DELIC Labs seeks to establish a research hub in Vancouver to study cannabis and mushrooms through process design, optimization, analytics, and formulation research. It collaborates with academic and industry partners globally. The document discusses psychedelic compounds and their medical potential but also highlights flaws in current clinical trials, a lack of knowledge about psilocybin mushroom composition, and Delic Labs' work using metabolomics to address this. It also covers the patenting of psilocybin crystal structures and questions whether this is appropriate given the medical applications of these compounds.
2. Introduction
DELIC Labs is a research venture that seeks to add fundamental scientific
insight to the field of cannabis and mushroom production.
We seek to support the cannabis and mushroom industries by
establishing a centralized hub in Vancouver, BC, for collaborative
research focused on:
• Process Design
• Process Optimization
• Process Analytics
• Formulation Research
3. Collaborative Research
DELIC Labs collaborates with academic, industry and private groups
around the globe. Some highlights of those collaborations are:
• University of British Columbia, Vancouver
• Loyalist College, Belleville
• Via Innovations by Dr. Monica Vialpando
• Verdient Science by Dr. Linda Klumpers
Fundamental Collaboration
4. Outline
• Psilocybin Mushrooms and Psychedelic Compounds
• Your Brain on Psychedelics
• Psychedelic Treatments, Trials and Traps
• Psilocybin Testing and a Universe of Molecules
• Psilocybin Patents and Crystal Engineering
4
5. Magic Mushrooms
• A polyphyletic group of >200
psilocybin-containing fungi
5
Psilocybe Mexicana
7. Magic Mushrooms
• A polyphyletic group of >200
psilocybin-containing fungi
• Potential therapeutic
• Alternative antidepressant
• Psychedelic therapy
• Undiscovered natural products
7
Neural interconnectivity for a brain functioning normally (a),
and following psilocybin treatment (b) (R. L. Carhart-Harris,
et. al., Proc. Natl. Acad. Sci., 2012)
8. Magic Mushrooms
• A polyphyletic group of >200
psilocybin-containing fungi
• Potential therapeutic
• Alternative antidepressant
• Psychedelic therapy
• Undiscovered natural products
8
Neural interconnectivity for a brain functioning normally (a),
and following psilocybin treatment (b) (R. L. Carhart-Harris,
et. al., Proc. Natl. Acad. Sci., 2012)
9. Interest in Psychedelics
• Everyone is interested in psychedelics
• Health Canada is granting a record
number of exemptions for
psychedelics research
• Have you seen the Netflix Show ”How
To Change Your Mind”?
• “Psilocybin induces rapid and
persistent growth of dendritic spines in
frontal cortex in vivo.” Shao LX, et al.
Neuron. 2021
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0
20
40
60
80
100
2017 2018 2019 2020 2021
Relative
Interest
Internet Search Term Trends (Global)
Psilocybin Therapy Psilocybin Microdosing
https://terpenesandtesting.com/the-dark-side-of-psychedelic-
research-and-how-we-can-improve/
10. Interest in Psychedelics
• “the dose of psilocybin significantly
reduced anxiety and depression
scores “ - 2011 Grob et. Al; UCLA
• “psilocybin, compared to placebo,
greatly improved anxiety and
depression scores” - Ross et al, 2016;
NYU School of Medicine
• “significant decreases in anxiety and
depression scores” - Griffiths et al,
2016; Johns Hopkins
• “the treatment significantly reduced
depression scores” - Carhart-Harris et
al, 2016
10
0
20
40
60
80
100
2017 2018 2019 2020 2021
Relative
Interest
Internet Search Term Trends (Global)
Psilocybin Therapy Psilocybin Microdosing
11. The Dark Side of Psychedelic Research
With Attention comes Scrutiny
• MDMA clinical trial by MAPS: patient
inappropriately touched, blindfolded, and
pinned down
• Additionally, accusations of sexually
assault by one therapist outside of the
clinic
• Health Canada halted all approved MDMA
trials for review!
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https://www.cbc.ca/news/canada/british-columbia/bc-mdma-therapy-
videos-1.6400256
Courtesy of New York Magazine's Cover
Story: Power Trip
12. The Dark Side of Psychedelic Research
Problems with MAPS clinical trials:
• Negative experiences were not included as adverse effects
• Mishandlings of data representation in publications
• Pooling disjointed results from different experiments
• Increasing suicidal thoughts developed, but were never listed
as adverse events
• Effectively no qualification requirements to be a counselor in
the MAPS trials
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https://www.cbc.ca/news/canada/british-columbia/health-canada-
mdma-trial-complaints-flaws-safety-issues-1.6409849
13. The Dark Side of Psychedelic Research
What to improve?
• Introduction of trial practices and boundary standards of other medical
fields
• Including trial preregistration
• Rejection the use of “nurturing touch” and approach of “equal footing”
• Stop encouraging therapists to experiment with the drug to gain insight
• Pick a lane: “natural,” “spiritual,” and “traditional” is not medical research
but ‘60 free love
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Brennan W, Jackson MA, MacLean K, Ponterotto JG. A qualitative
exploration of relational ethical challenges and practices in psychedelic
healing. Journal of Humanistic Psychology. September 2021.
