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March-May 2023

LSD – ageing of a ‘problem child’

On 19 April this year, Bicycle Day (not to be confused with UN World Bicycle Day on 3 June) marks 80 years since an unusual bicycle ride made by Swiss chemist Albert Hofmann after his first intentional dose of lysergic acid diethylamide (LSD).

Five years before that ride, while continuing work begun by biochemist Arthur Stoll (a senior colleague at Sandoz Laboratories) on isolating ergot alkaloids, Hofmann accidentally absorbed a lysergic acid derivative through his skin. What followed, wrote Hofmann in LSD: my problem child (bit.ly/3XFAeCJ) were a couple of hours of ‘fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors’.

Ergot is the common name for fungi of the genus Claviceps, which attack cereal crops such as rye. The medicinal properties of ergot extracts have been exploited for centuries, and Hofmann was investigating the pharmaceutical potential of ergot alkaloids using one of their key constituents, lysergic acid, as a starting point.

Archives of Hofmann’s research are now housed at the Institute for the History of Medicine in Bern, and the project ‘From Ergo to LSD’ (2015–2019), funded by the Swiss National Science Foundation, aimed to address some important gaps in the drug’s story.

Bern University associate researcher Beat Bächi, author of LSD in the country: production and collective action of psychotropic substances (Konstanz University Press, 2020), described the background to the project (bit.ly/40Az8u5):

What is completely lacking so far [in the story of LSD] is a history of the production of the starting material for LSD production, namely ergot. The selection, breeding and cultivation of appropriate types of grain as well as the vaccination, production and harvesting of the ergot show the complexity of producing a psychotropic substance in the field, so to speak. Only numerous negotiation processes between industrial research, science and agriculture made LSD and other products based on ergot possible.

Producing LSD from ergot was just one of many complexities in this story. In the 1960s, widespread misuse of LSD and other psychedelics prompted strong government interventions, and the early 1970s saw previously burgeoning psychedelics research virtually cease.

In a recent article in Psychological Medicine, Wayne Hall, Emeritus Professor at the National Centre for Youth Substance Use Research and Queensland Alliance for Environmental Health Sciences, reported that ‘The demise of psychedelic drug research was not solely due to the “War on Drugs”. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry’s lack of interest in funding clinical trials’ (bit.ly/3wwAgkw).

Although Hofmann’s unintentional LSD dose in the lab produced pleasant effects, his intoxicated bicycle ride in April 1943 was the beginning of a bad trip in every sense – Hofmann’s experience, described in his book, featured ‘wicked creatures’ and he felt ‘demonically possessed’. After Hofmann’s arrival at home, a kindly neighbour appeared as a ‘malevolent, insidious witch with a colored mask’.

In his foreword to LSD: my problem child, Hofmann remarked on both the potential help and harm of this psychedelic:

I share the belief of many of my contemporaries that the spiritual crisis pervading all spheres of Western industrial society can be remedied only by a change in our world view. We shall have to shift from the materialistic, dualistic belief that people and their environment are separate, toward a new consciousness of an all-encompassing reality …

… LSD finds such an application in medicine, by helping patients in psychoanalysis and psychotherapy to perceive their problems in their true significance.

Deliberate provocation of mystical experience, particularly by LSD and related hallucinogens, in contrast to spontaneous visionary experiences, entails dangers that must not be underestimated.

In the year before Hofmann’s death in 2008 at the age of 102, Swiss physician for psychiatry and psychotherapy Peter Gasser commenced psychotherapeutic experiments on patients with life-limiting diseases such as cancer, with the approval of Swiss medical authorities and a positive reception by Hofmann. After more than three decades, studies into the therapeutic uses of LSD were again underway.

In Australia, current clinical trials are investigating the use of a range of psychedelic substances as part of treatment for depression, opioid addiction and late-stage cancer, among others. On 3 February, the Therapeutic Goods Administration announced that ‘from 1 July this year, medicines containing the psychedelic substances psilocybin and MDMA (3,4-methylenedioxy-methamphetamine) can be prescribed by specifically authorised psychiatrists for the treatment of certain mental health conditions’ (bit.ly/3Rw4wWr). This follows applications and public submissions calling for these to be rescheduled in the context of medical use (from prohibited substances to controlled drugs) in the Poisons Standard.


Sally Woollett (editor@raci.org.au)

NEUROtiker, Public domain, via Wikimedia Commons

Lysergic acid diethylamide (LSD-25), Hofmann’s 25th lysergic acid derivative.

Benrr101, Public domain, via Wikimedia Commons

Ergotamine, an alkaloid first extracted by Arthur Stoll.

Although Hofmann’s unintentional LSD dose in the lab produced pleasant effects, his intoxicated bicycle ride in April 1943 was the beginning of a bad trip in every sense ...

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