Sometimes, when we discuss cleanroom technologies and contamination controlled environments, it’s a challenge not to fall headlong down the research rabbit hole of quirks, intriguing snippets, and absorbing information. And today’s topic is no different. As usual we’ll be chasing our intellectual curiosity in addressing some controversial questions regarding cleanroom-based research, but we’ll also be aware of the role of HACCP, cGMPs, and other safety protocols in addressing safety concerns. Why? Because the subject of interest today often falls victim to both media sensationalism and regulatory vilification and, for those exploring its clinical, medical, and bio-pharmacological potential, the line between romanticizing intoxication and pursuing hard science can be a narrowly-defined one indeed. What are we talking about here? Psychedelia…
So let’s begin today with a riddle: what is the connection between rabbit holes (figurative, literary, or literal) and psychotropics?
It’s an easy one: Lewis Carroll. Or more specifically, Carroll’s most beloved and genre-defining fantasy novel Alice in Wonderland. Published in 1865, the tale follows the eponymous heroine down a rabbit hole into a subterranean reality ruled by magic, confusion, and contrariness. Along the way Alice meets the Caterpillar, atop a very special mushroom, smoking a hookah pipe. As her first, albeit reluctant, guide to her altered state, the Caterpillar is widely interpreted as a drug culture reference, a nod specifically to entheogens – psychoactive substances that induce changes in consciousness, cognition, perception, or mood.(1) When she consumes some of the toadstool, Alice experiences powerful sensations of change that she interprets in corporal terms – heady growth spurts and rapid shrinking – but the magic of that particular mushroom was not, in fact, its potential for growth changes but in its psychoactive properties. In short, it gave the ingénue the trippiest of hallucinations.
Perhaps surprisingly, however, the Caterpillar’s fungus is not what is popularly referred to as a ‘magic mushroom.’ Unlike real world psychoactive ‘shrooms which tend to have dark-gilled caps atop slender stems, the fictional specimen is portrayed as an attractive bright cherry red cap dotted with salt crystal-like flecks sitting perched above a snow white stalk. In every way it appears to be the quintessence of a perfect fungus – fleshy, meaty, with a vibrancy that shouts ‘Eat Me.’ Mycologist fans of Carroll’s classic contend this depiction may be inspired by the fly agaric, a toadstool often found in close proximity to pines and birch trees. In a symbiotic relationship, the fly agaric assists in water and mineral absorption while receiving carbohydrate energy in return. The toadstool does not, however, extend such benign reciprocity to the animal kingdom: containing two psychoactive compounds – ibotenic acid and muscimol – its ingestion causes intoxication by mimicking neurotransmitter actions and is neurotoxic in high doses. The bottom line? Despite their aesthetic appeal, literary lure, and psychedelic potential, fly agaric toadstools can be fatal (albeit at a dose estimated at around 15 caps) and are therefore contraindicated, at least outside of Wonderland.
So what of the contemporary phenomenon of psychotropic – ‘magic’ – mushrooms? Why are we interested in them, what effect do they have, and how do we ensure that they are safe to consume? Before we jump down those particular rabbit holes, however, we must take a moment to issue a general disclaimer:
Outside of a notable handful of cities in the US, the use of psychoactive mushrooms is currently prohibited by the US Drug Enforcement Agency (DEA). According to the Drug Policy Alliance, both ‘[p]silocybin and psilocin are listed in Schedule I of the Controlled Substances Act, making it illegal to cultivate or possess psilocybin producing mushrooms for either personal consumption or distribution.’(2) With that in mind, our topic today is intended as food for thought, offering information only, and in no way validates, endorses, or promotes the use of prohibited drugs.
