill such a subject in school or a new language, practicing music, memorizing directions in a new city, and working on puzzles and memory games. It can also occur when a person loses a sense, such as hearing or sight, and their other senses start to overcompensate for the lost one.  

Many neurological and psychiatric ailments stem from a lack of neuroplasticity in the brain, which leads to poorly adaptive behavioral responses. Anxiety, depression, and substance abuse are common in people whose brains are unable to strengthen these beneficial circuits. Developing and maintaining neuroplasticity is crucial in promoting recovery from these brain and mood disorders that a large percentage of the adult population struggle with.  

Juvenile brains exhibit remarkable neuroplasticity, with both the ability to learn new things as well as the brain being able to quickly mend damaged circuits. But as we grow older, our brains become less plastic and we’re more prone to getting stuck in negative thought and behavioral patterns. This is why external intervention, often in the form of hallucinogenic drugs, is sometimes necessary to repair those broken connections and pathways.  

The science of neuroplastogens 

Neuroplastogens, also known as psychoplastogens, are a group of small-molecule drugs that are capable of producing rapid and long-lasting effects on both neural structure and function. Many are so potent that they are known to produce the desired therapeutic effects after only a single session. As such, neuroplastogens are quickly becoming the go-to option for treating these neurological disorders.  

Typically, hallucinogenic drugs like psilocybin and LSD, or dissociatives like ketamine and MDMA, are the gold-standard when it comes to improving neuroplasticity. Recently approved second-generation psychedelics like Spravato and COMP360 work via the same mechanisms. And as incredible as these substances may be, the problem is that not all patients have the time or desire for a psychedelic trip.  

A huge number of prospective consumers would prefer to reap the therapeutic benefits of these drugs, without the high. Not to mention, for reasons of liability, when doctors prescribe hallucinogens, the patient needs to be strictly monitored for the duration of their trip, which adds another layer of complexity (as well as higher costs) to the treatment process involving these drugs.  

That being said, there is a growing demand for neuroplastogens that are capable of promoting circuit-based plasticity in specific locations of the brain, without unwanted side effects (hallucinations). To meet this unfulfilled need, researchers are exploring the different ways that psychedelics can rewire key areas of the brain, should the psychedelic properties be excluded.  

For example, several studies show that ketamine can improve overall mood in humans, even if it’s administered when patients are unconscious. This means that patients who missed out on knowingly feeling ketamine’s dissociative effects, because they were not awake for them, still felt happier and less anxious after their operations – which suggests that you don’t need to consciously experience the high in order to benefit medicinally from the drugs.  

How do they work? 

Just like standard psychedelic drugs, these non-hallucinogenic neuroplastogens stimulate the same serotonin receptors, mainly 5-HT2A. When activated, the brain then produces a compound known as brain-derived neurotropic factor (BDNF), which functions as a sort of “brain fertilizer”, that promotes neural growth and survival. While activation of 5-HT2A is often associated with sensory hallucinations, this is not always the case. Different drugs bind to and activate receptors in a variety of ways, which results in very different effects. The focus of non-hallucinogenic psychoplastogens is to activate 5-HT2A serotonin receptors in a way that does not induce a trip.  

Some of these trip-free psychedelics are relatively new, like one that was synthesized two years ago (study published January 2022) by a team of Chinese researchers. The drug works by imitating the mechanisms of lisuride, an analog of LSD, as well as psilocin, the compound that our bodies convert psilocybin from mushrooms into. The drug does not have a name yet, just a serial number, IHCH-7113, and it’s currently undergoing animal trials.  

Per the study: “Here, we present structures of 5-HT2AR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride. Serotonin and psilocin display a second binding mode in addition to the canonical mode, which enabled the design of the psychedelic IHCH-7113 (a substructure of antipsychotic lumateperone) and several 5-HT2AR β-arrestin–biased agonists that displayed antidepressant-like activity in mice but without hallucinogenic effects.” 

Other non-hallucinogenic neuroplastogens, although not widely used, have existed for decades. For example, a compound known as 2-Br-LSD (an analog of LSD), was first synthesized in 1957 by Albert Hofmann, the Swiss chemist who created LSD. Renewed interest in this compound has led to new studies, which found that 2-Br-LSD can effectively relieve anxious and depressive behavior in mice, but without twitching and other actions that are common when hallucinations occur. Now, several decades after its initial discovery, a Canadian company, Betterlife Pharma, is planning on conducting the first in-human trials using this trip-free psychedelic. 

Are hallucinations just the side-effect? Or something more? 

For those of us who truly believe in the healing power of psychedelics, hearing people who have likely never used them talk about how much better these drugs would be without hallucinations… well, it can be pretty annoying, to say the least. Many people who have participated in a psychedelic trip describe it as one of the most meaningful and educational experiences of their lives. Not to mention, several studies on psilocybin concluded that the intensity of the trip had a direct correlation on the magnitude and longevity of the therapeutic effects.  

