UK: The Magic Of 'Magic Mushrooms'

Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics: hallucinogenic drugs that induce mind-altering and reality-distorting effects (the word ‘psychedelic' is of Greek origin, derived from psyche meaning ‘mind' and delos meaning ‘to show'). Hallucinogenic mushrooms of (predominantly) the Psilocybe genus are commonly known as ‘magic mushrooms'.

Magic mushrooms, though largely associated with the ‘hippie' movement of the 1970s, have ancient origins. Magic mushrooms have long been used in religious and healing rituals in indigenous Mexican and South American cultures and, in fact, are often referred to as teonanacatl (meaning ‘God's flesh') by some of these communities.

While the Mixtecs, Mazatecs, Zapotecs, and others, respect and often revere these mushrooms, the Western world has had a more turbulent relationship with ‘'shrooms'. Spanish missionaries in the 1500s, for instance, believed that the mushrooms allowed the Aztecs to communicate with demons and attempted to destroy all records and evidence of the use of these mushrooms.

In 1799, hallucinogenic mushrooms made a very brief appearance in European medicinal literature in the London Medical and Physical Journal. In the journal, an apothecary recalled being called to treat a child “attacked with fits of immoderate laughter” which neither “the threats of his father or mother” could refrain after having been served a rather exotic breakfast of Psilocybe semilanceata mushrooms, hand-picked from London's Green Park! Western interest in magic mushrooms remained diminutive until the late 1950s, when ethnomycologists Valentina Pavlovna Wasson and Robert Gordon Wasson travelled to Huautla in Mexico and slowly integrated themselves into a remote village of the Mazatec Indians of Oaxaca, eventually becoming the first ‘outsiders' to participate in the midnight rites of the cult of the sacred mushroom. The Wassons documented their experience in Life (one of America's most-read magazines at the time), and concurrent popularisation of magic mushrooms by other influential figures led to an explosion in use in the ‘hippie' counterculture.

Magic mushrooms are currently listed as Schedule 1 drugs under the United Nations 1971 Convention on Psychotropic Substances, supposedly having “a high potential for abuse” and “no recognised medical use”. However, new research seems to be uncovering huge therapeutic potential for these 'shrooms, with particular interest in the field of mental health and substance-use disorders, and as more and more evidence emerges, the legal status of these drugs is being called into question.

But what actually makes magic mushrooms magic? Well, magic mushrooms contain an indole-based secondary metabolite called psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). Inside the body, psilocybin is rapidly dephosphorylated to psilocin, which acts as an agonist at several 5-hydroxytryptamine (serotonin) receptors. Psilocin has a particularly high affinity for 5-HT_2A receptors (5-HT_2ARs): these receptors are widely distributed in the central nervous system, but have an especially high density in the limbic forebrain, where they play a role in perception and emotional-processing. Abnormal 5-HT_2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia and drug addiction. Activation of 5-HT_2ARs by psilocin initially produces ‘mystical-like' hallucinogenic effects but, over time, continued psilocin-induced 5-HT_2AR activation is thought to lead to a decrease in 5-HT_2AR responsiveness, ameliorating the hyperactivity in the pre-frontal cortex implicated in many of these conditions. Psilocin has also been reported to result in significant changes in functional connectivity between different areas of the brain, potentially making the brain more flexible and less entrenched in the negative thinking patterns associated with depression (Daws et al.  (2022), ‘Increased global integration in the brain after psilocybin therapy for depression', Nat Med, 28, pp. 844-851).

While psilocybin's exact mode of action remains unclear, evidence of positive clinical outcomes is mounting. Psilocybin has proven a powerful therapeutic for treatment-resistant depression. There have also been studies showing efficacy in alcohol and tobacco dependency and, more tentatively, anorexia, obsessive-compulsive disorder (OCD) and opioid addiction.

From an IP perspective, patenting drugs derived from magic mushrooms, or other natural sources of psychoactive compounds, requires careful drafting. Patentable inventions are necessarily novel, yet these compounds, by virtue of their natural origin, will already have existed in at least some form. So, whilst it might be possible in some jurisdictions to claim the natural product itself (for example by specifying appropriate purity levels or similar parameters to distinguish the claimed composition from the naturally occurring substance), in practice a more common focus is on new uses of the product and/or novel compositions comprising the product.

Psilocybin-based therapies clearly hold huge promise in the field of psychiatry, and interest in these drugs is rapidly growing. However, public perception and legal barriers to clinical use may take a little while longer to overcome.

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