As is the case with some other biopharmaceuticals we’ve discussed in previous articles, ‘magic mushrooms’ have a very well established role in human culture. In a helpful factsheet, the Drug Policy Alliance notes that ‘[p]sychoactive mushrooms have been used for thousands of years and have a long history of both medicinal and ceremonial use among indigenous peoples in many parts of the world, including Europe and the Americas.’(3) Traditionally employed for purposes of divination, healing, and spiritual euphoria, the mushrooms are a type of entheogen – also known as an hallucinogen, a psychedelic, or a psychotomimetic. Examples of similar substances would include the alkaloid mescaline (derived from the peyote cactus native to Mexico) and ayahuasca, a tea which is brewed from the leaves of Psychotria viridis shrub and stalks of the Banisteriopsis caapi vine, among others.
Given their historically venerated cultural role it is no surprise that ethnomycology (a subset of ethnobiology and ethnobotany) has developed to research the uses for and impacts of fungi, most commonly focusing on psychoactive specimens. Moreover, despite being a relatively new scientific field, ethnomycology is scarcely the sole preserve of cultural anthropologists. Re-popularized in the 1950s by the work of Swiss chemist Albert Hofmann, mushrooms became prominent tools in research aiming to use psychedelics to treat medical and psychiatric conditions, from depression and schizophrenia to substance abuse disorders and behavioral addictions. Now famous research such as Timothy Leary’s apocryphal ‘Marsh Chapel Experiment’ and that of Johns Hopkins’ psychopharmacologist Roland R. Griffiths explored the therapeutic value of psilocybin and its metabolite, psilocin, in inducing mystical experiences in test subjects. As a clinical psychologist at Harvard University, Leary was both fêted as a ‘brave neuronaut’ by Tim Robbins and vilified as ‘the most dangerous man in America’ by Richard Nixon. In 1963, he was relieved of his academic position amidst concerns for his experiments’ safety and legitimacy, ultimately leading him to embrace sixties counterculture and eventual drug-related incarceration. Thereafter, under the successive Johnson and Nixon administrations, America’s developing ‘Drug War’ saw the founding of the Department of Justice’s Bureau of Narcotics and Dangerous Drugs (BNDD), the passing of the Comprehensive Drug Abuse Prevention and Control Act (which included the Controlled Substances Act), and Nixon’s characterization of drug abuse as ‘public enemy number one in the United States.’(4) It was not until the early 2000s that clinical work focusing on psychedelics was able to resume and as recently as 2018 that the federal Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to psilocybin-assisted therapy for treatment-resistant depression, with its use in treating major depressive disorder approved one year later.
A different regulatory body, the Drug Enforcement Agency (DEA), however, does not take the FDA’s relaxed approach. In its primer on psilocybin, the agency swerves from the potentially therapeutic value of the drug, dwelling instead on the drug’s possible side-effects such as ‘an inability to discern fantasy from reality [and that panic] reactions and a psychotic-like episode also may occur.’(5) Moreover, far from the transcendental experience suggested from traditional ceremonial use, the agency lists the drug’s physical consequences as nausea, vomiting, lack of coordination, muscle weakness, psychosis, and possible death. Moreover, it also raises the question of poisoning – mushroom species are notoriously difficult to identify, with some highly toxic varieties closely resembling their benign counterparts: ‘Abuse of psilocybin mushrooms’ says the DEA, ‘could also lead to poisoning if one of the many varieties of poisonous mushrooms is incorrectly identified as a psilocybin mushroom.’(6)
But in the event that you partake of the correct mushroom – after all, according to Popular Science there are more than 100 varieties – and do not succumb to the maladies suggested by the DEA, there’s always the question of product contamination.
