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 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.
Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., … & Worth, L. (2022). Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA psychiatry, 79(10), 953-962.
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Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of psychopharmacology, 31(9), 1091-1120.
Cahill, K., Stevens, S., & Lancaster, T. (2014). Pharmacological treatments for smoking cessation. Jama, 311(2), 193-194.
Calder, A. E., & Hasler, G. (2023). Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology, 48(1), 104-112.
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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.
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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.
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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.
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.
Ann Shulgin, the wife of renowned chemist genius Alexander “Sasha” Shulgin, passed away at age 91 on July 9. Both were extraordinary human beings and pioneers in the field of psychedelic research, particularly due to their significant contribution in the development and therapeutic use of (novel) psychedelic compounds. To honor both, we gladly share some of her history and both their legacy.
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Laura Ann Gotlieb was born in Wellington, New Zealand on March 22, 1931, and shortly thereafter lived an extraordinary life, spending her time in various places around the world, including Italy, Cuba, Canada, and finally the Bay Area in the US when the Beatnik generation was in full swing. She got married, and divorced, three times and then met her fourth husband, Sasha Shulgin, in the Fall of 1978. After three years of spending time together, they got married in Sasha’s backyard during a surprise ceremony by an official of the Drug Enforcement Administration. Yes, the DEA.
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Ann used to work as a medical transcriber in San Francisco and probably became familiar with Jungian psychology through her third husband who was a Jungian psychiatrist. It was only later after marrying Sasha that she got involved in the development of novel psychedelic compounds. During this period, she started practicing psychedelic-assisted therapy in conjunction with MDMA or 2C-B at a time when these substances were still legal. She became a strong adherent of Jungian psychoanalysis and believed that psychedelics have huge potential for self-actualization when used within such a framework.
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The development and various discoveries of other psychedelics together led to the authoring of two books: PIHKAL: A Chemical Love Story and TIHKAL: The Continuation. Respectively, these titles are acronyms for “Phenethylamines/Tryptamines I Have Known and Loved.” Partly fictional autobiography and partly considered “pretty much cookbooks on how to make illegal drugs” by the DEA, both Ann and Sasha were filled with passion and courage to describe no more than over 179 different psychedelic compounds – all with the main goal of releasing information about psychedelic compounds and its therapeutic properties to the public. Psychedelics, they both believed, were there as valuable tools for human beings to explore and self-actualize. Ann briefly appears on a recent episode of Hamilton’s pharmacopeia,where we see that she continued to live in the house that contains the original lab of Sasha.
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We are forever grateful for their contribution to the development and therapeutic use of (novel) psychedelic compounds and aim to continue their legacy.
Joost Breeksema is the director of the OPEN Foundation and one of the main initiators of the Interdisciplinary Conference on Psychedelic Research. ICPR 2022 will be held in Haarlem from 23-27 Sept
As the director of the OPEN Foundation – founded in 2006 to advance the scientific research of psychedelics – Joost Breeksema has usually found himself being one of the main promotors of psychiatric research into psychedelics and therapies. That has changed, he says: “I find myself in a position of being somebody promoting more caution”.
“I think I still think that psychedelics have huge potential,” Breeksema says, “but I think it’s good to counterbalance this message a little bit and to have a proper balance between hype and hope.”
The OPEN director made his statement during the launch of PAREA, the Psychedelic Access And Research European Alliance, an association of European foundations and institutions advancing holistic and professional psychedelic research and therapy.
Breeksema commented in light of the recent psychedelic renaissance, which has brought renewed attention to the psychedelic field. Strong research results have shown the real efficacy of psychedelic therapy, but this has also spawned a world in which investment is luring, and potential risks of psychedelic therapy might be obscured.
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What the right balance is between hope and hype around psychedelic therapy, needs to be discussed, Breeksema says, because the need is dire: “There are many desperate patients out there. Between a quarter and a third of patients with mental disorders do not respond to conventional treatments. So there is a huge need for better and more effective treatments. But it’s also, I think, very important to remember that these are not magic bullets and there are interests.”
