Along with the psychedelic renaissance came a new type of drug: second generation psychedelics. Developed from classic psychedelics molecules, these upgraded compounds could offer improved therapeutic profiles with reduced side effects. For some companies in the psychedelics space, second generation psychedelics could be the key to success in an increasingly competitive market.
What Are Second Generation Psychedelics?
Although the health benefits of psychedelics such as psilocybin, MDMA and LSD are widely recognized (and more with each passing day), there are also plenty of reasons to be cautious of their repeated use. The long-term effects of some psychedelics may not be totally clear and their regular use could have some unknown consequences, especially for those that agonize serotonin 5-HT2B receptors, which have been linked to heart valve disease.
In the case of longer-acting psychedelics like psilocybin, time can also be a problem, since therapy can take up to 8 hours a day and become an exhausting process to both patient and provider. Moreover, not all patients are crazy about the “trip” and its hallucinogenic effects, but could still benefit from the anti-depressive and anti-anxiety effects of the drugs.
Psychedelics 2.0 enter the picture to solve those problems: artificially developed molecules with the same benefits as traditional psychedelics, but without the drawbacks. Of course, there is also a financial incentive to these substances—since current psychedelic drugs cannot be patented, proprietary compounds mean a more than interesting investment opportunity.
That is why the biggest names in the industry are bringing new drugs into the game. In no particular order, meet 5 of those companies:
Cybin CYBN is widely known for being the first psychedelics company listed in the NYSE. Their flagship second generation psychedelic, CYB003, is undergoing the latest stages of preclinical studies, with the hopes of completing them by the end of Q1 2022 and submitting a regulatory application in Q2 2022. Focused on treating major depressive disorder and alcohol abuse disorder, CYB003 is a “deuterated psilocybin analog designed to achieve less variability in plasma levels, faster onset of action, shorter duration of effect and potentially better tolerability versus oral psilocybin,” according to the company. That way, an 8 hour therapy session could take just 4 hours—less demanding for both patient and provider.
Also developed by Cybin is CYB004, a proprietary molecule aimed at treating depression, anxiety and substance abuse disorders. It is a deutered DMT analog, whose benefits when compared with DMT include a reduced dosage, and both the potential to increase the duration of the effect and to alleviate negative experiences. CYB004 is expected to be filed for a pilot study in Q2 2022.
Teamed up with Otsuka Pharmaceutical OTSKF, Mindset Pharma MSSTF is currently developing four families of novel psychedelics, two of which (#2 and #4) are being paid by Otsuka through the completion of phase 1B.
MSP-1014, the lead clinical candidate in the Family 1 of the company, is a second generation psychedelic inspired in psilocybin. According to the company, it has both a stronger 5-HT2A activity than psilocybin and an attenuated reduction in locomotor activity. Also, it is expected to be of simpler and more cost-effective manufacturing.
In the case of microdosing apt drugs, MSP-3002 is leading the charge in Family #3, with a similar binding profile to psilocybin, but a lower potency and a longer half-life.
Field Trip Health
The lead development candidate for Field Trip FTRP is FT-104, a novel 5HT2A agonist with psilocybin-like pharmacology and potency. As with many of the previously mentioned drugs, FT-104 offers a shorter duration time, reducing the “trip” from 8 to around 4 hours, and is expected to be especially effective when dealing with treatment-resistant depression and postpartum depression. The compound should be entering Phase 1 trials in New Zealand or Australia at the end of Q2 2022.
Regarding potential cardiovascular risk associated with 5-HT2B receptors, Field Trip is developing a new family of psychedelics: the FT-200 group. These drugs exhibit an improved selectivity between serotonin receptors, meaning that a lower 5-HT2B activity could provide safer medications and an increased dosage.
With the help of PsyAI (an AI tool developed by April19), Enveric Biosciences ENVB is currently managing a “Psybrary”: a catalog of possible molecule combinations and alterations, powered by machine learning, and with a focus on cancer related distress. From this extensive list of possible psychedelics, Enveric has, to this moment, filed 14 patents for second generation psychedelics: 4 of them are mescaline or MDMA derivatives, while 10 come from psilocybin and DMT, according to the company.
On march 15th, Enveric announced the publication of four patent applications for novel molecules of the tryptamine family.
According to the MindMed MNMD approach, what other companies might call second generation psychedelics, they call third generation psychedelics. In fact, they refer to 18-MC as such: a “structural analogue to classic psychedelics” that “requires a full development program” and has the “strongest available intellectual property.”
18-MC is MindMed’s flagship substance and is focused on treating opioid abuse disorders, with the added characteristic that this ibogaine-derivative drug is non-hallucinogenic. Earlier this year, MindMed successfully completed Phase 1 clinical trials of the drug.
Another drug under development by the company is MM-120, whose IND application was recently cleared by the FDA. It is a pharmacologically optimized form of LSD being developed for generalized anxiety disorder.
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