As an entity, all parts of the fungus are vulnerable to pathogens – from the mycelium (the fungus’ equivalent of a root system) to the fruiting bodies themselves (the individual mushrooms) and even the spores, with contamination threats coming from pests such as mites or gnats, as well as bacteria or fungal sources. On occasion, crops may be spoiled by the pathogens working in concert: after a gnat feeds on the mycelium, for instance, it will create a channel into the mushroom, damaging tissues which then become a veritable breeding ground for the bacteria that lead to soft rot. Moreover, according to data from Zamnesia, a European company ‘with a burning passion for all things mind-altering,’ threats to product purity can come from a very wide variety of directions. With the help of some (admittedly stomach-churning) graphics, Zamnesia notes that the multitude of potential spoilants include endospore-causing sour rot, bacterial blotch, aspergillus (or ‘black mold’), cobweb mold, neurospora (also known as ‘red bread mold’), a variety of air-borne blue-green molds, and dry bubble infection. Almost without exception, the cause of contamination is inadequate hygiene/sanitation, inappropriate humidity, poor air circulation, and physical vectors such as flies. In most cases, there is little remediation and cultures should be destroyed before the growing area is thoroughly decontaminated.(7)
Zamnesia’s ‘Shroomshop’ retails equipment for home consumers to create ‘semi-sterile conditions and equipment such as grow boxes, scalpels, and petri dishes’ as well as offering direct use products for those ‘looking to improve their cognitive function or voyage into alternate realities.’(8) So how do these psychedelics actually work? What, for example, distinguishes a magic mushroom from a regular shitake? It’s time to talk about serotonin receptors…
Following ingestion, psilocybin is metabolized in the intestine to form psilocin before binding to serotonin 2A receptors (5-HT2A). According to Ishier Raote et al writing in ‘Serotonin Receptors in Neurobiology’ (2007), these receptors have been ‘implicated in mental disorders with complex etiologies […], in processes such as learning and memory, and also in neurogenesis. […] Though the receptor has been studied largely in relation to its multiple functions in the CNS [central nervous system], high levels of receptor expression in other areas such as the intestine, platelets and endothelial cells suggest that it could play crucial roles in other aspects of physiology.’(9) Once linked to receptors in the brain, psilocin triggers ‘neuronal avalanching’ – a phenomenon described by Business Insider as ‘a domino effect of different changes […including] increased activity in the visual cortex, which leads to changes in […] perception, and then decreased network activity in the default mode network, which leads to a loss of ego.’(10) Furthermore, the drug facilitates communication between parts of the brain that are usually compartmentalized – different regions with little interaction now working in concert thanks to psychotropic influence.
And, arguably, this is where the drug’s greatest use may reside. In treating depression or addiction, many contemporary therapeutic modalities address the disorders’ manifest symptoms – with anti-depressants lifting the crushing shroud of depression or drugs like naltrexone blocking opioid effects, they cannot, however, reach the source of the malaise which, arguably, may have an existential cause outside of medical remit. We’ve already mentioned the potential of psychedelics in relieving, for instance, treatment-resistant depression and some studies indicate that they may also be of value in palliative care. Indeed as documented in a brief by Lexology, Canada recently announced the granting of a legal exception to that country’s ‘Controlled Drugs and Substances Act’ (CDSA) in the cases of four terminally ill cancer patients. According to Lexology, ‘[t]he successful exemption application was based on compassionate grounds for palliative care under section 56(1) of the CDSA [which] allows the Health Minister to exempt persons or controlled substances, if “the exemption is necessary for a medical or scientific purpose or is otherwise in the public interest” (Health Canada). Among other things, psilocybin is being studied for alleviating end-of-life distress in palliative patients.’(11) In conjunction with the four prospective beneficiaries, the initiative was supported by TheraPsil, a ‘non-profit coalition that advocates for legal and compassionate access to psilocybin therapy for palliative Canadians.’(12) The aforementioned erstwhile compatriot of Timothy Leary, Roland Griffiths, now director of the U.S. Center for Psychedelic and Consciousness at Johns Hopkins University, notes that ‘psilocybin produces conditions under which people report having a sense of increased efficacy, a change of world view, a sense of change of self, and that they’re able to re-engage in the world in very positive ways.’(13)
