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.
The objective was to avoid unforeseen birth defects in babies born to women in clinical trials. The result, however, is that most currently prescribed medications were approved by the FDA before 1993 – which means they’re prescribed to women and men at the same dose and were unlikely to have adequate representation of women in their clinical trials.
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.
This self-guided class investigates the history, science, and best practices for safe and effective microdosing; hosted by Adam Bramlage, founder of Flow State Micro, Dr. James Fadiman, the “father of modern microdosing,” and a dozen expert guest faculty. Enroll today!
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.
The impact of sex can differ across life stages, too. After menopause, the reduction of estrogen can alter aspects of brain plasticity. Preclinical studies have shown that at the neuronal level, estrogen can increase the density of dendritic spines.
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.
Check out this webinar on March 13 and other future events on our events page. To view webinars you may have missed, head to our YouTube page!
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.
Women-Only Trials
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.”
In this episode, Joe interviews Dr. Devon Christie: Senior Lead of Psychedelic Programs at Numinus, educator at CIIS and Vital, and MAPS-certified MDMA therapist; and Dr. Pamela Kryskow, MD: founding board member of the Psychedelic Association of Canada and Medical Lead of the nonprofit, Roots To Thrive.
Christie and Kryskow recently co-authored one of the first papers looking at MDMA for chronic pain, “MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder,” which came about after they received access to MAPS’ Phase 2 data from a lead-in PTSD study and noticed significant improvements in pain measurements – something the study was not looking for at all. They’re looking into where chronic pain fits within the frameworks of Western medicine and psychedelic-assisted therapy, and discuss the many reasons why MDMA should be tremendously helpful for chronic pain and other conditions that fall under the large umbrella of central sensitivity syndromes and nociplastic pain. They are currently working on a new study following the MAPS protocol that will research MDMA-assisted psychotherapy specifically for people with fibromyalgia, which some believe might be physicalized PTSD. If you’d like to contribute a tax-deductible donation, visit giving.viu.ca, select “other” from the dropdown, and type in “MDMA for Fibromyalgia.”
They talk about how research trials focus too much on the molecule while ignoring what the patient is saying; how a large percentage of physicians and patients don’t at all like the psychometrics used in measuring data; how physicians regularly use expectancy bias but research trials don’t (and how that affects results); why everyone needs to place higher importance on the biopsychosocial model; the idea of being more humble with science and using “theoretical” more often; the problems with microdosing trials; and the issues with evidence: If there isn’t sufficient evidence, why isn’t there? And what exactly would be sufficient?
Notable Quotes
“It’s kind of an irony because it’s really a single molecule pharmaceutical model to go: ‘Is it working?’ whereas every day, every clinician out there is using expectancy and placebo effect to their patients’ benefit. So, I would like us to have that conversation in a much more intelligent way, saying it’s going to be there, it’s not a bad thing, and in fact, if you don’t have that, you’re probably a bad clinician. So, let’s harness it, and then say, ‘and is the treatment [going] above and beyond that?’” -Pam
“Where’s the scientific curiosity? That’s what we need to be. When our patient says: ‘This is helping me,’ we should never be saying, ‘No, that’s not possible because there’s no evidence.’ We should be leaning in and being curious: ‘Tell me more.’” -Pam “Homogenizing through trying to do the randomized control trials, you end up sort of sterilizing to isolate one specific variable in trying to make your study population as similar as possible. And in the real world, that’s just not the case. In the real world, people are on 10 different medications. So what’s really even the applicability when we sterilize and homogenize so much [for] what we believe is giving us the best evidence?” -Devon
“If we really look and open our eyes, in many, many circumstances, the pathology is not individual whatsoever. The pathology is in our culture and in our society and how disconnected we are and the intergenerational trauma that’s passed along, and then parents without support and no hope of not passing that along because our society isn’t providing the optimal environment on a societal level for us to be thriving. So I think a cure on an individual level needs to be couched within thinking about a cure on a collective level.” -Devon
“The reason I got involved even in the research is because so many of my patients were coming to me and saying, ‘I am microdosing. It is helping.’ So it goes back to: Do you believe people? And I personally believe my patients when they say that. …When I have people coming in and saying ‘I’m out of bed now. I used to lay in bed for 18 hours a day and now I’m out, I bought a dog, I’m exercising’; if it’s a placebo or expectancy, awesome. I’m going to celebrate that.” -Pam
In this episode of Psychedelics Weekly, the rest of the team is out or at Cannadelic, so a new voice steps up to the plate: Julian Bost, who works with the Vital team and handles the majority of our email, records his first podcast with Ph.D. candidate in Neuroscience, friend of the show, and speaker at Convergence: Manesh Girn.
