A subcommittee of the Oregon Psilocybin Advisory Board (OPAB) is considering whether to provide special protections for religious practises involving the use of psilocybin.
The OPAB has been warned that the rise of a new psychedelics industrial complex could put psychedelic religions in jeopardy if Oregon fails to act quickly.
Attorney Jon Dennis of Sagebrush Law, warned the board that the industry has already begun engaging in aggressive tactics to prevent newcomers from entering into the industry, despite psychedelics not yet being legal at a state or federal level.
Although the US Supreme Court has already approved of granting religious liberties to churches that use psychedelic plants as sacraments, Oregon is the first state to decide the scope of freedoms for psychedelic religions through administrative regulation.
Oregon has one of the highest prevalences of mental illness in the nation, affecting one in every five adults. With the rise in promising results regarding the efficacy of psilocybin for mental health conditions, Oregon became the first state in the US to approve of legalised psilocybin under Oregon’s Psilocybin Services Act – “Measure 109” – in November 2020.
Measure 109 aims to develop a “long-term strategic plan for ensuring that psilocybin services will become and remain a safe, accessible and affordable therapeutic option for all persons 21 years of age…” and “establish a comprehensive regulatory framework concerning psilocybin products and psilocybin services under state law…” among other actions.
In a meeting with the OPAB, Dennis presented a set of draft regulations that would grant religious protections under Oregon’s new psilocybin law.
Addressing the board, Dennis cited the words of medicine woman Maria Sabina, whose sacred ceremonies in Mexico were based on the use of psilocybin. When the news of her ceremonies broke in The Times, Westerners flocked to Mexico in order to experience the mushrooms. This led to restrictions from the Mexican Government on their ritual use.
“Never, as far as I remember, were the saint children [the mushrooms] eaten with such lack of respect,” Sabina had commented – saying that foreign visitors ruined the purity of the mushrooms.
Dennis commented: “When we think about what Oregon is doing right now with this new psychedelic programme, we have to consider this history – part of this history is the emergence of the psychedelics industrial complex. This is the list of companies that are publicly traded.
“Keep in mind – with about $4.8bn in market cap – non of this is really legal yet. I don’t suppose that all of these companies are engaging in aggressive tactics – but we are already starting to see the intellectual property grabs and the land grabs, to corner out other types of access to psychedelic healing modalities that exist.
“If we as a society are to protect religious use the best way to do that is to do it now. Because as these companies get bigger and bigger and become more aggressive, and try to corner out other types of psychedelic healing and psychedelic use, it is not going to get easier as this psychedelic complex gets more entrenched.”
Concerns were also raised regarding lobbyists meddling in Oregon’s psilocybin programme.
Protections for entheogenic practitioners
Many people across the world use entheogens – psychoactive plants or substances that are used in a sacred or spiritual manner.
To reflect this use of psychoactive plants, within Dennis’ draft framework, the word “entheogenic” is used rather than “religious” to ensure that those who use these plants as part of any practice related to their sincere beliefs have their rights maintained.
Dennis proposed a partnership between the Oregon Health Authority and entheogenic practitioners that he believes would be beneficial to all parties, by bringing entheogenic practice out of the underground to “above ground”. This would provide oversight and accountability, ensuring that people are going through a screening process and safeguards are in place. It will also ensure practitioners will not have to face the risk of jail for practices related to their beliefs.
“This also helps with the tension inherent in Measure 109 around accessibility and affordability,” said Dennis. “I believe, particularly with the peer support model and homegrown mushroom model, that we can drive the price point down to something that is actually affordable.
“This cause is too important for it to be another vehicle to reinforce or deepen inequalities that exist along racial, health or financial mechanisms – it is going to be such a tragic thing as we enter into this new era where we re-establish relationships with plant medicines – it is critical we give small community-led organisations their own means of production and do something to protect that.”
Click here to read the draft framework
Bob Otis Stanley, pastor and chief garden steward of Oakland-based church, the Sacred Garden Community, which uses psychedelic plants as part of their religious ritual, also highlighted the importance of community-based healing.
Stanley commented: “We have a common faith in our church that the sacraments of our church are approached with care, respect and trust and can connect us with experience of divine presence within this lifetime.
“But we can accept many incoming faiths – atheism, Christian, Jewish, Islam, Pagan. So, we are trying to create a strong container for the diversity that we find here in Oakland, but also who have a sincerely shared faith.
“By trying to create this community framework that has deliberate harm reduction built-in we are recreating some of the benefits in long term culture that I have experienced in the many years visiting the Sierra Mazateca region. Each little village and valley that will have one or two, or several, curanderos [healers] will have culture integrated with that healing process – we are lacking here in the United States.
