The recent decision by the US Food and Drug Administration (FDA) to withhold approval for MDMA-assisted psychotherapy (MDMA-AT) has sent ripples of disappointment and frustration throughout the scientific, psychedelic and therapeutic communities. This decision, issued via a Complete Response Letter to Lykos Therapeutics, effectively delays access to a promising treatment for millions of patients suffering from Post-Traumatic Stress Disorder (PTSD) by years. At OPEN, we feel compelled to express our concerns, while also proposing a path forward: one that emphasizes both rigorous scientific validation and compassionate pragmatism.
Disappointment in the FDA’s Decision to Restrict Access to Mdma-at
The FDA’s decision represents a significant setback for those advocating innovative approaches in mental healthcare. MDMA-AT has shown remarkable potential in treating PTSD, a condition that remains notoriously difficult to treat with existing therapies. The evidence presented by MAPS (Multidisciplinary Association for Psychedelic Studies) and Lykos Therapeutics (formerly MAPS PBC) demonstrates substantial improvements in PTSD symptoms among patients treated with MDMA-AT. These findings are not only statistically significant but also clinically meaningful, offering hope to those for whom traditional therapies have failed.
The FDA’s decision, while ostensibly rooted in a commitment to safety and efficacy, ultimately restricts access to a treatment that could transform and even save lives. For patients who have exhausted all other options, this decision feels like a denial of hope.
Surprise at the Divergence from the Dutch State Committee Report “Beyond Ecstasy”
What is particularly surprising is the stark contrast between the FDA’s decision and the conclusions reached by the Dutch State Committee on MDMA. Based on the same body of evidence, the Dutch committee (consisting of scientists, psychiatrists, legal experts, drug prevention and harm reduction specialists) arrived at a radically different conclusion: MDMA-AT is promising, effective, relatively safe and warrants more scientific research to further explore its therapeutic potential.
The committee even concluded that based on the relatively low potential for harm, MDMA could be down-scheduled: moving the compound from List 1 to List 2 of the Opium Act. Finally, the Committee advised the Dutch government to start a naturalistic study to allow patients access to this new therapy form, while also allowing scientists to collect more data on an ongoing basis, all the while gaining important clinical experience in delivering this novel treatment form. These diverging perspectives raise important questions about the interpretation of scientific data and the role of cultural and institutional factors in regulating novel therapeutic approaches.
The Dutch committee’s recommendation reflects a nuanced understanding of both the risks and benefits associated with MDMA-AT. They recognize that while methodological and ethical concerns remain, the potential therapeutic benefits of MDMA-AT cannot be ignored. This discrepancy between the FDA and the Dutch committee highlights the need for international dialogue and collaboration in the evaluation of novel therapies.
Want to learn more about the Dutch State Committee Report? Click here.
Acknowledging Methodological Concerns In MDMA Assisted Psychotherapy
At the moment, the specific reasons why the FDA rejected the approval of MDMA-AT are not yet publicly available, but we presume these concerns are likely based on the report from the FDA’s scientific advisory panel. These concerns are not without merit. The methodological issues raised, particularly those related to expectancy and placebo effects, are valid and warrant careful consideration. In randomized controlled trials (RCTs), both the MDMA and control groups have shown dramatic improvements, raising the possibility that nonspecific factors may be contributing to the observed outcomes. The contribution of these nonspecific factors to treatment outcomes is not unique to MDMA-AT, but is of concern in the evaluation of any psychoactive medicine. It is also crucial to note that the magnitude of improvement in the MDMA group far exceeds that of the control group, suggesting that the effects of MDMA-AT are not merely due to placebo or breaking blind. Placebo effects, while powerful, tend to diminish over time, whereas the benefits of MDMA-AT have been sustained in many cases. This durability is a critical factor in assessing the therapeutic potential of MDMA and underscores the need for further research to refine our understanding of its mechanisms of action.
Questions that need to be addressed
In our view, specific open questions that need to be addressed in future research include:
Role of Expectations: What is the role of patient expectations in the therapeutic benefits associated with MDMA-AT?
Blinding Integrity: How many participants are able to accurately guess their treatment assignment, and how does this impact the study outcomes?
Prior Experience with MDMA: Does the therapy work equally well for patients with and without prior experience with MDMA?
Control Conditions: Could alternative control conditions with experiential components, such as breathwork, be equally effective as MDMA in improving PTSD symptoms?
Non-Responders: What are the characteristics of patients who do not respond well to MDMA-AT, and how can their outcomes be improved?
Therapist-Client Interactions: What checks and balances are necessary to ensure the standardization and careful conduct of therapist-client interactions in MDMA-AT?
Proper aftercare:How can we ensure appropriate, sensitive, and durable aftercare for patients who may struggle for a substantial period after having undergone MDMA-AT (or placebo-assisted therapy)?
These questions highlight the need for further evaluating the efficacy of MDMA-AT and underscore the need for open science practices, including transparent reporting and rigorous study designs, to address these issues.
Addressing Ethical Concerns
Ethical concerns surrounding MDMA-AT are significant and need to be taken very seriously, particularly regarding the risks related to boundary violations. We are acutely aware of the need for rigorous training, careful monitoring and adequate supervision of both therapists and patients involved in MDMA-AT. This is particularly true when these therapies do become approved, and will be rolled out at a large scale, to more diverse groups of patients. The therapy should only be conducted in controlled environments by qualified professionals who adhere to the highest standards of care. This includes official oversight of relevant professional associations, ideally with a thorough understanding of the nature of – and specific risk factors related to – psychedelic-assisted therapies.
A more difficult issue revolves around the standardization of the psychotherapeutic component of MDMA-AT. While some argue that standardized psychotherapy is essential to ensure consistent and safe treatment across different settings, others propose getting rid of psychotherapy altogether, while a third group suggests that common factors – like therapeutic alliance – are the defining feature, and that the specific form of psychotherapy is less important.
What we can be sure of, is that as the demand for MDMA-AT grows, there will be an increasing need for well-trained therapists who can deliver this therapy responsibly. The establishment of clear guidelines and protocols is imperative to mitigate risks and protect patient safety.
The Impact of the FDA’s Decision on the Legal Landscape & Future Research on MDMA-aT
The FDA’s likely requirement for a third phase-3 trial presents a serious hurdle to the timely approval of MDMA-AT. The time and costs involved in conducting such a study are substantial, and will require additional fundraising. It is likely that this will postpone the availability of MDMA-AT in the USA by years. This delay is particularly concerning given the urgent need for effective treatments for PTSD, a condition that affects millions of people worldwide.
The implications for Europe are uncertain. It remains unclear whether the results of a future phase-3 trial in the USA will be leveraged to apply for marketing authorisation from the European Medicines Agency (EMA) as well. Theoretically, another phase 3 trial could also partially take place in Europe (there are trained and experienced MDMA-AT therapists sites in multiple European countries), thereby overcoming the EMA’s wish to have studies conducted in Europe. If Europe is not included, and the EMA does require additional data, this will further delay the availability of MDMA-AT in Europe, leaving many patients without access to this potentially life-changing treatment.
A Pragmatic Approach: Naturalistic Studies and Early Access
In light of these challenges, we propose a pragmatic approach that balances the need for rigorous science with the urgent need for patient access to MDMA-AT. Specifically, we support the recommendation of the Dutch State Committee on MDMA to initiate a naturalistic study in which patients are given MDMA-AT by qualified therapists in specialized treatment settings.
Such a study would provide valuable data on the real-world effects and risks associated with MDMA-AT, while also offering patients access to a therapy that they might otherwise seek in the so-called ‘underground’ or ‘grey’ circuit. A naturalistic study has the dual benefit of providing potential relief to suffering patients while advancing our understanding of the roll out of MDMA-AT in a controlled and ethical manner.
Furthermore, implementing this approach in the Netherlands could position the country as a leader in psychedelic science and innovative mental healthcare. It would enable us to gather valuable real world data, understand the complexities of offering such a therapeutic innovation in the real world, and, importantly, ensure that an increasing number of qualified therapists can gain experience conducting MDMA-AT, putting in place structures, protocols, and guidelines to enable a smooth rollout when MDMA-AT eventually becomes a mainstream therapy.
Conclusion: Balancing Rigor with Compassion In Psychedelic Science
In sum, the OPEN Foundation believes that the FDA’s decision overlooks the immediate needs of patients who stand to benefit from MDMA-AT. We recognize the importance of rigorous science in establishing the safety and efficacy of this therapy, but we also advocate a pragmatic approach that allows for early access through naturalistic studies. Only by adopting this dual strategy can we ensure that MDMA-AT is administered safely and responsibly, while also collecting the data necessary to satisfy regulatory requirements. Ultimately, the goal of such an approach would be to minimize harm, maximize patient benefit, and pave the way for MDMA-AT to become a valuable tool in the treatment of PTSD.
We call on regulatory agencies, researchers, and clinicians to work together in the spirit of collaboration and innovation, to bring this promising therapy to those who need it most.
It’s been 2 months since the leading conference on psychedelic research in Europe, ICPR 2024, took place in Haarlem, the Netherlands. Despite having taken steps to integrate it all, the OPEN foundation team has accepted that we still lack the words to convey what the whole event felt like and meant to us.
Pia Dijkstra – Minister of Healthcare, The Netherlands – Opening ICPR 2024
From combating prejudice and stigma back in 2007 to having not one but two subsequent Ministers of Healthcare lining up to inaugurate ICPR, our mission to advance psychedelic research to benefit science, healthcare and society has come a long way.
At ICPR 2024, we had it all, from Minister from the Netherlands, Pia Dijkstra’s moving opening speech to the heartfelt realities shared by trial participants Maryam Zahra Jabir and Patty B., the Wet Blanket Award for presentations representing rigor and critical thinking’ awarded to Dr. Jamila Hokanson, M.D, MBA, the kind of deep thinking showcased by Leor Roseman, Erik Davis’ magnificent storytelling and accompanying visuals, the important discussions around decolonization curated by Yogi H., and so so so much more.
You might imagine why the OPEN Foundation & ICPR team was unable to attend most talks on-site. Yet, via the high-quality recordings (more on this will follow), we didn’t miss out. What we saw was consistently great.
Immense effort went into crafting ICPR’s mind-blowing programme. And no doubt those efforts have been worth it. ICPR embodied the true spirit of interdisciplinarity: from clinical trial design, neuroscience, archaeology, integration, psychotherapy, adverse events, spirituality, literary analysis—it was all there.
The programme and ICPR 2024 fulfilled their purpose: to gather and facilitate conversation and connection between open-minded, committed, curious, and caring individuals whose collective perspective creates a critical and constructive narrative for what psychedelics mean moving forward in 21st-century Europe.