You may remember the team covering some articles at the end of December and early January that were quite confusing and immediately met with a response of: “yea, we should have someone on to explain this to us.” This is that episode, with Manesh breaking down three very scientific articles into much simpler terms (at least we hope).
And a paper he co-wrote with Dr. Robin Carhart-Harris and many others, “Canalization and plasticity in psychopathology,” which aims to reframe neuroplasticity, disorders, and psychedelic interventions, and leads to a discussion on how adaptive thought patterns develop, the ability to relearn as “Temperature or Entropy Mediated Plasticity (TEMP),” Daniel Kahneman’s idea of fast and slow thinking, early trauma intervention, and the concept of viewing mental illness as a process rather than an identity.
As confusing (at least to the layperson) research seems to pop up daily, we may have Manesh on from time to time to help us understand some of these studies. How did he do? Did he clear up any of these articles for you? And should Julian be on the podcast more?
In this episode, Joe interviews Dr. Andrew R. Gallimore: computational neurobiologist, chemical pharmacologist, researcher, and writer of Alien Information Theory: Psychedelic Drug Technologies and the Cosmic Game.
Gallimore feels that DMT is the most efficient and effective reality switching molecule we’ve seen, and that there is no other psychedelic experience that is so in your face: If we really could communicate with entities not of our known universe (who may have created our universe), how can so many dismiss that as a hallucination? Why would we not want to pursue something so mind-bending and revolutionary? His hope for his newest book, Reality Switch Technologies: Psychedelics as Tools for the Discovery and Exploration of New Worlds, is that it will be the quintessential guide for how psychedelics work in the brain from all levels of organization, what happens when you perturb the brain, and the future: how we might be able to fine-tune our brains to access different realities at will.
He discusses the element of design used in his books; why understanding something as complex as DMT is a multidisciplinary practice; the genius of Terence McKenna; what Alien Information Theory was about; his work with Rick Strassman in researching intravenous infusion DMT pumps to keep someone in the DMT verse; Conway’s Game of Life and the unpredictable levels of complexity that can arise from simple rules; lucid dreaming; John Mack, alien abductees, and trusting a patient’s experiences as real; psilocybin yeast; and much more.
This one will definitely make you think!
Notable Quotes
“It’s always felt a little bit sci-fi in a way, in that you’re planning basically a program of inter-dimensional citizenship. It feels like that. I mean, Terence McKenna used to [say] ‘galactic citizenship,’ and it’s almost like we’ve leapfrogged over galactic citizenship and we’re now going straight to inter-dimensional, trans-dimensional citizenship (whatever you want to call it) where we’re interfacing and communicating with an intelligence not of this universe. I mean, that’s a wild idea. And we have the technology now. To me, this infusion technology; this is the way to do it.”
“We’re just at the beginning now. You take virtual reality technology and the way that that is progressing, then you add artificial intelligence into the mix, and then you add pharmacology and neuropharmacology, chemical pharmacology and other neural manipulation systems, and you begin to realize that our brain is this tool – this world-building machine that we can learn to tune to access other worlds.”