And with the renewed interest in leveraging the potentially therapeutic properties of psilocybin especially in the realm of compassionate care, it is unsurprising that supply is starting to address demand. Numinus Bioscience, a psychedelics manufacturer based in Vancouver, has reportedly become ‘the first in Canada to complete a legal harvest of magic mushrooms since the last wave of psychedelic research ended there in the 1970s.’(14) According to Forbes, the company was issued a license from Health Canada ‘to test, import, store, and distribute MDMA, psilocybin, psilocin […] DMT and mescaline. In May, the company went public on the TSX Venture Exchange, making it one of the first psychedelic firms to do so in North America.’ (15) Interestingly, the process of license acquisition may have been smoothed by the fact that the company has, for several years, operated a cannabis testing facility at a laboratory in British Columbia. With a 7000 square-foot, state-of-the-art facility, Numinus has reputedly one of the largest labs in Canada, testing cannabis products for contaminants such as pesticide or solvent residues, heavy metals, microbial pathogens, aflatoxins, and moisture control. Moving forward, the company anticipates leveraging the same adherence to validated methods and processes to move into the psychedelics testing sphere: ‘As psychedelic substances move to the mainstream and as health professionals look to apply these substances in safe, controlled, therapeutic environments, Numinus Bioscience will play an important role in the areas of psychedelic substance research, testing, and global distribution. Currently we can test and possess MDMA, psilocybin, psilocin, DMT and mescaline. We are also licensed to produce and extract psilocybin from mushrooms. We are amending our licence [sic] to soon include activities such as R&D, import/export, and packaging/labelling to become the leading psychedelics drugs marketing and distribution company.’(16)
So it certainly looks like the landscape is shifting when it comes to exploring the clinical potential of psychoactives and psychedelics. Although the approach here in the United States is markedly different from that of Canada, it may be that the acceptance of psilocybin-containing organics such as mushrooms will follow the same trail already blazed by cannabis as medical marijuana. Despite the DEA’s stance, the fact remains that the ‘risks from psilocybin are dependent on set and setting and differ from other types of drugs, including alcohol, benzodiazepines, and opiates, which produce relatively predictable physical and psychological effects.’(17) And a report by the Global Drug Survey revealed that mushrooms are the least likely illicit substance to result in a trip to the emergency room and, in comparison to LSD, amphetamines, cannabis, and alcohol, mushrooms come top of the list in terms of relative harmlessness.(18) Of course, any substance that acts on the brain to effect awareness and alter consciousness cannot be assumed to be completely harmless, but a case exists nonetheless for seeing the adoption of ‘shrooms as an option for harm reduction, a tool in palliative care, and a (relatively) safer route to personal consciousness expansion. Just a thought…
For or against – do you have strong thoughts on the use of psychedelics in the biomedical space? Do you see them differently than any other psychotropic, including marijuana? Will the Canadian research be replicated in our nation’s cleanrooms? We’d love to learn tour position on this topic!
References:
- Some have falsely assumed that the Caterpillar is a literary device to represent the use of lysergic acid diethylamide, or LSD. The publication of Alice in Wonderland, however predates the development of LSD by more than 70 years.
- https://drugpolicy.org/drug-facts/are-psilocybin-mushrooms-illegal
- https://drugpolicy.org/sites/default/files/Psilocybin_Mushrooms_Fact_Sheet.pdf
- https://www.pbs.org/wgbh/pages/frontline/shows/drugs/cron/
- https://www.dea.gov/sites/default/files/2020-06/Psilocybin-2020.pdf
- ibid
- https://www.zamnesia.com/content/546-how-to-identify-a-contaminated-mushroom-culture
- https://www.zamnesia.com/content/17-about-us
- https://www.ncbi.nlm.nih.gov/books/NBK1853/
- https://www.businessinsider.com/magic-mushrooms-psilocybin-psychoactive-drug-brain-denver-legal-2019-5
- https://www.lexology.com/library/detail.aspx?g=e579e512-260f-49a0-875f-5d79dcfafa65
- ibid
- ibid
- https://www.forbes.com/sites/amandasiebert/2020/10/23/numinus-becomes-the-first-canadian-psychedelics-company-to-legally-harvest-magic-mushrooms/
- ibid
- https://numinusbioscience.ca/
- https://drugpolicy.org/sites/default/files/Psilocybin_Mushrooms_Fact_Sheet.pdf
- https://www.popsci.com/magic-mushrooms-safe/
