In this episode, Joe interviews the Co-Founders of Enosis Therapeutics: researcher and scientist, Agnieszka Sekula; and psychiatrist, clinical advisor to the Australian Psychedelic Society, and leading Australian advocate for psychedelic-assisted psychotherapy, Dr. Prash P.
Enosis Therapeutics is a medtech startup that began with the question: how can we use VR – with or without psychedelics – to improve mental health outcomes? They feel that the biggest problem with powerful psychedelic experiences is that, once you’re back in reality, it’s oddly difficult to remember the insights and new ideas that were so clear during the experience, and even harder to make connections that lead to concrete change. They believe that the immersive nature of VR and the novelty of unique VR environments creates a sense of presence that can’t be recreated otherwise – a liminal, in-between state that’s just different enough to allow the patient to feel like they’re back in that non-ordinary state, and therefore more able to anchor their experience and begin to find connections and more clearly understand newfound insights.
This all happens by the user essentially creating nonlinear, abstract, multi-sensory VR paintings while describing what they remembered; allowing them to revisit these worlds later, bring in therapists (or anyone else) to work inside these environments, and hear their own voice describing what happened, thereby creating a mental map that can be worked with in completely unique ways.
They talk about the conflict between new technologies and traditionalists; the problems with moving away from psychoanalysis and not treating psychotherapy as a process; how VR could improve the efficacy of therapy (and improve therapists’ lives); how it could replace models of repeated dosage; how VR could generate analytics to actually quantify success in mental health treatment; and how (whether psychedelics are used or not) culture needs to bring the psychedelic way of thinking to mental health.
“Imagine that you build out that network, that you make it physically visible and tangible, and you can actually have someone that comes into that space and visits that network. So you can share your mental model with anyone that you want: it can be a therapist, it can be a guide, it can be a shaman, it can be a well-being specialist, it can be your partner, it can be your parent, it can be your child. It can be anyone that you wish had a better understanding of you, but they don’t. It’s hard to understand ourselves, [much less] understand each other based on those linear narratives. But if we actually see how people connect things [and] how they see those links, I feel like we have a much better chance to actually connect to each other and have a better understanding of consciousness.” -Agnieszka
“So much of the focus in psychedelic therapy has been on the dosing session, whereas a lot of us would like to think that it really should be on the psychotherapy, and the psychedelic is purely that stimulus that ignites the insights which you then take through psychotherapy. If that stimulus can be the stimulus which ignites a process of psychotherapy, and therefore the power of psychotherapy to produce change, and in that way, brings psychotherapy further to the forefront of mental health treatment (in a way, it’s completely disappeared and been replaced by biological methods), then I think we have won – just by that.” -Prash
“We can induce a similar psycho-emotional state with the use of VR during the integration sessions to help patients remember, at their psychological and at an emotional level, what the experience has been like. …A lot of studies (especially earlier studies) would report that within the first two weeks after the psychedelic experience [is] the most potent time for integration because patients are still in that emotional state that was evoked with psychedelics. So maintaining that for longer by repeat application of VR might give us more access to those emotions, and might enable patients to process things a little bit more deeply.” -Agnieszka
In this episode of Psychedelics Weekly, Kyle and David meet up to talk news, but end up mostly having a discussion about the numerous challenges facing the rapidly growing industry of psychedelic therapists, guides, and facilitators.
That discussion comes from the article, “Psychedelic workers of the world, unite!”, which breaks down the shortcomings and risks of an industry many are flocking to without realizing what they’ll likely have to deal with: unprecedented legal and financial risks, burnout, misalignment with management, transference and countertransference, and what happens when one finds themselves in the middle of a genuine emergency? While these issues could be found in any industry, a big reason why they seem so prevalent and dangerous in the psychedelic world is our lack of elders and passed-down experience – and the faster this all grows, the more we need that guidance.
And for news, they talk about Ohio State making history as the first U.S. University to receive a license to grow psilocybin mushrooms; a new study showing that LSD enhanced learning, exploratory thinking, and sensitivity to feedback; and the National Institute on Drug Abuse (NIDA) funding $1.5 million to research the efficacy of psychedelics for substance use disorder – which spurs a conversation about research, funding, and the idea that maybe we’re spending too much time and money on neuroscience.
