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Non-hallucinogenic Neuroplastogens Enter First-in-Human Trials 

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10 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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4 Ways Marijuana Can Help You Have A Better Thanksgiving

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2 days ago

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November 22, 2024

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If going the family Thanksgiving route, these gatherings can sometimes be stressful, especially when dealing with relatives you don’t see often or navigating potentially tense conversations. Marijuana can help reduce anxiety and create a more relaxed atmosphere. Microdosing is a popular trend with the younger generations, and it could be helpful in during the holiday. Numerous studies have demonstrated that cannabinoids such as THC and CBD can effectively reduce anxiety. By helping to calm nerves and ease social tension, cannabis can contribute to a more pleasant and harmonious family gathering.



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Can Big Alcohol Help The Cannabis Industry

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2 days ago

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November 22, 2024

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It has been a rough few months for the cannabis industry…could Big Alcohol help during another rough patch?

The cannabis industry was worth $33 billion in 2023 and is filled with mom and pop businesses. With the majority of the population having access to legal marijuana, consumer use is up, states are filling their coffers, and more patients are using medical marijuana.  It has become so mainstream, even the staid AARP has acknowledge a signifiant portion of boomers are using it for medical reasons.  But federal restrictions are crippling the industry, despite the growth. The industry needs federal help, can Big Alcohol help the cannabis industry. Alcohol is in a majority of grocery stores, restaurants, hotels, resorts, planes and homes.  They understand the consumers and sell $260 billion in booze a year, not counting the second level market up.  The alcohol industry spends over $20 million annually on lobbying, a drop compared to the $220+ million pharmaceutical spends, but an impressive amount. But Congress, the DEA, and members of the administration are not fans…and help is needed.

Alcohol has a $14+ billion investment in the industry and has a voice in the Congress. Cannabis is a brand and revenue extension for alcohol rather than a competitor. A major change in the beverage industry came with the introduction of purified waters by PepsiCo (Aquafina) in 1994 and Coca-Cola (Dasani) in 1999.  Seeing it as way to reach more consumers and revenue, the two soda giants are now the owners of the top two bottled water companies in the North America. WIth a stake in the outcome, the big liquor companies could guide Congress to open up more for cannabis. This would provide both industries access to more customers and more revenue for everyone, including government entities.

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Photo by Alexander Sanchez/Getty Images

“While alcohol and cannabis can play in the same sandbox, we more often see consumers using cannabis as a replacement for more harmful substances like alcohol. In cannabis, we find a paradigm shift—entertainment and relaxation without the costs of alcohol’s physical and social tolls.” shares Jesse Redmond, managing director at Water Tower Research, LLC.

Like bottled water, alcohol could open up markets to an additional set of consumers.  They have the expertise and relationships most cannabis businesses lack. Already, hemp beverage are in mainstream retailers like Total Wine (Texas) and in convenience stores.

The incoming administration has few cannabis champions with both the Speaker of the House and the President of the Senate and the cabinet doesn’t seem to be focused on marijuana legalization at all. But the majority of members are a fan of booze and that can be used to marijuana’s advantage.

Both would benefit from product development,  producing and marketing cannabis-infused beverages and edibles. From a marketing point of view it also makes sense consider the consumer reach.  In addition, research shows that people often pair cannabis with alcohol rather than replacing one with the other. The proportion of consumers pairing cannabis with spirits or liquor increased from 12% in 2018 to 22% in 2022. The next 14 months will shape the cannabis industry path for years to come, let’s see if Big Alcohol plays a role.



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The Best Cocktails For An Easy Festive Thanksgiving

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2 days ago

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November 22, 2024

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Why just have wine or beer for your Thanksgiving gatherings? Why not have a fun, festive cocktail around Turkey Day. 

Whether a family affair, a Friendsgiving, or just having fun on the long holiday weekend, why not spice it up with something delicious to drink? Here are the best cocktails for an easy, festive Thanksgiving.

RELATED: Beer Sales Flatten Thanks To Marijuana

Pumpkin Margaritas

Most people indulge in pumpkin pie during the holidays.  Why not mix it and wow the taste buds with the classic flavor mixed with a a favorite drink?  While making the pie, set aside a little of the pumpkin and use it to make defiantly a crowd pleaser.

