On a Psychedelic Future
Note: The views expressed here are my own.
Over the last year, Helena has undergone a deep-dive in the space of psychedelics. That journey has culminated in the opportunity to partner with Lykos, formerly known as MAPS PBC. We announced on January 5th, 2024 that Helena is the lead investor of Lykos’ oversubscribed Series A funding round. The round marks a capital infusion of more than $100m over the last 12 months, arriving on the heels of the company’s official submission of MDMA-assisted therapy to the FDA for approval.
This experience has been one of the most profound things I have been involved with. As with every effort we take on at Helena, our work with Lykos goes beyond just an investment. While much of our diligence process excavated the promising path forward for financing, developing, and deploying psychedelic therapies, Helena’s decision to partner with Lykos was rooted in a profound belief in the powerful societal-scale benefits psychedelic medicine will unlock. The more nuanced “why” behind Helena’s investment, which I intend to explore here, exemplifies core philosophical elements of Helena’s thesis and mission.
We are living though a species-defining moment where multiple Manhattan Projects are running in parallel. The development of AI, biological engineering, and other technology platforms absolutely deserve the attention and scrutiny they receive. Their impact today has already reshaped daily life, and their Nth order effects are far out of reach of human cognition.
What is clear to me as well, however, is that we are making contact with another, very different, technology with the potential to create ripple effects at a similar order of magnitude. Yet in this case, the R&D has been taking place over billions of years, in the evolution of botanical compounds harboring incalculable healing potential. That technology stack in its complete form has been sitting in plain sight on our planet. And unlike other exponential technologies, some of Earth’s oldest and wisest cultures have been perfecting how to safely and effectively administer it for thousands of years, only to be marginalized and ignored.
Psychedelic compounds encompass a wide array of substances that, when interacting with the human body under the correct protocols, can treat some of the most intractable problems we face in mental health. Peel away the next layer, and the applications go far beyond that. Psychedelics could serve as a needed “OS update” for our inward selves during a time in which other technologies create unprecedented transformation in the world around us. My hope is that Helena can play a small role in the needed advocacy, research, capital allocation, and policy work necessary to shepherd the safe and effective implementation of this technology on a global scale.
The Current Moment: MDMA-Assisted Therapy for PTSD and Why it Matters
Helena’s narrow function is to identify potential solutions to societal problems, conduct the best diligence we can to ascertain whether a given solution could be effective and whether we can meaningfully help, and then implement that solution. Our exploration of the psychedelic space began from that vector. PTSD is an inarguably critical societal problem exacting an enormous quantitative economic and human toll. Its qualitative effect on humanity is perhaps more dire — listen to a patient talk about what they were prevented from doing, from feeling, from experiencing, due to this condition. Now scale that up to devastating global effect.
The legacy treatment paradigm of PTSD is insufficiently effective and driven by flawed incentives. Selective serotonin reuptake inhibitors (SSRIs) are the only medications approved by the FDA to treat PTSD. While it would be wrong to attack them in a binary, it’s also clear they are in no way a systemic solution. Among a host of other salient problems, an estimated 40-60% of patients do not respond to SSRIs.
It is fair to say that a therapeutic which primarily increases serotonin is not an optimal counterpunch to the highly complex, and still not understood, functions of the human brain and body represented in PTSD. Complicating this, patients must often rely on SSRIs indefinitely, which obviously creates a troubling economic relationship between the pharmaceutical industry, our healthcare system, and its constituents.
Talk therapy, still critically undervalued in our society, is one of the strongest tools we have in addressing PTSD. But it alone is not a panacea. Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. summarized it best in Nature Medicine: “Although evidenced-based trauma-focused psychotherapies such as prolonged exposure and cognitive behavioral therapy are considered to be the gold standard treatments for PTSD, many participants fail to respond or continue to have significant symptoms, and dropout rates are high. Novel cost-effective therapeutics are therefore desperately needed.”
MDMA-assisted therapy promises to be that desperately needed therapeutic. Pioneered by the Multidisciplinary Association for Psychedelic Research for nearly 40 years – culminating in the establishment of its public benefit corporation Lykos – MAPS doggedly pursued its goal of shepherding the treatment through regulatory channels against insurmountable odds.
It is hard to overstate the barriers to entry MAPS Founder Rick Doblin (and the countless leaders that paved this path forward) faced in the service of creating greater legal access to psychedelic medicine. Getting a single drug through the FDA pipeline costs north of hundreds of millions of dollars, and it is exceptionally rare to do so if you are not an existing pharmaceutical giant or directly affiliated with one. That MAPS was none of these things was politely noted to us by detractors as “the kiss of death.” Another complication: from a regulatory standpoint, the treatment is the first-of-its-kind. No psychedelic-assisted therapy has ever gone through the FDA process. To make matters even more challenging, and up until the creation of Lykos, the for-profit entity taking MDMA-assisted therapy through Phase 3 trials and commercialization, MAPS was marshaling resources through a non-profit, donation by donation.