In this episode, Joe interviews Nick Kadysh: Founder and CEO of PharmAla Biotech and member of the board of directors for The Canadian Psychedelic Businesses Association.
PharmAla Biotech is a Toronto-based Life Sciences company with two focuses: contracting with manufacturers to provide researchers with GMP MDMA (created under Good Manufacturing Practice regulations), and creating and researching novel analogs of MDMA. And just today, they announced that Health Canada has authorized them (and their distribution partner, Shaman Pharma) to supply their LaNeo™ MDMA for the treatment of a patient under Canada’s Special Access Program – the first time this has happened in Canada.
He discusses the creation of PharmAla and why their model changed from primarily researching analogs to manufacturing; why they’re operating out of Canada and using manufacturers instead of running the lab themselves; the excitement around Australia’s recent about-face on MDMA and psilocybin-assisted therapy; the bureaucracy of U.S. drug policy and how much a broken supply chain affects the whole industry; bad IP and companies filing rapid fire patents; why creating new analogs of MDMA is so important; and why the psychedelic space needs to bring culture along with us.
He also talks about Spravato, cannabis and risks of cancer, THC nasal sprays, and research he’s most excited about: that MDMA seems to alleviate dyskinesia caused from Parkinson’s disease, and that MDMA could improve social anxiety in people with autism. He’s aiming to run a clinical trial and believes they have developed a safe MDMA analog that the autistic community will respond to very well.
“I don’t want to give the impression that we think that MDMA is unsafe. In the case of PTSD-assisted psychotherapy the way that it’s being presented by MAPS, I think it’s remarkably safe. But, you know, better is still possible.”
“If you told me that you have a brand new drug that was developed in a lab that nobody has ever seen or tried or tested before, and let’s call it drug A. And then you have drug B, which is derived from a mushroom, that people have been consuming regularly for the past 5,000 years and no one’s died. And you’re asking me which one is safer? It’s the mushroom, man. It’s not even a question.”
“We owe it to ourselves in this industry to take the population along for the ride. This is why I think safety is so important, because if you’re working on safety, people like that. People trust that. That’s what happened last time: there was the counterculture and the culture, and the culture won, and we’re still paying for it today. So let’s bring the culture along.”
Psychedelics are a fascinating class of compounds that have potent effects on our consciousness. After a multi-decade hiatus, scientific research on psychedelics has now resumed with full force. One field that has rapidly developed in recent years is psychedelic neuroscience, which applies the cutting-edge frameworks and tools of modern neuroscience to understand how psychedelics affect the brain and nervous system to elicit their profound effects. The latest findings from this breakthrough field have increasingly spilled into popular culture and are often profiled in the media – it’s now commonplace to hear terms like ‘default mode network’ and ‘neuroplasticity’ casually thrown around when discussing psychedelics and their effects.
However, much of the research is quite technical, and typical media treatments are often either highly simplistic and watered-down, or plainly inaccurate and sensationalistic. Most people just don’t have the necessary background to properly understand and communicate findings beyond repeatable buzzwords and trickle-down narratives.
It’s easy to wonder: what’s the practical relevance of psychedelic neuroscience for psychotherapy or for individuals navigating their own psychedelic experiences?
Don’t Worry – It’s Only Temporary
Understanding the science of psychedelics can be really helpful for therapists and clinicians preparing their clients for psychedelic experiences, and helping clients conceptualize and understand their experiences afterward. Psychedelic experiences can sometimes be quite overwhelming and hard to make sense of. It can be challenging to experience the profound alterations of consciousness they can elicit, which span from complex dream-like images and vivid memory recall, to ego-dissolving mystical-type effects, to perceptual distortions and synesthesia.
By reminding and reassuring clients that the intense effects they are experiencing are directly related to temporary changes in brain activity, clients may be less concerned that they are “gone without return” or that there is something inherently “wrong” or “bad” about their experience. It can also provide a useful model or framework to ground and interpret what emerges during their journey. They can rest assured that no matter how radical and reality-shattering their psychedelic experience is, it’s being underpinned by temporary changes in how brain regions are communicating and interacting over time.
