As the world grapples with multiple mental health crises, including depression and anxiety, PTSD, and rising suicide rates, psychedelics have shown great promise in early clinical trials.
But while compounds such as psilocybin, ibogaine, and DMT all are showing signs of being efficacious, they are by no means perfect medicines. All have potential downfalls that limit their ability to meet the massive scale we need to put a dent in the mental health crisis.
Therefore, while it is essential that the pace of study into classical psychedelics continues to ramp up, companies are simultaneously editing the chemical formulas of these entheogens to create better medicines.
Now, there will always be those who argue that there is no point in spending the tens of millions necessary to create new psychedelics, saying that “we already have perfect medicines given to us by nature.”
This argument is nonsensical. First, as will be expanded upon further in this article, in a medical context, medicines such as psilocybin and ibogaine do indeed have shortcomings. If we can harness the power of science to eliminate them, we should.
Second, many current medicines were originally derived from plants, and then were improved upon over the decades. Take for example ibuprofen, the painkiller found in brands like Advil. Ibuprofen is a synthetic derivative of the natural substance salicylic acid, which is found in the bark of trees such as a willow tree.
The ancients used to chew this bark, or turn it into a brew, to treat pain. But since its synthesis in the early 1900s, scientists have constantly been tweaking the formula to avoid negative side effects such as gastrointestinal irritation. Yet no one in their right mind would argue we go back to chewing on willow bark because it is “more natural.”
With this in mind, this article aims to shine a spotlight on five next-generation psychedelics that are expected to enter clinical trials this year. Keep in mind that all of these new drugs are closer to the beginning of their scientific study than the end, and any and all claims made by the companies producing them will have to be proven in multiple, rigorous, clinical trials. Furthermore, it is far too early to tell which of these will be the most efficacious.
Also note that this list is not exhaustive, and the compounds are not presented in any particular order.
18-MC / MM-110: Entering a Phase 2a Trial
18-MC, now being rebranded as MM-110, is perhaps the furthest advanced in the long line of next-generation psychedelics. Set to enter Phase 2a efficacy trials this quarter, attempting to treat Opioid Use Disorder, the MindMed (Nasdaq: MNMD. NEO: MMED) molecule already completed a Phase 1 safety trial which showed the compound to be well tolerated, without any serious adverse events.
MM-110—as it is now known—is a synthetic molecule based on the extremely hallucinogenic ibogaine, which is found in the iboga shrub in Africa. While some early studies have shown ibogaine may be effective in treating various addictions, the medicine does carry with it some downsides.
First is the long psychedelic experience. An ibogaine hallucination can last upwards of 48 hours. And while this may be fine in a ritual setting, in a medical one it raises many problems, not the least of which would be the cost of monitoring a patient for two days.
The next issue is a medical one; use of ibogaine can lead to cardiovascular side effects and there are even cases—albeit rare—of ibogaine use leading to cardiac arrest and death.
18-MC—excuse me, MM-110—claims that it has solved both of these issues. First, the compound does not cause a hallucination. A patient could take MM-110 like they would any other prescription. Second, MindMed claims that the cardiovascular side effects have been eliminated.
If these claims hold true as MM-110 makes its way through the clinical trial process, and if it is found to be effective in treating Opioid Use Disorder—and eventually perhaps other addictions as well—then 18-MC could be a game-changer in addiction treatment.
CYB003: Entering a Phase 1/2a Trial
CYB003 is Cybin’s (NYSE: CYBN, NEO: CYBN) next-generation psilocybin. Assuming regulatory approval, they intend to start the Phase 1 portion of their Phase 1/2a trial in mid-2022. This trial will attempt to treat Major Depressive Disorder.
While psilocybin has had some very promising results in Phase 2 clinical trials, mostly attempting to treat forms of depression, it is not a perfect medicine. In particular, there are two problems that medical psilocybin possesses.
The first is the long duration of the experience. While not nearly as long as ibogaine, a psilocybin experience can still last upwards of 6 to 8 hours. Included in this is the long time it takes for the compound to reach a therapeutic effect after ingestion, often at around an hour. This would make a therapy session very expensive and may price out lower-income people.