But these obstacles still pale in comparison to the biggest barrier MAPS and the psychedelic community had to overcome over the last half century: culture. For decades, institutional actors within media, government, academia, regulatory agencies, and law enforcement bodies mounted a concerted effort to disorient, discredit, and even at times manipulate data to oppose psychedelic research. Thanks in no small part to Doblin and his colleagues, we now live in a vastly more curious and accepting environment for this work, with bipartisan coalitions across the FDA, VA, White House, and Congress championing the medical and societal benefits of psychedelics. Especially for members of my generation, we forget this was not the case until recently.
The prevailing view of MDMA for much of the last 30 years was that it was a dangerous drug causing neurotoxicity, among other severe health effects. While the science has now debunked the neurotoxicity claim, the ability to even produce the research to demonstrate that falsehood was discouraged and at times illegal.
The history of America’s “War on Drugs” is tragic, fascinating and deeply complex. One of its many detrimental consequences has been a structural bias that curtailed deep investigation into the mechanisms and effects of psychoactive substances.
Such bias was codified through legislation, including a long-enforced federal policy prohibiting government funding of “any activity that promotes the legalization of any drug or other substance in Schedule I” of the Controlled Substances Act. (Psychedelics including LSD, psilocybin, and mescaline were classified as Schedule 1 by the DEA in 1970.) Today, bipartisan efforts, spearheaded by the unlikeliest of allies —including legislation recently submitted by Representatives AOC and Dan Crenshaw — are focused on reversing such policy. But while in place, it significantly impeded scientific advancement in the field, stigmatizing researchers and forcing them to risk their careers in order to take part in the work.
In 2002, an existential event nearly wiped out public support and funding for MDMA-assisted therapy research, delighting detractors. A scientific study titled “Severe Dopaminergic Neurotoxicity in Primates after a Common Recreational Dose Regimen of MDMA” was peer-reviewed and published in one of the world’s top academic journals, Science. The paper claimed that monkeys injected with MDMA demonstrated severe neuron death in their dopamine pathways. What’s more, the researched contended that as little as one session of MDMA could cause severe brain damage and potentially leave subjects susceptible to Parkinson’s disease.
The repercussions were immediate. Organizations like MAPS experienced an influx of funding withdrawals from key donors and legislative pushes aimed at curbing MDMA research, including the RAVE Act of 2003, were ratified. Referencing the study, former Director of the National Institute on Drug Abuse (NIDA) and head of the American Association for the Advancement of Science (AAAS) Alan Leshner asserted in The Washington Post that “even a single evening’s use [of MDMA] is playing Russian roulette with your own brain.”
Meanwhile, trouble was brewing at Science, the journal that had first published the study. After letters to the publication from MAPS and other researchers questioned the findings and asked for them to be re-tested, lead researcher and author George A. Ricaurte doubled down, adding claims that undergoing lab-grade clinical MDMA research risked brain injury on subjects.
Nevertheless, under pressure from the scientific community, the research team did attempt to run the study again and reproduce the same results. They couldn’t. An investigation into the original study’s methodology ensued – revealing an extraordinary falsification at its center. Instead of MDMA, researchers had administered methamphetamine (yes, meth) to its subjects. In what was dubbed “the great retraction,” Science issued a formal withdrawal of the paper in September 2003, almost exactly a year after its original publish date. It was a shocking outcome that completely invalidated the study, but the reputational damage to MDMA research had been solidified.
If you are party to the view that American political incentives influence academia and the peer-review system, so much of this situation is worth scrutinizing. Remember Alan Leshner, former director of NIDA and then-head of AAAS? It’s worth noting that Science is AAAS’ own journal. Nature, another world-class academic publication, wrote an excellent 2003 analysis of this episode and its political undertones. Calling the saga “one of the more bizarre episodes in the history of drug research,” Nature noted that “Some observers have in the past questioned NIDA‘s ability to maintain its independence in the face of the immense pressures brought to bear by those who stand behind America’s interminable ‘war on drugs.” On Leshner and the curious timing of his comments, the report pressed on: “Another remarkable aspect of this episode is the public endorsement of the study, at the time of its publication, by Alan Leshner, chief executive of the AAAS and former director of NIDA. It isn’t clear why an officer of the AAAS should be involved at all in publicly promoting a particular result published in its journal, least of all one whose outcome was questioned at the outset by several experts. The AAAS issued the retraction late in the afternoon on Friday 5 September, resulting in low-key media coverage, which contrasts sharply with the hype surrounding the initial paper.”