Their findings also appear to suggest that priming subjects to reduce theta power before taking a serotonergic psychedelic may help increase the depth of their mystical experience. For example, an individual could reduce theta with neurofeedback training, in which feedback from an EEG headset would allow them to modulate their brain activity to achieve a desired brain and psychological state. Although further research is required before any definitive conclusions can be drawn, emerging research like this suggests that capturing information about brain states – beyond what can be subjectively reported – may prove to be a valuable tool in predicting an individual’s psychological readiness for a psychedelic experience.
The Nuances of Psychedelically Boosted Neuroplasticity
The proliferation of interest in serotonergic psychedelics, MDMA, and ketamine is in no small part due to their remarkable ability to act as ‘psychoplastogens’ – compounds that enhance neuroplasticity in the brain. Neuroplasticity refers to the ways in which neurons in the brain change their connections with each other or create new ones, which is critical for the brain’s ability to learn, adapt to new experiences, and recover from injury. Psychedelics’ ability to enhance neuroplasticity has frequently been highlighted as central in eliciting therapeutic effects across a range of mood disorders and stress-related conditions such as depression, anxiety, and PTSD, which makes sense because impaired neuroplasticity has been reported for all of these disorders.
Research in rodents has suggested that, generally, for most psychedelics, the period between six and 72 hours post-psychedelic experience is when neuroplasticity is at its highest.
However, changes may last for much longer. For instance, LSD has been shown to promote the expression of neuroplasticity-related genes in rodents even one month after treatment had ceased. More and more research is being conducted on these effects, but there is clear practical relevance for clinicians, therapists, and everyday people. Understanding the nuances of psychedelically boosted neuroplasticity – including how long the effects last and where in the brain they occur for a given substance – is critical for designing optimal integration practices.
An in-depth understanding of psychedelic neuroscience can serve as a valuable tool for therapists and individuals seeking to navigate the intricate and potentially transformative realm of psychedelics. Familiarity with scientific research can empower practitioners to tailor their approach to preparation, the acute experience itself, and integration, thus optimizing therapeutic outcomes.
She discusses her path to psychedelics, how she ended up running the Initiative 81 campaign (the Entheogenic Plant and Fungus Policy Act of 2020), and how she came to realize that decriminalization efforts can’t be the only option we go for – that, like it or not, we live in a system where politics and money are major factors behind any systematic change, and if we want to make any headway, we have to play the game. The Psychedelic Medicine PAC (Political Action Committee) was created to open up federal funding for psychedelic research, as nearly all research today (of which there still isn’t enough) is being funded by private companies. They will use donations to support politicians who are on our side and can advance psychedelic progress, who will push for federal funding to get the new and necessary data people who aren’t bought in yet need to see.
They talk about speaking with people from the other side of the aisle at a recent education campaign in DC; how federal funding is neutral money; what she learned from DC’s deprioritization of cannabis policing; how personal stories and one-on-one human connection can change minds better than traditional confrontational activism; and the need to get ahead of the inevitable wave of big pharma propaganda they’ll bring when they officially step up to the table. She believes the path to helping the most people is advancing science and data through federal funding, and that begins with education and getting more politicians on our side. If you agree, follow them for details about their upcoming event in May, visit their table at Psychedelic Science this June (use PT15 for 15% off tickets), and donate to the PAC or the coalition.
Also, as a bonus, this episode begins with a mini version of Psychedelics Weekly. Joe and Kyle didn’t have enough time to record a full episode, but still wanted to check in and review a few notable stories and highlight our recent Vital graduation ceremony. See you next week!
“I dipped my toes with the microdosing [and] I found immediate effects of that. I engaged with my children for the first time in many years, and with my son for, really, the first time since he was born. So that was a really mind-blowing experience of taking something for only a few days and feeling my humanity come back again.”
“I think when you take the media out of it and you isolate them in a place they feel very safe (in their office) and there’s no cameras around and they don’t feel the need to get their talking points across, and you have a human-to-human conversation with them about this issue, the result is that much better because you isolate all of these external influences that they’re constantly under and you say, ‘Listen, I am talking to you as a human being. This was my experience. This is what I did to heal myself.’ …Watching them have their epiphany about this is so fun.”
“When these campaigns win with very small margins (like 1%, 3%, 5%), that means half of the state voted against it, and that means half the state wasn’t being spoken to in these campaigns in the right way. …The U.S. is extremely diverse, and not just racially, but within perspectives that exist in this country, and we cannot just be speaking to one side of this issue. We have to really engage with the public in a meaningful way, and that is speaking to the half of the country that doesn’t understand this.”