“So to have an intentionally created community that can provide some of that support for the frameworks you may find in other traditional cultures is part of our goal.”
Frontiers in Pharmacology: challenges and gaps in psychedelic research
Psychedelic Health spoke to Miami University researchers about how future research can address research challenges and knowledge gaps in the field of psychedelics.
The therapeutic benefits of many psychedelics have been clearly demonstrated through clinical trials, where the use of psilocybin-, ketamine-, and MDMA-assisted psychotherapy showed striking long-term improvements in addiction, anxiety and depressive symptoms, and post-traumatic stress disorder. Yet, clear gaps in our knowledge of their mechanisms of action remain.
In a recent Research Topic – a special collection of articles – entitled What is up with psychedelics anyway? included in the Neuropharmacology section of the well-regarded journal Frontiers in Pharmacology, Professor Matthew McMurray, from Miami University’s Department of Psychology and colleagues, explored the mechanisms of psychedelic drugs in the context of the altered states of consciousness induced by the drugs, and how that relates to the therapeutic effect of these agents.
Psychedelic Health spoke to Professor McMuray and his post-doctoral researcher, Dr Ryan Rakoczy, about some of this Research Topic, current research challenges and knowledge gaps, and how future research could come to address them.
What are the current knowledge gaps regarding the mechanisms of action of psychedelics?
Mechanism is a tricky word. First, we must acknowledge that all drugs cause multiple effects, and that the mechanisms of each effect vary. For example, the mechanisms of psychedelic-induced hallucinations may differ from the mechanisms of the therapeutic effects of psychedelics. So, we must first choose an effect to study.
Next, we much acknowledge that drug mechanisms exist at numerous levels, from cognitive/perceptual to systems-level neural circuits to bio-molecular processes. Psychedelic drugs clearly shift our cognition and perceptions through the hallucinations they induce at higher doses. Numerous human and animal studies have also shown that they have the power to grow and reshape neural circuits, within and between brain regions. These drugs also act on particular molecular targets, such as serotonergic receptors. All these mechanisms are independently well-studied, so perhaps the largest gap in the literature is the connection between them.
To what extent do their molecular actions drive changes in brain circuits? To what extent do changes in perception reshape molecular processes? These are not simple questions to answer, and they are not unique to the field of psychedelic drugs; however, psychedelic drugs carry their unique challenges.
There are often legal restrictions associated with these compounds that must be navigated, many of which preclude using them in human studies. This has led researchers to focus on animal studies but translating the findings from animal studies to humans is also challenging. Even in the existing human studies, there are a lack of standardized “tools” available to quantify and control for the highly subjective and variable responses to psychedelic drugs. For example, the lack of reliable placebo controls has been a significant barrier. This lack of standardized methods has made it challenging to draw conclusions across human studies.
Lastly, we know that both treatment context and patient history matter, but controlling for these across studies is challenging, especially in the context of the aforementioned issues. So, there are many challenges to understanding the mechanisms of psychedelic drugs.
Despite these challenges, human and animal studies have begun to focus on a shared mechanism of all drugs that cause hallucinations: activation of serotonin 5-HT2A receptors in the brain. Experiments using the selective 5-HT2A blocker ketanserin have shown that it can block many of the effects of psychedelics in both humans and rodents. More widespread use of this pharmacological tool is needed to truly understand the role of this receptor system, especially in clinical studies.
However, despite sharing this one target (5-HT2A), psychedelic drugs (and ketanserin) are highly variable in their mechanisms and affect a wide array of other neurotransmitter systems, including dopamine and norepinephrine. These “off-target” effects are likely responsible for the unique pattern of each compound’s effects, but more research on this is clearly needed to relate these molecular targets with the neural and perceptual processes affected by each drug. A deeper understanding of the relationship between the micro- and the macro- processes affected by each drug will undoubtedly lead to more effective usage of these compounds in clinical settings.
What is the current understanding of how the altered state of consciousness (ASC) contributes to therapeutic benefits?
This is a major question in the field, and it’s hotly debated. It’s currently unclear how altered states of consciousness contribute to the therapeutic benefits of psychedelic drugs, or even if an altered state is required at all.
There have been two approaches to studying this topic. First, blockade of the 5-HT2A receptor with ketanserin has been shown to block the hallucinations induced by psychedelics. This approach has been widely used in animal studies, but less frequently used in human studies. In animal studies, this approach has shown that ASC may not be required for many of the therapeutic benefits, but this has yet to be verified in well-controlled clinical studies.
