Amid the jam-packed field of biopharmaceutical companies developing psychedelic therapies for everything from cluster headaches to chronic depression, one compound stands apart from the rest as a reality-blasting instrument for transformation: 5-MeO-DMT.
Found in low concentrations in a variety of plants, and higher intensities in the defense toxins of Sonoran Desert toads, the drug is now being studied in a number of clinical studies. Featuring a quick onset within seconds of inhalation and a short duration of action at roughly 15-20 minutes, 5-MeO-DMT is being examined as a potential tool for drug makers looking to condense treatment times — and the resources required to treat patients — while providing a profoundly life-altering impact for people suffering from psychiatric conditions.
More often than not, peak experiences on the drug are described as awe-inspiring, a merging into “the unitary consciousness that underlies all of reality,” says writer and 5-MeO-DMT specialist Martin W. Ball. Others speak of encountering oceanic boundlessness and communion with the divine. When science-minded drugs researcher and psychedelic sleuth Hamilton Morris first encountered 5-MeO-DMT on his show Hamilton’s Pharmacopeia, his simple response was one word he recited over and over again: “Love. Love. Love.”
While it is no wonder that for over 40 years psychedelic devotees have found the potent entheogen a useful means of transcendence, it is somewhat remarkable to see millions of dollars pumped into studies of 5-MeO-DMT by laser-focused interests with deep pockets. With encouraging clinical results as a therapy for the debilitating symptoms of treatment-resistant depression (TRD), 5-MeO-DMT is emerging as a medicine with the capacity to relinquish some individuals from depressive conditions.
As Johns Hopkins psychologist and psychedelic researcher Bill Richards said of such transcendental encounters: “Once you discover mystical consciousness in your memory banks, you can’t pretend to be worthless anymore.”
Along with the steep capitalization into research and development of 5-MeO-DMT, one key indicator that the drug is on track to become a viable therapeutic medicine is the DEA’s decision in December to greatly increase production quotas of 5-MeO-DMT for research purposes. The agency boosted quantities that can be produced from 35 grams in 2021 to a significant 2,550 grams for 2022. The increase, says the DEA, is due to “estimates of the medical, scientific, research, and industrial needs of the United States for 2022, as well as lawful export requirements and establishment and maintenance of reserve stocks.”
The following are the primary companies that are, to varying degrees, engaged in R&D of the compound known by its acolytes as “the God molecule.”
An Ireland-based clinical-stage biopharmaceutical company, GH Research, made a speedy rise in 2021 announcing its aim to develop novel and proprietary 5-MeO-DMT therapies for patients with TRD. Currently singularly focused on studies of the molecule, the company’s lead product candidate (GH001), a synthetic 5-MeO-DMT formulation, is administered via a “proprietary inhalation approach” intended to produce ultra-rapid durable remissions in depression.
GH Research became highly visible on the psychedelic therapy scene last year with its IPO on Nasdaq and capital contributions reported at an impressive $309 million. That substantial backing has helped fund trials of GH001, which is showing potential to relieve symptoms of TRD. A Phase 1 preliminary safety trial enrolled 46 healthy volunteers and showed no serious adverse events. Findings from the successful outcome of the Phase 2 part of a Phase 1/2 clinical trial of GH001, which enrolled eight participants with TRD, revealed that seven of the eight patients were brought into an ultra-rapid remission of their symptoms.
While the 5-MeO-DMT molecule itself is not patentable, GH Research is putting considerable energy into developing IP around its novel formulation and delivery, saying it has “filed several patent applications covering novel aerosol compositions of matter of 5-MeO-DMT, novel manufacturing methods for the purification of 5-MeO-DMT, high purity 5-MeO-DMT and novel uses of 5-MeO-DMT in various disorders.”
The company is working on two more products currently in preclinical development: a proprietary injectable (GH002) and a proprietary intranasal (GH003), which they anticipate developing in subpopulations within their focus area of psychiatric and neurological disorders.
Another frontrunner in the pursuit of 5-MeO-DMT therapies to treat the symptoms of TRD is England-based Beckley Psytech. The private company was formed in 2019 as a close strategic partnership with the non-profit Beckley Foundation, led by Lady Amanda Feilding, who has dedicated over 50 years of her life to the exploration of psychedelics. Beckley Psytech’s clinical research – currently in Phase 1 in collaboration with King’s College London – is evaluating the safety and tolerability of intranasal 5-MeO-DMT in psychedelic-naïve healthy subjects.
While its present research seeks to understand the pharmacokinetics of the drug – meaning its absorption, distribution, metabolism, and excretion within the body – Beckley Psytech is looking ahead and anticipating the inevitable deficit of psychedelic practitioners to administer therapies once the drug becomes legal for medical use. The entire psychedelic therapy sector faces a bottleneck in this respect, making Beckley Psytech’s proactive approach a key factor in its business strategy.
Led by CEO Cosmo Feilding Mellen (son of Lady Amanda Feilding) last year the company entered a collaboration with educational platform Fluence, which provides professional training in psychedelic therapy for psychiatrists, psychotherapists, and social workers. In January, Beckley Psytech announced that a first cohort of psychotherapists had entered training to understand the unique demands of psychedelic-assisted psychotherapy using 5-MeO-DMT. Beckley Psytech’s Phase 1 trials have an estimated completion date of March 2022, with Phase 2 trials expected to begin later in the year.