Now let’s circle back to those studies about ketamine. Despite people feeling happier after ketamine administration even when they didn’t trip out, there are some questions there that remain unanswered. Comparatively, would the antidepressant effects have been stronger had they felt the hallucinogenic effects? How long did the positive effects last after their surgeries, in contrast to patients who experience the drugs in their full scope?  

And what about microdosing? Those who take subtherapeutic doses of psychedelic drugs claim to experience many of the neurological benefits – better mood, enhanced creativity, improved focus, and so on – even though the doses they are taking are so low they don’t feel a “high” or experience any sensory hallucinations. However, there are few studies to back up these sentiments, and some people don’t do well with small doses. I personally get very anxious and uneasy when I take low doses of psilocybin, compared to happy, positive highs when I use larger doses.  

So, while technically, yes, the hallucinations are a side effect, anyone who has used psychedelics in a meaningful and serious way can attest to the fact that visuals and other sensory feelings are informative and eye-opening in an extremely powerful way. Are they everything these products have to offer? No. Can people benefit from using these drugs without tripping? Absolutely. But are they missing out on a very important piece of the puzzle? Probably so.  

Final thoughts 

Like most aspects of this industry, more studies need to be done in order to determine how much we are really missing when we remove the trip from psychedelics. Non-hallucinogenic neuroplastogens certainly have an important place in wellness and pharma, as they will expose an entirely new population of mental health patients to the benefits of psychoplastogenic drugs. But which will reign superior? New age neuroplastogens with no hallucinogenic side effects? Or classic entheogens that help transport your senses and your entire being to transcendent new heights? Only time and more research will tell.  

Hello readers. We’re happy to have you with us at Cannadelics.com; a news source here to bring you the best in independent reporting for the growing cannabis and hallucinogen fields. Join us frequently to stay on top of everything, and subscribe to our Cannadelics Weekly Newsletter, for updates straight to your email. Check out some awesome promos for cannabis buds, smoking devices and equipment like vapes, edibles, cannabinoid compounds, amanita mushroom products, and a whole bunch more. Let’s all get stoned together!



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How Cannabis Can Help With Dysmenorrhea

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Millions suffer, but relief could be here thanks to science and a simple plant.  Here is how cannabis can help with dysmenorrhea.

It is an uncomfortable topic to discuss, but the painful truth is a majority of women will suffer it at some point and finding relief is invaluable. Around 80% of women experience period pain at some stage in their lifetime. Dysmenorrhea is the medical term for pain or discomfort during menstruation. It is a common gynecologic problem, but the pain can range from dull cramps to indescribable agony. Here is how cannabis can help with dysmenorrhea.

Medicinal cannabis has emerged as a potential treatment option for dysmenorrhea, offering hope for the tens of millions of women who suffer from menstrual pain. Current medical management options primarily consisting of over-the-counter pain relievers and hormonal contraceptives. The effectiveness of these treatments vary greatly.

The endocannabinoid system plays a role in uterine function and pain perception. Cannabinoid receptors CB1R and CB2R, as well as TRPV receptors, have been identified in human myometrial tissue. Tetrahydrocannabinol (THC), a primary component of cannabis, can act as a cannabinoid agonist, potentially triggering myometrial relaxation and easing menstrual pain.

Photo by Esther Kelleter/Getty

The potential benefits of cannabis for dysmenorrhea includes pain relief, improved sleep quality, and reduced reliance on pharmaceutical pain relievers. While research specifically on cannabis for dysmenorrhea is growing, studies on chronic pain provide some insights:

  • A systematic review of 18 randomized controlled trials found that synthetic cannabis products with high THC-to-CBD ratios may offer moderate improvement in pain severity.
  • A meta-analysis of 32 trials showed that medical cannabis or cannabinoids resulted in small to very small improvements in pain relief, physical functioning, and sleep quality among chronic pain patients.

There is significant interest in using cannabis for gynecologic pain management:

  • A survey found that 61.2% of women who had never used cannabis and 90.0% of those who had were willing to try it for gynecologic pain.
  • After cannabis legalization in Canada, current cannabis use increased from 13.3% to 21.5% among women with self-reported moderate-to-severe pelvic pain.

With th American Medical Association, American College of Physicians and even AARP recognizing the medical benefits of cannabis, it is critical more research is funded.  Millions of women may be in pain needlessly due to untreated dysmenorrhea.



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Science Says Cannabis Can Be Making Us Healthier

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As it it becomes available to more people, there is a positive health change going on according to data.

Cannabis is becoming more mainstream and and the side effects are doing even better than expected.  It seems the availability of legal marijuana is helping with the health of the general population. Studies in California, Canada and the now New Zealand have shown the upside of legalization. While cannabis has been used for health benefits for millions of years, reduction in more harmful intoxication products is another important wellness trend.

RELATED: Can CBD Oils Help With Anxiety & Depression

Alcohol consumption is associated with significant health risks, including liver damage, cardiovascular issues, and certain cancers. In contrast, marijuana has not been linked to the same level of severe physical health consequences. The Centers for Disease Control and Prevention (CDC) reports that over 36,000 annual U.S. deaths are attributed to chronic alcohol use, while there is no comparable category for marijuana-related deaths. Alcohol is also much more addictive than marijuana, causing long term physical and mental issues.