The second approach to studying this topic has been to administer sub-hallucinogenic doses of psychedelics (e.g., “micro-doses”). This approach has been widely used in both human and animal studies, but these studies have shown minimal and inconsistent findings that are challenging to interpret. Given the fast rate of metabolism of these compounds, it is unclear how much (if any) of the drug is reaching the brain, and major differences in study design (e.g., chronic vs. acute dosing) has made it difficult to compare the results of these studies to studies using hallucinogenic doses.
Lastly, and perhaps most significantly, the lack of adequate placebos has been a major barrier to understanding the necessity of an ASC to therapeutic effects. Without good controls, answering this question may be impossible.
You recently led a Research Topic in Frontiers in Pharmacology entitled ‘What is up with psychedelics anyway?’ Can you tell us a little more about this – what it was designed to achieve?
The underlying purpose of this special issue is to provide a venue for the publication of research related to psychedelic-induced altered states of consciousness and their therapeutic benefits. Currently, articles related to altered states of consciousness have limited publishing options, and those options that do exist may not be widely read by others studying psychedelic drug action. We hoped that by providing a more accessible and more widely read publication space for both clinical and pre-clinical researchers, we could begin to address the question of whether altered states of consciousness are required for the therapeutic benefits.
The editorial team consists of myself, Dr Sarah Mennenga, Dr Candace Lewis, and Dr Stephen Helms Tillery. When we first met to discuss the idea behind this issue, we debated its focus; should it be broad or more focused? In the end, we decided that the field would benefit from the more inclusive perspective we adopted.
The special issue now includes research using qualitative, quantitative, human, and animal methods to investigate this topic, and includes investigators from across the world. We see the inclusive nature of this issue as a real strength.
How important is it for large and influential journals such as Frontiers in Pharmacology, which has recently seen its Impact Factor increase to 5.988 and its CiteScore reach 6.6, to cover such topics as psychedelics?
Public and medical perceptions regarding psychedelics have recently shifted towards the positive, as increasing numbers of clinical trials have demonstrated their therapeutic benefits in some contexts.
Therefore, it is paramount that any peer-reviewed research performed with psychedelic drugs be published in an open access and high-profile manner to allow and encourage more well-informed decisions to be made regarding clinical trials, drug policy, and basic science experimental designs.
Frontiers in Pharmacology has provided just such an opportunity to the field.
To focus in on some of the themes of the Research Topic: how can we better inform our understanding of psychoactive impact vs. biological impact of sub-hallucinogenic doses that may have anti-inflammatory or pain-reducing effects and how either of these may impact mental health?
Whether we consider sub-hallucinogenic or higher doses, the anti-inflammatory effects of many psychedelics may be essential to any therapeutic benefits. There are countless studies exploring the role of inflammation in psychiatric disease, especially neuroinflammation, and such psychedelic effects would certainly tap into those mechanisms.
Unfortunately, these anti-inflammatory effects are largely understudied in the psychedelics field. Most research with psychedelics has focused on their neural and/or behavioral effects, so there is a real need for more research in this field. Additionally, experiments investigating the effects of psychedelics on the periphery (i.e., gut microbiome or cardiac and smooth muscle tissue) may uncover novel mechanisms for therapeutic effects. For example, modulation of the gut-brain axis may serve as a novel therapeutic route for treating a variety of mental health disorders.
Lastly, such studies may also uncover novel uses for psychedelics in the treatment of other diseases not directly related to mental health. For example, the same serotonin receptors psychedelics bind within the brain and cause hallucinations (5-HT2A) are also found in the gut and mediate intestinal motility. So, it is necessary that we expand our research to focus on the full spectrum of effects psychedelics have, not just those taking place at synapses.
How can mechanism of action research help us understand the role of psychedelics as biological response modifiers?
Understanding how a drug works (its mechanism) is the key to unlocking a few important pieces of information. First, it can inform us of the drug’s effectiveness. If a novel drug’s mechanism is similar to an existing effective compound, this would suggest it may work as effectively. If it’s a new mechanism, then we need to spend more time evaluating the effectiveness of the drug.
Additionally, identifying new mechanisms can inform us of a second key piece of information: the biological basis of the disease. In other words, if a drug affects target A, it’s likely that target A is disrupted by the disease state. This information then provides us with an opportunity to develop better drugs to affect target A, or we can use this information to help identify at-risk individuals to prevent the onset of the disease.
