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Therapeutic Application

Capturing the different health conditions that PAP may adress

Psychedelics vs. Traditional Treatments —How Do They Stack Up for Mental Health Disorders? – Part 1

The treatment landscape for mental health conditions has evolved significantly over the past decades, with selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and cognitive-behavioral therapy (CBT) being the primary therapeutic interventions. While these conventional approaches have demonstrated considerable efficacy and improved countless lives, clinical data indicates that a substantial portion of patients exhibit treatment resistance or experience relapse over time. 

This therapeutic gap has prompted researchers to investigate novel approaches, leading to renewed scientific interest in psychedelic-assisted therapy (PAT). The potential therapeutic applications of classical psychedelics such as psilocybin and LSD, as well as entactogens like MDMA, have garnered attention in contemporary psychiatric research. As clinical trials advance and mechanistic studies deepen our understanding of these compounds, the field moves forward in balancing hope with caution.

This review examines the distinct mechanisms, therapeutic potentials, and limitations of both conventional and psychedelic-assisted treatments, providing a comprehensive analysis of their roles in modern psychiatric care.

Psychedelic-Assisted Therapy vs traditional treatments – In a nutshell

Traditional Treatments Psychedelic-Assisted Therapy (PAT)
Primary Approaches SSRIs, benzodiazepines, cognitive-behavioral therapy (CBT) Psilocybin, LSD, MDMA, often combined with psychological support
Mechanism of Action Targets neurotransmitter systems (e.g., serotonin for SSRIs, GABA for benzodiazepines) Primarily acts on serotonin 5-HT2A receptors; impacts the default mode network (DMN)
Duration of Treatment Long-term, often months to years Short-term, typically involves 2-3 sessions over a few months
Therapeutic Effects Effective for symptom management, but may not address underlying trauma Facilitates neuroplasticity, may lead to psychological breakthroughs and sustained improvements
Side Effects Physical and emotional side effects (e.g., nausea, insomnia); potential dependency risks for benzodiazepines Low toxicity, but may cause psychological distress; requires controlled settings
Limitations Treatment resistance, relapse risk, and long wait times for psychotherapy Potential for adverse effects in vulnerable individuals, lack of long-term data
Implementation Widely available in healthcare systems, often requires ongoing adherence Requires structured setting and trained facilitators; typically includes preparation and integration phases

Mechanisms of Action: Different Pathways, Different Potentials

Traditional psychiatric interventions and emerging psychedelic therapies operate through distinct neurobiological pathways. Conventional treatments primarily target specific neurotransmitter systems: SSRIs treat depression by blocking serotonin reuptake in the brain, allowing more serotonin to remain active in neural synapses (IQWiG, 2024). Benzodiazepines reduce anxiety by enhancing GABA activity, which decreases overall brain cell excitability (Benzodiazepine Information Coalition, 2022). These pharmacological mechanisms typically require sustained administration to maintain therapeutic effects (Donald et al., 2021). CBT complements these approaches by promoting neuroplasticity through systematic modification of thought patterns and behaviors, leading to structural and functional changes in regions associated with emotional regulation (Nakao et al., 2021).

Psychedelic compounds exert their effects primarily through serotonin 5-HT2A receptor agonism (Vargas et al., 2023). This mechanism induces rapid alterations in neural connectivity and information processing (Smausz et al., 2022). Of particular interest is their impact on the default mode network (DMN), where overactivity correlates with various psychiatric conditions (Chou et al., 2023). Research indicates that psychedelics may temporarily disrupt DMN connectivity, potentially facilitating the formation of novel neural pathways. This neuroplastic effect, combined with the compounds’ ability to enhance emotional processing, provides a neurobiological basis for the acute and sustained therapeutic effects observed in clinical trials (Gattuso et al., 2022).

The distinct mechanisms of action between conventional treatments and psychedelic interventions present both advantages and limitations. Traditional approaches effectively target symptom management but may overlook underlying psychological trauma (IQWiG, 2024). PAT shows potential for deep neurobiological restructuring, yet the intensity of these interventions can be difficult and result in lasting negative effects for some individuals (Evans et al., 2023).