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Professional field
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The mix of patients with severe traumas and big expectations, the potential intenseness of the psychedelic experience, and the history of a black market involvement in the supply of many substances, make the need for safe, professional treatment a necessity: “When you ask patients… it’s hard work. People have challenging experiences, and these are vulnerable patients for the most part. These experiences can be powerful but also potentially destabilizing.”
“These are not typical pharmaceutical drugs: It’s the experience that’s central, and that means people guiding patients through those experiences need to be properly trained. You need to be a mental health professional, but you do also need additional training.”
The Way of the Psychonaut Vol. 1: Encyclopedia for Inner Journeys. Stanislav Grof. MAPS. ISBN: 9780998276595
Written in an easy, understandable tone, this comprehensive work is a tour de force works its way through the worlds of psychology and psychotherapy, Holotropic Breathwork, maps of the psyche, birth, sex, and death, psychospiritual rebirth, the roots of trauma, spiritual emergency and transpersonal experiences, karma and reincarnation, higher creativity, great art, and archetypes.
Background: The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the REFE.
Methods: Twenty-two healthy volunteers participated in a pilot, proof-of-concept, randomized trial. Study variables included a REFE task performed before and 4 hours after drug intake, subjective effects (self-reports/observer impressions), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. The REFE task was applied again 1, 7, 14, and 21 days and 3 months after drug intake. Stability of ayahuasca alkaloids during the study was also assessed (room temperature, 18 months).
Findings: Compared with placebo, ayahuasca did not modify the REFE. No significant effects were observed on cardiovascular measures and brain-derived neurotrophic factor levels. Volunteers reported visual effects, tranquility/relaxation, and well-being, with few reports of transient anxiety/confusion. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. A significant time-dependent deterioration of alkaloids was observed, especially for dimethyltryptamine.
Conclusions: Absence of significant effects on the REFE task could be due to lack of effects of ayahuasca (at the doses used), alkaloid degradation, learning effects, and the high educational level of the sample. Further trials with different samples are needed to better understand the effects of ayahuasca and other serotonergic hallucinogens on the REFE. Future trials should improve methods to guarantee the stability of ayahuasca alkaloids.
Rocha, J. M., Rossi, G. N., de Lima Osório, F., Bouso, J. C., de Oliveira Silveira, G., Yonamine, M., Campos, A. C., Bertozi, G., Cecílio Hallak, J. E., & Dos Santos, R. G. (2021). Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial. Journal of clinical psychopharmacology, 41(3), 267–274. https://doi.org/10.1097/JCP.0000000000001396
Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.
Objective: To investigate the effect of psilocybin therapy in patients with MDD.
Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).
Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.
Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).
Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).
Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285
The present study examines the association between the ceremonial use of ayahuasca-a decoction combining the Banistereopsis caapi vine and N,N-Dimethyltryptamine-containing plants-and changes in personality traits as conceived by the Five-Factor model (FFM). We also examine the degree to which demographic characteristics, baseline personality, and acute post-ayahuasca experiences affect personality change. Participants recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 256) completed self-report measures of personality at three timepoints (Baseline, Post, 3-month Follow-up). Informant-report measures of the FFM were also obtained (N = 110). Linear mixed models were used to examine changes in personality and the moderation of those changes by covariates. The most pronounced change was a reduction in Neuroticism dzself-reportT1-T2 = – 1.00; dzself-reportT1-T3 = – .85; dzinformant-reportT1-T3 = – .62), reflected in self- and informant-report data. Moderation of personality change by baseline personality, acute experiences, and purgative experiences was also observed.
Weiss, B., Miller, J. D., Carter, N. T., & Keith Campbell, W. (2021). Examining changes in personality following shamanic ceremonial use of ayahuasca. Scientific reports, 11(1), 6653. https://doi.org/10.1038/s41598-021-84746-0
Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.
Uthaug, M. V., Mason, N. L., Toennes, S. W., Reckweg, J. T., de Sousa Fernandes Perna, E. B., Kuypers, K., van Oorsouw, K., Riba, J., & Ramaekers, J. G. (2021). A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats. Psychopharmacology, 238(7), 1899–1910. https://doi.org/10.1007/s00213-021-05817-8