Ingredients

  1. Start by adding brown sugar, pumpkin pie spice, and water to a saucepan on low-medium heat

  2. Whisk to combine and bring to a very low simmer

  3. Once the sugar has dissolved, take the pan off of the heat

  4. Pour the syrup into a container and place in the fridge to cool for 10-15 minutes

  5. Add a handful of ice cubes to a cocktail shaker

  6. Pour in the tequila, cointreau, pumpkin syrup, lime juice, pumpkin puree, and 3 dashes of angostura bitters

  7. Close the lid tightly and shake for 15-30 seconds

  8. Remove the lid from the cocktail shaker and gently strain the drink into ice filled glasses

  9. Garnish with any herbs and spices like cinnamon sticks, freshly grated nutmeg, or rosemary

Amaretto Sour

The Amaretto Sour was likely created in 1974 by the importer of Amaretto di Saronno as a promotional push. The original recipe was two parts amaretto liqueur to one part lemon juice. 

The Amaretto Sour became popular in the 1970s and 1980s. It was a favorite among bartenders and patrons because of its distinct almond flavor and refreshing sourness. It is a cozy drink perfect for a small gathering to celebrate Thanksgiving.

  • 1 1/2 ounces amaretto liqueur
  • 3/4 ounce cask-proof bourbon
  • 1 ounce lemon juice, freshly squeezed
  • 1 teaspoon simple syrup
  • 1/2 ounce egg white
  • Garnish: lemon twist
  • Garnish: 2 brandied cherries

Create

  1. Add amaretto, bourbon, lemon juice, simple syrup and egg white to a shaker and dry-shake (no ice) for 15 seconds
  2. Add ice and shake again until well-chilled
  3. Strain into a rocks glass over fresh ice
  4. Garnish with a lemon twist and 2 skewered brandied cherries

Apple Pie Bourbons

What is more Thanksgiving than apple pie and bourbon? While not settle into a nice drink contain both of them. A rich, luscious, flavor to enjoy watch football or as a pre drink before the big meal.

Ingredients

  • 2 apples (green and red), chopped
  • 1 1” piece fresh ginger
  • 1 whole nutmeg, slightly shaved
  • 4 cinnamon sticks, plus more for garnish
  • 1 1/2 cup bourbon
  • 3 sugar cubes

Create

  1. Fill a mason jar with bourbon, apples, sugar, nutmeg, cinnamon, and ginger.
  2. Let mixture sit 2 to 4 days. (Taste after 2 days and let sit longer as desired.)
  3. Pour mixture into shot glasses and garnish with a cinnamon stick.

Rose Kennedy

This cocktails also known as a “VSS” (vodka soda splash) is about refreshing as possible, and a low calorie alternative to other options.  Developed in DC in the late 80s, the original Rose Kennedy was garnished with lemon only and contained only enough cranberry to make the drink barely pink making the squeezed lemon and cranberry flavors faint but equal. At the time, the use of a lime made it an Ethel Kennedy.

Ingredients

  • 2 ounces vodka
  • 1 1/2 ounces soda
  • 1/2 ounce of cranberry

Create

  1. In a glass filled with ice, add vodka and soda
  2. Splash cranberry juice and garnish with a lemon wedge

RELATED: 8 Ways to Enjoy Marijuana Without Smoking It

Apple Cider Margaritas

While apple pie is the third favorite holiday (behind pumpkin and pecan), it is a delicious flavor to mix into the classic margarita…it give it an autumn feel and pairs perfectly with the tequila.

Ingredients

  • 1 medium lemon
  • 2 ounces Reposado or silver tequila
  • 1 1/2 ounces apple cider or unfiltered apple juice
  • 1/2 ounce maple syrup
  • 1 pinch ground cinnamon
  • 1 cinnamon stick or thin apple slices for garnish

Create

  1. Juice  medium lemon until you have 3/4 ounce
  2. Place the lemon juice, 2 ounces tequila, 1 1/2 ounces apple cider, 1/2 ounce maple syrup, and 1 pinch ground cinnamon in a cocktail shaker
  3. Fill the shaker halfway with ice Seal the and shake vigorously, about 20 seconds.

Pour through a strainer into the glass

Garnish with a cinnamon stick and thin apple slices if desired



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