The Demand for Stockpiles of Psilocybin

Editor’s note, October 2026: When Dr. Lupoi wrote this piece in 2021, legal psilocybin supply was a genuine bottleneck: the DEA’s federal production quota for that year began at just 30 grams. What follows is his original article, unchanged — a look at the fungal biology and the 1960s fermentation research behind the question of where stockpiles would come from. For how the supply picture has changed since, including quotas a thousand times larger, licensed production in Oregon and Colorado, and a federal scheduling review, see the update at the end.

Along a spore’s journey to developing into a mushroom, there are several integral phases. A spore will bloom into highly branched structures reminiscent of treetops called hyphae. A forest of hyphae is called mycelium (Figure 1), which acts like roots reaching deeper into organic matter to obtain water and nutrients, breaking down large molecules (like cellulose) into simpler ones (like glucose) that the fungi can utilize.

A hardened mass of mycelium, called sclerotia, may form. The sclerotia acts as an emergency food bank, helping fungi survive environmental extremes. Some sclerotia are edible like the growths on birch trees known as chaga mushrooms (Figure 2). And the sclerotia of mushrooms like Psilocybe cubensis or Psilocybe mexicana contain the psychedelic molecules psilocybin and psilocin.

Psilocybin Culture, Subculture

When Albert Hoffman discovered the hallucinogenic properties of P. mexicana [1], there was interest amongst other researchers to unlock more of the mushroom’s secrets. To do so requires more of the compounds, and traditional ways of cultivating mushrooms can be very time-consuming, potentially requiring many months. The question was how to quicken the pace to obtaining larger stockpiles of psilocybin and psilocin? A mushroom culture provides a proliferative way to get more mushrooms by reproducing them in a growth medium under controlled conditions. A subculture involves removing some or all cells to put them into new batches of growth media. This method can lengthen the life of and augment the number of cells in the culture.

Submerged culture fermentation, where the fungi is placed within a closed flask containing a rich nutrient broth, has become one of the most popular methods for mycelium proliferation. A 1964 paper, in fact, explored whether this now common technique would prove viable for psilocybin and psilocin production. [2] Mycelial cultures were added to flasks containing 30 mL of nutrient media and were put on a shaker for 4 to 7 days at 25°C. The mycelium that grew were homogenized and added to new flasks to serve as inocula for subsequent growth over a period of 5 to 15 days.

Replacement cultures were created much the same but used a longer homogenization step. This homogenized product was added to 300 mL of medium and put on the shaker. Mycelium pellets were washed with distilled water and aliquots were removed and added to the replacement medium. The researchers also evaluated the addition of the amino acid tryptophan since it was speculated as being a biosynthetic precursor to psilocybin.

Old School Analytics

The mycelium pellets were ground, extracted with methanol on the shaker for eight hours, and centrifuged to remove solids. The cleaned-up extracts were spotted on filter paper and “formed” with a mixture of n-butanol-acetic acid-water (4:1:5). Old school paper chromatography! Indole derivatives were identified by spraying the paper with a 2% solution of p-dimethylaminobenzaldehyde in hydrochloric acid and drying the sprayed sheet with a heat gun. A minimum quantity of 1 µg psilocybin could be detected. Ultraviolet spectrophotometry was used to confirm the presence of psilocybin.

The P. cubensis mycelium pellets grown via submerged culture produced psilocybin, but two other Psilocybe species (P. cyanescens Wakefield and P. pelliculosa (Smith) Singer & Smith) did not. Psilocin was not detected.

The researchers determined the optimum growth period and how it related to maximum psilocybin production over 5 to 15 days. Peak psilocybin (~ 0.54%) was obtained on the 7^th day when the pH of the medium was between 4 and 5. The maximum growth of mycelium was achieved after nine days, but mycelium and psilocybin production decreased thereafter as the pH rose from acidic conditions to a slightly basic pH 8.

Media Omissions

Once the optimum conditions were demonstrated, the researchers purposefully left out media constituents like glucose, glycine, thiamine, yeast extract, and ammonium succinate. The omission of glucose, a vital source of carbon, dramatically inhibited growth of mycelium and no psilocybin was produced. Excluding yeast extract initially stunted growth, but interestingly, the researchers report that “the organism adapted to this deficiency and subsequently underwent vigorous growth and comparable psilocybin production.” This produced a peak psilocybin concentration of 0.86%. When glycine was left out, psilocybin production slightly increased to approximately 0.75%.

Media Concentrations

Conversely, the researchers evaluated using different concentrations of media ingredients. When the glucose concentration was raised from 0.25 to 1.0%, an acidic medium pH was sustained, thereby providing a boost in psilocybin production (1.06%) on the 7^th day. This growth didn’t last over time, however, as psilocybin concentration plummeted to 0.16% by day 11.

The addition of tryptophan to the growth medium did not boost psilocybin production. The authors scaled their submerged culture, increasing the volume from 30 to 300 mL without measuring much difference in psilocybin concentration after seven days.

There once was a time where psilocybin mushrooms were studied for their prospective medicinal benefits. Fortunately, many within the scientific community have resurrected their interest. Although humanity was strongarmed into lives without these mushrooms, it was a short separation in what has otherwise been an ancient relationship between the mushrooms and the human beings who ate them.

Original references

1. Hofmann A, Heim R, Brack A, et al. Psilocybin, ein psychotroper Wirkstoff aus dem mexikanischen Rauschpilz Psilocybe mexicana Heim. Experientia. 1958;14:107–109.
2. Catalfomo P, Tyler V. The production of psilocybin in submerged culture by Psilocybe cubensis. Lloydia. 1964;27:53–63.

