OPEN Foundation

Mushrooms / Psilocybin

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

  1. Barber, G. S., & Dike, C. C. (2023). Ethical and practical considerations for the use of psychedelics in psychiatry. Psychiatric Services, 74(8), 838–846. https://doi.org/10.1176/appi.ps.20220525
  2. Belouin, S. J. & Henningfield, J. E. (2018). Psychedelics: Where we are now, why we got here, what we must do. Neuropharmacology, 142, 7-19. https://doi.org/10.1016/j.neuropharm.2018.02.018
  3. Benzodiazepine Information Coalition. (2022, July 27). Mechanism of action – Benzodiazepine Information Coalition. https://www.benzoinfo.com/mechanism-of-action/
  4. Brennan, W. & Belser, A. B. (2022). Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model. Frontiers in Psychology, 13. https://doi.org/10.3389/fpsyg.2022.866018
  5. Brooks, M. (2018, July 20). Psilocybin “Bad trips” underscore need for research safeguards. Medscape. https://www.medscape.com/viewarticle/874136?form=fpf
  6. Chou, T., Deckersbach, T., Dougherty, D. D., & Hooley, J. M. (2023). The default mode network and rumination in individuals at risk for depression. Social Cognitive and Affective Neuroscience, 18(1). https://doi.org/10.1093/scan/nsad032
  7. Donald, M., Partanen, R., Sharman, L., Lynch, J., Dingle, G. A., Haslam, C., & van Driel, M. (2021). Long-term antidepressant use in general practice: a qualitative study of GP’s views on discontinuation. Br J Gen Pract., 71(708), e508-e516. https://doi.org/10.3399/BJGP.2020.0913
  8. Evans, J., Robinson, O. C., Ketzitzidou Argyri, E., Suseelan, S., Murphy-Beiner, A., McAlpine, R., Luke, D., Michelle, K., & Prideaux, E. (2023). Extended difficulties following the use of psychedelic drugs: A mixed methods study. PLOS ONE, 18(10). https://doi.org/10.1371/journal.pone.0293349
  9. Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L. A., Pagni, B. A., Galvao-Coelho, N. L., Nutt, D., & Sarris, J. (2023). Default Mode Network Modulation by Psychedelics: A Systematic Review. Int J. Neuropsychopharmacol., 26(3): 155-188. https://doi.org/10.1093/ijnp/pyac074
  10. Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology, 36(2). https://doi.org/10.1177/02698811211073759
  11. Hu, Y., Xue, H., Ni, X., Guo, Z., Fan, L., & Du, W. (2024). Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis. Psychiatry Research, 337, 115926. https://doi.org/10.1016/j.psychres.2024.115926
  12. Institute for Quality and Efficiency in Health Care (IQWiG). (2024, April 15). Depression: Learn More – How effective are antidepressants? InformedHealth.org – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK361016/
  13. Ko, K., Knight, G., Rucker, J. J., & Cleare, A. J. (2022). Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic review. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.917199
  14. Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2020). Reported effects of psychedelic use on those with low well-being given various emotional states and social contexts. Drug Science Policy and Law, 6, 205032451990006. https://doi.org/10.1177/2050324519900068
  15. Mitchell, J. M., Ot’alora G., M., van der Kolk, B. et al. (2023). MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med, 29, 2473–2480. https://doi.org/10.1038/s41591-023-02565-4
  16. Morgan, L. (2020). MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t. Annals of General Psychiatry, 19(33). https://doi.org/10.1186/s12991-020-00283-6
  17. Marrocu, A., Kettner, H., Weiss, B., Zeifman, R. J., Erritzoe, D., & Carhart-Harris, R. L. (2024). Psychiatric risks for worsened mental health after psychedelic use. Journal of Psychopharmacology, 38(3), 225–235. https://doi.org/10.1177/02698811241232548
  18. Mulder, R. T. (2011). The influence of personality on the treatment outcome of psychopathology. Word Psychiatry, 10(2), 115-116. PMID: 21633687
  19. Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., Iosifescu, D. V. (2013). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biological Psychiatry, 74(4), 250-6. https://doi.org/10.1016/j.biopsych.2012.06.022
  20. Nakao, M., Shirotsuki, K., & Sugaya, N. (2021). Cognitive-behavioral therapy for management of mental health and stress-related disorders: Recent advances in techniques and technologies. Biopsychosocial Medicine, 15(1), 16. https://doi.org/10.1186/s13030-021-00219-w
  21. National Institute on Drug Abuse (2024, June 24). Psilocybin (Magic Mushrooms) | National Institute on Drug Abuse. https://nida.nih.gov/research-topics/psilocybin-magic-mushrooms
  22. NHS (2021, December 8). Side effects – Selective serotonin reuptake inhibitors (SSRIs). https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/side-effects/
  23. NHS (2022, November 10). Overview – Cognitive behavioural therapy (CBT). https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/talking-therapies-and-counselling/cognitive-behavioural-therapy-cbt/overview/
  24. NHS (2024, September 30). Side effects of diazepam. https://www.nhs.uk/medicines/diazepam/side-effects-of-diazepam/
  25. PricewaterhouseCoopers. (n.d.). “Waiting times” in mental healthcare. https://www.pwc.nl/en/insights-and-publications/services-and-industries/public-sector/social-determinants-of-health/waiting-times-in-mental-healthcare.html
  26. Simonsson, O., Goldberg, S. B., Chambers, R., Osika, W., Simonsson, C., & Hendricks, P. S. (2023). Psychedelic use and psychiatric risks. Psychopharmacology. https://doi.org/10.1007/s00213-023-06478-5
  27. Stein, D. J., Shoptaw, S. J., Vigo, D. V., Lund, C., Cuijpers, P., Bantjes, J., Sartorius, N., & Maj, M. (2022). Psychiatric diagnosis and treatment in the 21st century: paradigm shifts versus incremental integration. World Psychiatry, 21(3), 393-414. https://doi.org/10.1002/wps.20998
  28. Raison, C. L., Sanacora, G., Woolley, J., …, & Griffiths, R. R. (2023). Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial. JAMA, 330(9), 843-853. https://doi.org/10.1001/jama.2023.14530
  29. Roseman, L., Haijen, E., Idialu-Ikato, K., Kaelen, M., Watts, R., & Carhart-Harris, R. (2019). Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory. Journal of Psychopharmacology, 33(9). https://doi.org/10.1177/0269881119855974
  30. Smausz, R., Neill, J., & Gigg, J. (2022). Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology. Journal of Psychopharmacology, 36(7), 781-793. https://doi.org/10.1177/02698811221092508
  31. van der Kolk, B. A., Wang, J. B., Yehuda, R., Bedrosian, L., Coker, A. R., Harrison, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R. (2024). Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS ONE 19(1). https://doi.org/10.1371/journal.pone.0295926
  32. Vargas, M. V., Dunlap, L. E., Dong, C., Carter, S. J., Tombari, R. J., Jami, S. A., Cameron, L. P., Patel, S. D., Hennessey, J. J., Saeger, H. N., Mccorvy, J. D., Gray, J. A., Tian, L., & Olson, D. E. (2023). Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Neuroscience, 379, 6633. https://doi.org/10.1126/science.adf0435
  33. Williams, M. L., Korevaar, D., Harvey, R., Fitzgerald, P. B., Liknaitzky, P., O’Carroll, S., Puspanathan, P., Ross, M., Strauss, N., & Bennett-Levy, J. (2021). Translating psychedelic therapies from clinical trials to community clinics: building bridges and addressing potential challenges ahead. Frontiers in Psychiatry, 12. https://doi.org/10.3389/fpsyt.2021.737738
  34. Yaden, D. B., Berghella, A. P., Hendricks, P. S., Yaden, M. E., Levine, M., Rohde, J. S., Nayak, S., Johnson, M. W., & Garcia-Romeu, A. (2024). IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models. Pharmacological Research, 199, 106998. https://doi.org/10.1016/j.phrs.2023.106998