“We forget that the traditional pharmaceutical industry has yet to step in on this issue. I think that they’re very closely watching what’s going to happen with psychedelics, but they have yet to stick their lobbyists on the hill. And that is the day that I am not looking forward to, because they have one of the most powerful lobbies in the country and they have budgets for this kind of work in the billions of dollars, really. So how is the psychedelic industry going to compete with that? How you counter that is: you educate members of congress, you educate those influential people before the pharmaceutical industry gets there so they can’t fill their heads with misinformation.”
In this episode, Joe lets Court Wing take lead in interviewing two of the leaders behind Clusterbusters: Founder and Executive Director, Bob Wold; and President, Eileen Brewer.
A long-time friend of the show, Court Wing has become our resident expert on chronic pain, writing articles about how psilocybin relieved his chronic pain, and hosting Timothy Furnish, MD & Joel Castellanos, MD in their episode about phantom limb pain. Now he speaks with Clusterbusters, a non-profit dedicated to educating people about the horrors of cluster headaches, funding ongoing research into new treatments, and normalizing the miracle that psilocybin has been to so many sufferers in alleviating their headaches.
Wold and Brewer discuss their past struggles (Wold is a cluster sufferer and Brewer has migraine disease) and discovering the amazing intervention of psychedelics; the battles they’ve gone through in spreading this knowledge; how using psychedelics is also helping people work through PTSD; the barriers that legal psilocybin is creating; the concept of schools having a drug education program; the research looking at cluster headaches and other headache diseases; their creation of the Pain And Psychedelics Association, and more. While cluster headache sufferers have a lot to be frustrated about; as psilocybin becomes more mainstream and more and more research is funded, they now have a lot of hope.
“A couple of people started growing their own mushrooms and self-treating themselves just to try it to see if it might actually help, and the results were incredible. It was better than anything that any of them had tried in the past. It wasn’t really an abortive (it wasn’t treating one headache) and it wasn’t really a preventive, where you would take it and you would prevent some of your cluster attacks. It was something that was actually doing both of those things, and people were getting long-lasting results by one or two doses of magic mushrooms.” -Bob
“It makes sense that that would happen within a disease community, it happens outside of disease communities too. Some people just use psychedelics occasionally just to get that perspective back and to work within themselves (and without themselves) to sort it all out, [and] get themselves back together. And I think there’s a real division there between people who do that and people who don’t.” -Eileen
“The two or three years before my first dose of psilocybin, my medical bills were like $20,000 a year trying to treat my clusters. That included hospital stays and specialists and travel. …The first time I grew my own mushrooms, it cost me a hundred dollars to grow a year’s supply and I didn’t have to go to Walgreens to pick up my medicine. So my medical treatment for the following year for my cluster headaches was $100 versus $20,000 and I was able to take as much as I needed when I needed it. And at this point, that’s what most people with headache disorders are doing; they’re growing their own because the system is going to take years and years to be built into something that’s actually accessible to everybody – and affordable.” -Bob
“People are dying while we’re waiting for these policies to happen, and I’m really struggling with the fact that we are setting up more barriers. I know that all the intentions are good, but we are hurting people.” -Eileen
In this episode, David interviews neuroscientist, artist, and educator, Melanie Pincus, Ph.D.; and Ph.D. candidate in Neuroscience, lead or co-author on over a dozen scientific publications, and regular contributor to PT, Manesh Girn.
They tell their stories of how they became interested in neuroscience, and stress the importance of staying radically open-minded (or “epistemically naive”) when it comes to how much we can claim we understand about the brain, the mind-body connection, and consciousness itself – that while fMRI and other advances have brought us a long way, there are still a ton of “unknown unknowns,” especially around creativity, decision making, and imagination. They discuss the misconception that we only use 10% of our brains; comparisons between the brain and the universe; society’s misunderstanding of “happy hormones” (dopamine, serotonin, etc.); how chronic stress takes a toll on all parts of the body; how MDMA works with memory processing; and how stacking modalities with the psychedelic experience (like play or activities focused on emotion regulation) can really help with personal goals and growth.
Class begins on May 17, and if you sign up before April 12, you can get $100 off!