Treatment Protocols: Contrasting Continuous Care with Rapid-Acting Interventions

Building on the neurobiological foundations, treatment duration and efficacy present notable distinctions between conventional and psychedelic-assisted approaches. While traditional pharmacotherapy has proven effective for many individuals, it typically requires extended periods of administration, with patients maintaining antidepressant regimens for months to years (Hu et al., 2024). This prolonged treatment course often accompanies various side effects (NHS, 2021b). Additionally, resource limitations in mental health services frequently result in extended wait times for traditional psychotherapeutic interventions like CBT (PricewaterhouseCoopers, n.d.).

Emerging clinical evidence suggests that PAT may achieve therapeutic outcomes through significantly fewer interventions. Research with psilocybin in major depressive disorder demonstrates that a single 25mg dose, combined with psychological support, can produce substantial and sustained reductions in depressive symptoms (Raison et al., 2023). Similarly, MDMA-assisted therapy for PTSD has shown remarkable efficacy, with over 50% of participants no longer meeting diagnostic criteria after two sessions (van der Kolk et al., 2024). The treatment typically involves 2-3 guided sessions integrated with psychotherapy over several months (Mitchell et al., 2023).

The intensity of psychedelic experiences may pose challenges for some individuals, potentially inducing anxiety or distress, particularly when compared to conventional treatments like SSRIs or talk therapy which typically have more predictable response patterns. While the shorter treatment duration offers an attractive alternative to traditional long-term therapeutic approaches, the long-term implications of PAT require more thorough investigation.

Emotional Breakthroughs and Psychotherapeutic Integration

The therapeutic mechanisms of conventional and psychedelic treatments further diverge in their capacity to facilitate psychological breakthroughs. Psychedelic compounds can induce altered states of consciousness that enable patients to access and process repressed emotional content and trauma (Roseman et al., 2019). These experiences, when conducted in controlled therapeutic environments, often represent critical junctures in the treatment process.

Conventional therapeutic approaches primarily emphasize symptom management and gradual cognitive and behavioral modification (Stein et al., 2022). While traditional psychotherapy facilitates emotional understanding, it rarely produces the acute psychological insights characteristic of psychedelic experiences. MDMA-assisted therapy demonstrates this distinction, with patients reporting to process traumatic memories with reduced emotional activation (Morgan, 2020), potentially achieving therapeutic outcomes that conventional methods find challenging to replicate.

PAT functions not as a standalone treatment but as a catalyst within a comprehensive therapeutic framework (Brennan & Belser, 2022). The process involves three key phases: preparation, the psychedelic experience, and integration therapy (Mitchell et al., 2023). This structured approach, combined with careful consideration of patients’ psychosocial resources and support systems, is essential for optimizing therapeutic outcomes and minimizing risks.

Side Effects and Safety Concerns

Treatment modalities demonstrate distinct safety profiles and contraindications. SSRIs commonly induce physiological and emotional side effects, including nausea, insomnia, and sexual dysfunction (NHS, 2021). Long-term benzodiazepine use presents risks of dependency and cognitive impairment (NHS, 2024). While CBT exhibits minimal adverse effects, accessibility limitations and duration requirements pose practical constraints (NHS, 2022).

Psychedelic compounds demonstrate favorable physiological tolerability, with substances like psilocybin showing low toxicity and minimal addictive potential (National Institute on Drug Abuse, 2024). However, psychological risks emerge particularly in non-controlled settings (Barber et al., 2023). Adverse psychological reactions require careful therapeutic management to maintain safety parameters (Brooks, 2018).

Research indicates specific risk factors in PAT, including potential psychotic episodes in vulnerable individuals (Simonsson et al., 2023). Recent data suggests 16% of participants experience decreased psychological well-being four weeks post-treatment, with elevated rates among those with personality disorder diagnoses (Marrocu et al., 2024). Personality traits, particularly neuroticism, further influence treatment outcomes in both conventional and psychedelic interventions. While high neuroticism correlates with increased acute adverse effects in PAT, these individuals often report enhanced long-term outcomes (Mason et al., 2020). Similarly, conventional treatments consistently demonstrate reduced efficacy in individuals with high neuroticism scores (Mulder, 2011).

