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Non-hallucinogenic Neuroplastogens Enter First-in-Human Trials
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.
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Some times you want to relax and just chill in your own head – and that is 100% ok
Trivia night, parties, hanging with friends, sporting events…all group activities when you might imbibe in something to add to the fun atmosphere. Heading to a bar, going out to eat, or family events might including a bit of booze or a small toke. Both can put you in the right mood. But here are the benefits of consuming marijuana alone.
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Drinking alone can cause issues as alcohol can have different effects. A big difference between marijuana and alcohol is the latter is a depressant. Cannabis, in the right dosage, tends to reduce anxiety and can help battle depression. Also, overindulges with weed leads to falling asleep, where overdoing it with cocktails can lead to blackout and serious help issues.
Marijuana is surprisingly effective and malleable when consumed alone. If you challenge yourself, it can be used for different activities including creative, social and physical. When getting the dosage right, weed can act as a stimulant for your brain, helping you journal and doodle, or for your body, pushing you to workout or clean and sort through your closet.
Another benefit is you can enjoy the wonder of being in a high state of mine. Experts express they love watching a movie on a large screen as it makes them feel they are in the movie (probably not a good idea to watch horror films). It can almost make you feel like you meld with music. when you’re high because cannabis affects your sense of timing. When you smoke weed, your brain slows down and becomes more sensitive to the rhythms in music. It makes it easier to appreciate the subtleties in the music
Personal reflection and growth are other prime reasons for solo cannabis consuming. It allows individuals to immerse themselves in a deep journey into their own being, stripped of the distractions and outside influences that often cloud our understanding. For introverts, this can be time to balance and recharge.
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The best part about marijuana is you can enjoy it without ahangover allowing you the next day to be productive. Before diving in to your solo marijuana journey and all of the perks it can result in, here are the best & safest practices.
In a historic move the Drug Enforcement Agency announced it plans to reschedule cannabis. Monumental shift in the marijuana industry.
After three years of waiting for President Biden to fulfill his promise of doing something about legal cannabis, the Drug Enforcement Agency (DEA) announced its plan to reschedule cannabis. This follows the recommendations from Health and Human Services (HHS) and the Food and Drug Agency (FDA). They are sending their recommendation to the White House Office of Management and Budget for review of the impact on the budget. The shifts acknowledged the medical benefits of cannabis and can pave the way for PTSD treatment for veterans, something the President and Senator Patty Murray (D-WA).
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“Moving to Schedule III is the single biggest thing that can happen to the US cannabis industry. It removes the 280E tax burden, increases medical research, and opens the investor base. Today is truly a tipping point for this burgeoning industry.” declared Jesse Redmond, Managing Director at Water Tower Research.
“This historic move from the Biden Administration to reclassify cannabis from Schedule I to Schedule III reflects changes in the scientific and medical understanding of cannabis. It echoes moves in other countries around the world. Domestically, it lays the groundwork for federal tax benefits for the cannabis industry, as cannabis businesses will be treated like other businesses with regard to deductions and credits. It will also lower the costs and hurdles of conducting research on the plant and its products. Despite skeptics arguing that this spells the beginning of the end of the cannabis industry as we know, those doomsday scenarios fail to answer a basic question: why would the Biden Administration want to crack down on a substance that it classifies as “less dangerous” when it refused to crack down on the substance when it was a Schedule I substance? Little, if anything, will change at the state regulatory level, but that should not take away from the historic nature of this decision. Cannabis has been a Schedule I substance for 54 years, and despite multiple opportunities to reclassify it in decades’ past, today is the first time the US Government has been willing to say otherwise” shares John Hudak, Director, Maine Office of Cannabis.
Hudak is widely respected in the industry and has been a thought leader for the growing industry. The move reclassifies cannabis from Schedule 1 of dangerous drug with zero medical benefits to to Schedule III such as ketamine, Tylenol with codeine, and anabolic steroids. The timing is still unsettled, but there is hope it will have an impact in 2024. The industry as been struggling under schedule III despite a huge growth of consumers. This will also open the door more for mainstream companies to become involved in the market.
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“While this is great news for the cannabis industry, it’s too early to break out the Champagne,” said Lonnie Rosenwald, Partner at Zuber Lawler, LLP. “We don’t know yet when rescheduling will occur, or, perhaps more important, when the tax changes will take effect. For companies and entrepreneurs considering entering the industry, rescheduling alone shoudl provide an incentive to launch their businesses. But existing cannabis businesses will have to wait to see whether they’ll be able to deduct business expenses on their 2024 or 2025 returns. We expect answers to these questions in the coming weeks.” says Lonnie Rosenwald, an attorney for Zuber Lawler, a national law firm which covers the cannabis industry.
This is a historic shift for the federal government and puts in more in line with the American Medical Association, most medical professionals, Canada and the general public.