“There’s so much good science now, and good neuroscience that can inform how people work with their clients in terms of helping them set up for and make sense of their psychedelic experience and ways to optimize the preparation before going into a psychedelic journey, the actual psychedelic journey in terms of thinking about dosing and type of substance to work with, and then also in the integration period, where there’s this heightened window of neuroplasticity and how one could really work with a client to best take advantage of that window of opportunity to lead to lasting change.” -Melanie
“It’s just this blob, this squishy blob of matter. And you think: for that person, their entire life, experiences, memories, [and] hopes were all happening in this little blob that’s in my hand. And just seeing all the layers of blood vessels and how everything’s connected to each other, it’s just fascinating and it’s downright bizarre that somehow, this thing can give rise to experience and consciousness. It’s like, how the hell is that even possible?” -Manesh
“For people who are interested in stacking modalities, there’s other modalities that are really potent at promoting neuroplasticity. So if you want to synergize with the window of plasticity during the integration period, you could for sure partake in regular exercise, because that’s one of the most well-known plasticity promoters.” -Melanie
“How do we respond adaptively to times of change? How do we adjust ourselves? How do we create homeostasis in a changing environment, and how do we adapt to new circumstances? And this is also a whole brain/nervous system/body affair as well, on how to regulate your entire organism to deal with change and to be resilient and to be adaptable. It’s not just in the brain. It’s not just in the brain at all.” -Manesh
In this episode, Joe interviews Ph.D. student in the Drug Use and Behavior Lab at the University of Alabama Birmingham, Haley Maria Dourron.
She talks mostly about the paper she co-authored last year with Dr. Peter Hendricks and Camilla Strauss: “Self-Entropic Broadening Theory: Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis,” which analyzes the long-standing comparisons between the psychedelic state and psychosis, and points out important distinctions between the two – that science should be looking more at the way one processes information and their level of self-focus rather than similarities in outward behavior. She discusses what she calls entropic processing, which is essentially how one’s brain creates novel ideas, relations, and insights based on very loosened mental schemas: with new information being considered in new ways (with no filter), do the connecting pathways that seem like eureka moments actually make sense?
She discusses the broaden and build theory and the broadening of intentional scope; entropy; chronic LSD use and risk of psychosis; schizophrenia and psychedelics; why science needs to embrace naturalistic research, and more. As of this release date, there are still a few participatory spots left in her current study on the effect of psychedelic experiences on people who have a history of psychosis, so if you had an episode of psychosis at some point and have gone on to use psychedelics, she wants to hear your story.
“It’s such a wide open space where there’s still so much room to learn. And to me, it feels as if we’re opening a time capsule of all these different questions that have been kind of covered up, and we now have better technologies to probe what’s really going on.”
“A lot of work was actually done in the 1950s, giving people with schizophrenia LSD, psilocybin, [or] DMT, [and] oftentimes, apparently they had a reduced response. So that just shows how much more room we have to learn what really could be happening with these drugs, what populations necessarily should be excluded, [and] who is actually likely to experience adverse responses.”
“The acute experience might kind of serve as a catalyst for people creating changes, but then it’s ultimately the changes that they make in their daily lives afterwards, and if they’re putting in the work of building those enduring resources, if you will. It might be [easier] to do so in the immediate afterglow of a psychedelic experience, but you’ve still got to try if you want those enduring effects.”
In this episode of Psychedelics Weekly, Joe and Kyle are back at it, talking about news and what’s going on at Psychedelics Today (applications for Vital close this Sunday, March 26, and we’ve just announced a new neuroscience course!).
Following up on last week’s news that Field Trip Health had closed five clinics, they start with more unfortunate news: that Field Trip is laying off a lot of people, Ronan Levy has resigned as the CEO, trading has been suspended, and the company has obtained CCAA Protection (which, through the Companies’ Creditors Arrangement Act, essentially allows a struggling company a chance to restructure its finances to avoid bankruptcy, all through a formal Plan of Arrangement). And in similar news, all Ketamine Wellness Centers (an Arizona company recently acquired by Delic Holdings) would be closing immediately, with employees let go with little warning or explanation. These stories (and Synthesis Institute’s downfall) highlight the sad reality many of us in the psychedelic space forget: that just because a business is heart-centered and psychedelic-minded, it’s still a business, and businesses need to be profitable to survive.