Vibrant lunch breaks @ICPR
We are honored and humbled by the ICPR 2024, the progress in the field of psychedelic research and therapy, and what lies ahead. Lastly, gratitude. Gratitude, for our co-creation, persists. Fortunately so, as it’s our fuel to do our part in this ongoing process of integrating psychedelics safely and responsibly into healthcare and society.
Thank you, The OPEN & ICPR team
And please, a big applause for….. the rockstar volunteers who made ICPR 2024 possible!
In a landmark moment for drug policy, the Dutch State Commission on MDMA has released its highly anticipated report, “Beyond Ecstasy“. Spanning over 200 pages, this document explores the multifaceted dimensions of MDMA, including its recreational use, potential therapeutic benefits, and broader implications for public health and policy. We aim to provide you with the key highlights of this thorough examination aimed at guiding the Dutch government in its future decisions regarding MDMA.
Context of the Dutch State Commission on mdma
The formation of the State Commission on MDMA was a response to a coalition government promise to re-evaluate the drug’s status within the Dutch Opium Act. The commission, which included experts from various fields such as addiction psychiatry, criminology, emergency medicine, and drug prevention, worked from April 2023 to May 2024. This multidisciplinary approach ensured a holistic understanding of MDMA’s impact.
report presentation by wim van den brink, md, phd
Wim van den Brink, professor of Addiction Psychiatry at the Amsterdam University Medical Centers presented the report 2 days after its release at the ICPR conference in Haarlem, June 2024.
A central aspect of the report is its exploration of MDMA’s potential therapeutic benefits, particularly in the treatment of PTSD. The commission reviewed existing research and concluded that MDMA-assisted therapy shows promise for patients with treatment-resistant PTSD.
efficacy and Safety in Treating PTSD
The report discussed current research and clinical trials, highlighting the effectiveness of MDMA-assisted therapy in treating PTSD. To ensure safety and efficacy of MDMA-assisted therapy, the report highlights the importance of context.
“MDMA-assisted therapy has shown significant promise in the treatment of PTSD, particularly for patients who have not responded to traditional therapies. This could represent a major advancement in psychiatric treatment” — MDMA /// Beyond Ecstasy Report
“The therapeutic use of MDMA must be conducted under strict medical supervision to ensure safety and efficacy.” — MDMA /// Beyond Ecstasy Report
Need for Further Research: state commission Proposing a Naturalistic Study in the Netherlands
“Further research is needed to explore the long-term effects and potential applications of MDMA in various psychiatric and neurological conditions.” — MDMA /// Beyond Ecstasy Report
To facilitate the use of MDMA in therapy to treat PTSD, the commission proposes a large naturalistic study in the Netherlands. This study would help gather more data and refine treatment protocols. Wim van den Brink highlighted, “A large naturalistic study will provide the necessary data to support the safe and effective use of MDMA in clinical settings”
education and training to meet the need
“Investing in training programs and specialized centers is essential for the successful implementation of MDMA-assisted therapy.” — MDMA /// Beyond Ecstasy Report
Establishing specialized centers and training therapists are critical steps for implementing MDMA-assisted therapy. While some qualified therapists are already available, more are needed to meet the potential demand.
Prevalence and Risks of Recreational MDMA Use
“The prevalence of MDMA use in the Netherlands is among the highest in the world, yet the number of MDMA-related deaths remains relatively low, highlighting a unique consumption pattern and harm reduction practices in place” — MDMA /// Beyond Ecstasy Report
The second central theme of the report is the prevalence and associated risks of recreational MDMA use in the Netherlands. Despite the high prevalence, the report highlights that the frequency of use and the number of pills consumed per session are relatively low compared to other countries. This pattern may contribute to the lower number of MDMA-related deaths observed in the Netherlands.
The Dutch approach to drug policy heavily emphasizes harm reduction, which is reflected in the safety measures implemented at events where MDMA use is common. As noted in Wim van den Brink’s presentation at ICPR 2024, who emphasized the importance of “set and setting” in minimizing harm during MDMA use, factors such as the availability of care facilities, water, and first aid services at events significantly reduce the risks associated with MDMA use.
The report calls for improved postmortem evaluations to better understand the exact causes of MDMA-related risks. Currently, the lack of comprehensive postmortem studies makes it difficult to determine the precise role of MDMA in fatalities, especially when other substances or external factors might be involved.
Public Health and Drug Policy
The report emphasizes a public health-focused approach to drug policy, advocating harm reduction overcriminalization. It criticizes the current lack of a cohesive national drug policy and calls for an integrated prevention program. The importance of targeted drug education and continuous monitoring of drug trends is also highlighted.
“The Dutch drug policy should remain primarily aimed at public health, avoiding the criminalization of users. Prevention strategies must be evidence-based, focusing on harm reduction rather than punitive measures.” — MDMA /// Beyond Ecstasy Report
to conclude
The Dutch State Commission on MDMA’s report “Beyond Ecstasy” is a pivotal document that could shape the future of drug policy and medical treatment in the Netherlands. By addressing the risks and potential benefits of MDMA and MDMA-assisted therapy, the report aims to provide a framework for policymakers.
As the Dutch government considers these recommendations, patients in need, therapists, researchers and the general public will be paying attention. At OPEN Foundation, we are hopeful that this may be a step toward responsible, safe, and beneficial integration of psychedelics into society and healthcare.
In recent years, there has been an increasing interest in the potential of psychedelic therapy as a novel approach for the treatment of addiction. This interest stems from a growing body of research exploring the therapeutic effects of psychedelic substances on addictive behaviors, particularly psilocybin and LSD. In his past seminar titled “Euphoria: The New Science of Addiction and Psychedelic Therapy,” Dr. Rayyan Zafar, a prominent researcher in the field, delves into the key insights and findings spanning from observational studies, clinical trials, and historical investigations with psychedelics in addiction treatment. Dr. Zafar sheds light on the historical context, scientific progress, and prospects of psychedelic therapy in addiction treatment. This blog post aims to summarize and analyze the key takeaways from Dr. Zafar’s seminar, providing readers with a deeper understanding of the evolving landscape of addiction treatment and the role of psychedelic therapy within it.
Key Takeaways from “Euphoria: The New Science of Addiction and Psychedelic Therapy”
Comprehensive Review of Psychedelic Therapy in Addiction Treatment
Dr. Zafar’s past seminar offered an in-depth examination of the potential of psychedelic therapy in treating addiction, drawing on a diverse range of research sources. The exploration begins with historical studies dating back to the mid to late 1900s, shedding light on the origins of psychedelic research and its developmental trajectory. Both classic (e.g. psilocybin, LSD, and DMT) and non-classical psychedelics (e.g. 6-MeO-DMT, ketamine, and MDMA) were discussed but due to the limited scope of this article, only the classic ones, psilocybin and LSD, will be highlighted.
The first realization of the powerful effect of LSD on mood and cognition in 1943 presumably marked the beginning of a modern era in which psychedelic drugs could be used to treat certain mental and behavioral conditions. From the 1940s and early 1970s, classic psychedelics were actively researched in humans as both a pharmacological tool to understand its effects on the mind and brain and as a therapeutics. Collectively, LSD was seen as a promising treatment for numerous serious mental health disorders such as depression, alcoholism, and other substance use disorders (Hofman, 1980). Furthermore, it has a favorable safety profile and had profound short-term psychological effects (Krebs). This led to a potential breakthrough in the treatment of various mental illnesses, including different forms of drug addiction (Belouin).
Between the late 1950s and early 1970s, approximately 40,000 patients worldwide suffering from various mental disorders, including substance use disorders, received treatment with psychedelics such as LSD, mescaline, and psilocybin, are documented over 1000 publications (Grinspoon). A key finding was that psychedelics are well-tolerated and induce a low risk of adverse side events (online event).
A controlled study investigating LSD’s efficacy in adjunction to psychotherapy in treating heroin addiction was influential. It was revealed that 33% of 36 participants in the treatment group (n= 73) maintained a abstinence after one year compared to the control group with a mere 5% success rate. However, only 5% maintain complete abstinence after the fulfilling the treatment program (Savage, 1973). Furthermore, a meta-analysis collected data about LSD in alcoholism from six randomized controlled trials that were published in the 1960s with over 500 participants and showed that LSD doubled the odds that patients would be abstinent at first follow-up, as defined by (OR = 2.07). Yet, this was not seen after a year (Krebs).
Even though there is quite a large amount of historical data showing a positive trend toward the therapeutic role of psychedelics in addiction treatment, the evidence from these studies remains inconclusive due to methodological inconsistencies. More specifically, these inconsistencies encompassed deficiencies in study design, such as the lack of proper controls, blinding, follow-up protocols, statistical analyses, and the utilization of validated assessments, as evaluated through contemporary research standards (Rucker).
Groundbreaking Investigations into Addiction Treatment with Psychedelic-assisted Therapy
The widespread use of psychedelics in the 1960s fueled a counterculture movement, prompting a political backlash and leading to increased regulatory controls by the FDA. This culminated in the establishment of the Controlled Substances Act (CSA) in 1970 under Richard Nixon, effectively halting psychedelic research (Belouin). However, efforts to explore the therapeutic potential of psychedelics resumed in the 1990s with renewed scientific interest and advanced research methodologies (Belouin; Zafar).
Dr. Zafar provided an overview of the latest findings from these investigations, illuminating the favorable prospects of psychedelics in addiction recovery. Ongoing clinical trials exploring the potential therapeutic role of psychedelics in addiction cover a diverse spectrum of substances and addiction types, ranging from alcohol and tobacco to methamphetamine and gambling addiction. Due to the limited scope of this article, only psilocybin in alcohol and tobacco will be highlighted. These trials aim to expand upon initial findings and set the stage for larger-scale studies that would ultimately secure regulatory approval.
The promising results of earlier research on psychedelics and alcohol addiction have prompted a modern replication open-label study examining psilocybin-assisted treatment for alcohol dependence (Bogenschutz et el., 2015). In the little sneak preview of last week, the study of psilocybin in conjunction with Motivational Enhancement Therapy (MET) was discussed. The figure illustrates the change in percent drinking days and percent heavy drinking days. The blue line in the graph represent the % of drinking days while the red line represent the % heavy drinking days. After the first administration with psilocybin, both percent drinking and heavy drinking days were statistically significant lower than baseline in all the follow-up points.
To explore the relationship between the intensity of the psilocybin-induced experience with changes in drinking behavior, the acute effects of psilocybin were measured by the Mystical Experiences Questionnaire (MEQ). It was also found to correlate with changes in drinking behavior, craving, and self-efficacy (Bogenschutz, 2015).
