Enveric Biosciences Inc. (NASDAQ: ENVB) reported its financial results for the third quarter of 2024 and provided a corporate update yesterday.

Enveric said it made “important progress” in the development of EB-003, its lead neuroplastogenic molecule designed to treat depression, anxiety and addiction disorders without causing the hallucinogenic effects common to DMT and related analogs.

According to the company, studies confirmed EB-003 can potentially be delivered orally and penetrate the brain “at levels expected to elicit the desired therapeutic effect.” Preclinical data also showed EB-003 targets desired serotonergic receptors while minimizing potentially harmful off-target interactions.

“These are clear differentiators for EB-003, which we believe will add to its value potential,” CEO Joseph Tucker said in a statement. The company plans to submit an Investigational New Drug application for EB-003 to the FDA in the second half of 2025.

For the quarter ending Sept. 30, Enveric reported a net loss of $2.1 million, or 24 cents per share, versus a net loss of $2.8 million, or $1.30 per share, a year earlier. The company ended the quarter with cash of $3.1 million.

According to Enveric’s quarterly report filed with the SEC, the company’s operating expenses for the quarter totaled $2.1 million, down from $3.4 million in the same period last year. The reduction was primarily driven by lower G&A expenses and reduced R&D costs.

As of Sept. 30, Enveric had an accumulated deficit of $102.9 million. The company noted in its 10-Q filing that it anticipates further losses as it continues to develop its product candidates. Enveric’s operations have been funded principally through the issuance of equity, and the company stated it will require additional capital to fund additional research and development efforts.

In addition to advancing EB-003, Enveric announced it expanded patent protection for a broad range of molecules in its EVM301 portfolio and granted licenses for two of its drug candidates. The company granted Aries Science & Technology a license to its patented radiation dermatitis topical product. It also licensed its EB-002 drug candidate and EVM201 Program to MycoMedica Life Sciences.

“These agreements not only validate the company’s platform but also generate nondilutive revenue to support the development of EB-003 and further building stockholder value,” Tucker said.

In May, Enveric received a letter from the Nasdaq stating that the company was not in compliance with the minimum bid price requirement for continued listing. The company had until earlier this week to regain compliance and is considering a reverse stock split in 2025 if the bid price does not close above $1 per share for at least 10 consecutive business days before the end of the compliance period. It did not comment on the issue in its earnings release.

Algernon Pharmaceuticals Inc. (CSE: AGN) (OTCQB: AGNPF) reported the close of its non-brokered private placement, previously announced on August 7, 2024 and updated on August 13, 2024, for gross proceeds of C$235,200 of units at an issue price of $0.12 per Unit. The private placement was upsized from the original amount of C$150,000.

The company said it will use the proceeds of the private placement for working capital purposes. Algernon mostly repurposes already-approved drugs for new uses. The company is advancing a stroke program using N,N-Dimethyltryptamine (DMT).

The company announced that some insiders participated in the offering for C$60,000 making it a related party transaction.  The common shares purchased by insiders exceeded 25% of the company’s market capitalization.

Algernon paid cash finder’s fees totaling C$4,800 and issued 40,000 finders warrants to eligible finders for investors introduced to the Company by the eligible finder.

Going Concern

The psychedelics company last reported its earnings at the end of July when Algernon told investors it had C$609,524 in cash at the end of May 2024. It reported a net loss of C$1.4 million for the quarter ending May 31, 2024.

At the end of May 2024, Algernon reported it had an accumulated deficit of C$30,435,365 and for the nine months then ended incurred a net loss of C$81,548 (May 31, 2023 – C$4,254,809). The company told investors in July that it would need to raise sufficient working capital to maintain operations.

Also at the end of May, Algernon reported it had a working capital deficit of C$1,244,049 compared to working capital on August 31, 2023, of C$2,379,931. The company’s current liabilities were C$1,931,044.

DMT studies

Algernon said in its MD&A in July that its decision to investigate DMT and move it into human trials for ischemic stroke was based on multiple independent, positive preclinical studies demonstrating that DMT helps mitigate tissue damage and promote neurogenesis as well as structural and functional neural plasticity. The company wrote, “The reason that the Company conducted a Phase 1 study and did not move directly into a Phase 2 study is that it was investigating prolonged intravenous infusion of DMT, for durations which have never been clinically studied. The resulting data generated is helping the Company to plan both its Phase 2 acute stroke and rehabilitation studies more effectively. The Company along with CHDR presented its Phase 1 stroke study data at the Interdisciplinary Conference on Psychedelic Research being held from June 6-8, 2024 in Haarlem, the Netherlands.”