Next, they cover Melissa Lavasani and the Psychedelic Medicine Coalition creating the Psychedelic Medicine PAC (Political Action Committee) to get more government funding behind psychedelic research. Members of PMC went to D.C. last week, presenting a psychedelic briefing to begin the process of educating legislators about the realities of plant medicines and psychedelic-assisted therapy (and Joe was there).
And they discuss more: concerns over Australia’s recent about-face on MDMA and psilocybin being used legally; a recent study where researchers used EEG and fMRI together to record what is happening in the brain while under the influence of DMT (and we should probably have Manesh Girn on again to explain it better than we could); and an interview with Eric Andre at SXSW where, in about 2 minutes, he brilliantly shines a light on drug exceptionalism, the lies of the drug war, and the need for more education on psychedelics – all to a bewildered reporter who didn’t seem prepared to talk to Eric Andre (we are- please come on the podcast!).
In this episode, Joe interviews the Co-Founder and CEO of Beckley Retreats, Neil Markey.
Markey describes Beckley Retreats as comprehensive well-being programs, and talks about the importance of holistic wellness – that, while the retreats are centered around two group psilocybin experiences, the true benefits come from complementary factors: the four weeks of online prep and community building before the retreat, the six days in Jamaica surrounding the experiences, the six weeks of integration work after, and the depth of connections people find in the new community they may not have realized they needed so badly. He breaks down the details of the retreats and what they look for in facilitators, and tells a few success stories that really highlight how trauma, opposing ideas, and an infatuation with material objects and amassing wealth can all get in the way of real relationships and meaning.
Beckley Retreats is currently working on two new projects: an observational study with Heroic Hearts and Imperial College London on using psilocybin for-traumatic brain injury, and a study with Bennet Zelner and the University of Maryland to bring executives through a retreat to see how it affects leadership and decision-making: can they prove that these types of experiences lead to more heart-centered leaders?
We are currently running a giveaway where you can win a one-on-one meditation class with Neil and a custom Beckley Retreats tote, as well as many other prizes. Click here to enter!
“The problem, a lot of times with Western medicine, is if you can’t understand the mechanics of it, then we kind of discard it, or if you can’t isolate a single variable, then we discard it. It’s like: well, some things work in tandem. If you actually peel the physics back, it looks like everything’s connected to everything, so we’ve got to think about more comprehensive approaches. I think that you can learn a lot from looking at traditional practices and some of the Indigenous wisdom that’s out there; that there’s a method to how this work has been done for quite some time and we shouldn’t disregard it.”
“If we can help people in a clinic model, let’s do that. But [with a] clinic, again: when you take someone, you give them a mystical experience, and then they go right back home or right back to work and right back into life, are you creating enough space for there to be optimal change? I think we need to keep studying it and asking those questions.”
“[Amanda Feilding] never saw a rule that she didn’t want to break. She’s [this] lifelong badass that has just gone against the grain for her entire career. But it was never about money for her, it was all because she thought she could help people. It’s so inspiring. We need more of those stories; less stories about people that made a billion dollars or whatever and more material things, and [more of] these stories about folks that are just out there trying to help others. It fires me up.”
In this episode of Psychedelics Weekly, David is joined by Kyle, who is finally home after a lot of traveling, to talk shop and dig into the articles they found the most interesting this week.
They begin with the news that Paul Stamets now has a species of mushroom named after him (Psilocybe stametsii), then take a look at a recent self-report study called “Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics,” which aimed to collect data on just how many psychedelic users (in this study, anyone who had ever tried a psychedelic) felt that they had had a challenging or difficult experience. They discuss the results and highlight some interesting data: that LSD was the most commonly associated substance, that smoking cannabis was one of the most commonly reported interventions, and of course, the question of whether or not these experiences were beneficial.
They then talk about Synthesis Institute closing its doors, the possible hope Synthesis could have, and the sadness in this – when businesses fail, it’s easy to look at numbers and profit margins and be dismissive, but we forget the people involved; not just at Synthesis, but the hundreds of would-be students.
And lastly, they look at an article about a California-based startup called the Reality Center, which uses a combination of pulsing lights, sounds, and vibrations to create a drug-free but seemingly very psychedelic experience, reminding us yet again that you do not need a substance to achieve non-ordinary states of consciousness.