The mystical experiences induced by psilocybin are characterized by immediate sensations of unity, sacredness, a sense of understanding beyond ordinary knowledge, positive mood, transcendence of notions of space and time, and an inability to adequately describe the experience (e.g., ineffability; Griffiths, 2006). These dimensions seem to be common across ages, cultures, ethnicities, and genders (online seminar Johnson). The hallmark of the mystical experience lies in the profound sense of being influenced by forces greater than oneself, often accompanied by intense emotions, sparking enduring and transformative changes in one’s life (Miller).
To build upon the findings of the study of Bogenschutz et al. (2015), the research group investigated psilocybin in a so-called phase 2 double-blind randomized clinical trial (Bogenschutz, 2022). On one hand, it was observed that the psilocybin group had lower percentage in heavy drinking days and mean daily alcohol consumption (number of standard drinks per day) compared to the group that was given diphenhydramine as a control. On the other hand, the percentage of drinking days was not statistically reduced (29 in psilocybin group vs 43 in control groups). However, important limitations need to be pointed out. There were some methodological issues that could lead to a higher risk of making incorrect inferences about the data.This study is currently undergoing replication in larger phase III trials across multiple centers, advancing toward creating more data regarding the efficacy of the psychedelic drug and potential marketing authorization for this indication (Zafar).
The effects of psilocybin have also been investigated in conjunction with CBT for the treatment of tobacco addiction. In this open-label study, individuals were given two to three moderate to high doses (20 and 30 mg/70kg) of psilocybin (Johnson, 2017). Results based on urinary and breath analyses showed that 60% of the group did not smoke after one year of follow-up. This is a seemingly big difference compared to the 35% of what is usually observed in traditional tobacco treatment paradigms (Cahill, 2014). In the acknowledgment of the lack of drawing definitive conclusions based on open-label studies and the lack of a control group, a randomized comparative efficacy study has been performed and the results remain yet to be published.
Future Applications with Neuroimaging Techniques
Various neuroimaging techniques are able to provide insights into the neurobiological mechanisms of psychedelic therapy and how these relate to clinical outcomes in the treatment of addiction. These techniques include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) scans and enable researchers to map changes in both brain activity and connectivity, offering a deeper understanding of addiction mechanisms and treatment outcomes. Despite the relative scarcity of literature on the neurobiological mechanisms of psychedelics in addiction, recent studies have shed light on potential pathways such as reward, inhibitory control, and stress (Hayes).
Neuroimaging studies are invaluable in identifying biomarkers associated with substance dependence. These biomarkers serve as an objective measurement of bodily activity and, thus, aim to elucidate the mechanisms and conditions under which treatments prove effective. For instance, PET and SPECT, have enabled researchers to delve into the molecular dynamics of addiction within the living human brain. These methods have unveiled specific neuroreceptor biomarkers associated with different subclasses of addiction. Take, for example, the findings regarding dopamine receptors in alcohol and stimulant use disorder (Nutt et al., 2015), opioid receptors in cocaine (Gorelick et al., 2005), and opioid dependence (Williams et al., 2007).Such insights have not only paved the way for a deeper understanding of addiction pathology but also presented novel targets for therapeutic intervention.
Furthermore, by utilizing radioligands, neurotransmitter release studies have offered valuable insights into the dynamics of neurotransmission in addiction. The dopamine system has been widely implicated in addiction theory (Nutt, 2015; Zafar). In addiction, specifically, a blunted dopamine release in a brain region called the nucleus accumbens has been observed after a drug was given. When investigating the effect of psychedelics on addiction, it has been suggested that there is a potential link between psychedelics and dopamine release (Martin et al., 2024; Vollenweider et al. 1999). Yet, so far neurochemical studies have been done in non-humans and futher research is warranted (Nutt, 2015).
Dr. Zafar discusses that advanced multimodal neuroimaging techniques are necessary to directly assess the effects of psychedelic therapy on neurotransmission and brain function in individuals with addiction. For example, multimodal imaging studies combining PET and fMRI have proposed that psychedelic therapy may lead to increases in endogenous dopamine levels in addiction disorders, potentially reflecting improved brain function and treatment outcomes. One of his future scientific endeavors will investigate using fMRI and EEG to investigate differences between pre-and post-administration with psilocybin. Ultimately, these advances ultimately pave the way for more personalized and efficient approaches to address substance dependence (Moeller).
Addressing Challenges and Knowledge Gaps
While the collective data on psychedelics and addiction suggests a positive trend toward reducing substance use, and cravings, and fostering abstinence compared to conventional treatments, several critical knowledge gaps and controversies persist, necessitating further exploration and clarification. Besides the limitations associated with naturalistic, observational, open-label, and animal studies, we will highlight some knowledge gaps that are critical to address when exploring psychedelics and addiction. Indeed, when one door closes, another hundred seem to open.
One of the main remaining questions is: “What mediates the long-term effects of psychedelics?”.
The enduring psychological and behavioral changes observed after psychedelic use may be partly influenced by the immediate, often subjectively positive effects of 5-HT2A receptor agonists, which are occasionally described as mystical or transcendent (Bogenschutz 2015; Calder; Griffiths 2006, 2008, 2011; Johnson 2017; Rothberg; Tap; Yaden). Griffiths (2011) even found that psilocybin can affect the Big Five personality traits, typically considered stable, by increasing openness. Similar associations between greater mystical experiences and improved outcomes were observed in psychedelic-assisted therapy (PAT) for smoking cessation (Johnson, 2017). The findings suggest that psilocybin-assisted treatment has lasting impacts beyond the drug’s immediate effects, with participants ranking their psilocybin experiences as some of the most personally significant and spiritually impactful, correlating with higher smoking cessation rates (Johnson 2017).
While these studies did not explicitly focus on spirituality, the findings raise questions about its role in the effects of psychedelic drugs on addiction. The emotion of awe is suggested as a crucial mechanism driving mystical experiences during psychedelic-assisted psychotherapy (Kan). Awe fosters feelings of interconnectedness and unity, which are central to the transformative effects of psychedelic therapy (Griffiths, 2008). Data indicates that more profound mystical experiences increase the likelihood of smoking cessation (Johnson, 2017). However, not all mystical experiences lead to lasting change, and individuals may return to their previous state. Future randomized, placebo-controlled clinical trials with multiple follow-up assessments are necessary to establish causality and determine the clinical significance of these mechanisms.
Another remaining question concerns the use of a particular therapeutic framework when psychedelics are administered to individuals with addiction. The literature is clear that psychotherapy plays a crucial role in addiction treatment, but it remains unknown what the right amount and particular type of psychotherapeutic intervention and relapse prevention is best. Some studies indicate that group therapy alongside psychedelic use may enhance group connectedness and interpersonal understanding, potentially promoting prosocial behavior (Ponomarenko). While mystical experiences often foster profound connections with others and the universe, solo settings remain prevalent, though both solo and group therapies have shown no significant differences in mental health perceptions (Byrne).
Another remaining question is “How do psychedelics impact the neural circuits implicated in addiction?” Answers to these questions can give insights into how to optimize the development of psychedelic-assisted therapies. Psychedelics may disrupt networks associated with addiction and enhance connectivity across the brain, fostering neuroplasticity and facilitating the relearning of behaviors (Carhart-Harris; Calder; Nutt 2023; online event; Tap). However, understanding these neuroplasticity mechanisms remains limited, with studies primarily conducted on animal models and cell lines (Calder)
Become a member if you would like to know the details of the past online seminar about psychedelics and addiction!
Conclusion
In conclusion, the field of addiction treatment is undergoing a profound transformation with the exploration of psychedelic therapy. Early research indicates that psychedelics like psilocybin and LSD show a positive trend in reducing addictive behaviors, supported by both historical and somewhat by modern clinical trials. By leveraging cutting-edge techniques, neuroimaging studies, researchers can elucidate the underlying mechanisms of psychedelic interventions and tailor treatments to individual needs. Despite the promising data, methodological inconsistencies and knowledge gaps remain, necessitating further rigorous research. Looking ahead, the future of psychedelics and addiction holds some promise, fueled by groundbreaking research, innovative treatment modalities, and a growing understanding of the complex interplay between neuroscience, psychology, and pharmacology.
By Gwendolyn Drossaert
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References
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Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Journal of psychopharmacology, 29(3), 289-299.
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Grinspoon, L., & Bakalar, J. B. (1979). Psychedelic drugs reconsidered (Vol. 168, pp. 163-166). New York: Basic Books.
Hayes, A., Herlinger, K., Paterson, L., & Lingford-Hughes, A. (2020). The neurobiology of substance use and addiction: evidence from neuroimaging and relevance to treatment. BJPsych Advances, 26(6), 367-378.
Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American journal of drug and alcohol abuse, 43(1), 55-60.
Gorelick, D. A., Kim, Y. K., Bencherif, B., Boyd, S. J., Nelson, R., Copersino, M., … & Frost, J. J. (2005). Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving. Biological psychiatry, 57(12), 1573-1582.
Krebs, T. S., & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994-1002.
Lingford-Hughes, A., Reid, A. G., Myers, J., Feeney, A., Hammers, A., Taylor, L. G., … & Nutt, D. J. (2012). A [11C] Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions. Journal of Psychopharmacology, 26(2), 273-281.
Martin, D. A., Delgado, A., & Calu, D. J. (2024). The psychedelic, DOI, increases dopamine release in nucleus accumbens to predictable rewards and reward cues. bioRxiv, 2024-03.
Miller, W. R., & C’de Baca, J. (2001). Quantum change: When epiphanies and sudden insights transform ordinary lives. Guilford Press.
Moeller, S. J., & Paulus, M. P. (2018). Toward biomarkers of the addicted human brain: Using neuroimaging to predict relapse and sustained abstinence in substance use disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 80, 143-154.
Nutt, D. J., Lingford-Hughes, A., Erritzoe, D., & Stokes, P. R. (2015). The dopamine theory of addiction: 40 years of highs and lows. Nature Reviews Neuroscience, 16(5), 305-312.
Nutt, D., Spriggs, M., & Erritzoe, D. (2023). Psychedelics therapeutics: what we know, what we think, and what we need to research. Neuropharmacology, 223, 109257.
Ponomarenko, P., Seragnoli, F., Calder, A., Oehen, P., & Hasler, G. (2023). Can psychedelics enhance group psychotherapy? A discussion on the therapeutic factors. Journal of psychopharmacology, 37(7), 660-678.
Rothberg, R. L., Azhari, N., Haug, N. A., & Dakwar, E. (2021). Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial. Journal of Psychopharmacology, 35(2), 150-158.