Implementation of PAT requires comprehensive screening protocols to identify contraindications and optimize patient selection. Clinical settings provide essential safeguards, resulting in predominantly positive therapeutic outcomes with minimal adverse effects (Williams et al., 2021). Further research is needed to better understand how individual differences, particularly personality traits, influence treatment responses. This knowledge would enable more precise patient selection and personalized treatment approaches, ultimately enhancing safety and therapeutic efficacy.

Durability of Therapeutic Effects: Comparing Long-Term Outcomes Across Treatment Modalities

Potential long-term therapeutic efficacy represents a significant advantage of PAT. Clinical trials demonstrate sustained symptom reduction across multiple conditions: psilocybin for depression (Gukasyan et al., 2022), MDMA for PTSD (van der Kolk et al., 2024), and ketamine for treatment-resistant depression (Murrough et al., 2013). These outcomes contrast with conventional treatments’ requirement for continuous medication administration without addressing underlying pathological mechanisms.

The potential for achieving substantial therapeutic change within limited sessions warrants methodological consideration. While preliminary data indicates promising results, psychedelic research in psychopharmacology is still in its beginning. Current limitations include a lack of longitudinal and follow-up studies, resulting in an incomplete understanding of delayed adverse effects and individual response variations.

Where Do We Go from Here?

Current evidence necessitates a balanced evaluation of PAT. While contraindications and methodological challenges persist, clinical trial data demonstrates significant therapeutic potential, particularly for treatment-resistant conditions including PTSD, depression, and substance use disorders (Belouin & Henningfield, 2018). These novel interventions may address limitations inherent in conventional treatment approaches.

The evolution of psychiatric medicine suggests an integrative framework incorporating both established and emerging therapeutic modalities. Psychedelic compounds, when administered within structured clinical settings, represent a promising pharmacological class that may complement existing treatment paradigms (Yaden et al., 2024). This integration has the potential to advance therapeutic mechanisms beyond symptom management toward sustained psychological transformation, directly addressing underlying trauma and promoting long-term healing.

The successful implementation of psychedelic-assisted therapy (PAT) requires a multi-faceted approach encompassing patient screening, preparation protocols, and integrated aftercare support. Critical research priorities include understanding neurobiological mechanisms, identifying reliable biomarkers for treatment response, and examining interactions with concurrent therapies. While current evidence supports PAT’s potential, limitations in longitudinal data and study population diversity constrain its broader clinical application. Ko et al. (2022) highlight the need for expanded research across diverse demographic groups to establish standardized safety protocols and treatment guidelines. Future studies should focus on systematic outcome assessment, monitoring of adverse effects, and analysis of population-specific treatment responses to optimize clinical effectiveness and safety standards.

The emerging evidence base supporting PAT’s therapeutic potential, combined with increasing institutional support and methodological refinement, indicates a promising direction for psychiatric medicine. As research continues and treatment guidelines evolve, these interventions may significantly expand the therapeutic options available to clinicians and patients, potentially transforming the landscape of mental health treatment.

References

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The Role of Psychedelics in Palliative Care: Real-World Cases – Dr. Houman Farzin, M.D.

Introduction to Psychedelic-Assisted Therapy in Palliative Care

Psychedelic-assisted therapy is emerging as a transformative approach in palliative care, offering new hope for patients facing the profound challenges of advanced cancer and end-of-life distress. In his presentation at the ICPR 2024, Dr. Houman Farzin, MD, a palliative care physician and clinical faculty member at McGill University, provided insights into the evolving field of psychedelic therapy, specifically focusing on its application in advanced cancer care. Drawing from real-world case studies in Montreal, Canada, Dr. Farzin highlighted the therapeutic potential of psilocybin and MDMA in alleviating physical and psychological suffering, offering a compelling vision for the future of palliative care.