Psychedelics, once heavily restricted for research, are now being rigorously tested through clinical trials to explore their potential therapeutic benefits. But how are women represented in the search to uncover the efficacy of psychedelic medicines?
While the inclusion of women in psychedelic clinical trials is clearly important – both to understand the effects of these medicines on all genders as well as to develop effective treatments for conditions that primarily affect women – women have historically been underrepresented in clinical trials.
Why has this become the norm? Is it because women aren’t as available as men to participate in studies? Or perhaps women don’t suffer from the illnesses being studied as often as men?
Spoiler: it’s neither.
The Clinical Trial Process – An Overview
The clinical trial process is, largely, a series of research studies that evaluate the safety and effectiveness of new drugs, treatments, or medical devices on human subjects. To fit into a pharmaceutical model, a.k.a. develop a drug or treatment protocol that clinicians can prescribe and health insurance will cover, psychedelic medicines must follow the same clinical trial process that all new drugs and treatments undergo.
If it seems like there’s a new clinical trial announced each week – from psilocybin for depression to MDMA for PTSD to LSD for cluster headaches – it’s because these trials are crucial (and non-negotiable) for biotech companies seeking to bring their compounds and modalities to market. These trials aim to prove the effectiveness of a particular compound or method of use, and ultimately secure the holy grail of U.S. Food and Drug Administration (FDA) approval.
Clinical trials are conducted in several phases, each with specific goals:
Phase 1: A small number of healthy volunteers receive the drug or treatment to evaluate its safety and determine the appropriate dosage.
Phase 2: A larger group of volunteers with the condition that the drug or treatment is designed to treat receive the treatment to assess its effectiveness and side effects.
Phase 3: An even larger group of volunteers with the condition receive the treatment in a randomized and controlled study to confirm its effectiveness and monitor side effects.
Phase 4: The drug or treatment is approved and marketed for public use, and ongoing studies continue to monitor its long-term safety and effectiveness.
Throughout the clinical trial process, participants are closely monitored and data is collected to evaluate the drug or treatment’s safety, efficacy, and potential side effects.
Francesca Minale, President of Vici Health Sciences and an expert at working with the FDA to bring new medications through clinical trials to approval, says the lack of gender differentiation in dosing persists despite known differences in disease states by gender.
“There is a lack of incorporation of gender data and generic specific dosing and administration on FDA-approved prescription labels,” said Minale. “This gender bias in the research needs to be addressed, especially as it is well documented that many diseases, such as mental health or heart disease, are recognized to have gender differences.”
Excluding women from early-stage clinical trials led to a vast shortage of data around how today’s drugs affect women – a knowledge gap that scientists are still trying to fill. Even though the NIH now requires women to be included in all clinical research funded by the government agency, there are still many criteria that make it difficult for women to participate in clinical trials.
Women in Psychedelic Clinical Trials
The results of clinical trials play a critical role in informing regulatory decisions about whether to approve new medicines for widespread use. However, in the past, clinical trials often failed to accurately reflect the populations they intended to serve – especially women.
As psychedelic clinical trials seek to determine the safety and efficacy of new psychedelic treatments, it’s imperative we learn from past mistakes. A recent study identified 86 medications approved by the FDA that are more likely to cause complications for women than men.
But yet it’s common practice to prescribe equal doses of medications to men and women – contributing to the overmedication of women and female-biased adverse drug reactions.
In fact, because women were excluded from many pivotal clinical trials, many drugs have been withdrawn from the market or have had their labels changed to include warnings about increased risks for women after they were already approved by the FDA and widely used.
Modern Barriers to Women’s Participation in Clinical Trials
Amy Reichelt, Ph.D.,Director of Neuropharmacology at Cybin explained, “In early-stage clinical trials (i.e., Phase 1) where drugs are tested in healthy volunteers, key inclusion/exclusion criteria can bias genders tested.”
Typical protocol wording includes: “Women of childbearing potential (WOCBP) must be non-lactating and have a negative pregnancy test. Females who are not WOCBP must be either surgically sterile or post-menopausal.” Reichelt said. “This immediately excludes a number of women, particularly when age ranges of trials can have cut-offs of 55-60 years.”
