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Non-hallucinogenic Neuroplastogens Enter First-in-Human Trials 

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11 months ago

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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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3 Wise Men

Three Wise Men Give Marijuana Strain Gift Suggestions

Published

2 days ago

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December 20, 2024

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It has become a popular gift with over 20% of the population putting it under the train. So we asked 3 wise man what to give (or consume) during the season.

The holiday season is a special time of year with a combination of Christmas, Hannakuh, and more are the modern hoildays descended from pagan holidays. Food, celebrations, gifts and a hint of something magical are all part of the holidays.  With Christmas, the three wise men bring gifts to the baby Jesus being steered by a star.  As we head into the last part of the season, why not think of the perfect gift to give or for yourself.  We have three wise men give marijuana strain gift suggestions to share with our readers.

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Terran Cooper, one of the rising stars of the industry and a part of the firm Falcon Rappaport & Berman who works in the cannabis industry.  New York based, he says while there are several great strains, he has two to share for the holiday season.

One of my favorite day time strains, Pineapple Express has skyrocketed in popularity following the 2008 film by the same name. This strain is one of the more energetic strains that I’ve come across, allowing for a nice balance between productivity and relaxation this holiday season. Its joyful and uplifting effects may pair nicely with last minute holiday tasks in addition to any festivities. Though infrequent consumers beware – its relatively high THC content means that a little can go a long way.

Beautifully wrapped Christmas gifts under a festive tree with glowing lights.

Andrew Laub, managing partner of Keneh Ventures and CEO of Cannabition, is a leader in the industry and shared his favorites. Golden Goat is my secret to finding joy in any moment, especially during the holiday season. Its tropical, citrusy flavor is bright and uplifting, just like its effects. I love how it gives me an energized, creative boost without feeling overwhelming, making it perfect for everything from decorating the house to hosting friends. It’s my reminder to savor the fun and chaos of the holidays.

Granddaddy Purple is like my personal escape when the holiday rush gets overwhelming. I love its rich, grape-like flavor and how it helps me unwind at the end of a busy day. Whether I’m binge-watching holiday movies or enjoying quiet time by the fireplace, this strain makes everything feel a little cozier and more magical.

Sour Diesel is my motivation when there’s too much to do and not enough time. Its energizing, citrusy aroma wakes me up, and its focus-boosting effects help me tackle long to-do lists with ease. I love using it to power through holiday prep, whether I’m wrapping gifts, planning meals, or brainstorming creative ways to make the season special.

RELATED: Holiday Hangover? Here’s How To Stop It Before It Strikes

Online cannabis influencer Miguel a.k.a Miggy420 (@miggy420) believes consumption of cannabis is a personal experience with everyone being different. He sees the endocannabinoid system as unique as snowflakes in winter. Some smoke to wash away ills, others to wash away the ills of society. He shared his two favorites.

Vin Diesel Diesel is a sativa grown by Dewey’s Cultivars. Her beauty matches her taste with gassy hits reminiscent of early 2000 diesel strains I would buy in the traditional market. These growers come with a biochemical background and it shows with this plant, pure bliss – and this is coming from someone who prefers indicas.

If you’re looking for something post family events i.e you just realized the debt you incurred for the little ones or you’re just happy your conspiracy Uncle is gone, I recommend Gelato Cake by Agro Couture. This indica dominant hybrid will have your mind drifting away and able to focus on what it is you really wanted to do, hot box your bedroom and binge watch YouTube.

Enjoy these suggestions and may everyone have a great holiday season.

 



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The Best Cocktails To Make You Feel Festive

Published

3 days ago

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December 19, 2024

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Lean into the joy of the holiday season with this merry cocktails – delight your taste buds and favorite people!

According to TikTok, it s the most wonderful, stressful, fun, boozy time of year. So why not lean into the season and make merry with something fun. Here are the best cocktails to make you feel festive, no matter what the situation. Plus, these are drinks you can make quickly with minimum effort and maximum fun. Pour one of these concoctions and have a moment of peace or share them with the one you like, love or tolerate at work. Sip, savor and bring a little ho ho ho into the moment.

RELATED: Beer Sales Flatten Thanks To Marijuana

Christmas Old Fashioned

Here is a way to settle into a cozy beverage which will warm your body and soul. Bourbon has been part of the holidays for generations…and you can make this a new tradition.