Rucker, J. J., Iliff, J., & Nutt, D. J. (2018). Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology, 142, 200-218.
Savage, C., & McCabe, O. L. (1973). Residential psychedelic (LSD) therapy for the narcotic addict: a controlled study. Archives of general psychiatry, 28(6), 808-814.
Stokes, P. R., Benecke, A., Myers, J., Erritzoe, D., Watson, B. J., Kalk, N., … & Lingford-Hughes, A. R. (2013). History of cigarette smoking is associated with higher limbic GABAA receptor availability. Neuroimage, 69, 70-77.
Vollenweider, F. X., Vontobel, P., Hell, D., & Leenders, K. L. (1999). 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man—a PET study with [11C] raclopride. Neuropsychopharmacology, 20(5), 424-433.
Yaden, D. B., Berghella, A. P., Regier, P. S., Garcia-Romeu, A., Johnson, M. W., & Hendricks, P. S. (2021). Classic psychedelics in the treatment of substance use disorder: potential synergies with twelve-step programs. International Journal of Drug Policy, 98, 103380.
Williams, T. M., Daglish, M. R., Lingford-Hughes, A., Taylor, L. G., Hammers, A., Brooks, D. J., … & Nutt, D. J. (2007). Brain opioid receptor binding in early abstinence from opioid dependence: positron emission tomography study. The British Journal of Psychiatry, 191(1), 63-69.
Online event
Tap, S. C. (2024). The potential of 5‐methoxy‐N, N‐dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action. Addiction Biology, 29(4), e13386.
Zafar, R., Siegel, M., Harding, R., Barba, T., Agnorelli, C., Suseelan, S., … & Erritzoe, D. (2023). Psychedelic therapy in the treatment of addiction: the past, present and future. Frontiers in Psychiatry, 14, 1183740.
Dutch Minister Pia Dijkstra to Open Interdisciplinary Conference on Psychedelic Research
The Dutch minister of Medical Care, Pia Dijkstra (D66), will inaugurate the sixth edition of the Interdisciplinary Conference on Psychedelic Research (ICPR) on June 6th. We are excited about the growing support by the Dutch government for psychedelic-assisted therapy, a field gaining significant momentum across Europe.
Previously held by Ernst Kuipers, the role of Minister of Medical Care has passed to Dijkstra, who continues the support for research into the therapeutic potential of psychedelics.
The shift in leadership, while maintaining support for psychedelic research, underscores a broader acceptance and interest in psychedelic research among politicians, thanks to increasing evidence of its effectiveness. The upcoming ICPR and Pathways to Access Summit promises to further explore these possibilities, continuing the Netherlands’ influential role in this important field of medicine.
For more insights into psychedelic-assisted therapy and the critical perspective of OPEN’s director Joost Breeksema & Ernst Kuipers, check out the video below. (DUTCH)
EUROPEAN SUPPORT
You might wonder whether this support for psychedelic-assisted therapy is only reserved to the small and progressive country of the Netherlands. But this is certainly not the case. In the past year, support has been gaining momentum and is expanding towards the scale of European support.
Recently, Joost Breeksema, the executive director of the OPEN Foundation chaired the meeting at the European Parliament to launch PsyPal – a 6.5 million EU-funded multi-site research consortium with over 19 different partners, including OPEN Foundation, that seeks to alleviate suffering from existential distress in patients with a incurable illness through the use of psilocybin.
Only a few days later, Breeksema participated in a two-day workshop at the European Medicines Agency to explore the views of stakeholders and experts on the therapeutic potential of psychedelics, providing further clarity on defining the safe and effective use of psychedelics, informing on regulatory challenges associated with the development and evaluation of psychedelic medicines, and defining areas for which further regulatory guidance is required.
towards safe and responsible integration of psychedelic-assisted therapy
As thrilling as it is to witness the rapidly increasing support for psychedelic-assisted therapy, a critical perspective and patience are the keys to shaping a future where psychedelic therapy can be integrated safely and responsibly for the benefit of science, healthcare and society.
For the moment, we look forward to welcoming you to the sixth edition of ICPR, which will be held from June 6 to June 8 at the PHIL in Haarlem, the Netherlands.
co-create the future pathways to access in Europe
The full-day Pathways to Access Summit (Paths) convenes key stakeholders from Europe and beyond to explore the opportunities and challenges around the development, approval, and eventual integration of psychedelic medicines into mainstream European health care. Join us in co-creating the future of psychedelic medicine.
We are extremely happy to be able to socialise with all of you soon at ICPR 2022. Yet we are fully aware of multiple ongoing crises right now. Out of care and concern for our living environment and other species, we decided to reduce ICPR’s ecological footprint per person compared to earlier conferences.
We have opted for vegetarian, mostly organic meals, have created a digital conference booklet instead of a printed one, and have dispatched with the tradition of physical swag bags.
We also reduced our oversees marketing, introduced livestream-tickets (including scholarship tickets) and have now started a fundraiser to compensate for the conference’s carbon footprint and to give back to the cultures whose knowledge informs psychedelic science today.
Green fundraiser To compensate for the travel emissions involved in getting speakers and attendees to Haarlem, we have launched a fundraiser through One Tree Planted. OPEN will ‘plant’ the first few thousand trees, and we hope to triple or quadruple that number with your help. Go to our fundraiser on One Tree Planted to contribute.
One Tree Planted is a non-profit organization focused on global reforestation. Your donation is tax-deductible.
Reciprocity fundraiser We acknowledge and honor the responsible relationships that indigenous peoples have forged with psychedelic plants over the past centuries. We recognize that the Global North benefits from their knowledge, and we believe that it is critical to support the organizations working to conserve the biocultural communities that have taught – and continue to teach – the rest of the world about how entheogenic plants can benefit individuals and societies.
Our partners at the Chacruna Institute recently launched the Indigenous Reciprocity Initiative, which we applaud and want to support with a second ICPR fundraiser. Please consider donating if you feel that you have benefited from psychedelics in any way.
The Indigenous Reciprocity Initiative (IRI) is a community-directed biocultural conservation program connecting directly with grassroots Indigenous organizations with the aim of ‘giving back’ to the cultural regions that support indigenous plant use and knowledge. IRI created a pool of funds that supports Indigenous initiatives with a proven track record, addressing a broad range of efforts from food security and environmental health, to economic and educational support.
IRI strives to foster a relationship of reciprocity between the rapidly growing industry generated by the mainstreaming of psychedelics in the Global North, and the Indigenous peoples who have historically received little benefit from the commercialization of their cultural and biological heritage.
No swag bags, but… We’re not handing out notepads and swag bags anymore, so we kindly request that all attendees bring their own writing gear. But, of course, we will not let our guests go home entirely empty-handed either! There will be some surprises that do not cause unnecessary garbage.
Right after new results from his research on alcohol addiction and psychedelics emerged, Michael Bogenschutz confirmed his attendance at ICPR. A professor of Psychiatry at NYU Grossman School of Medicine and Director of the NYU Langone Center for Psychedelic Medicine, Dr. Bogenschutz is well known for launching the first contemporary study of psilocybin-assisted psychotherapy for alcohol use disorder in 2015. He has published extensively on the topic of addiction and the therapeutic potential of psychedelics.
Just one week ago, he reached another milestone in psychedelic research through his publication of the first double-blind randomized clinical trial of psilocybin for alcohol use disorder. This trial took a long time to complete, as the recruitment process took place from 2014 until 2020. But the wait seems worth it, as the final sample reached a total of 95 participants.
For Dr. Bogenschutz, this means a giant leap from his initial pilot study from 2015, which consisted of a sample of only 10 individuals – an issue that often looms over contemporary psychedelic research.
The fifth edition of OPEN’s conference on psychedelics is almost here. ICPR 2022 will be held from 22-24 September 2022. Get your tickets before we sell out. Live stream tickets for remote viewing are available.
The study
All the individuals who participated in the study struggled with excessive drinking. More specifically, those randomized to the psilocybin or placebo (diphenhydramine) group, respectively drank an average of 7.5 and 6.6 drinks per day. Both groups received 12 weeks of manualized psychotherapy and were administered either psilocybin or diphenhydramine at week 4 and week 8.
The study wanted to assess, most of all, whether the percentage of heavy drinking days was reduced following psilocybin. They found that the psilocybin group was associated with “robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy.”
The researchers assessed this 32 weeks after their first dosing session. The percentage of heavy drinking days was still 23,6% for the placebo group, meaning they drank heavily about once every four days, but for the psilocybin group, it was only 9.7% – once every ten days.
On top of that, there were also higher reports of individuals in the psilocybin group who had stopped drinking entirely. 24,4% of the placebo group did so, compared to 47.9% of the psilocybin group.
Future research
Through these results, Dr. Bogenschutz is genuinely changing the field of psychiatry, as there have been no new drug approvals in nearly twenty years for alcohol addiction. The only three approved conventional drugs for the treatment of alcohol use disorder are currently disulfiram, naltrexone, and acamprosate. Psilocybin, as such, might become a lifesaver for many people suffering from alcohol addiction.
But Dr. Bogenschutz is not done yet, as he recently announced that there will be a subsequent trial that aims to include more than 200 participants. This time the study will consist of only one single dose of psilocybin and will be compared to the vitamin niacin as another active placebo. The Food and Drug Administration has recently approved this trial. It will be the largest to date to examine the efficacy of psilocybin-assisted therapy for the treatment of alcohol use disorder.
In recent years, there has been an uptick in attention surrounding the substance known as 5-Meo-DMT. It is popularly known as a toad’s psychedelic gift – but is now also being scientifically studied in clinical research. The compound seems ideal as a fast-acting tool for ego-dissolution, with potential therapeutic use. The substance produces stunning effects that no other psychedelic seems to match, and does so within a manageable time frame.
And oh yes: it also happens to be legally available in many locales.
This is why 5-MeO-DMT might be one of the most fascinating – and potentially useful – psychedelics there is. Just like its first cousin DMT, 5-MeO-DMT is a naturally occurring compound. It can be found in both fauna and flora, like seeds, bark, and leaves from a number of plants in the Amazonian rainforest. The Sonoran Desert Toad, official name Incilius alvarius, is its most well-known carrier and has parotid glands that provide the toad’s primary defense system: a poison potent enough to kill a grown dog. This milky secretion also happens to contain 5-MeO-DMT, or 5-Methoxy-N,N-DiMethylTryptamine. If it is collected, dried, and smoked, the toxin produces a powerful, 15-20 minute psychedelic experience that completely differs in its effects from all the other classic psychedelic compounds – including DMT, its closest molecular cousin.
The fact that it hasn’t been scheduled in many countries facilitates research into the substance. Scientists and therapists wanting to work with substances like LSD and psilocybin, which have been put on international drug control lists, need to jump through many hoops in order to get research started.