Moreover, it is often written into the trial protocol that a woman of childbearing potential must agree to practice an effective means of birth control/contraception during their participation in the clinical trial, and following the trial for several months. This could impact individuals who are trying to start a family for many months, again discouraging women from participating.
Reichelt pointed out, “Later stage trials (i.e., Phase 2b, Phase 3) can be less restrictive as they are testing in patient populations and initial safety tests are fulfilled in the healthy volunteers in early stage trials, but still there are often requirements for contraceptive use that fall upon the women’s responsibility.”
In addition, body weight restrictions may also prevent women from participating if they are below the protocol threshold i.e., less than 60 kg/132 pounds.
Biological Gender Differences and Why They Matter
The differences between the sexes in circulating levels of sex hormones, such as testosterone and estradiol, can affect pharmacokinetic or pharmacodynamic parameters – which help determine how the drug is absorbed, distributed and metabolized in the body, and how the drug affects the body, Reichelt explained.
Body composition can impact how a drug is processed and eliminated from the body, too. “Women typically have a lower body weight than men, so when the same dose of a drug results in a higher level of drug circulating by body weight. As women generally have a greater body fat content than men, some drugs can be distributed through the body differently,” said Reichelt.
This brain phenomena may subtly affect mood and cognition during a woman’s estrous cycle, and could affect clinical outcomes. More studies are needed to fully understand these impacts, especially when it comes to psychedelic medicines which are closely tied to brain plasticity and dendritic spines.
“We don’t yet have a clear understanding of how different biological factors, such as hormonal fluctuations, including menstrual cycle and menopause, may impact the psychedelic experience. However, it does seem that psychedelics may have an impact on menstrual function,” she said.
Gukasyan co-authored a recent study published in the Journal of Psychoactive Drugs on the impact of psychedelics on menstrual function. While the study looked at only three women ranging from 27 to 34 years of age, the results were significant enough to warrant more research.
“Although phenomena related to menstrual and reproductive function have been largely overlooked in the psychedelic literature to date, these effects may have therapeutic utility and warrant further study,” the study concluded.
Where To Go From Here
In the field of psychedelic medicine, where compounds are being extensively studied scientifically for the first time, the underrepresentation of women in clinical trials could have serious consequences for the safety and efficacy of these treatments. Without data on the experiences of women, it is impossible to accurately assess the potential benefits and risks of these new medicines before bringing them to the masses.
By working to increase the representation of women in clinical trials for psychedelics, we can help to ensure that these treatments are developed in a way that is safe, effective, and equitable for all.
Thankfully, many psychedelic clinical trials are moving forward with this ethos. For example, two-thirds of the participants in the MAPS’ Phase 2 and 3 clinical trials of MDMA therapy for the treatment of PTSD were women.
Rick Doblin, the founder of MAPS, said, “When it comes to PTSD, we talk a lot about the veterans, but it’s mostly women who are sexually abused or have childhood traumas that have PTSD. I think that the media attention on veterans sort of distracts people from the understanding that it’s mostly women that we are treating. Two-thirds of the people in the [MAPS] study are women.”
Other groups conducting clinical trials actively seeking women participants include Psycheceutical Bioscience, which has partnered with clinical research organization (CRO) iNGENū in Australia to conduct its Phase 1 and Phase 2 trials of a topical ketamine cream to treat PTSD.
“iNGENū takes gender balance in clinical trials very seriously and the diversity of participants is one of the key metrics we strive to achieve. We naturally want our clinical trials to recruit participants who closely match the intended population who will benefit from the drug when it is eventually approved,” said iNGENū CEO Dr. Sud Agarwal.
While the inclusion of women in psychedelic clinical trials is critical to the success of this new paradigm in medicine, there’s also a whole realm of largely untapped research on the benefits of psychedelics for health conditions experienced only by women.
Felicity Pharma is a psychedelic biotech company focused on women’s health that’s secured a proprietary psilocybin-based drug for premenstrual dysphoric disorder (PMDD), a very severe form of premenstrual syndrome that affects up to 10 percent of women globally as well as postpartum depression.
Olivia Mannix, Felicity Pharma co-founder and CEO, said “We are passionate about transforming women’s healthcare. Women have been traditionally excluded from clinical trials because of hormonal fluctuations and general biological makeup. We are making a stand to develop female-focused therapeutics, where women will be the only patients used in trials.”
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