A study from New Zealand has found some interesting trends regarding the relationship between marijuana legalization and the consumption of alcohol and opioids.

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Photo by megaflopp/Getty Images

Following the legalization of marijuana in New Zealand, researchers observed a notable decline in alcohol consumption:

This suggests for adults, marijuana may be serving as a substitute for alcohol in some cases, particularly when it comes to heavy drinking episodes.

The relationship between marijuana legalization and opioid use appears more complex:

  • There was no clear evidence of marijuana legalization directly reducing opioid use or abuse.
  • However, some research indicates that people who use cannabis are more likely to initiate opioid use, with an odds ratio of 2.76 compared to non-cannabis users.
  • The likelihood of transitioning from opioid use to opioid use disorders among cannabis users was found to be 2.52 times higher than non-cannabis users.

The study also revealed some additional findings regarding substance use patterns:

  • Marijuana use increased by 16% among adults aged 21 and older following legalization.
  • There was a 5-6% increase in marijuana use initiation among adolescents and young adults aged 12-20. This would be go with the greater North American trend of California sober and Gen Z drifting away from alcohol and more into marijuana.
  • No significant changes were observed in the use of hard drugs like cocaine or heroin in any age group.

RELATED: Marijuana Use And Guy’s Member

These findings suggest while marijuana legalization may lead to decreased alcohol consumption among adults, it does not necessarily translate to reduced use of other substances, particularly opioids. The relationship between cannabis use and other substance use behaviors is complex and multifaceted. Time and more research should yield more benefits.



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Try These Delicious Autumn Cream Drinks

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Want something delicious with an “oomph” – these yummy creamy concoctions will make your mouth happy!

Fall is a time of coziness, cuffing and nights in front of the fire. Want better way to accent it with a nice tasty cocktail? Try these delicious autumn cream drinks and enjoy the pre-holiday season. Bailey’s was the commercial first cream liquor and made available to the public in 1971. But Irish monks have blended whiskey with fresh dairy cream since the 14th century.  These new and classic connections will bring a smile on crisp nights.

RELATED: Beer Sales Flatten Thanks To Marijuana

Important note, using cream instead of milk in alcoholic cocktails can significantly enhance the drink’s texture, flavor, and overall experience. Cream provides a richer and smoother texture compared to milk. The higher fat content in cream (typically around 36% or more) creates a luxurious mouthfeel that can elevate the drinking experience.

White Russian

The White Russian’s development took about 30 years. The first mention of the drink is in a newspaper was in 1965 in the Oakland Tribune. The 1961 edition of the Diner’s Club Drink Book included a recipe for a Black Russian, with a note suggesting adding cream to make a White Russian. The White Russian’s popularity increased after the 1998 movie The Big Lebowski, where the main character, Jeffrey “The Dude” Lebowski, drinks it throughout the film.

Ingredients

  • 2 ounces vodka
  • 1 ounce Kahlúa
  • 1 ounce heavy cream

Create

  1. Add the vodka and Kahlúa to a rocks glass filled with ice
  2. Top with the heavy cream and stir
White Russian cocktail

Churro Cocktails

A churro is a fried dough pastry originated in Spain and Portugal. They are a fast-growing dessert and breakfast item on menus, and are a popular treat at theme parks and sporting events in Europe and North and South America.  Somrus, who makes cream liquors, made a cocktail from the flavor.

Ingredients

  • 1 1/2 parts Somrus Coffee
  • 1/2 part cinnamon whiskey

Create

  1. In an ice-filled shaker, add ingredients and shake
  2. Strain and pour

Brandy Alexander

This is was a classic “go to drink” for X. It was rumored to have been created at the Paris Ritz in 1922. Or it could have been made in 1915 by celebrate pitcher Grover Cleveland Alexander during a World Series. It was considered a posh way to end the evening, especially after other cocktails.It’s creamy and boozy or a delicious replacement for dessert for those who like to drink their sweets. In the 2000s, it has moved to the back of the line, but is still a great way to cap off a night drinking.

  • 1 1/2 ounces cognac
  • 1 ounce dark creme de cacao
  • 1 ounce cream
  • Grated nutmeg for garnish

Create

  1. Add cognac, dark creme de cacao and cream into a shaker with ice and shake until well-chilled
  2. Strain into a chilled cocktail glass or a coupe glass
  3. Garnish with freshly grated nutmeg

RELATED: Rainy Weather Cocktails

Mango Fizz

For those who are holding on to every last bit of summer, this mango cocktail can add a a little sunshine. The fruit is considered the world’s most popular fruit with over 20 million tons consumed each year. Mangoes are a symbol of friendship and love, which can add to special evening.

Ingredients

  • 2 parts Somrus Mango
  • 1 part citrus vodka
  • ½ part simple syrup
  • Club soda

Create

  1. Combine Mango liqueur, vodka and simple syrup in an ice-filled shaker
  2. Shake vigorously
  3. Strain into ice-filled glass
  4. Top with club soda

 



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