In the upcoming ICPR 2024, leading experts and cutting-edge research around 5-MeO-DMT will be presented.
‘Fast-acting therapeutic relief’
Maybe that’s part of the reason why scientific research into the useability of this substance has now taken off. In 2019, Maastricht University investigated the effects of 5-MeO-DMT. They found that in a naturalistic setting, a single inhalation resulted in enhanced satisfaction with life and decreased psychopathological symptoms, including depression, anxiety, and stress – all of which were sustained for up to 4 weeks after the experience. ¹
This year (2022), the group, led by Johannes Reckweg, published a review of the current knowledge of 5-MeO-DMT and hypothesized mechanisms underlying its effects. It mapped the workings of the drug, and weighed its potential utility for mental health. It concluded that ongoing research was justified: “The current therapeutic potential of 5-MeO-DMT is mainly hypothetical and based on preliminary evidence. […] Although limited, the studies offer converging evidence of the potential ability of 5-MeO-DMT to provide fast-acting, and potentially immediate, therapeutic relief for depression, anxiety, and stress-related disorders (such as PTSD) in particular.” ²
When a psychedelic molecule finds its way into the 5HT2A receptor binding site, depending on its shape and charge distribution (and thus the interactions formed within the binding site), it will distort the receptor and shift it into a distinct active conformation (ON state). pic.twitter.com/d4t2KQg9yD
Dr. Chris Timmermann has also been investigating the effects of 5-MeO-DMT at the Center for Psychedelic Research, at Imperial College London. He described the gripping psychedelic for us: “What makes 5-MeO-DMT truly unique,” Timmermann says, “is its apparent ability to induce states of ego dissolution in such a reliable fashion. The structure of the experience is fundamentally altered compared to other psychedelics – which usually provide a very rich visual experience. With ‘5-MeO’, users apparently experience a ‘white light’ that is closely associated with the ego-death experience. It is that ego-death experience that appears to have a radical impact on the user, especially in the case of addiction.”
According to Dr. Timmerman, the reliability with which 5-MeO-DMT appears to induce ego dissolution and non-dual consciousness is as interesting for consciousness research as it is for experimental psychiatry. Indeed, 5-MeO-DMT appears to induce a state of “non-dual consciousness,” which refers to a state of being in which subject and object are undifferentiated, similar to that reported by experienced meditators.
Cultural origins
Unlike Ayahuasca, which has a clear indigenous lineage found in the shamanic traditions of amazonian tribes, the cultural heritage of 5-MeO-DMT remains unclear. Although numerous ceramic frog motifs found in the Santarem Territory of the Amazon suggest an indigenous connection to the animal, and some local names could allude to an elevated status of the toad, the evidence is often too ambiguous to make any direct connection to the psychedelic properties of Incilius Alvarius. Maybe future anthropological findings will shine more light into cultures that might have used it in the past. For now, its culture is a more modern tale.
5-MeO-DMT was first synthesized in 1936 by chemists Toshio Hoshino and Kenya Shimodaira but lay dormant as far as use went. Until 1983, when the book Bufo Alvarius: the psychedelic toad of the Sonoran Desert was published by a writer calling himself Albert Most. This latin name was used for the toad until its new classification as Incilius in 2006.
“Bufo Alvarius” is a seminal work describing the toad, its milky defense system and possible 5-MeO-DMT harvesting methods. The book opened the door to the modern culture of smoking the ‘toad venom’, as some tabloids called it and which -by the way- is an inaccurate term. In biology, ‘venom’ would mean the substance is injected by the toad, but it is not: it is sprayed.
That’s not the only confusion around the psychedelic toad. The taxonomy of the toad itself has changed. In 2006, it was classified as a member of the Incilius genus, so the book’s name is now dated. Also, the person laying the foundation for this new culture of toad toxin smoking, ‘Albert Most’, remained an enigma for many years.
The person behind the pseudonym was unknown for three decades, until he was revealed by psychonaut-journalist Hamilton Morris to be a man called Alfred Savinelli – who then was revealed to be an impostor by that same Hamilton Morris! In the third season premiere of his VICE Series Hamilton’s Pharmacopeia, Morris uncovers the lie of Savinelli, and exposes the real author of ‘Bufo Alvarius’ : Ken Nelson.
Nelson turns out to be a reclusive psychedelic researcher, environmentalist and veteran from Texas. To right past wrongs, Nelson and Morris released a new version of Nelson’s pamphlet, featuring Morris’ synthesis of 5-MeO-DMT.
Mainstreaming
There is still plenty of runway for the substance to create a culture of its own. It was readily available online as a ‘research chemical’ in the United States, and enjoyed limited attention. But its scheduling in the USA in 2011 provided a bolt of attention that increased its popularity. In 2019, the substance was potent enough to knock out former heavyweight boxing champion Mike Tyson, who openly talked about the spiritual awakening that resulted from his use of 5-MeO-DMT.
Soon after, others followed. Media outlets such as Forbes and the New-York Times featured stories about the transformative effects of the substance and included testimonials from ex-Navy SEAL Marcus Capone and his ongoing battle to help other Special Operations veterans access 5-MeO-DMT. All this media attention contributed to the mainstreaming of this compound in the last few years, despite its illegality.
These restrictions have hampered research into 5-MeO-DMT in the countries where it has been forbidden. But in countries like the Netherlands, multiple studies into 5-MeO-DMT are now underway.
ECOLOGICAL DAMAGE
As said, there is no indigenous ritual surrounding the use of 5-MeO-DMT, yet treatment centers using the toad’s poison have started to spring up incorporating rituals from other psychedelic cultures. These psychedelic sessions can set you back from $250 up to $8500.
This new popularity has not been good for the Sonoran Desert Toad itself, a risk voiced by Robert Anthony Villa, president of the Tucson herpetological society. Although the toad seems comfortable in human-made constructions like irrigation ditches, suburban yards and near water tanks on ranches – it is now often poached for psychedelic purposes, after which it is stressed out to produce its venom.
A solution for this animal cruelty could be a synthetic variant of the drug which would be preferable over one involving stressing out animals. That’s one of the reasons why Hamilton Morris included the synthesis process for 5-MeO-DMT in one of his episodes. The new edition of Bufo Alvarius: the psychedelic toad of the Sonoran Desert, also features Hamilton Morris’ synthesis of 5-MeO-DMT in a Mexican lab.
5-MeO-DMT is illegal in the United States, China, Australia, Sweden, Germany and Turkey, but is legally available in many other locales. Dutch webshops sell the substance together with many other tryptamines over the internet for use at home.
THE USER EXPERIENCE
When vaporized, a single deep inhalation of 5-MeO-DMT produces strong psychoactive effects within 15 seconds. After inhalation, the user usually experiences a warm sensation, euphoria, and strong visual and auditory hallucinations, due to 5-MeO-DMT’s high affinity for the 5-HT2A serotonin receptor subtype. The duration of these effects are comparable to those of DMT, lasting between 15 and 20 minutes. According to trip reports, at commonly-used doses, 5-MeO-DMT may possess the most complex and overwhelming effects of the classic psychedelic family.
Physical effects can include changes in perceived gravity, pupil dilation, muscle spasms, temperature regulation suppression, and feelings of loss of breath, but also an overwhelming intensity of physical and tactile sensations that can lead to the sensation of repeated, full-body orgasms.
Cognitive effects include distortion of space and time, amnesia, ego dissolution and auditory verbal hallucinations. Visual effects can include visual acuity enhancement, with drifting, color-shifting and morphing of complex geometrical patterns, but more often, reports mention visual suppression, where a blinding white light replaces all the visual complexity usually associated with hallucinogens. Much of this is often preceded by nausea, according to Drug Science UK.
An anonymous OPEN member described his 5-MeO-DMT experience for us as follows: “If LSD is a rollercoaster, 5-MeO-DMT is an intergalactic faster-than-light rocket that takes you to a wholly unrecognizable state of being. Landing back from a high-dose experience you are left with more questions than you came in with, but what an amazing ride it is.”
The combination of all these effects often results in transpersonal effects, during which the sense of identity of the individuals experiencing them extends beyond the personal level to humankind, nature and even the cosmos, which makes for the mystical quality of the experience. As mentioned earlier, 5-MeO-DMT also reliably induces ego dissolution, a phenomenon characterized by a complete change in normal, everyday, self-referential awareness.
Check out the speaker list to discover which experts might be speaking about the latest advancements in 5-MeO-DMT research!
CLINICAL TRIALS
So far, very little clinical research has been done on 5-MeO-DMT. The limited number of published studies suggest the compound might be safe and useful in a clinical context. If it turns out that 5-MeO-DMT does indeed have beneficial therapeutic effects, as anecdotal and early scientific evidence suggests, the promising aspects in terms of its practical use in a clinical context would be the duration of its effects.
The Beckley foundation has recently mentioned that MDMA or psilocybin-assisted therapy usually take up an entire working day for the therapist, which “poses a potential bottleneck to patient access in the future,” so a short-acting psychedelic like 5-MeO-DMT would help with both the clinical trial process and subsequent access to psychedelic therapy. As Michael Pollan mentioned in 2018: “a psychedelic therapist wants to be home for dinner too.”
Indeed, 15-20 minutes of medical and psychological supervision is a lot more manageable for clinical trials and therapists compared to the 3-6 hours that are necessary for psilocybin, or the 6-12 hours necessary for LSD. And this could eventually help in making the mystical experience more accessible.
LESS IS MORE?
The properties of 5-MeO-DMT lead to fascinating questions about its future potential utility in psychedelic-assisted therapy. But is the psychedelic indeed capable of the same types of transformations that have resulted from LSD, psilocybin and MDMA-assisted therapy? In other words: does the short-acting nature of 5-MeO-DMT come at the cost of its therapeutic benefit?
The answer to those questions is unclear as of yet. The potency of its effects suggests that the short-acting nature of the experience does not impede on its quality, but ongoing clinical trials could shed more light on them.
In many ways, ongoing research on 5-MeO-DMT will give us a window into the feasibility of short-acting psychedelic-assisted therapy, and might very well determine the fate of the emerging short-acting psychedelic field. ㅤ
There are many documentaries about psychedelics nowadays, but only so little time to watch them all, let alone figure out which one’s are worth it! That’s why we came up with a list of documentaries on psychedelics that you can watch, or binge, comfortably from your own living room. They’re selected for their scientific soundness, cultural insight, or overall high quality.
All of them are worthy study material before you join us at ICPR 2024 near Amsterdam – where some of the speakers are actually some of the people featured in these series and films. Their work is at the basis of this renaissance in psychedelic research and the new generation of documentaries that it has spawned. Enjoy our dose of inspiration.