Recording of ICPR 2024 talk. Discover more recordings here.

about Dr. Houman Farzin: Pioneer in Psychedelic-Assisted Therapy and Palliative Care

Dr. Houman Farzin, M.D. is a leading physician specializing in psychedelic-assisted therapies, nutrition, and lifestyle modification to address trauma, existential distress, and enhance overall well-being. As an attending physician in the Division of Palliative Care at the Jewish General Hospital in Montreal, Dr. Farzin integrates emerging treatments and digital health technologies with mindfulness, music, and psychedelic medicine to improve quality of life and alleviate suffering across all life stages.

A lecturer at McGill University Medical School, Dr. Farzin also contributes to the McGill Programs in Whole Person Care, where he teaches resilience and Mindful Medical Practice to future physicians. His extensive training includes expertise in MDMA, psilocybin, and ketamine therapies, and he has been instrumental in organizing Quebec’s first psilocybin therapy training programs.

Dr. Farzin’s research focuses on the societal views of psilocybin therapy for existential distress and innovative treatments for chemotherapy-induced peripheral neuropathy. His contributions to the field are further exemplified by his role as a site physician for MAPPUSX, a study on MDMA-assisted psychotherapy for PTSD. He is also a co-founder of injoy (formerly Phyla), a digital health tool utilizing AI to connect diet, lifestyle, and microbiome health.

Passionate about indigenous cultures and altered states of consciousness, Dr. Farzin’s work is deeply informed by Eastern philosophies and his anthropological studies of ancient practices. His commitment to advancing psychedelic therapies in mainstream healthcare continues to inspire confidence in their potential to transform palliative care and mental health treatment.

Case Studies: Real-World Applications of Psychedelic Therapy

Dr. Farzin’s presentation at ICPR 2024 was grounded in the real-world application of psychedelic therapies, illustrating their profound impact on patients with advanced cancer. His work highlights the effectiveness of individual and group therapy sessions, tailored to each patient’s unique needs.

Case 1: Floran’s Journey with Psilocybin Therapy

One of the most compelling cases involved a patient named Floran, who underwent psilocybin-assisted therapy as part of her treatment for advanced cancer. Her first session, which involved a five-gram dose of psilocybin mushrooms, was characterized by intense emotions and a confrontation with deep-seated fears. However, it also opened up new pathways to healing, as depicted in a drawing she created afterward, illustrating her experience of moving from darkness to vibrant colors.

Case 2: A Retired Nurse Finds Peace

Another case involved a retired nurse in her seventies, suffering from advanced cancer and severe anxiety. Despite her reliance on multiple medications, the psilocybin session had a profound impact, providing her with a sense of peace and acceptance that had eluded her for years. Months after the session, she reported a transformative change in her outlook on life, illustrating the long-term benefits of psychedelic therapy.

Case 3: Rediscovering Poetry Through Psychedelic Therapy

A younger cancer patient rediscovered her love for poetry during her psilocybin-assisted therapy. The experience allowed her to reconnect with her inner child, a part of herself suppressed due to the trauma of her illness. This reconnection empowered her to express her emotions and creativity in ways that had previously been inaccessible.

The Importance of Somatic Awareness and the Mind-Body Connection

A critical component of Dr. Farzin’s approach to psychedelic therapy is the emphasis on somatic awareness—the recognition and processing of emotions and trauma stored in the body. This concept, supported by experts like Dr. Gabor Maté, posits that trauma can manifest as physical ailments, including cancer and autoimmune diseases. In psychedelic therapy, patients explore these bodily sensations to access and resolve deep-seated emotional issues.

For instance, during a session, a patient might experience intense physical sensations, which are then explored as manifestations of underlying trauma. By addressing these sensations directly, patients often access emotions and memories that are not readily available in their normal state of consciousness. This process aids in the release of stored trauma and fosters a deeper understanding of the mind-body connection, crucial for holistic healing.