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.

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.

Get €100 off on all tickets by using the code OPENBLOG100

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!

True Hallucinations: Being an Account of the Author’s Extraordinary Adventures in the Devil’s Paradise

True Hallucinations: Being an Account of the Author’s Extraordinary Adventures in the Devil’s Paradise. Terence McKenna. Ebury Publishing. ISBN: 978-1846044250

McKenna recounts a psychedelic journey in the Colombian Amazon with his brother. 

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

Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers

Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers. Richard Evans Schultes, Albert Hoffman and Christian Rätsch. Healing Arts Press. ISBN: 978-0892819799

Ritual uses of psychoactive plants; detail the uses of hallucinogens in sacred shamanic rites while providing lucid explanations of the biochemistry of these plants and the cultural prayers, songs, and dances associated with them

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

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

Psilocybin Mushrooms of the World: An Identification Guide

Psilocybin Mushrooms of the World: An Identification Guide. Paul Stamets. Ten Speed Press. ISBN: 978-0898158397

Detailed descriptions and color photographs for over 100 psilocybin-containing mushroom species are provided, as well as an exploration of their long-standing (and often religious) use by ancient peoples and their continued significance to modern-day culture.

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

Psychedelic Medicine: The Healing Powers of LSD, MDMA, Psilocybin, and Ayahuasca

PSYCHEDELIC MEDICINE: THE HEALING POWERS OF LSD, MDMA, PSILOCYBIN, AND AYAHUASCA. Dr. Richard Louis Miller. Park Street Press. ISBN: 978-1620556979

Clinical psychologist Dr. Richard Louis Miller discusses what is happening today in psychedelic medicine. Dr. Miller and his contributors explore the ongoing efforts to restore psychedelic therapies to the health field. They also discuss the newly shifting political climate and the push for new research, offering hope for an end to the War on Drugs and a potential renaissance of research into psychedelic medicines around the world.

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

interested in becoming a trained psychedelic-assisted therapist?

Management of Psychedelic-Related Complications - Online Event - Nov 20th