Lastly understanding a drug’s mechanism can help us understand what undesirable effects a drug may have. For example, psilocin (the active form of psilocybin) has a relatively high affinity for serotonin 5-HT2B receptors, which are essential for healthy cardiac function. Its action at this target could raise concerns about the potential for heart complications if the drug is used clinically or recreationally.
In general, more research is desperately needed on the mechanism of action of psychedelic drugs. One could say there is still a lot of “low-hanging fruit” in this area, but with barriers of high-cost, lack of access, legal restrictions, and lack of adequate standardized controls, these questions are harder to answer than in other fields. A better understanding of the effects these drugs have at the cellular level would help provide a foundation for defining their effects at the level of the whole animal.
For example, LSD and psilocybin both bind with the same receptor (5-HT2A); however, upon binding they activate different intracellular second messenger signaling pathways (beta-arrestin vs. Gq-GPCR, respectively), causing different down-stream effects on the cell. The differential activation of these cellular signaling pathways by LSD and psilocybin may explain why they elicit somewhat different biological and behavioral responses.
Can a better understanding of altered states of consciousness (ASC) inform the therapeutic understanding of the mystical experience, and can it inform our understanding of the role of compounds such as ketamine as much-needed “fast-acting” antidepressants?
It is unknown if an ASC is a prerequisite for achieving antidepressant effects with psychedelics. Studying non-drug-induced ASCs (hypnosis, meditation, etc.) and comparing them to psychedelic-induced ASCs may uncover common physiological mechanisms. If ASCs are the sole mechanism by which psychedelic drugs exert their therapeutic effects, it may be possible to induce these same effects without exposure to the drug.
Additionally, identifying the brain regions participating in the psychedelic-induced “mystical experience” may help pinpoint where in the brain psychedelic drugs exert their therapeutic effects, and perhaps even suggest the brain regions involved in the pathogenesis of mental health disorders.
Similarly, identifying the receptors and cellular signaling pathways activated during ASCs could suggest therapeutic targets for the development of more focused medications.
Can mechanism of action research inform our understanding of pharmacological factors vs. non-pharmacological factors of the compounds’ effects (set/setting), such as how the compounds impact neurobiological responses to enriched environments, and whether or not this has therapeutic effects? And, therefore, how the use of these compounds can be implemented in healthcare?
This is an essential question in the field of psychedelics. There is substantial evidence that the set/setting has a significant impact on the effectiveness of these drugs, especially the individual’s expectations. This is one of the reasons why more research is needed with healthy volunteers and why better controls (environmental and placebo) are needed in clinical studies. Additionally, we must know how the set and setting affect the targets of psychedelic drugs. For example, if set or setting bias 5-HT2A levels, we would expect them to affect the hallucinations caused by psychedelics. Thus, we must understand both the mechanisms of the drugs, but also the mechanisms of the set and setting.
To address these questions, we need to compliment clinical and whole-animal work with research using ex vivo and in vitro methods, to remove the “emotional” and “sensory” response to environmental stimuli that may influence the subjective response to psychedelics.
For example, cell culture experiments with ex vivo brain tissue could determine if changes in synaptic plasticity, receptor density, or gene expression, among other things, change during and after psychedelic drug exposure, in the absence of any particular setting. Should these compounds be made more widely available for healthcare uses, we should expect their use to occur in a variety of uncontrollable settings. Therefore, optimizing their dosage, route of delivery, etc. must be done in a way that embraces variance in set and setting.
Can it help us understand psychedelic-induced neuroplasticity and/or give us a broader understanding of mental health in general?
Mechanism exists at multiple levels of the organism, from cognition to molecules. To understand any disease and the best way to treat it, we must understand the disease’s mechanisms, as well as the mechanisms of the drug we wish to use to treat it. By matching the two sets of mechanisms, we can best tailor the drug to the disease. Psychedelics have broad effects, from cognitive to molecular.
The unique mechanism of each drug may even suggest the particular mental health disorder it is best suited to treat. Without more research on the mechanisms of psychedelics, and a deeper understanding of disease mechanisms, all drug development is basically a guessing game.
Looking beyond the scope of your Research Topic, what other areas could future article collections in Frontiers in Pharmacology focus on to either help fill the aforementioned knowledge gaps or address completely different areas related to psychedelics?
Some suggestions for future issues include:
- Molecular effects of psychedelics (research using ex vivo tissue, isolated cells, or other reductionist methodology)
- Effects of psychedelics on non-central systems (peripheral nervous system, gut, renal function etc.,)
- Mechanisms of non-drug induced Altered States of Consciousness
Matthew McMurray, PhD
Department of Psychology
Center for Neuroscience and Behavior
Dr Ryan Rakoczy
Department of Psychology
90 N. Patterson Ave.
Oxford, OH 45056
Canada’s SAP patients to receive Blue Serenity psilocybin
Optimi Health has launched Blue Serenity – Canada’s first natural therapeutic psilocybin product, in collaboration with psilocybin patient advocate Thomas Hartle.