Next, is the variability of effect between individuals. In other words, similar-sized people could ingest the same amount of psilocybin and metabolize it differently, causing vastly different intensities of effect. This can also lead to side effects in certain populations.
Cybin says that their pre-clinical evidence shows that CYB003 counteracts these issues. First, in duration of effect, Cybin says that their next-generation psilocybin’s onset action is twice as fast as the original, and the overall experience may likewise be halved. This would greatly expand accessibility.
On the safety side, Cybin says that the effects of CYB003 are less variable than traditional psilocybin, which they measured by looking at plasma concentration levels. In other words, using CYB003 would cause similar effects in different individuals. Combine this with improved brain penetration ratios, which again were found in preclinical animal studies, and CYB003 may lead to fewer side effects and “safer dosing options and more predictable patient outcomes.”
SPL028: Entering a Phase 1 Trial
SPL028 is Small Pharma’s (TSXV: DMT, OTCQB: DMTTF) next-generation DMT. Assuming regulators are satisfied, Small Pharma hopes to launch a Phase 1 safety trial in the second half of 2022.
Unlike ibogaine and psilocybin, DMT’s therapeutic issue is not that it lasts too long, but rather that its effects are too short. Traditionally, a DMT experience, whether administered through smoking or by IV, only lasts up to 20 minutes—and that is on the generous side.
While there has been much less study on DMT than psilocybin—in fact earlier this year Small Pharma initiated the world’s first Phase 2 trial on DMT—it is hypothesized that the short duration may not be sufficient for a clinical effect to take hold.
SPL028 will last longer than regular DMT, but it will still be significantly shorter than a psilocybin trip. Essentially, Small Pharma hopes to find the sweet spot in terms of duration. Their Phase 1 trial will also test whether an IV delivery or an intramuscular delivery is best.
It is also important to note that Cybin is likewise planning on launching a pilot study this year on their own modified DMT candidate, CYB004, which also aims to lengthen the experience.
FT-104: Entering a Phase 1 Trial
FT-104 is Field Trip Health’s (Nasdaq: FTRP, TSX: FTRP) first next-generation psychedelic, which they aim to have in a Phase 1 clinical trial before the end of the first half of 2022. FT-104 is a pro-drug to the little-known psychedelic, 4-HO-DiPT, which means that FT-104 metabolizes in the body to form 4-HO-DiPT.
Once it makes its way out of Phase 1 and into later phase efficacy tests, Field Trip wants to test treating Treatment-Resistant Depression and Postpartum Depression with FT-104.
4-HO-DiPT is a psychedelic that is similar in effect to psilocybin, but with a shorter duration of effect, only lasting between 2-3 hours. As mentioned above, this could make it more practical to use in a clinical setting.
In terms of practical differences from 4-HO-DiPT, Ft-104 is more soluble, which may make it easier to use as a medicine.
Note, soon Field Trip Health will be dividing into two separate companies. When this happens, FT-104 and all other drug discovery programs will be under the purview of the new company, Reunion Neuroscience.
MEAI: Entering a Phase 1 Trial
MEAI, unlike all other molecules on this list, is not based on a current psychedelic. Rather, Clearmind Medicine (CSE: CMND, OTC Pink: CMNDF) has a more unique molecule on its hands.
Aiming to enter Phase 1 trials by the end of this year, MEAI will attempt to treat Alcohol Use Disorder.
Essentially, according to Mark Haden, the VP of Business Development for Clearmind, MEAI induces the sensation of satiation in a subject. This means if a person takes MEAI in conjunction with alcohol, after several drinks the person will feel done with the substance, and not feel the need to have another.
Mr. Haden uses the analogy of having eaten two rich cheesecakes, and then someone places a third one down in front of you. Sure, you could have another. But you don’t want to. You are satiated.
This is interesting, since —if it’s proven to work— MEAI could be used with a prescription from a doctor, but it could also possibly be available —given regulatory approval— as an alcohol substitute that anyone could buy.
The subjective effects of MEAI are said to feel similar to one to two beers after the first and second dose of it, and more similar to a low dose of MDMA after a third dose. Interestingly, after the third dose, Clearmind says that the prospect of having more is unsavory.
If proven to work —all we have so far is anecdotal and animal evidence— MEAI could revolutionize alcohol addiction treatment.
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