14. The Foundations of Psychedelic Research
• Psychedelics won’t burn holes in our brain
• They can cause hallucinogen persisting perception disorder
• They can increase suicidal thoughts
• They are known to change the regulation of brain pathways
• For botanical therapies, we have no idea what and how much the patient
is taking
14
Trends Pharmacol Sci. 2021;42(11):929-942
Nature. 2015. doi:10.1038/nature.2015.16968
15. Analytics
To treat a patient, we need to know what we are giving them!
• Delic Labs’ approach to metabolomics
15
16. 16
• Openly available analytical
data not usually verified
• Low statistical power and
comparison
Little Historical Data
GCMS of 5-HT,
Huestis,
1991
Psilocybin
FTIR,
SWGDR
G
2007
HPLC-UV of 5-MeO-DMT,
Jenks, 2014
Malaca S, et.al.. Toxicology and Analysis of Psychoactive Tryptamines. Int J Mol Sci. 2020
22. Crystal Structure
To treat a patient, we need to have the legal right to giving it!
• A little primer on patent law and crystal structure
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23. Psilocybin as Medicine and Patent
• Psilocybin cannot be patented as a
molecule
• Therefore, patent on Composition
of Matter
• Compass Pathways was granted a
patent for a crystalline form of
psilocybin, Polymorph A.
• This patent grants exclusive rights
• But does it hold up? Do we care?
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https://terpenesandtesting.com/crystallizing-the-relationship-between-patents-polymorphs-and-psilocybin/
24. Crystal Engineering
• Three States of Matter: gas, liquid, or solid.
• Solid: molecules scrambled or highly
ordered structures (crystals)
• Crystals: infinitely repeating patterns
• Nature of the repeat pattern matters,
“polymorphs”
• Over half of all organic molecule crystals
have at least two polymorphs
• Each polymorph has unique properties
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25. Unique Crystalline Forms of Psilocybin
• Psilocybin is hydroscopic, (in this case, a trihydrate)
• Hydrate A (below) contains water molecules
• Depending on storage conditions psilocybin can gain or lose water
molecules
• Polymorph A’ unit cell is in the shape of rectangular prisms with 90°
• Polymorph B is rhomboid-shaped prisms with roughly a 95°
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Baertschi SW, Alsante KM, Reed RA. Pharmaceutical Stress Testing; CRC Press: Boca Raton, 2011.
26. What about the Compass Pathway Patent
• Compass claims discovery of
new crystalline form of psilocybin
(Polymorph A)
• X-ray crystallography shows
distinct diffraction peak at 17.5˚
• New, undiscovered structure
or
• Mixture of 81% Polymorph A’,
19% Polymorph B, and small
amounts of Hydrate A.
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Acta Crystallogr C Struct Chem. 2022;78(Pt 1):36-55
27. Summary
• Many psychedelic compounds, botanical and synthetic
• Many medical applications
• But current clinical trials are flawed
• We don’t even know what is in psilocybin mushrooms
• Delic Labs works on closing that knowledge gap with metabolomics
• Crystal structure or psilocybin can affect medical properties
• Crystal structures can be patented, but should they?
Thank you! Any Questions?
27
Dr. Markus Roggen
markus@deliclabs.com
These things might make some participants feel more welcome, but they also put them at risk of being touched when they are unable to give consent. The level of individualistic makes it difficult to know how much the reduction of depressive symptoms is due to the drug, and it also makes it difficult to pool the experiences of patients when they are each having such different experiences. In some cases, it has led to patients becoming overly dependent on their therapists and seeing them as a friend, which led to distress when the treatment suddenly ended.
Toxicology and Analysis of Psychoactive Tryptamines (nih.gov)
Malaca S, Lo Faro AF, Tamborra A, Pichini S, Busardò FP, Huestis MA. Toxicology and Analysis of Psychoactive Tryptamines. Int J Mol Sci. 2020 Dec 4;21(23):9279. doi: 10.3390/ijms21239279. PMID: 33291798; PMCID: PMC7730282.
Classical MN:
Consider all fragmentation patterns in a sample as vectors.
Compare spectral vectors to each other,
The similarity between the two numbers is defined as the cosine angle between vectors.
It is likely that Polymorph B showed up due to challenges in maintaining uniform heating and preventing microenvironments as a result of their large-scale production, which is easier to control on a smaller, lab scale.
Further, since psilocybin is hygroscopic, a dried crystalline sample corresponding to Polymorph A would quickly absorb water, changing it back to Hydrate A. This calls into question the shelf stability of Compass’s crystalline psilocybin, and whether they would truly be selling a pure form of Polymorph A. Many of these concerns would need to be addressed going forward if Compass Pathways is to hold onto and defend the rigor of their patent.
If Compass Pathways is unable to address these concerns, they are most likely to lose their patent preventing sole claim on the production of Polymorph A, keeping medical psilocybin in the public domain for research and commercial purposes. However, if their patent is granted, it could lead to monopolistic control over the production of medical psilocybin. How? Only one group can be granted a patent for a polymorph structure, and US Food and Drug Administration (FDA) approval often follows. If Polymorph A is granted approval as the first FDA–approved medical psilocybin, then Compass would be the sole supplier of medical psilocybin until other companies succeed in discovering a new structure, getting a patent, and FDA approval.