This is the environment in which MAPS and other research organizations were fighting within for much of their lives. The Great Retraction took precious years off the timeline of MDMA-assisted therapy and related research, leading to some of the darker moments in the movement. During this period, the treatment became increasingly difficult for those in need to access. A tragic story involving involving a Florida resident named Zulfi Riza is reflective of the era. Riza had been suffering from severe PTSD, depression, anxiety, and anger-management issues, and had tried multiple therapeutic treatment options to no avail. In 2006, he reached out to MAPS founder Rick Doblin to enlist his help in accessing MDMA-assisted therapy. His symptoms were severe and he described MDMA-assisted therapy as his last hope. At the time, Doblin was performing a high wire act to advance government-approved research trials under intense scrutiny. Riza had a history of seizures that Doblin worried would expose a therapist to liability should an episode occur during treatment. He also worried about intensified public criticism in the wake of such an incident. Doblin wrote back saying he sadly couldn’t help. Riza ended his life the same morning, noting in his suicide letter that he granted permission to use his story if it helped advance the cause.
Venture capitalists love to talk about audacious founders and moonshot projects that change the world. I don’t want to diminish the achievements of others. But if you want to be real about audacity, this is it. Over the course of decades and against layers upon layers of resistance, MAPS, Lykos and its peers simply refused to let this research die. That’s a big reason why we are partnering with them.
Beyond PTSD: Unleashing the Healing Potential of Psychedelics
Helena’s decision to lead Lykos’ landmark Series A financing reflects not just our desire to advance the puck on providing meaningful treatment to the millions affected by PTSD, but also our belief in the wider unearthed potential of psychedelic science. We hope that this key moment for MDMA-assisted therapy will usher in a new “golden era” of psychedelics and their myriad applications.
This chart should scare you.
In only 20 years, the leading causes of death of the most economically vital population segment of the most important country on the planet have completed shifted from transportation accidents to opioid addiction and suicide. And we haven’t gotten much better at preventing car crashes.
This is a “metacrisis” — a symptom of an underlying problem with unfortunately far wider implications. Its causes are complex and multitudinous; reducing the issue to a single explanation both exacerbates the issue and doesn’t do it justice. But when we look at the severity of death and suffering in the world’s richest society emanating from two places —opioids and mental health — certain throughlines emerge.
Our system is one of sick-care rather than preventative care, and mental health is the frontline. Nearly 1/5th of the US GDP is spent on healthcare, yet it is a system in which capital allocation structurally prioritizes reaction over prevention, amongst other critical issues.
Psychedelics can play a role in changing this. This scientific field represents an incredibly powerful new way of approaching treatment of the complex adaptive system that is the human brain. Across the highly diverse array of psychedelic compounds and treatments currently known, not all of them will, or should, progress toward approval for use at societal scale. But many should, and it is imperative that we continue to advance efforts to safely shepherd these treatments through the necessary channels.
Think about it this way: a treasure-trove of highly advanced and potentially effective treatments to some of the most critical ailments we face already exists, but thus far they have failed to be thoroughly researched. For reasons political, cultural and economic, an arbitrary slow down has been placed on the investigation into and development of these compounds for the betterment of humanity.
We feel this paradigm is finally changing, and we want to do whatever we can to responsibly accelerate that change. MDMA-assisted therapy represents a “here and now” project that could affect millions, but right behind it are a multitude of deeply exciting developments.
Ibogaine is an example.
It is one of those origin stories you just can’t make up. Extracted from the root bark of a shrub plant called iboga native to Central and West African countries like Gabon, this psychoactive substance has been shown as an astoundingly effective treatment for those addicted to heroine and cocaine. Like MDMA-assisted therapy, the history of ibogaine research stretches more than 100 years into the past, with heavy institutional resistance that is finally giving way.