“There’s also deja vu of course, the sense of having been there before – this very profound, deep sense of deja vu; not like we’ve all had, that occasionally you get that sense of deja vu that something has happened before. This is like, ‘I really, really have been here before. This is the most bizarre place I couldn’t possibly have imagined or conceived of; an impossible place of impossible geometry, and yet at the same time, it seems bizarrely familiar. ‘Why? Why would some place that should be the most unfamiliar place possible– There isn’t a more unfamiliar realm that you could imagine than the DMT world, and yet people think, ‘Oh my God, I’ve come home.’ And the entities, the elves will sing and cheer and bells will ring and lights will flash and [they’ll] say, ‘He has returned! The one has returned home! Welcome back! We’re so pleased to see you!’ This great uproar, this great celebration as you burst into this space. Why would that happen?”
In this week’s episode, Joe and David meet up to talk about Vital, Convergence, and the latest news:
-Tryp Therapeutics and Mass General signing a letter of intent for a Phase 2 clinical trial investigating the effects of psilocybin-assisted psychotherapy for the treatment of Irritable Bowel Syndrome – interesting because it further highlights the likely effect of psychedelics on the brain-gut connection and that psychotherapy is involved;
-New York lawmakers pre-filing a bill to legalize DMT, ibogaine, mescaline, psilocybin and psilocyn (and remove them from the state’s banned substances list) for 2023;
-New York’s first cannabis dispensary finally opening on December 29;
-British Columbia responding to their opioid crisis (the latest data reports 14k deaths since 2016) by beginning a Portugal-like decriminalization model, allowing people 18 years and older to carry a combined 2.5 grams of drugs (heroin, fentanyl, cocaine, methamphetamine and even MDMA);
and finally, an interesting but confusing (maybe a follow-up is necessary) article showing that what we’re learning about ketamine could lead towards a better understanding of psychosis and schizophrenia.
In this week’s episode, Joe and Kyle are together again before Kyle sets off for a 2-month road trip centered around Vital retreats, where we hope he’ll be able to report in from live while in Jamaica.
In this week’s episode, Joe and David team up again to discuss what news interested them the most this week: the DA dropping a felony drug charge against a mushroom rabbi in Denver due to the passing of Proposition 122; Numinus Submitting a Clinical Trial Application to Health Canada that would give in-training practitioners the ability to experience psychedelics with their psilocybe-containing EnfiniTea; and a University of Exeter-led trial moving forward with the next step in a study using ketamine for alcohol use disorder (with 2/3 of the money coming from the National Institute for Health and Care Research).
They also review a paper that analyzed the economics of psychedelic-assisted therapies and how insurers come into play; as well as The Journal of the American Medical Association stating that, based on current trajectories compared to cannabis legalization, they believe the majority of states will legalize psychedelics by 2037. So nice to see these continued steps in the right direction!
And if you missed it, we just announced that applications are open for the next edition of Vital. There are incentives to paying in-full by certain dates, so if you missed out on last year’s edition or have been curious, attend one of our upcoming Q+As!
In discussing these articles, much is covered: methylation and genetic memory; addiction; gut biome; cesarian births; how much inequality is built into the “psychedelic renaissance” due to it primarily evolving out of inherently unequal Western societal paradigms; permaculture; new ways to be together; Burning Man; the concept of the nuclear family; the power in working with your hands; creativity; harm reduction and the lack of readily available drug testing kits; and more.
In this week’s episode, Joe and Alexa talk about the excitement brewing around our first conference-meets-festival, Convergence (March 30 – April 2 at the Wisdome in LA), and some of the sponsorships starting to come in (interested? email Alexa@psychedelicstoday.com).
Then, they dive into what intrigued them the most this week: a study looking into potentiality and possible causes of 5-MeO-DMT reactivation (and what reactivation actually is); New York cannabis farms sitting on $750 million worth of cannabis as the government drags its feet on licenses; and the story of a woman who used cannabis and psilocybin as an adjunct to standard therapy in the treatment of advanced metastatic breast cancer.