Once approved by health authorities under Canada’s Special Access Program (SAP) or an authorized clinical trial, patients, doctors, and researchers will receive Blue Serenity in blister packs of eight psilocybin capsules.
Blue Serenity is standardised to contain a total of 25 milligrams of natural psilocybin in the form of EU-GMP biomass grown as Panaeolus cyanescens mushrooms cultivated at Optimi Labs Inc. in Princeton, British Columbia.
Optimi’s Chief Science Officer, Justin Kirkland, and Head of Cultivation, Todd Henderson, collaborated with Hartle to breed a specific genetic strain based on Hartle’s previous therapeutic experiences.
Optimi CEO, Bill Ciprick, commented: “Anyone who has entered the psychedelics space in the last two years will tell you that Thomas Hartle’s story of compassion and kindness inspired them in some way to want to make a difference.
“We are tremendously excited to be partnering with Thomas to become the first Canadian company to launch a natural psilocybin product specifically to help patients seeking relief through the Special Access Program.”
Proceeds from the sale of Blue Serenity will directly benefit psilocybin patients through Hartle’s new charity, a venture that will provide access to psilocybin therapy for underserved adults.
Optimi will also make a $5,000 monetary donation to the charity in commemoration of the two-year anniversary of Hartle’s Health Canada approval to undergo psilocybin-assisted therapy.
Ciprick said: “It’s an excellent opportunity for Optimi to give back to those in need, while helping to build a network of trust between business, advocacy, patients, and doctors, that we hope will further the framework for compliant access and increase the overall confidence of practitioners in this medicine.”
Optimi Health has explained that Hartle’s choice of the name “Blue Serenity” touches on the emotional and visual aspect of his psilocybin experience, specifically in how he was able to redefine the inner sense of peace his therapy brought him.
Hartle said: “Blue Serenity was born from an experience that took me from a state of extreme anxiety to a feeling of calm that I never knew existed.
“Knowing that my journey will live on in a natural substance that others will be able to access goes to the core of everything that is right about psychedelic therapy, and that in itself is an incredibly moving experience for me.”
Study to investigate Hallucinogen Persisting Perception Disorder and anxiety
The study will be community-led and is being launched on Quantified Citizen.
Launched by Subreddit r/HPPD in partnership with the scientific research app Quantified Citizen, the retrospective, observational study aims to investigate possible links between Hallucinogen Persisting Perception Disorder and anxiety.
Subreddit r/HPPD is an online community that provides support for and resources about Hallucinogen Persisting Perception Disorder (HPPD) – a disorder in which a person experiences persisting visual hallucinations following the use of psychedelic drugs, or other drugs such as SSRI’s.
There is currently limited research on HPPD, which has been associated with conditions such as epilepsy, manic episodes and anxiety disorders.
The study, entitled Anxiety and Hallucinogen Persisting Perception Disorder, Can You See It?, will investigate potential connections between anxiety and HPPD, as well as HPPD symptom clusters and current substance use. Substances include alcohol, nicotine, psychedelics and other non-psychedelic drugs.
r/HPPD moderator and study lead Sophia Alcala provided the research focus, drawing from observations of community members frequently discussing experiencing anxiety with HPPD.
Alcala stated: “I wanted to partner with Quantified Citizen in order to figure out how anxiety relates to HPPD symptoms reported by our members.
“I’ve noticed that anxiety seems to worsen our member’s HPPD, and it would be helpful if we could find out more about it and other factors that may relate to HPPD symptoms’ worsening or improvement.”
The study will target r/HPPD community members but will also be open to anybody who has or has had HPPD. Participants can join by downloading the Quantified Citizen app available on iOS and Android.
Psychedelic Researcher at Quantified Citizen, a citizen science-powered health research app, Sarah Paschall, MSc, stated: “With this community-led study, we hope to help shed light on this understudied disorder that can be quite debilitating.
“We hope that the personalised insights shared with participants at the end of this study will help daylight links between HPPD and certain disorders or substances so that folks can make more informed decisions moving forward.”
- Frontiers in Pharmacology: challenges and gaps in psychedelic research
- Canada’s SAP patients to receive Blue Serenity psilocybin
- Study to investigate Hallucinogen Persisting Perception Disorder and anxiety
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- New research suggests low addiction risk with medical ketamine use
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