Used for centuries as a sacred indigenous ceremonial and healing modality, the Iboga plant was embraced by psychonauts like Howard and Norman Lotsof in the 20th century. Like Doblin, the Lotsof’s labored relentlessly for decades in an attempt to legitimize and fund scientific trials. Weathering setback after setback, the small community they and others fostered gradually began to treat those facing severe cases of opioid addiction and PTSD in treatment centers outside of the United States. The staggeringly effective outcomes these sessions yielded are now coinciding with research generating from elite academic institutions. A study by Alan K. Davis et al., demonstrated significant reductions in suicidal ideation, depression, and PTSD symptoms amongst US Special Forces Combat Veterans, who have become a core and vocal constituency for further ibogaine research. In a pioneering first program in the United States, the State of Kentucky plans to allocate $42m to ibogaine research for opioid addiction treatment. The funds come via the Kentucky Opioid Abatement Advisory Commission, which is tasked with effectively utilizing the nearly $850m the state has received from landmark settlements with major pharmaceutical corporations over their roles in the American opioid epidemic.
Dr. Nolan Williams, who leads Stanford’s Brain Stimulation Lab and is triple-board certified in general and behavioral neurology, psychiatry and neuropsychiatry, has recently published a new study that confirms and further expounds upon ibogaine’s effectiveness in treating one of the most severe indications in neuroscience: traumatic brain injury. The study, published in Nature Science, was conducted with Special Operations veterans, who began the course of treatment with an average disability assessment scale rating of 30.2 —equivalent to mind to moderate disability. After one ibogaine treatment, their rating decreased to 5.1 — equivalent to no disability. Their PTSD symptoms in the same time frame? 88% decrease. Suicidal ideation? Plummeted from 47% to 7%. Anxiety and depression? Down 81% and 87% respectively. All of this occurred while cognitive factors ranging from concentration to memory to information processing increased. Williams summarized it plainly: “No other drug has ever been able to alleviate the functional and neuropsychiatric symptoms of traumatic brain injury.”
Research into compounds like Ibogaine has produced staggering evidence suggesting that major treatments for opioid addiction and mental health, the two leading causes of death for the young adult population of the United States, exist. Considered through this lens, the dearth of funding for these treatments, when compared to far less effective pharmaceutical treatments, poses a dangerous reality.
To the extent that psychedelic treatments are being researched and commercialized, however, another key problem has arisen. The discovery and understanding of most of these compounds derive from indigenous communities dating back thousands of years. In large part, these communities are being marginalized and harmed by the Western psychedelic awakening. In the case of ibogaine, for example, the iboga plant is already gravely over-harvested from the land of indigenous nations and communities by Western actors in pursuit of profit.
This is not a sideline issue for psychedelics; it is an existential one. For years, indigenous knowledge has been the portal through which the western world has encountered and understood the transformative power of psychedelic compounds. It is therefore imperative that these communities share in the economic windfall of the commercialization of psychedelic therapies. Representatives from these groups must also be deeply integrated at a leadership level – not pushed aside. Beyond the moral obligation to ensure that the burgeoning field includes, rather than exploits, those with whom the underlying practices and methodologies originated, the involvement of indigenous peoples in the scaling and dissemination of psychedelics will help safeguard foundational knowledge around how to effectively administer them.
The “set and setting” in which psychedelic therapy takes place, as well as the “integration” component that takes place after treatment, are both integral to its effectiveness. Pharmaceutical capitalism does not understand this very well. The economic model in which the lowest cap-ex solution — “sell the pill” — is perceived to yield the highest shareholder value disincentivizes the holistic framework psychedelic therapy requires. Those leading the movement forward must act as a standard-bearer in the scaling of these treatments – ensuring that holistic criteria are met and appropriate representation is achieved. MAPS and its public benefit company Lykos, have demonstrated just such a commitment to the values that must accompany the ethical and safe deployment of psychedelic therapy.
The Long Term
The short and medium term applications of psychedelic compounds in a medical context will furnish profound societal-scale benefits. But the as-yet-unknown future applications may be even more exciting.
We now laugh at the idea that the mid 19th century invention of the telephone was regarded by most as a device for elocution lessons and an aid for the deaf. 100+ years from now, I think that we will laugh at the notion that compounds from MDMA to psilocybin or ibogaine were once viewed in isolation as party drugs or therapeutic answers to individual medical questions. It is possible that existing use cases will be the least impactful, and the least impressive, ways in which psychedelics affect our species.
The untapped potential of ibogaine is a prime example. We simply do not understand how it works. Affecting and interacting with a multitude of neurotransmitters in parallel, the compound is a masterclass in complexity science. Biologists, chemists, and computational computer scientists who don’t even study health or neuroscience are captivated by the compound because it presents one of the most fascinating enigmas in modern science.
I’m optimistic that continued research into psychedelics, paired with future breakthroughs in computation and artificial intelligence will decode the underlying functions of these incredibly complex agents. At Helena, we hope that our support of Lykos and future work in psychedelics helps catalyze the chain reaction necessary to reach these outcomes. The results could be a generational benefit to humanity.