Ingredients

  • 2 oz bourbon
  • 1/2 oz simple syrup
  • 2 dashes bitters
  • 2 dashes orange juice
  • Garnish: cinnamon stick and orange peel

Create

  • Combine ingredients in a mixing glass and add ice

  • Stir for 20 seconds

  • Strain into a rocks glass with ice

  • Garnish with orange peel and a cinnamon stick

White Bishop

Easy, Tasty Egg Nog

You either you love it or hate it, but Egg Nog is a holiday staple. This recipe makes it lighter, tasty and a wee dangerous since it is so good. It bring a whole new take on a staid drink.

Ingredients

  • 2 oz store bought egg nog
  • 1 oz milk (2% is the best)
  • small splash vanilla
  • 1 oz Licor 43

Create

  1. Combine egg nog, milk and vanilla
  2. Stir until well mixed
  3. Add Licor 43 and stir again
  4. Pour into a fun glass and enjoy

White Bishop

The Bishop’s Wife is a great holiday movie filled with the Christmas spirit and some never ending booze. This drink is an embraces the fun, warmth, snow, and spirit of the evening.  Perfect as a dessert drink, a morning treat or just to lift your holiday mood.

  • 2 oz vanilla vodka
  • 1 oz heavy cream
  • 1 oz Frangelico or Licor 43
  • Small splash of vanilla

Create

  1. Combine all ingredients in shaker with ice
  2. Shake for 20 seconds
  3. Strain into a martini glass

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Poinsettia Champagne Cocktail

Nothing says celebration like bubbles. Whether you use champagne or prosecco, this is bound to bring a smile to your face. And the poinsettia is Christmas tradition since

Ingredients

  • 1/2 oz orange liqueur
  • 3 oz cranberry juice
  • 3 oz of champagne or prosecco
  • Garnish with fresh cranberries

Create

  1. Pour orange liqueur and cranberry juice into a chilled champagne flute
  2. Stir well
  3. Top with champagne
  4. Garnish with a few fresh cranberries

Have a great holiday season!



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The Best Tips If You Are Giving Marijuana As A Gift

Published

4 days ago

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December 18, 2024

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Roughly 25% of people are planning to give cannabis as a holiday gift….here are some practical suggestions to make it a success.

Last year was a watershed year for Santa with 1 in 4 planning to add cannabis into their gift giving, the trend is only going up in 2024. Since the plant has become mainstream (except for a few in DC), it is to be found under the tree, next to the menorah and during festive gatherings. Gen Z and Millennials are leading the trend with 78% (vs. 56% of Gen X and Boomers) in planning to include cannabis in their holiday plans. But you you want to do it right, here are the best tips if you are giving marijuana as a gift.

RELATED: Science Says Medical Marijuana Improves Quality Of Life

While giving alcohol is a long tradition, giving cannabis is does have some variances.  To start, so far most can’t grab it out of personal stock or fish it out of Christmas gifts already given for the year. While Costco, groceries stores and Total Wine are the booze top sellers, it can be also purchased in bodegas, gas stations and other locations. Cannabis still has to be purchased at specialized dispensaries.

marijuana dispensary
Photo by smodj/Getty Images

First, plan ahead when you shop. The good news is most dispensaries keep hours similar to a grocery store – open by 9 am and closing around or after 10 pm. This makes dashing in for a last minute gift or squeezing it in during the day easy. Remember to bring cash, have a plan and chill out.

The good news isyou can’t seem to be “cheap” giving weed. Most edibles are in a small price range, whereas wine bought at a grocery stores can go for $6-$100.  And the quality of the wine can vary greatly. Most edibles, including gummies, are within the same price point and potency while caring on quality.  Wana Brands, one of the nation’s leading gummy makers, hits the mid spot on price.  Also, unless you are doing a hefty gift basket, you are can give one or two items as a trail.

Never overestimate someone’s usage. Think about the recipient’s experience level and preferences when selecting cannabis gifts. For most, consider starting with low-dose or CBD-dominant products. Gummies, vapes, oil, or gift cards are all popular choices.  Also, ask the budtender what the best sellers for mid level consumers.

RELATED: The Most Popular Marijuana Flavors

If you are in the less than 50% of the population where legal cannabis is available, consider hemp beverages. It can provide a quick, similar high but is legal.  In Texas, they are huge sellers and can be found in some Total Wines, local convenience stores and other locations.

Lastly, have a hint of discretion, it might not be the best public secret Santa gift, but gummies can be a fun White Elephant!



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