The Evolution of Psychedelic Therapy in Canada

Psychedelic-assisted therapy has a complex history, marked by periods of intense research interest followed by decades of legal and cultural suppression. In Canada, psilocybin, the active compound in magic mushrooms, was banned in 1974, closely following the United States’ regulatory actions. However, a significant shift occurred in 2020 when an advocacy campaign led by four terminally ill patients resulted in legal exemptions for psilocybin use under Section 56 of the Controlled Drugs and Substances Act.

This legal breakthrough marked the beginning of a new era in Canadian healthcare, enabling patients facing end-of-life distress to access psilocybin-assisted therapy. The initial exemptions allowed patients to source psilocybin from the black market, setting a precedent that has since expanded into the Special Access Program (SAP), allowing broader clinical use under regulated conditions.

Dr. Farzin’s involvement with TheraPsil, a Canadian nonprofit dedicated to advancing legal access to psilocybin therapy, underscores the collaborative effort required to integrate these treatments into mainstream healthcare. The inclusion of psilocybin and MDMA in the SAP represents a significant milestone, enabling healthcare practitioners to apply for the use of these substances on a case-by-case basis for patients who do not respond to conventional treatments.

Psypal, The First EU-Funded Multi-Site Clinical Study into Psychedelic-Assisted Therapy

The EU marked a significant step forward in integrating psychedelic-assisted therapies into mainstream palliative care practices as it granted Psypal, a multi-site clinical study into psychedelic-assisted therapy, over €6.5 million. PsyPal aims to study the use of psilocybin in treating psychological distress in patients with progressive, incurable illnesses requiring palliative care. It consists of a European consortium of 19 partners, including the OPEN Foundation learn more.

Ethical Considerations and the Future of Psychedelic Therapy in Palliative Care

While the benefits of psychedelic therapy are increasingly recognized, the field is not without its ethical challenges. Dr. Farzin addresses these concerns by acknowledging the complexities of offering these treatments to vulnerable populations. One primary ethical consideration is the potential for these therapies to alter a patient’s perception of their illness and treatment choices, particularly in the context of end-of-life care.

Some may argue that providing psilocybin or MDMA therapy to terminally ill patients could influence their decisions regarding medical aid in dying (MAID). However, as Dr. Farzin notes, the goal of psychedelic therapy is not to steer patients away from MAID but to offer them additional tools for coping with their illness. In some cases, patients may still choose MAID after undergoing psychedelic therapy, but with a greater sense of peace and acceptance.

Conclusion: A New Paradigm in Palliative Care

Dr. Houman Farzin’s work represents a significant step forward in integrating psychedelic therapies into mainstream healthcare, particularly in palliative care. His pioneering efforts in Canada demonstrate the profound impact these therapies can have on patients facing the challenges of advanced cancer and end-of-life distress. By combining rigorous scientific research with compassionate patient care, Dr. Farzin is helping to pave the way for a new paradigm in palliative care—one that embraces the transformative potential of psychedelics to heal the body, mind, and spirit.

As the field of psychedelic therapy continues to evolve, healthcare professionals, researchers, and policymakers must collaborate to ensure that these treatments are accessible, ethical, and grounded in the best available evidence. Through innovation and teamwork, the potential for psychedelics to revolutionize palliative care is immense, offering new hope and healing to those who need it most.

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Psychedelic Assisted Therapy for Treating Addiction – Part 2

Psychedelic Assisted Therapy for Treating Addiction – Part 2

Introduction

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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  29. 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.
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  31. Online event
  32. 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.
  33. 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.

Michael Bogenschutz has new research on psychedelics and alcohol – AND IS COMING TO ICPR

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.

Why 5-MeO-DMT is one of the most fascinating psychedelics there is

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 

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

9 quality documentaries about lsd, mushrooms and other psychedelics you should watch

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.”

Quote of the movie

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 five days 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.

psychedelic clinical trial participants share their stories

Story by Vardit Kohn
Illustration by Anna Temczuk

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. 

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.

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.