War, relationships, political news, work at home or office, all adding to the stress of life. For some, they can manage it and move forward, for others, it can be a pit of sadness…but most it seems experience anxiety and depression at some point. In a surprise, the Census Bureau’s Household Pulse Survey finds half (50%) of adults ages 18-24 reported anxiety and depression symptoms. It can causes sleep deprivation, loss of energy, and high blood pressure and general uneasiness.
It is tough to deal with it while maintain your life. It is always good to talk to a trained medical professional and there are prescriptions, but can CBD oils help with anxiety & depression?
What Is CBD?
Cannabidiol(CBD) can be extracted from cannabis plants, marijuana leaves, and hemp flowers. CBD products act as a natural remedy. By consuming or using this product you will not get high or have any psychotic reaction. Numerous studies have been carried out on different products of CBD and a quality check has also been approved by the FDA.
Reports say that CBD has less than 0.3 % THC, which is very safe than a lot of other drugs and pills that are taken for mental health.
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CBD products are now legally consumed and distributed in many states and countries. The list includes countries like German, Canada, Denmark, Sweden, The USA & The UK.
Just like different brands of marijuana, there are also various brands of CBD oils available.
In the USA you can only use CBD products for medical purposes. It has to be prescribed by a licensed doctor for you to buy and consume it.
If your state has legalized the sale and consumption of cannabis products then it will be easier to find CBD oils in some particular cannabis clinics, shops, and online stores like CBD Oil Uk.
The Difference Between Stress And Anxiety
Stress is a short-term ailment that can happen regularly or once in a while and does not cause any serious damages. Besides, it can be managed easily.
If you face problems like frustration, exhaustion, muscle pain, digestive issues, and difficulty sleeping frequently then it is likely you are dealing with stress.
Anxiety is more severe than stress. It can not be alleviated easily. Instead, it is considered as non-stop excessive worry and fear even when everything is perfectly fine in your life.
Anxiety leads to a set of symptoms that are almost identical to stress but very serious. These include insomnia, difficulty in concentration, fatigue, and muscle tension.
It is important to differentiate the signs of stress and anxiety. Stress is a common cause of anxiety and to avoid anxiety symptoms, it is important to catch them early.
How CBD Products Can Help
Here are 4 ways CBD products can help reduce anxiety and depression-
1.CBD Improves Your Sleep Cycle
People suffering from anxiety often complain about the lack of sleep.
Excessive anxiety often interrupts your sleep cycle and lack of sleep can, in turn, result in more anxiety.
CBD has claimed to reduce anxiety levels. It has even shown positive results in clinical trials that is why the FDA has approved CBD in the first place.
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CBD helps calm our minds and increases the chances of falling asleep naturally and without any disruption.
Also, studies have proven that little extra dosage of CBD creates a sedative effect on your body and helps to sleep and lets your brain rest. CBD products are now used to treat people with insomnia as well.
2.CBD Reduces Pain & Inflammation
Earlier we have discussed that stress and anxiety can cause muscle pain, headaches, and chronic inflammation.
CBD products are completely natural. The products have been proven to be a muscle relaxant and work better than any standard painkillers since it has no side effects.
CBD also works as anti-inflammatory drugs. It controls cytokine production which is generally responsible for various inflammatory diseases in our body.
This increased inflammation is also connected to higher levels of anxiety. Just like sleep and anxiety, this one is also a chain reaction.
Inflammatory diseases like psoriasis and arthritis can cause depression and anxiety in the long run. CBD oil helps to reduce inflammation and pain by reducing cytokine and affecting CB-2 receptors. This reduces pain and decreases the chance of getting an anxiety attack.
3. CBD improves mood
CBD is considered as a “Neuroprotective” material. “Neuroprotective” actually means it will protect nerve cells by keeping a safe functioning state of the nervous system.
Moreover, it decreases the oxidative stress of your brain.
By keeping your negative emotions in check, CBD helps you to improve your mood and keeps your brain calm and relaxed. It reduces unnecessary stress and anxiety.
4. CBD Helps Enhance Metabolism
If you have a poor digestive and metabolism system, it will affect your quality of life.
It will make you feel bloated and lethargic. Illness disrupts the natural functioning of your body and if it becomes more serious it causes stress and ultimately, leads to anxiety.
If you start consuming CBD regularly, it will improve your metabolism, burn unnecessary fat, and make you feel better.
How To Choose CBD Products
CBD has various types of products in the market including oil, tablets, edibles, beverages, creams, and vape. Although the overall vape sales slowed down during this year. Things are starting to look better.
But still, the CBD oils are the most popular ones by a large margin. Each of the types provides almost the same benefits with some unique advantages of their own. CBD oils have to be consumed daily and provide the most health benefits. They are also the most concentrated ones. CBD gummies are sweet and take a long time to take effect. CBD lotions are best for exterior physical discomfort.
Depending on your medical condition, you should consult with a healthcare professional who has experience with CBD to choose the right product.
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