The company said it is planning to conduct this study at multiple locations in Europe using its existing finished product supply of intravenous DMT. Ethics submission is scheduled for 2024 with the study starting a short time after approval.

Individuals in a survey reported greater gratitude, nature relatedness, and nature appreciation after embarking on an ayahuasca retreat experience. 

The active chemical in ayahuasca is DMT (dimethyltryptamine) and it also contains monoamine oxidase inhibitors (MAOIs) that play a role. The survey respondents rated effects on several scales to determine which effects were most prominent.

PsyPost reported Tuesday that 65 participants were observed who attended a well-known ayahuasca retreat in Costa Rica frequented by Americans. The study, “Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study,” was published recently in the Journal of Psychoactive Drugs. The study was led by Jacob S. Aday and a team of researchers associated with Central Michigan University in Mount Pleasant, Michigan. Aday was assisted by Emily K. Bolesch, Alan Kooi Davis, Sarah E. Domoff, Kyle Scherr, Josh D. Woolley, and Christopher C Davoli.

Sixty-five participants attended the Soltara Healing Center in Puntarenas Province, Gigante, Costa Rica. Soltara is an all-inclusive ayahuasca retreat center where attendees pay to participate in ayahuasca ceremonies with indigenous Shipibo curanderos (plant healers) from Peru. It’s attracted celebrities such as former New York Jet and commentator Aaron Rodgers. As compensation for their participation, study authors entered participants in a drawing to potentially win $100.

The participants stayed at the Soltara center for 5-12 nights and participated in 2-7 ayahuasca ceremonies during their stay. Participants received an email with the study survey, and in it, they completed assessments of gratitude using an Appreciation Scale, relatedness to nature using a Nature Relatedness Scale, and the appreciation of nature using an Appreciation of Nature Scale.

The second survey contained the same three assessments from the first one, plus more related to their ayahuasca experiences: mystical experiences during the ceremonies using an Mystical Experience Questionnaire, awe using an Awe Experience Scale, and ego dissolution using an Ego Dissolution Inventory.

Researchers observed that gratitude increased significantly after the retreat. Nature relatedness and appreciation of nature were also more pronounced after the retreat. These increases were more pronounced in participants who reported stronger mystical experiences.

“Here, participants completed validated surveys related to gratitude, nature relatedness, and nature appreciation one-week before, one-week after, and one-month after attending an ayahuasca retreat center,” the study reads. “Compared to baseline, there was a significant increase in gratitude, nature relatedness, and nature appreciation at the one-week and one-month follow-ups. Ratings of mystical-type experiences and awe, but not ego dissolution, during participants’ ayahuasca sessions were weakly-to-moderately correlated with these increases.”

Researchers were also able to learn several more things about the impact of an ayahuasca experience.

“The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change,” the study continues. “Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age. In the context of study limitations, the results suggest that mystical-type experiences and awe occasioned by ayahuasca may be linked to prosocial changes in gratitude and relationships with nature that may be beneficial to mental health.”

Interestingly, the strength of ego dissolution experiences and the number of ayahuasca ceremonies attended were not associated with significant changes in the level of gratitude, appreciation of nature, and nature relatedness.

Other Effects of Ayahuasca

Many other potential uses for ayahuasca in therapy are being explored. A study published earlier this year, for instance, found that ayahuasca may help individuals become less narcissistic.

The findings, published in April 2023 in the Journal of Personality Disorders and based on a three-month evaluation of more than 300 adults, suggested that after “ceremonial use of ayahuasca, self-reported changes in narcissism were observed,” although the researchers did urge some caution.

“However, effect size changes were small, results were somewhat mixed across convergent measures, and no significant changes were observed by informants. The present study provides modest and qualified support for adaptive change in narcissistic antagonism up to 3 months following ceremony experiences, suggesting some potential for treatment efficacy. However, meaningful changes in narcissism were not observed. More research would be needed to adequately evaluate the relevance of psychedelic-assisted therapy for narcissistic traits, particularly studies examining individuals with higher antagonism and involving antagonism-focused therapeutic approaches,” the researchers wrote.

Another study published in the British Journal of Pharmacology in February explored how ayahuasca (shortened to AYA for the use in this study) and DMT interacts with serotonin receptors in the part of the brain that regulates fear.

In that study, ayahuasca was found to affect serotonin receptors in the infralimbic cortex of the brain, where fear is regulated.

With a better understanding of how ayahuasca impacts gratitude and a connectedness with nature, we can better understand how it could be applied in psychedelic-assisted therapy.