Ian Rouillier and Leonie Schneider, featured in this article, will share their full stories at ICPR 2022, organised by the OPEN Foundation and held in Haarlem from 22-24 September 2022. Get €100 off on all tickets by using the code OPENBLOG100

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.

How Depression Can Be Treated with a Psychedelic Trip

If you’re interested in psychedelics, then you might have heard of the work of Robin Carhart-Harris, who conducted much of the most relevant research in the world of psychedelics together with his team at Imperial College in London.

In this look back at ICPR 2016 we will highlight the talk he held about his team’s trials with psychedelics-assisted psychotherapy, where he also showed some beautiful visuals of his team’s brain research, which happened to become some of the most famous psychedelic brain imagery known on the internet. 

Like our upcoming ICPR 2022 near Amsterdam, the edition in 2016 strove to bring together as many relevant studies from psychedelics as possible, and Carhart-Harris’ talk was most certainly a highlight. His research has been cited often and his talk was one of the best-watched from that year’s ICPR on our Youtube channel.

In his talk, Carhart-Harris talks about the results of his research – that psychedelics can cause a rise in cognitive flexibility, neuroplasticity, creative thinking, imaginative suggestibility, emotional lability, positive moods, and optimism. 

He also touches on the idea of depressive realism, a trend he has seen in patients suffering from depression. He describes their depression as a “sort of delusion”, where his patients “don’t see the world as it really is. There is this really quite evident pessimism bias, that is normalised post-treatment with psilocybin.”

A testimony of one of the participants is featured in the talk:

26:35 — ‘Although it’s early days yet, the results are amazing. I feel more confident and calm than I have in such a long time. My outlook has changed significantly too, I’m more aware that it’s pointless to get wrapped up in endless negativity. I also feel as if I’ve seen a much clearer picture. [Now] I can enjoy things the way I used to, without the cynicism, without the oppression. At its most basic. I feel like I used to before the depression.”

Brain Scans

One way to go about investigating psychedelics is by making fMRI brain scans. These scans are made of healthy and depressed individuals before, during and after a psychedelic experience. This way, the brain can be observed for changes.

Through these scans, the team got insights into the inner workings of the brain during psychedelic trips, and how they correlate with described experiences of volunteers, like ego-death. This is a type of experience in which people who are under the influence of psychedelics describe a certain loss of self, and a deeper connection with the wider universe or nature. 

Carhart’s studies have highlighted that the Default Brain Network may be connected with our sense of self – our ego –  and that the lower activity of this network during a psychedelic session may be associated with the occurrence of ego-death.

Some of the brain scans from the research team at Imperial, from 2012.

12:40 — “We see quite reliably a relationship between the magnitude of the disintegration and the default brain network. [..] The greater the disintegration of the default mode network, the greater our volunteers’ ratings of ego-dissolution. ”

During the psychedelic experience induced with psilocybin, the parts of the brain associated with the Default Brain Network show a drastic reduction in activity, often creating the experience of ego-death. The compulsive activity of the Default Brain Network also has been associated with patients that scored higher in depression ratings.

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The Default Brain Network and the Self

Robin Carhart-Harris’s argument is that the Default Brain Network may be the source of what most adult people call the ‘ego’. This network is known as the Default Mode Network because, during our daily lives, this brain network becomes more active when we are idle

The Default Mode is actually a really important part of our mental stability. This network is responsible for keeping our routines in check, making sure that our pending matters stay afloat, and that we’re not overlooking anything.

The mental activity generated by the Default Mode Network is usually stable and consistent day after day. This daily consistency in addition to the fact the DMN is the ‘standard’ mental voice, may contribute to the illusion that the Default Mode Network is the self.

12:58 — [The Default Brain Network is]: “Arguably the best candidate we have for the neural substrates of the self, or the ego, or our identity and personality.” – Robert Carhart-Harris

By analyzing the brains of participants who consumed psilocybin, Carhart’s team noticed that there was a process of renewal happening within the structure of the brain, almost like a general mind reset. This process of rebirth has been reported many times by psychedelic subjects.