Hamilton’s PharmaCopeiaㅤ
If there is one documentary that hits all the marks when it comes to information about psychedelics, as well as other psychoactive drugs, while simultaneously delivering a high entertainment value, it is – without a doubt – Hamilton’s Pharmacopeia, of which there are now three seasons.
This documentary series is written, directed, and produced by Hamilton Morris, a journalist and scientific researcher who explores the history, chemistry, and social impact of various psychoactive substances across the globe.
Hamilton illustrates how ubiquitous psychedelic drugs are and goes out on a limb to try several of them himself – showcasing his dedication and genuine curiosity when it comes to studying the effects of these extraordinary substances. It is beyond the scope of this article to discuss the merits of every episode on its own, but we compiled a hit list of our favorite episodes shown at the end of this commentary. That’s right – more stuff to binge this coming summer! Just watching these will suffice for at least 8 hours of entertainment, where Hamilton Morris meets with underground chemists that illegally synthesized MDMA; travels to Huautla de Jimenez in Mexico to visit the family of the legendary curandera María Sabina’s to talk about psilocybin-containing mushrooms; smokes 5-MeO DMT in the Sonoran desert under supervision of a shaman; and talks with Amanda Feilding about how she helped to fund the very first neuro-imaging study of LSD. Be sure to absolutely check this series out!
Quote of the series
“It is so strange that these compounds exist. What is the purpose of any of this? 5-MeO-DMT? This? In a toad’s venom? And people may have only started using it 30 years ago? And it produces this peak experience of love? I can’t believe it! It is so amazing!” – Hamilton Morris
Our hitlist for best episodes:
Season 1
Episode 4 – Magic Mushrooms in Mexico
Episode 6 – The Lazy Lizard School of Hedonism
Season 2
Episode 1 – The Psychedelic Toad
Episode 2 – Peyote: The Divine Messenger
Episode 4 – Wizards of DMT
Episode 5 – Ketamine: Realms and Realities
Episode 6 – A Clandestine Chemist’s Tale
Season 3
Episode 1 – Synthetic Toad Venom Machine
Episode 4 – Synthetic Ibogaine: Natural Tramadol
Episode 6 – UItra LSD
Descending the mountain (2021)
Filled with aesthetically pleasing images, jaw dropping cinematography, a great psychedelic soundtrack, and a pinch of neuroscience, Descending the Mountain excels at every front. The documentary includes renowned psychedelic researcher Prof. Dr. Franz Vollenweider and Zen master Vanja Palmers. Their mission? To set out to a monastery on top of mountain Rigi in Switzerland to conduct a novel experiment in which experienced meditators received psilocybin-containing mushrooms in a group setting for the first time in their life. This experiment was double-blind, where neither the researchers or the participants knew what dose they received. Some of the meditators received an active dose of psilocybin, whereas others were ‘unfortunate’ (in their words) and received a placebo. It is amazing, to say the least, how these experienced meditators were able to deepen their meditation due to psilocybin, even after thousands of hours of meditation practice. One individual was completely ecstatic from the beginning till the end and amazed by what he was experiencing. Others felt it to be a collective experience, rather than an individual one, as they were able to feel the energy in the room. Ultimately, placebo or no placebo, the group setting was conducive to the experience at the mountain.
Quote of the movie
“What can the mushrooms tell us today?” – Descending the Mountain
Halfway through the documentary, Prof. Dr. Vollenweider explains briefly how psychedelics work and that neuroscientific research of today has consistently demonstrated that they deactivate the Default Mode Network (DMN) – a key brain region involved in self-referential processing. With their experiment on Mount Rigi, they too found that the participants who received psilocybin were able to enter a deep(er) meditative state and showed less activity in the DMN when compared to the placebo group. Vollenweider explains how it: “makes you less focused on yourself because, in a way, you lose your ‘self’, and that this tends to make you focus more on others around you.” This dovetails neatly with the hypothesis that psychedelics are able to alter personality and political beliefs, something that the documentary explores briefly as well through asking significant questions as: “What can psychedelics do for society today? What will happen if great leaders take these substances and make us think about our place in the world?”
Michael Pollan’s How To Change Your Mind (2022)
Four years after the release of his book under the same name, Michael Pollan hit the big screen on Netflix with a documentary series: How to Change Your Mind. To say that his book had somewhat of an influence on the psychedelic renaissance is an understatement. Individuals even talk about a Pre-Pollan era and Post-Pollan era within psychedelic research. And now, with this new and cinematic tour du force, Pollan might continue to increase his reach by showcasing these tools to people all over the world sitting in their living room.
The documentary consists of a total of four episodes, each focusing on a specific psychedelic. The first episode focuses on the synthesis of LSD by Dr. Albert Hofmann in 1938, the research of its therapeutic use when treating alcoholism, and how it ultimately became a Schedule I substance – as it ended up on the streets through evangelist Timothy Leary and the CIA project MKUltra, that serendipitously turned on Ken Kesey. In the second episode, the viewer is brought to the world of psilocybin-containing mushrooms and features ICPR speakers William Richards, Paul Stamets, and Roland Griffiths. Here, Pollan discusses their historic use in religious settings, the introduction of the mushroom to the West, and how it is currently being researched for various debilitating psychiatric disorders, such as depression, end-of-life anxiety, obsessive compulsive disorder, and cluster headaches. The third episode features ICPR speaker Rick Doblin and is all about the therapeutic use of MDMA for the treatment of post-traumatic stress disorder. Pollan interviews Ann Shulgin, the wife of renowned chemist Alexander Shulgin, – who recently passed away – about her personal experiences with MDMA and how it ended up becoming illegal through the so-called “Second Summer of Love”’ during the 1980s. Finally, Pollan takes a deep dive into the ceremonial use of the peyote cactus by indigineous Americans that are part of the Native American Church.
The documentary provides a solid starting point for anyone who is new to the world of psychedelics and likes to be prepared for what we have to offer at ICPR. It presents some of the most recently conducted preliminary research studies and their implications. Contrary to contemporary media headlines, it is refreshing to see that Pollan remains centered throughout the entire documentary with regards to the therapeutic potential of psychedelics and messages to the audience to do the same. This is a welcoming message that is to be embraced if we do not wish to repeat past mistakes.
The Psychedelic Drug Trial (2021)
Major depressive disorder (MDD) is the leading cause of disability in the West, says ICPR speaker and Professor of Neuropsychopharmacology David Nutt. Across the globe, MDD is estimated to affect 350 million individuals and is responsible for more ‘years lost’ than any other psychiatric condition. Psychiatry has been desperate for novel treatments.
One of the current mainstays of treatment in psychiatry is escitalopram, a selective serotonin reuptake inhibitor (SSRI), better known under its brand name Lexapro. This psychotropic drug increases the amount of the neurotransmitter serotonin in the brain and has been proven by earlier clinical research to be effective and well tolerated in the treatment of MDD. But this begs the question: “How does escitalopram, or Lexapro, compare to psilocybin when used for treating depression?” This is what the research team in the Psychedelic Drug Trial set out to do.
Quote of the movie
“If psychedelics can change the world, let’s put it to the test.” – Dr. Robin Carhart-Harris
The documentary presents an extensive in-depth look into how the study was conducted by displaying easy-to-comprehend visuals and various infographics. The documentary really shines here and you immediately get a clear understanding of what the study design looked like. It also exemplifies how current psychedelic therapy operates and provides the three important stages involved, which includes: preparation before the dosing session, the psychedelic dosing session itself, and the integration that follows.
What is more, you get to know some of the recruited participants who were told that they are randomized to one of two conditions. They will either receive 1) psilocybin or 2) escitalopram, not both. Almost all of the participants have been on antidepressants for decades and suffer from various side effects, including weight gain, sleep paralysis, and a flat affect. The psilocybin trial represents a “lifeline” according to some of the participants – a viable alternative to their current situation of “concentrating on staying alive” and trying “to live with this joylessness.” One participant is at the end of her ropes and tells the camera: “I would probably end my life if I didn’t go [through the trial].”
Soon after this introduction, we are taken into a living room like environment where the psychedelic therapy session took place. Participants at this point are talking about their extraordinary experiences and the various symbols they encountered during their psychedelic dosing session. The documentary really excels here due to its slow presentation of recorded monologues and by displaying aesthetic visuals that are aimed at encapsulating the participants’ experience while on psilocybin. One participant talks about one of her peak experiences where she found herself at the roots of a tree and: “was connecting with everything up there. The thing I really felt most … was a joy. Joy like I’d never experienced. It is really, really powerful stuff.”
The documentary would not have been complete without a brief presentation by ICPR speaker David Nutt on how psychedelics such as psilocybin work in the brain and how they differ from escitalopram. Nutt first explains that antidepressants as escitalopram take about an average of six weeks to work and do so primarily in the limbic system, the emotional center of the brain that is overactive in depression: “It dampens the system and you become incubated against stress, which is good, but you also become incubated by everything else.” Psilocybin, on the other hand, works differently by targeting the serotonin 2A receptor, which are widely prevalent in the neocortex. Psilocybin also works through the disruption of the Default Mode Network that Franz Vollenweider similarly talked about in Descending the Mountain. Both professor Nutt and lead researcher of the study Dr. Robin Carhart-Harris believe that psilocybin works better and faster than escitalopram.
The results of this landmark study have been published in the highly esteemed The New England Journal of Medicine. Their conclusion? Both psilocybin and escitalopram work in the treatment of depression. But when taking into account secondary outcome measurements such as suicidality, psilocybin looks better than escitalopram. More recent neuroscientific findings of the current study have been published as well, which looked at how psilocybin affects the brain and how it differs from antidepressants. All in all, more research is needed as we venture forth in our pursuit to help people alleviate their depressive symptoms.
In the upcoming ICPR 2024, leading experts and cutting-edge research around the use of psilocybin for therapy will be presented.
Journeys to the Edge of Consciousness (2019)
Journeys to the Edge of Consciousness is a unique animated film that chronicles the very first psychedelic experiences of Timothy Leary, Aldous Huxley, and Alan Watts. The film is interspersed with commentaries on these historical and influential events by ICPR speakers Rick Doblin and Amanda Feilding, and various other researchers within the psychedelic field.