Where supply stands now: a 2026 update

This section was added by the editors in October 2026; the article above is Dr. Lupoi’s original.

The shortage this article anticipated was real, and the clearest measure of it is the DEA’s aggregate production quota, the annual ceiling on how much psilocybin can legally be made in the United States. The 2021 quota began at 30 grams of psilocybin and 50 grams of psilocyn; in September 2021 the agency proposed raising those to 1,500 and 1,000 grams.^[1] For 2022 it set the quotas at 8,000 and 4,000 grams, above its own proposal, citing applications from registered manufacturers.^[2] Further proposed increases brought psilocybin to 30,000 grams and psilocyn to 36,000 grams by 2025,^[3] and the quotas effective January 2026 stand at 50,000 and 80,000 grams.^[4] From 30 grams to 50 kilograms in five years is not a supply chain easing; it is a different industry.

Where the material comes from, though, is not where this article’s 1964 research pointed. The flagship clinical programs do not brew mycelium in submerged culture: COMPASS Pathways’ COMP360, now through one positive phase 3 trial with two further readouts expected in 2026, is a synthesized crystalline psilocybin — the subject of the polymorph patent fights we cover in our report on psilocybin patents and polymorphs.^[5] Usona Institute’s uAspire phase 3 trial in major depressive disorder runs on a 25 mg psilocybin dose of its own.^[6] The main botanical route is not fermentation either: Filament Health, since April 2026 a subsidiary of Rhelion Life Sciences, supplies PEX010, a GMP-manufactured botanical psilocybin extracted from whole mushrooms, most recently under a September 2026 agreement with the Centre for Human Drug Research in Leiden.^[7]

The second thing 2021 did not predict is production licensed outside the research pipeline entirely. Oregon’s Measure 109 program reported 11 licensed manufacturers, 25 service centers and 377 facilitators in 2025, with 18,877 psilocybin products sold for about $749,000, serving 5,935 clients — grown fruiting mushrooms, sold as whole or homogenized fungi and edibles, never for take-home use.^[8] Colorado’s Proposition 122 regime licensed its first healing center in April 2025.^[9] Derek Chase saw the shape of this coming in our 2022 conversation: purchase tied to administration, “no take home goods.”

Federally, psilocybin remains Schedule I. In late 2025 the DEA asked the Department of Health and Human Services to review psilocybin’s scheduling, following years of Right to Try litigation,^[10] and an April 2026 executive order directs a scheduling review for Schedule I products that complete phase 3 trials and are ultimately approved by the FDA.^[11] As of early October 2026, no announced outcome of that review had been published. The demand side of Dr. Lupoi’s title, meanwhile, has only grown: the depression trials driving that demand are the subject of our full evidence review.

Image Credits: Ps0304.JPG: Zergboy derivative work: Ak ccm, Public domain; Rob Hille, CC BY-SA 3.0; Björn S…, CC BY-SA 2.0

References

1. DEA, Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled Substances (2021). Federal Register, 2 September 2021, document 2021-18935. https://www.federalregister.gov/d/2021-18935
2. DEA, Established Aggregate Production Quotas for Schedule I and II Controlled Substances for 2022. Federal Register, 2 December 2021, 86 FR 68513. https://www.govinfo.gov/content/pkg/FR-2021-12-02/html/2021-26227.htm
3. DEA, Proposed Adjusted Aggregate Production Quotas for 2024 and Proposed Aggregate Production Quotas for 2025. Federal Register, September 2024, documents 2024-21960 and 2024-21962. https://www.federalregister.gov/d/2024-21962
4. DEA, Established Aggregate Production Quotas for Schedule I and II Controlled Substances for 2026. Federal Register, effective 5 January 2026, document 2025-24277. https://www.federalregister.gov/d/2025-24277 ; announced in: DEA Releases 2026 Aggregate Production Quotas, 9 January 2026. https://dea.gov/press-releases/2026/01/09/dea-releases-2026-aggregate-production-quotas
5. COMPASS Pathways, third-quarter 2025 report (COMP005 primary endpoint met June 2025; COMP006 fully enrolled; 26-week readouts expected 2026). SEC Form 8-K press release, 4 November 2025. https://www.sec.gov/Archives/edgar/data/1816590/000181659025000149/q32025pressrelease.htm
6. Usona Institute announces launch of uAspire phase 3 clinical trial investigating psilocybin for major depressive disorder. BioSpace, 20 March 2024 (ClinicalTrials.gov NCT06308653). https://www.biospace.com/usona-institute-announces-launch-of-uaspire-phase-3-clinical-trial-investigating-psilocybin-for-major-depressive-disorder
7. Rhelion Life Sciences. Filament Health signs supply and licensing agreement with the Centre for Human Drug Research for PEX010. Newsfile, 17 September 2026. https://www.newsfilecorp.com/release/314769
8. Oregon Health Authority, Psilocybin Services: 2025 Year-End Data Summary. https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Documents/2025-Year-End-Data-Summary.pdf
9. State licenses Denver psychedelic therapy center, first in Colorado. BizWest, 1 April 2025. https://bizwest.com/2025/04/01/state-licenses-denver-psychedelic-therapy-center-first-in-colorado
10. Reason Foundation, Psychedelics Policy Newsletter: DEA considers rescheduling psilocybin. 6 October 2025. https://reason.org/psychedelics-policy/psychedelics-policy-newsletter-dea-considers-rescheduling-psilocybin-fda-releases-rejection-decision-and-more
11. Executive Order 14401, Accelerating Medical Treatments for Serious Mental Illness, 18 April 2026. https://www.whitehouse.gov/presidential-actions/2026/04/accelerating-medical-treatments-for-serious-mental-illness/

Last updated October 2026 · Originally published May 3, 2021.