17:50 — “We can think of the mind or the brain is reset in the same way that you can think of a computer is malfunctioning and throwing up an error message and you are wondering what you can do. And then you press the reset button and it comes back working nice and smooth as it should.”

In more recent years, Carhart-Harris has worked on building a more unified model of the workings of psychedelics in the brain. He founded the Psychedelic Research Group at Imperial College in London and focuses on the action of psychedelic drugs in the brain, and their clinical utility as aides to psychotherapy, with a particular focus on depression. He still studies the brain effects of LSD, psilocybin (magic mushrooms), and MDMA. 

Robin Carhart-Harris will not be speaking at ICPR 2022, but his colleague and the new head of the Psychedelic Research Group at Imperial College will: David Nutt

Notes about the author: Alexandre Perrella is a writer for Cabbanis!

The Netherlands should be ‘at forefront’ of psychedelic research, says Dutch government

‘The Netherlands can play a pioneering role in developing the right frameworks, limiting potential risks, and designing training programs,’ the Dutch health minister said.

Ernst Kuipers, the new Dutch Minister of Health, Welfare, and Sports, has given his green light to more research in psychedelic therapy, citing “promising results” for typically difficult-to-treat mental illnesses through psychedelics-assisted therapy. His endorsement came in response to questions from three members of parliament from the Dutch political party D66. Kuipers summed up his stance on psychedelic research in a letter directed to the Speaker of the Dutch House of Representatives, and its content is factual and amenable to recent scientific results.

This is a departure for the Dutch government, which in recent years produced more prohibition-focused or avoidant language when it came to issues surrounding psychedelics. The new government has also announced that a state committee will look into the medical use of MDMA – a political compromise arising from the ongoing discussion in the Netherlands about the possible legalisation of MDMA for recreational use.

The new government’s health minister demonstrated conviction about the prominence psychedelic therapy will gain in global healthcare in the coming years, and envisions how the Netherlands could become a leader at the forefront of psychedelic research: “It is paramount that these and other potentially innovative treatments are safely accessible to the target population,” the minister writes. “The Netherlands is one of the leading countries in research into psychedelics in mental health care. In addition, the Netherlands can play a pioneering role in developing the right frameworks, limiting potential risks, and designing training programs for therapists. I am in favour of sharing earned knowledge with parties in the field across different countries.”

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The Netherlands at the forefront of psychedelic research

Apart from MDMA, other psychedelic substances – such as psilocybin1 and ketamine2 – have also demonstrated promise. Kuipers strikes a more cautious tone when speaking about these compounds, affirming the need for more research due to the preliminary nature of current results: “Most of these substances are still in the investigative phase of research. […] It is up to the relevant field parties to follow up on these results. This concerns conducting the necessary research, completing the step-by-step registration process for approval of the substance, and the development of guidelines and protocols necessary for treatment.”

Kuipers further stresses the need for extensive education, the training of psychedelic therapists, and the need to better understand individuals engaged in self-experimentation. He adds that he is “willing to play a facilitating and advising role” in implementing psychedelic research and that his ministry has recently conducted exploratory meetings with researchers and mental healthcare institutions.

He envisions the Netherlands as playing a major role internationally in the coordination and promulgation of psychedelic research, writing that “[t]he Netherlands can stimulate cooperation in a European and international context. In addition, the Netherlands can draw attention to removing barriers in conducting research. In the framework of the United Nations Commission on Narcotic Drugs, I continue to advocate for the removal of barriers to therapeutic use and research into substances on United Nations drug convention lists.

New Research

According to Kuipers, an estimated 1.2 million Dutch citizens currently seek curative mental healthcare each year. Another 215,000 citizens suffer from severe psychiatric illness, a segment of the patient population that is very difficult to treat with current therapies. Kuipers has announced he will allocate 35 million euros to mental healthcare research over the next four years, made available through the Dutch grant organisation ZonMw. Grants will support multidisciplinary studies focused primarily on clinical applied research.