The Dropout Drug
We first witness how Timothy Leary got involved with LSD through meeting Michael Hollingshead, a British researcher who studied psychedelics at Harvard University in the mid twentieth century. Leary’s first LSD trip was: “the most extraordinary experience of his life.” Yet to my surprise, he also felt a terrible sense of loss after this trip, as he did not know what to do with these new insights: “Once you see how it is all composed, it is hard to get back to the game.” This experience demonstrates that even psychedelic evangelists as Leary, a very intelligent man who was probably one of the most well-known proponents of psychedelics, would have benefitted from the importance of integration. The world would have been a very different place indeed if Leary underwent this integral part following psychedelic use. Instead, he decided to leave the highly esteemed university of Harvard and famously told students to: “tune in, turn off, and drop out.” This resulted in the then U.S. president Richard Nixon to call him the most dangerous man of America.
Commentaries from other experts on Leary’s psychedelic experience are very informative. They exemplify how psychedelics are able to lift the veil of ordinary reality, which can either facilitate, or in the case of Leary, diminish our well-being, because we see through the illusion, i.e., the play of life. You’re catapulted out of your ego and you can spend years of life making sense of it all, which might have happened to Timothy Leary according to Dr. Tim Read. Yet, Dr .Gabor Maté states that bad trips can also be interpreted differently: “Yes, a trip can be challenging, but what you need is proper integration. This is the work of healing. The psychedelic experience and its healing properties were lost during the 60s because there was a lack of intention.
The Doors of Perception
Next we get a close look at Aldous Huxley’s famous psychedelic experience with mescaline that led him to write his famous work The Doors of Perception: and Heaven and Hell. During his experience, he realizes that “this is how one ought to see” and that the ordinary mode of consciousness is but one form of consciousness. Huxley talks about the suchness of things while on mescaline and develops his metaphor of the reducing valve of the mind, which limits our view of reality and who we really are.
According to ICPR speaker Rick Doblin, Huxley’s insights demonstrate where we should put our meaning: “not on consuming, but on something deeper.” Other psychedelic researchers talk about how people ‘wake up’ after their psychedelic experience, including alterations of the perception of the self and various changes in their value system.
The Joyous Cosmology
Finally, we witness Alan Watts taking modest amounts of LSD while in California and who decided to casually go for a stroll. His first undertaking was to listen to a priest in a church during a mass. He witnesses how people are putting on an “act of a person”, which is one of the key phrases of Alan Watts. His feeling of self became no longer confined to the insides of his skin as he felt connected to everything: “my individual of being seems to grow out to the rest of the universe.” The animated re-enactment of Alan Watts’ psychedelic experience gives us a glimpse into how psychedelics helped shape his philosophy.
Quote of the movie
“Come off it shiva, you rascal, who do you think you’re kidding!? It’s a great act, but you’re not fooling me!” – Alan Watts
Neurons to Nirvana (2013)
Neurons to Nirvana is filled with numerous psychedelic researchers who will be attending ICPR, including Rick Doblin, William Richards, David Nutt, Roland Griffiths, and Amanda Feilding. The film gives a brief overview of classic psychedelics, including psilocybin, ayahuasca, and LSD. In addition, the entactogen MDMA is briefly discussed plus the medicinal benefits of other (non-)psychoactive substances as marijuana and cannabidiol.
The film starts with the serendipitous event of how psychedelics helped shape modern psychiatry and neuroscience. LSD, as it turns out, has a very similar structure to serotonin that led to the discovery of the serotonin neurotransmitter system. As a result, psychiatry started including brain chemistry into the disease process, whereas before all the accountability went to either the individual or the environment.
It was a revolutionary period for which the famous psychedelic researcher Ralph Metzner said that discovering psychedelics: “was like discovering another continent, like Marco Polo.” Both ICPR speakers Rick Doblin and David Nichols mention how psychedelics are able to occasion a mystical experience and how this helps experience the world as one as it breaks down certain barriers. Roland Griffiths adds: “there is this quantum change during a psychedelic experience – it belongs among the most spiritual and personal meaningful experiences of peoples’ lives.”
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“What is being purged actually, is psychological contents that you’ve been holding onto. You’re purging anger, you’re purging pain, you’re purging some false story about the self.” –Gabor Maté M.D.
A great feature of the film that is worth mentioning here is that it shows the capability of human individuals being able to change their beliefs when it comes to esoteric substances such as psychedelic drugs. This is illustrated when Dr. Sanjay Gupta appears on the big screen, an Emmy award-winning doctor for his show on CNN who used to vehemently oppose the use of marijuana. This was until the year 2009, as the scientific evidence started accumulating and Dr. Gupta discovered that it was used for thousands of years. He also found out that before there was a strong focus on the negative. Most importantly, Dr. Sanjay Gupta was illuminated by the benefits of marijuana: “the science is there!”. This clearly demonstrates how scientific evidence can pave the way for reconstructing our beliefs about psychedelics. Hopefully, other physicians, researchers, and politicians will follow suit.
Check out the speaker list to discover which experts might be speaking about the latest advancements in MDMA, LSD, and Psilocybin research!
The Last Shaman (2016)
The Last Shaman follows young adult James who is battling with crippling bouts of depression ever since he went to university. He is desperate for a way out as he tried doing everything according to the book on both a medical and personal level. In general, this involved seeing several psychiatrists, taking antidepressants, and picking up a regular meditation practice. Despite his arduous efforts, he remains depressed. At the end of his ropes, he travels to Peru to meet several shamans that might be able to help him.
The documentary is not for the faint of heart and can be very shocking in demonstrating how debilitating depression can be. James suffers from extreme anhedonia, which refers to the inability to feel pleasure: “I see a beautiful woman or a sunset and I feel nothing.” He explains how his depression affects him in front of the camera and this raw footage makes the documentary feel very personal, but also heart-wrenching to watch at times, as his eyes are filled with tears and his voice is featured by a tremendous amount of frustration and despair. He ends up meeting various shamans in different regions and engages in multiple ceremonies to finally reach salvation.
James’ journey ends deep within the forest at the Shipibo community – a place that resembles just the right amount of authenticity he is looking for. Shamans here do the practice because it is a calling, whereas the business side of things are left aside. James ventures deeper into his emotions, revealing one layer from another layer, and becomes a passionate ascetic. He maintains a very strict diet and stays in isolation for a total of four months, eating nothing but fish and rice and smoking the Mapacho tobacco. This experience ripped him of all attachments of his previous life. He believes he: “no longer has an inferiority complex anymore” and feels no more anger towards his father.
Quote of the movie
“I’m here to be a very small part of something much larger than myself, and that is extremely liberating” – James
Iboga Nights (2014)
David Graham, the director and producer of the renowned and brutal documentary Detox or Die, returns to the big screen with Iboga Nights. His first documentary consists of his mission to cure himself of his opiate addiction through ibogaine – a psychedelic substance with dissociative properties that is extracted from the root bark of the iboga tree (Tabernanthe iboga). His film became a resounding success that resulted in an explosion of media, press and news articles. This inspired other addicts to follow in his footsteps by taking up ibogaine and get rid of their opiate addiction once and for all. Iboga Nights follows several of David’s ‘apprentices’.
Iboga Nights is basically split up in three sections. The first is where we are introduced to a shaman from the Netherlands who has treated an approximate of 1,000 patients with ibogaine for their opiate addiction. To my surprise, there was almost no guidance involved; the shaman plainly administers the drug and then lets ibogaine take its course while the participants stay in their assigned bedroom. It was quite astounding to see how most turned out fine and even managed to go through the treatment without experiencing any withdrawal symptoms. However, the documentary quickly takes a dark turn that illustrates the significance of taking into account proper screening and guidance. For instance, one participant stopped breathing due to an underlying heart condition and was taken away to the hospital. Ibogaine is known for slowing down the heart rate that might be fatal. Fortunately, he survived. But another participant left the house and was hit by a truck. David wanted to end the film right there: “how can I be a spokesperson for something so dangerous?”
After these horrific events, David meets up with Dr. Ben Sessa and Dr. Jeffrey Kamlet to talk about psychedelic research and ibogaine. Both share a pessimistic view with regards to pharmaceutical companies and how they supposedly “treat” patients, as they make billions of dollars on pain pills that generally require daily use. Naturally, they scoff at this predicament: “Why do they want ibogaine that requires one dose to cure people. That does not make money?”
Quote of the movie
“Does it not feel weird to have had that life, among such affluence, and now be living in a hotel shooting up crack and heroin and taking up methadone?” – David Graham
Fortunately, the documentary also contains the amazing journey of Sid who was severely addicted to morphine and completely transformed through his ibogaine treatment. He was sexually abused by an older man when he was only 11 years old. During his session, both David and Sid are serious by taking screening and guidance into account. For example, they check if Sid is allergic to ibogaine and during the ibogaine treatment will frequently measure his heart rate and blood pressure. It is astounding to see that even after fivedays of taking ibogaine and no morphine at all, any symptoms of withdrawal are virtually non-existent. But Sid knows that the real treatment starts after ibogaine, which requires integration and (simply) staying off the drug. Several months later David returns to visit Sid and witnesses another person in front of him. He has become a completely transformed person and has much more energy and life in his eyes. Sid talks briefly about his ibogaine experience: “I did not have many visions or anything, but it took my physical dependence away.” The urge, or craving to use drugs, is totally gone. Sid simply does not: “want to do that anymore.”
From Shock to Awe (2018)
The documentary From Shock to Awe chronicles the transformative journey of two military veterans that suffer from severe post-traumatic stress disorder (PTSD). Because of this, everything they encounter on a day-to-day basis within their natural environment signals danger. With their bodies still in war and drugged by an arsenal of pharmaceuticals, they turn to the Amazonian brew ayahuasca as a last resort.
Quote of the movie
“I left the warrior behind and let the sunlight take the steering wheel now.”
Both veterans are filmed during their ayahuasca retreat that consisted of four ceremonies, two during the day and two at night. During all dosing sessions, we see grueling raw footage of both veterans struggling with their deep-rooted trauma. The entire retreat resembles the archetypal hero’s journey of diving into the unconscious and coming back into the real world reborn. Through ayahuasca, they realized that all life is sacred, which is: “the exact opposite of what is learned during military training.” Their perception of everyday ‘signals as danger’ changed after only one weekend, as they heard a gunshot in the woods, locked eyes, and started laughing immediately. The PTSD response was no more.
Until recently, there was no advocacy or central voice for the participants in clinical trials involving psychedelics. Now, there is PsyPAN, a non-profit organisation set up to connect and empower psychedelic participants. Founders Ian Roullier and Leonie Schneider both participated in such trials. Ian took part in the psilocybin for depression trials at Imperial College (2015) and Compass Pathways (2019). Leonie took part in the second phase of the psilocybin for depression study at Imperial College (2019) and the DMT for depression trial at Small Pharma (2022). They were later invited to take part in Dr. Rosalind Watts’ one-year integration programme, where they met.