Mindset Pharma creates novel drugs inspired by psychedelics like psilocybin and 5-MeO-DMT. Looking to mimic the positive attributes of those substances, while minimizing the potentially hazardous effects that can be inherent to such drugs, a focal point of its business strategy is to develop drugs with improved efficacy and reduced toxicity. To that end, Mindset Pharma is developing a pipeline of pre-clinical psychedelic drug candidates optimized for pharmaceutical use, two of which are the drugs MSP-4019 and MSP-4020 (compounds inspired by 5-MeO-DMT).
Founded in 2019, the Toronto-based drug discovery company says its recent preclinical results of the two drugs demonstrated improved safety profiles via a mouse head-twitch assay, says Mindset Chief Scientific Officer Joseph Araujo. The mouse head-twitch response induced by hallucinogens is a widely used behavioral assay for 5-HT2A serotonin receptor activation.
Citing potential concerns about the risks that 5-MeO-DMT may pose to patients in terms of serotonergic toxicity, Araujo notes of their novel formulation, “our next generation compounds showed no signs of 5-HT syndrome, a serious potential health risk associated with first-generation drugs, 5-MeO-DMT and DMT.”
Pre-clinical stage biotech company Parow Entheobiosciences (PEB), in partnership with Back of the Yards Algae Sciences (BYAS), recently announced they had created the first known 5-MeO-DMT from parotoid gland cells harvested from a Sonoran Desert toad. The process, which does not harm the donor toad, is similar to a technique used extensively in the cultured or lab grown meat industry.
While being a key step toward toad conservation of vulnerable Incilius alvarius populations, the company’s greater aim is to study the cell-based, cruelty-free drug material extracted from toad parotoid cells — which contain a range of defense toxins that include 5-MeO-DMT — to explore whether natural, full-spectrum 5-MeO-DMT outperforms synthetic psychedelics in psychiatric conditions.
The cell-based process, says BYAS founder and researcher Leonard Lerer, MD, has proven to produce good yields and concentration of 5-MeO-DMT. “We also have proof of concept that we can produce immortalized cell lines that are essentially a bio-factory,” says Lerer. Also working in collaboration with Hadassah BrainLabs in Israel — which studies non-human models of psychiatric and neurological diseases — BYAS and PEB are exploring whether natural, full-spectrum entheogens including psilocybin outperform synthetic psychedelics in conditions such as depression, OCD, and PTSD.
Lerer believes the data from those tests will inform their cell-based toad secretion work moving forward, noting the first results will be available later in 2022 and presented at conferences and published in peer-reviewed journals.
Biomind Labs is an R&D biotech company creating novel pharmaceutical drugs for a variety of psychiatric conditions with a focus toward creating nanotech delivery systems. In November, it announced development completion of a “thermosensitive nasal gel delivery system” for its 5-MeO-DMT product candidates. Creating 5-MeO-DMT analogs to treat the symptoms of eating disorders (BMND04) and chronic pain (BMND05), the company says its nasal gel consists of an “adequate viscosity liquid, which turns into a mucoadhesive gel almost immediately after insertion into the nasal cavity upon contact with the mucosa at body temperature.”
Biomind Labs CEO Alejandro Antalich remarks that “the delivery system has the potential to allow for decreased doses compared to the doses necessary to achieve similar results through other forms of systemic administration.” While Biomind Labs is involved in Phase 1 and 2 studies of both of ayahuasca and DMT, its work with 5-MeO-DMT is still in the evaluation and pre-clinical stage.
Lexston Life Sciences Corp.
Canadian company Lexston Life Sciences Corp. has previously focused on providing cannabis testing and research services and is now expanding into research of naturally derived 5-MeO-DMT. The company announced in January an agreement with Egret Bioscience Ltd. and Alvarius Research Inc. to investigate the entourage of various tryptamines produced in the Colorado River toad.
Alvarius is an R&D company focused on conservation and genomic resource development for the amphibian. Lexston says that Alvarius recently “commenced an ex situ conservation program with eight individual toads from two independent captive populations and has developed ethical means to harvest parotoid gland secretions.”
The company’s aim is to characterize key tryptamine profiles with the goal of optimizing future breeding populations. The teams say they will also jointly develop an alternative to synthetic toad-free tryptamine production, using a cell-based culture pipeline to produce the compounds of interest while seeking to retain the natural entourage effect.
Cybin is aimed at progressing psychedelics to therapeutics for a range of indications including depression, alcohol misuse, neuroinflammation, and anxiety. Part of its recent work with respect to 5-MeO-DMT has been the pursuit of a patent position for R&D evaluating “deuterated” tryptamines for psychedelic-based treatments.
Deuteration refers to the process of modifying a drug molecule to create improved pharmacokinetic or toxicological properties. The increasingly prevalent IP tactic using deuterated compounds has been employed by Cybin as a strategy for filing its novel analog of the drug 5-MeO-DMT, a tryptamine, with the U.S. Patent Applications Office (USPTO).
In February, the company announced it was granted a USPTO patent for its investigational compound CYB004, which includes a range of deuterated forms of DMT and 5-MeO-DMT. Cybin CEO Doug Drysdale says this development gives his company an edge in creating next-gen drugs using 5-MeO-DMT. Drysdale said in a statement that the USPTO grant adds “strong protection for our growing intellectual property portfolio of psychedelic-based compounds, supporting and protecting the investments that we are making in our CYB004 program.”
Image: Nicki Adams