The availability of these funds presents psychedelic researchers with a rare opportunity. Results from these new studies could further elucidate the therapeutic mechanisms by which psychedelics function, thereby putting their clinical application on firmer scientific footing.  Ultimately, Kuiper’s initiative offers the promise of advancing the field beyond its “investigative phase” and imagines a not-too-distant future in which psychedelics are used as legitimate therapeutic agents in clinical contexts, offering hope to the millions who suffer from severe psychiatric illness around the globe.

Barriers to breakthrough therapy status

The three representatives of D66 asked further questions surrounding the current “breakthrough therapy status” of certain psychedelics in the United States. A breakthrough therapy designation is granted to a drug that treats a serious or life-threatening condition, where preliminary clinical evidence indicates that the drug might demonstrate substantial improvement on clinically significant endpoints over available therapies.

Recently, the American Food and Drug Administration (FDA) granted ‘breakthrough therapy status’ to psilocybin for treatment-resistant depression and to MDMA for PTSD. Kuipers explains that a similar status within the Netherlands and other countries in Europe can be attained through organisations such as the European Medicines Agency (EMA).

The minister acknowledges the barriers that still exist for psychedelic research, like “a lack of financial resources for doing the necessary clinical research and developing an approved product for the patient. In addition, psychedelics are substances that are generally non patentable and thus do not fit the ordinary development and revenue model. The potential high costs for the therapeutic treatment with these substances (due to the large amount of hours therapists dedicate to patients during treatment) might also impede incorporating psychedelics as a standard treatment.” 

The issue of the relative expense of psychedelic therapy bears further scrutiny. How, for instance, would the cost of psychedelic therapy compare to that of treatment as usual (TUA) if we take into account factors such as the economic burden of different psychiatric illnesses and/or disability-adjusted life years (i.e,. the number of years lost due to an illness)? To resolve the issue of financial expenditure, cost-effectiveness analyses of psychedelic therapy should be conducted, such as that performed in 20203. This study found that MDMA-assisted psychotherapy versus TUA per 1,000 patients produced savings of up to $103.2 million over 30 years including costs, and surmised that “third-party payers are likely to save money within three years by covering this form of therapy [MDMA].” This, however, is just the conclusion of one study, and the issue of financing deserves further investigation.

Central management and the Netherlands

Kuipers acknowledges the risks involved in the lack of central management of psychedelics. Possible risks include personal experimental use of psychedelics and the development of  commercially exploitative practices that fail to the interests of patients first. Kuipers emphasises the urgency with which these questions need to be answered, and references the Dutch researchers and clinicians who authored Therapeutic use of psychedelics4: “[…] they can develop a framework for this new form of treatment by means of high quality guidelines, standards, and protocols.”

Finally, the new government of the Netherlands has called for more research into MDMA and the possible legalisation of it in the near future. Kuipers mentions that there will be a state committee specifically for MDMA. The state committee will “investigate the status of MDMA in the context of public health and provide advice surrounding the pros and cons of medicinal use by adhering to a multidisciplinary analysis, which takes into account potential risks for health, prevention, and the European context and its relevant treaties.” Kuipers expects to inform the House of Representatives of the committee’s findings in the second quarter of this year.

References:

1. Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., … & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA psychiatry, 78(5), 481-489.

2. Nieuwsuur (2022). Keta kan ‘revolutionair’ middel zijn tegen depressie, maar er zijn ook zorgen.  Consulted on 27 March 2022.

3. Marseille, E., Kahn, J. G., Yazar-Klosinski, B., & Doblin, R. (2020). The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD. PloS one, 15(10), e0239997.

4. Universitair Medisch Centrum Groningen. Manifest therapeutische gebruik van psychedelica. Retreived March 20, 2022.

A Really Good Day : How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life

A Really Good Day : How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life. Ayelet Waldman. Little, Brown Book Group. ISBN: 978-1472152893

A first-hand account of microdosing and its positive effects. Waldman charts her experience over the course of a month and looks into the newest research and policies governing LSD. This book will be interesting for anyone curious about how microdosing LSD can affect daily living.

Buy this book through bookdepository.com and support the OPEN Foundation

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