Towards the end of the programme, Leonie and Ian discovered they had a shared interest – both in advocating for the spread of psychedelic treatment for mental health as well as having the patients’ perspective duly represented. No organisation representing the patient’s viewpoints existed, while the number of participants in psychedelic trials is increasing by the day. And as the standards for these novel treatments are now being developed, both felt that the voice of the patient needed to be heard louder.
So, in 2021, Leonie and Ian founded the Psychedelic Participant Advocacy Network: PsyPAN. It’s a non-profit organisation set up to connect and empower all psychedelic participants. PsyPAN aims to give a collective voice to all participants and help improve participant safety and wellbeing, by working on developing best practices across all levels of the global psychedelic sector – clinical and non-clinical alike.
As the psychedelic sector is expanding at a breathtaking pace, companies, clinicians and modern-day curanderos alike have a lot to learn from the persons seeking their help. We talked to Leonie and Ian for this interview.
Leonie and Ian will also be speaking at ICPR 2022, the psychedelic conference organised by the OPEN Foundation, which has been promoting psychedelic research and therapy since 2007.
What motivated you to set up PsyPAN? Ian: We both participated in clinical trials designed to test the effects of psilocybin and DMT on depression. Our wildly varied, but generally positive personal experiences triggered a wish to bring these treatments to more people and at the same time ensure the treatments are delivered safely and responsibly.
Leonie: We want to ensure the ‘participant’s voice’ is taken into account when clinical trials are designed, so that the trials can be tailored to meet the wide range of experiences. Despite some unifying themes across the psychedelic experience,, it is such a personal process, and deep trauma and psychological issues can present in so many different ways. We want to provide a feedback loop: taking what participants say, giving that to industry, and having industry respond to what participants require in this process. So that we can ensure these treatments are tailored and take nuances and details into account.
Ian: Next to the ‘participants’ voice’ we keenly engage in advocacy work, destigmatizing the image of psychedelics, dispelling misunderstandings and fear. We are keen to ensure that more people can benefit from these treatments in a safe and appropriate way.
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Ian Roullier and Leonie Schneider recently launched the Psychedelic Participant Advocacy Network – PsyPAN. With their new organisation, they want to represent the voice of the participants of psychedelic trials. In this video, we go over some of the highlights of our conversation.
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Is psychedelic therapy especially prone to safety risks? Ian: Yes, psychedelic therapy is more risky than, for example, giving someone an SSRI. Psychedelic substances lay you bare and much more vulnerable, you can’t just get up and go back to work as if nothing happened. It is also their strength; but therein also lies the potential for healing.
Leonie: Safety is therefore key, so developing psychedelic safeguarding guidelines is where we can help organisations.
Where do you see your contribution to the rapidly developing market of psychedelic therapy? Ian: We work with organisations to ensure that they have the finer details in place, and we hope to develop a model of best practice that organisations could follow.
Leonie: Sometimes there are issues organisations simply haven’t thought of because those involved haven’t suffered from the issues that people with a clinical diagnosis have gone through, nor have they taken part in clinical trials, so our feedback is valuable. We aim to help ensure that trials or treatments are delivered safely and appropriately, because the more corners cut, the less effective the treatment will be.
What have you learned so far in the process that you were not expecting? Ian: We found out that simply connecting people who have been through similar experiences is in itself of vital importance.
Leonie: Yeah. There is no community, or a place where you can go, to land after your experience. So it can be incredibly isolating. If you’ve been through a profound experience but can’t speak to anyone about it, you may still feel as isolated as you did pre-treatment, only in a different way. The circle of family and friends you go back to can’t necessarily understand what you have been through. We learned that there is a lot of value in simply creating a peer community for support.
If there was one thing you as participants in clinical trials would like to draw attention to, what would it be? Ian : Open-label trials, in other words making sure that all participants who go through the process have access to a treatment dose. Contributing to science is wonderful, but if you’re so desperate as to be willing to participate in a clinical trial of a new substance, you really are in need of relief. To go through the process and only have a placebo is quite heartbreaking and potentially re-traumatising. To have access to the full treatment dose could therefore be life-saving for some.
Leonie: Integration. Both of us participated in Rosalind Watts’ “Connectedness” program at Synthesis Institute which was the precursor to Dr Watts’ ACER Integration Programme, which was hugely beneficial. It connected us in monthly group meetings and group work (two groups of 10 participants each) for one full year. The psychedelics are catalysts, they likely allow more progress to be made during the integration. But this kind of deep, long-term integration and connection work has been hugely beneficial.
Tell me more about Integration Leonie: Having a space in which to integrate these experiences brought about by psychedelics is incredibly important, whether one-on-one or in a group, especially if the person has had long-term mental health issues. There is a need for longer-term and deeper level integration, not just a courtesy call of ‘how are you’. It’s about witnessing and supporting people every step of the journey.
As mentioned, we both participated in Rosalind Watts’ 1-year long “Connectedness” program. Due to Covid-19, the whole program was delivered online, which wasn’t the plan at all! And still it was so valuable. It kept many of us afloat, especially considering the pandemic. As long as there is a safe container, an online program can genuinely work.
The sweet spot could be to have online content enhanced with in-person meetings, hopefully in smaller, local groups (as treatments become more common) and outdoors, which allows for engagement with Nature.
What part did the connection with Nature play in your healing process? Leonie: Reconnecting with Nature and with every living thing is very powerful. For example, watching the same tree go through its year-long cycle, especially during the dark, deathly-looking winter months, realising this period is part of a longer cycle, realizing there is still a lot happening under the surface even if above ground the tree looks barren – this was all very meaningful.
Most of mental illness is exacerbated by trying to avoid feelings as opposed to accepting them. When you learn to see low moods as “this is my Wintering, and Spring will come”, it creates a meaningful marker, a reference point.
What should organisations emphasise as the most important factors for a patient to consider before deciding to join a clinical psychedelic study? Leonie: Organisations running clinical trials must make potential participants aware that the ‘trip day’ is just a catalyst. You’re in the process for the long run and there will be plenty of long-term, steady work that only starts after the day at the clinic. The importance of long-term integration and connection after the ‘trip day’ cannot and should not be underestimated.
Ian: Expectations should also be carefully managed regarding the chances of getting into the trial. Many people aren’t accepted. Furthermore, organisations would do well to question the kind of support networks potential candidates have in place, because a lot of support is needed right from the recruitment and screening stages. What further support is available during and after the treatment? Is there a community and family in place that can hold your experience, so you do not end up in crushing isolation, which might negate any benefit you could get from the treatment?
Organisations engaging in double-blind trials should also make it very clear that participants have a 50-50 chance of getting a placebo, which may result in disappointment. In the case of depression, you need to come off the anti-depressant medication, which makes you more vulnerable. You hope for an improvement but may end up with a placebo, with all the disappointment and anxiety this may cause. You may potentially end up in a worse position than you were before entering the trial.
To what extent if any does treatment with different psychedelic substances require different guidelines? Leonie: It is certainly important to bear in mind what medicine you’re working with and then tailor the guidelines appropriately since the experiences vary in intensity, the type of in-session interaction and the kind of post-treatment support required depending on the medicine used. Furthermore, the theme of the session matters, too. As an example, if sexual issues are likely to arise, two therapists present and a recording of the sessions may provide more accountability.
How could the current positive hype around psychedelics impact patients and therapists? Ian: There’s a risk in the current media hype for psychedelic therapy to be seen as a ‘one dose and you’re fixed forever’ treatment. It sets expectations too high, and, in the absence of legal treatments, people may opt to try the psychedelics themselves without appropriate support.
Psychedelics are catalysts, not cures. In reality, when it comes to mental health a lot of the healing work happens afterwards. It’s a long process that involves a lot of integration and support going forward. The focus should be more on the psychotherapy, not completely on the psychedelic aspect of the process. If this point isn’t made clear, the risk is that the treatments will be seen as ineffective, which would be a shame as there is huge potential in psychedelics.
How do participants’ opinions get heard through you? Leonie: Participants who have been through the clinical trial setting are the ones most interested in our work, We raise awareness within organisations who run such trials and invite participants informally to join our efforts. Going forward, we want references to PsyPAN to be built into the treatment protocol so that participants can be seamly signposted to us and welcomes to participate if they choose to.
Speaking at ICPR and other events where participants are present is another way of creating awareness of our work. We also help organisations put together a working or focus group, so participants can share their experiences and have a say in the way trial protocols are designed.
Ian: As far as we know, there’s nobody doing exactly what we’re doing. If there are other such groups or networks, we will be delighted to connect with them and support each other. We’re all doing it for the greater good of people who are struggling with mental health conditions.
How do you view depression, as you were both treated for it. Leonie: Depression is a disease of disconnection. In society we are disconnected in so many ways. Depression alerts us to a deep need to slow down, take deep rest and to reconnect: to Nature, to ourselves, to our feelings – all of them, including the painful ones.
Ian: We live in a world where we’re atomized and isolated, and the pandemic only exacerbated that. We are raised to dismiss a large part of our emotional range as human beings. We try to deny the more challenging parts of ourselves and our histories.
Leonie: Antidepressants are a powerful intervention when you are in an acute, overwhelming crisis. But they should be seen as a short-term, symptom management intervention. They should not be viewed as something that is taken indefinitely, as if depression was a terminal disease that you had to learn to live with, as they don’t just numb you to the negative emotions; they limit and numb you in many other ways, too. If you don’t deal with the underlying causes of your depression, the issues come up in a different way at a different time.
Ian: Psychedelics work in the completely opposite way: they enable you to connect with your full range of emotions and learn to be comfortable with your fuller self. Psychedelics help you dig down to the roots of your depression and work out new ways to deal with difficult feelings within a natural container that is larger than just yourself.
You mentioned several spiritual themes: connection to Nature, connection to something that is larger than us, the Cycle of Life. How does that sit with the current clinical, medical training? Leonie: No participant or clinician starts the trial thinking clinically-diagnosed patients need more trees in their life… We must be careful not to be too reductionist – depression is not solely a function of neurochemistry. There needs to be some space for mystery, too.
Ian: Psychedelics can engender deeply profound spiritual experiences, which can manifest in different ways; we must not be prescriptive as to the nature of the spiritual experience to be expected. Yet organisations who run the studies must be aware that these experiences do happen.
Leonie: The concept of connectedness is a good place to start. Everyone can understand how being better connected to ourselves, each other and Nature is beneficial to all. It is definitely a point to bring to the discussion, otherwise we will be selling the psychedelic treatment short.
Online Event - Psychedelic Care in Recreational Settings - 3 October 2024
The Dutch minister of Medical Care, Pia Dijkstra (D66), will inaugurate the sixth edition of the 