In this episode, Victoria hosts a bit of a microdosing roundtable, speaking with three champions of microdosing: “The Father of modern microdosing,” James Fadiman, Ph.D.; Adam Bramlage, Founder/CEO of Flow State Micro (a functional mushroom company and microdosing educational platform); and Conor Murray, Ph.D., a neuroscientist at UCLA who conducted the world’s first EEG microdosing study.
Fadiman and Bramlage recently launched a very popular course through our Psychedelic Education Center: “Microdosing Masterclass,” which covers the history and science of microdosing, as well as best practices for microdosing safely and effectively. They discuss the roots of microdosing, decriminalization and concerns over the corporatization of psychedelics, what we’ve seen so far in research, and how we’re finding ourselves in an era where people are going to be allowed to actually help themselves.
Murray is hoping to make big waves in the promotion of microdosing with the world’s first take-home EEG microdosing study: participants will be mailed a wireless headband that will be able to track brain activity in real world scenarios – the citizen science we’ve so desperately needed in comparison to lab studies that couldn’t be more different from how people actually live day-to-day. There is no criteria to participate, and, in contrast to lab studies, they want all data possible: people who are in therapy or not, people following different microdosing protocols, people microdosing for different reasons, etc. Will microdosing improve brain scores on cognition and emotion? Will participants see measurable improvements? And how will these numbers look when comparing scores months after initial peak neurological windows?
If you’d like to participate, head to psynautics.com and sign up. The first 50 people to do so will receive the wireless EEG to track their brain for one month for only $40.
Notable Quotes
“Because it’s inherently interesting for people to find that their consciousness can be improved (not necessarily changed) and that their whole physical system can also be improved, microdosing has found a natural niche which is: it might be good for you, and as far as we can tell, it’s very, very, very, very, very rarely bad for you. And that’s a nice risk/reward ratio.” -James
“It’s hard to fool the brain. You can maybe have a good placebo effect if you’re trying to ask someone: how much do you think your cognition’s improving today or emotion’s improving today? But it’s harder to fool the brain into having a different answer.” -Conor
“There’s so many people who will not buy into this until it’s proven by modern science, and that’s why Conor and his work is so important, and this new study with the wireless headbands and the idea that every citizen scientist on the planet can write Conor at Conor@psynautics.com and be a part of this study and get a wireless headband – I mean, that is fascinating. That is taking microdosing out of a sterile lab and putting it into the natural environment where it came from, as hunter-gatherers, for hundreds of thousands of years.” -Adam
“That’s really the metaphor, which is: the more windows, the more you see different views, and there’s nothing good or bad about any particular window except how clean it is. …We’re opening up bigger windows in more directions than has been the case in the past.” -James
This week features David Drapkin, Joe Moore (for the first part), and introduces Alexa Jesse, who you’ve probably heard in ads, but who makes her first appearance on the podcast.
They discuss two big political moves in the advancement of psychedelics: the creation of the Congressional Psychedelics Advancing Clinical Treatments (PACT) Caucus (led by Representatives Lou Correa (D-CA) and Jack Bergman (R-MI)), and the filing of the Breakthrough Therapies Act by Senators Cory Booker (D-NJ) and Rand Paul (R-KY).
And they talk about the story of Jim Harris overcoming paralyzation through psilocybin; NICE (National Institute for Health and Care Excellence) determining that Esketamine is not cost-effective; new progress in Germany and Finland; MDMA-assisted therapy (and other psychedelics) showing alleviation of chronic pain; a ramp up in LSD research for Alzheimer’s studies; and more.
Plus, we hear a bit of Alexa’s story, wish Joe and Johanna happy birthdays, and talk about what’s most immediate in the PT world: Early Bird pricing ending today for our first conference, Convergence (use code PTINSIDER10 for a 10% discount!), and the next round of Navigating Psychedelics launching next week.
