This discussion is intended for the archival of information only as it relates to the medicinal use of substances with a narrow window for therapeutic effects and the power to kill. This is also a conversation I am reticent to initiate due to potential for abuse, however it is a topic I have found zero discussion about anywhere else on the web, or in psychonaut literature. The ethics of the Nexian attitude are the only reason I feel comfortable sharing this here. The pharmacology of chiric sanango is enormously relevant to the prevention and management of life-destroying neurodegenerative disease, and it secondarily holds keys to understanding mystical/religious practices that historically involved the use of nightshades.
Chiric Sanango is a very unique plant, in that it contains both numerous poisons in its roots, and their respective antidotes in the aerial parts. Scopolamine is in the roots, and the aerial parts contain scopoletin.
Here is a compilation of all the peer reviewed data on the plant, compiled into tables where you can see which parts contain which chemicals at what concentrations, and which countries use which parts for which specific ailments
Thank god for Leslie Taylor!Pausing for a moment to shine a laser pointer on a massive failure of language, and something that is easily confused with the potential for loads of harm: scopolamine is a deadly tropane alkaloid with a high anticholinergic burden. It kills hippocampal neurons and introduces major ROS to the brain. Scopoletin is a healthful coumarin found widely in the plant kingdom with powerful antioxidant and memory protectant effects. It scrubs accumulated tau protein from the brain, and all current research points to it being a powerful ally for management and amelioration of neurodegenerative disease. Rich sources of scopoletin include noni fruit (Polynesian herbal medicine), Hawaiian baby woodrose roots (Ayurveda), sophora flavescens (traditional Chinese Medicine); its power has been historically utilized in herbal medicine systems around the world.
I sat for 14 days with chiric sanango; I have many tales to tell, but relevant to this particular topic, I ingested far more leaf (scopoletin) than root (scopolamine). N=1, again, but I experienced no ill cognitive effects either during or after, and a resolution of severe neurological symptoms, which was what I had sought help for.
Twist of fate, some time after that, I was unexpectedly prescribed pure transdermal scopolamine.
Prior to getting sick, I would have told you I hands-down had no interest in the poison path. But it had an interest in me, and it was up to me at that moment if I wanted to answer the phone or not.The situation was actually very scary; it was prescribed after abnormal CT scan findings, but no one knew the cause. The scopolamine worked to address the symptoms, but there were no actionable biomarkers found to address the cause, so I had no choice but to take an indefinite time off work and chill at home on scopolamine.
I have never been tested for CYP etc. deficiencies because it's expensive, and getting insurance to cover the testing is next to impossible. But I've had a laundry list of heavy duty neurological reactions to common pharmaceuticals, and OTT reactions to small amounts of psychedelics. I have deduced by looking at the metabolic pathways for the giant list of substances I cannot tolerate that I'm probably CYP2D6 deficient, along with possibly other enzymes, and it has worsened with age. That, combined with the fact that I survived an illness smashing my brain like a tomato, makes me like a canary in the coal mine when it comes to any kind of psychoactive effects from substances, good or bad. And scopolamine is contraindicated for people taking CYP2D6 inhibitors.
When I was in the thick of illness, I lost comprehension of my first language and went nonverbal. I forgot how to play an instrument I've played for 20+ years. I thought I was living in a house I moved out of years ago. I did things like wander around the house and set my hands down on a hot stove because I had no idea what I was doing. I had to throw away pots and pans because I forgot them on the stove for hours. I recovered, but have some PTSD about it, and am not keen on the implications of significantly increased anticholinergic burden.
So the plan was to put Chiric Sanango's hot take to test, and preload every scopolamine administration with scopoletin. Scopolamine binds indiscriminately to muscarinic receptors M1-M4, and atypically in a subset of people to M5. M5 is implicated in addiction pathology; yet one more reason to never abuse this class of substances. Of M1-M4, only M1 is associated with delerium.
But scopoletin binds preferentially to M1.
My hypothesis: scopoletin will bind first to M1, protecting against delerium, and then the scopolamine will be forced to bind only to M2-M4, so I can reap the medical benefits more safely. After all, I had experienced nothing but cognitive benefits when I sat with chiric sanango, but I did not run a control experiment with just the root (scopolamine) and no leaves (scopoletin).
For science (I seriously wanted to know if this would work or not), I had to first run a control experiment with the scopolamine patches. For my first dose, I used only the patch with nothing else. I wasn't crazy about it. The patches released 1mg over the course of three days. My doctor assured me the patch was a microdose. The internet assured it would be a microdose. For most people, it probably would be.
It most definitely wasn't, and I didn't even use a broom. Another post for another day. But what surprised me most was this: the ill effects of tropanes that everyone warns about didn't hit until about three days after removing the patch, which tracks with the half life. I can ABSOLUTELY understand how people who aren't seasoned users of entheogens could mistake the experience for psychosis instead of rebound, and cave into all kinds of wild delusions. It was very dark. It was real in a way nothing else is real. The sense of power it imparted was enormous. The closest thing I can compare it to is Peter Gorman's chapter on black magic in Ayahuasca In My Blood. I understood completely in those moments how nightshades were tied to European witchcraft. It probably also tickled M5 because, while I did not indulge beyond what was needed or refill my script, it left a lingering lust for more that was awfully pushy for a couple of weeks.
My short term memory and sense of time were also negatively affected for about a week.
The patch worked like a charm for what it was prescribed for, but symptoms later resurfaced, so I had to resume use. I had a huge stash of noni because I was already using it intermittently for the neuroprotective effects. The most comprehensive study on noni fruit that I could find concluded the optimal therapeutic dose for noni was between 4-8g/day. I don't know how much scopoletin this practically was, but decided to use the amounts in the study because it's within the range that achieved the most drastic positive health outcomes consistent with purported effects of scopoletin.
Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose - PMC
We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Starting at two capsules twice daily (2 grams), the dose ...
www.ncbi.nlm.nih.gov
I was shooting in the dark, and experimented with different intervals of time between noni and using the patch. I achieved excellent results with a 30 minute gap: I experienced zero dissociation from time, zero hallucinations, zero rebound, zero hangover. It also changed the tone and color of the experience entirely. With noni, that sense of darkness, magic, and sense of all consuming power was gone. What remained was a clear and deep euphoria, and I would be FASCINATED to once experience how this overlaps with Ayahuasca.
I didn't have the courage to mix the patch with anything else because I didn't want to die. I did not feel confident about dosing through a patch because it was not specific enough. I would feel much more comfortable working with a high scopolamine cultivar of brugmansia and making an oil infusion, that I could further dilute to near homeopathic levels and apply one and only one drop for a loading dose. It is THAT strong. All the literature says people aren't even supposed to begin experiencing effects until 4+ hours in to wearing the patch; I was FLYING consistently after 45 minutes. I'm so suspicious of lacking CYP.
A note in the spirit of harm reduction: it potentiated cannabis 5-10x.
I used five patches total over the course of two months. The last patch left me with another bad episode of rebound. I didn't feel psychosis-adjacent, but I was extremely depersonalized and my short term memory was disturbingly bad for 3-4 weeks. I don't know if it was just that I waited too long, or I had exceeded the anticholinergic burden my body could handle from intermittent use of the patches, or both. If I were to ever engage again entheogenically, I would not use this substance without at least a year's break between uses, and I would do it with one highly, highly, highly diluted drop from the culebra cultivar (80% scopolamine).
For the purposes of our knowledge base
Protective effect of fruits of Morinda citrifolia L. on scopolamine induced memory impairment in mice
Effects of the coumarin scopoletin on learning and memory
These people gave scopolamine, and then scopoletin, to zebrafish
Novel insights on acetylcholinesterase inhibition by Convolvuluspluricaulis, scopolamine and their combination in zebrafish - PMC
Acetylcholinesterase (AChE) inhibitors increase the retention of acetylcholine (ACh) in synapses. Although they alleviate cognitive deficits in Alzheimer’s disease, their limited benefits warrant investigations of plant extracts with similar ...
www.ncbi.nlm.nih.gov
Rats
Manasamitra Vatakam on Scopolamine-Induced Amnesia in... : Journal of Pharmacy and Bioallied Sciences
rials and Methods: MMV was compared with DPZ as a standard in the present study to determine the behavioral parameters through elevated plus maze (Hebb William maze/rectangular maze)and locomotor activity in scopolamine-induced memory loss in female Wistar rats. Results and Discussion: The...
journals.lww.com
Noni & neuroprotection
Morinda citrifolia and Its Active Principle Scopoletin Mitigate Protein Aggregation and Neuronal Apoptosis through Augmenting the DJ-1/Nrf2/ARE Signaling Pathway - PMC
Given the role of oxidative stress in PD pathogenesis and off-target side effects of currently available drugs, several natural phytochemicals seem to be promising in the management of PD. Here, we tested the hypothesis that scopoletin, an active ...
www.ncbi.nlm.nih.gov
Epicatechin and scopoletin rich Morinda citrifolia (Noni) leaf extract supplementation, mitigated Osteoarthritis via anti-inflammatory, anti-oxidative, and anti-protease pathways - PubMed
The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia L. (MC) Noni leaves are non-toxic (unlike the fruits) and consumed as vegetables. The anti-osteoarthritis effects of the MC leaf extract against joint cartilage degradation and inflammation were investigated through...
pubmed.ncbi.nlm.nih.gov
Scopoletin in Hawaiian Baby Woodrose roots
Scopoletin: Antiamyloidogenic, Anticholinesterase, and Neuroprotective Potential of a Natural Compound Present in Argyreia speciosa Roots by In Vitro and In Silico Study - PMC
Alzheimer’s disease (AD) is characterized by depositions of amyloid β (Aβ) peptides aggregates resulting in plaques formation in the central nervous system (CNS). This study evaluates the disease-modifying potential of scopoletin against multiple ...
www.ncbi.nlm.nih.gov
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