The History of Psychedelics

February 16, 2023

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From giving ancient civilisations the ability to communicate with God, to being criminalised for decades, to being at the centre-stage of a wave of new research, psychedelics have been through quite a trip of their own (excuse the pun). So, what’s their story?

Ancient Civilisations and Psychedelics

Psychedelics have been stealing the spotlight in recent years, and they’ve been waiting thousands of years to do so. Although its taken modern civilisation some time to see the benefits of psychedelics, drawings of psilocybin mushrooms (more commonly known as magic mushrooms) have been found on cave paintings from as early as 4000-6000 BC, and psychedelics were also thought to have been used in ancient rituals and religious ceremonies as a way of communicating with gods. 

Bicycle Day

You’re probably thinking – what the heck do bicycles have to do with psychedelics? Alternatively, if you’re thinking ‘damn, I wish it was bicycle day’ you probably have a very eventful April 19th every year.

Well, the story of bicycle day all started with a compound called ergot, a fungus which grows on rye. In 1918, a scientist named Arthur Stoll isolated the chemical ergotamine from ergot, and found that this drug could be used in the treatment of migraine. 

Skip forward twenty years to 1938, and the father of psychedelics, Dr Albert Hofmann, was busy in the labs of the Swiss company Sandoz (which you probably now know as Novartis). He started out by mixing ergot with, to put it in our best jargon, a bunch of other chemicals to try and create a synthetic but therapeutically superior drug. This road led him to accidentally synthesising the first form of LSD, which he thought might be an alternative to a cardiorespiratory stimulating drug known as nikethamide.

Unfortunately, instead of achieving the desired effect of cardiorespiratory stimulation, all it did was make experimental animals restless, and so the research was discontinued. However, Hofmann couldn’t quite forget his accidental discovery and so LSD stayed on his mind for another 5 years until 1943, where he decided to reproduce LSD with the intention of using it for further testing. That’s the moment at which he became the first person to accidentally absorbed LSD through his skin.

 He described the experience in the following way:

In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.

Doesn’t sound half bad huh.

It didn’t feel so bad to Hofmann either, so a few days later he decided to take a larger, experimental dose of 250 micrograms of LSD at 16:20 on the 19th April 1943. His diary reads as follows: 

4/19/43 16:20: 0.5 cc of 1/2 promil aqueous solution of diethylamide tartrate orally = 0.25 mg tartrate. Taken diluted with about 10 cc water. Tasteless.
17:00: Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.
Supplement of 4/21: Home by bicycle. From 18:00- ca.20:00 most severe crisis. (See special report.)

He explained the experiment he’d carried out to his lab assistant and therefore asked them for some help getting home. During the time of World War II, there were restrictions regarding cars so the only way to get home was with, you guessed it – a bicycle.

On the way home, my condition began to assume threatening forms. Everything in my field of vision wavered and was distorted as if seen in a fun-house mirror. I also had the sensation of being unable to move from the spot. Nevertheless, my assistant later told me that we had travelled very rapidly. 

 

Delysid

LSD hit the markets in the early 1950s as Delysid, and was primarily used by psychiatrists. Initial results were promising, and over 40,000 patients were treated with LSD. Dr Ronald Sandison of Powick Hospital in the UK used it to deliver psychotherapy, whilst Dr Humphry Osmond used LSD to treat alcoholics. The real problem began when LSD caught the interest of people outside of the healthcare sphere.

As use of psychedelics started to extend to recreational uses in the 1960s, and reports of their potential harms started to grow, concerns regarding psychedelics as drugs of abuse began to materialise.

Stop Tripping

Scare-stories surrounding the recreational use of psychedelics grew, and with that, political concern, culminating in LSD being outlawed in 1968. Shortly thereafter, the Controlled Substances Act of 1970 was established, which classed psychedelics as Schedule I controlled substances meaning they have “high potential for abuse, no accepted medical use in treatment, and there is a lack of accepted safety for use of the drug under medical supervision”. Clinicians as a consequence were forced to abandon research surrounding the area of psychedelics, resulting in a gap in knowledge for many years.

The Psychedelic Renaissance

In recent years, the attitude towards psychedelics has undergone a major cultural and scientific shift. Not only is the use of psychedelics becoming increasingly socially acceptable, the boom of research output in the industry has served as evidence that psychedelics shouldn’t necessarily be advertised as things to be frightened of, but rather, the promising beneficial therapeutics they truly are. 

If you haven’t noticed the psychedelic renaissance, you’ll certainly have noticed the shift in attitude towards mental health. This previously neglected area of healthcare is finally receiving the importance it deserves, particularly considering the whopping statistic that 1 in 4 people suffer from a mental health condition. Yet our frontline treatment for the most common mental health conditions like Anxiety and Depression remains SSRIs, a class of compounds discovered in the 1980s and with a dubious track record in clinical use. Mental health treatment is in need of a breakthrough. 

Our current psychedelic renaissance began in 2016. In quick succession the results of several feasibility clinical trials were published in 2016 by groups at NYU, Imperial College London, and John Hopkins. The results showed Psilocybin had promising effects on treatment resistant depression and anxiety, kicking off a wave of further studies and research which has broadly confirmed the therapeutic promise of psychedelics, including:  

  • The Multidisciplinary Association for Psychedelic Studies (MAPS) conducted a phase 3 study investigating the efficacy of MDMA-assisted therapy on PTSD. The results showed sustained improvement over a placebo and therapy, a huge step forward for a condition that has historically been difficult to treat
  • Compass Pathways recently published results of a phase IIb study which showed people who took a 25mg of Psilocybin were significantly more likely to show sustained improvements in treatment resistant depression vs those who took a 1mg dose (well below Psilocybin’s threshold dose). 

That’s not to say psychedelics aren’t a complex therapeutic area. They, like most therapies, are not harm free and these certainly need to be taken into account when considering them as possible medical treatments. However, given the decades-long hiatus in research combined with the potential for good, psychedelic research is more important now than ever before.

With psychedelic start-ups raising $236 million between July 2021 and 2022, we’re clearly not the only ones who think so. We’ve listed some of the companies disrupting the psychedelic space here:

  1. Allied Corp: A clinical stage company using psychedelics to treat PTSD. https://allied.health/
  2. Botanix: Botanix are using cannabidiol in an interesting and unique way; for the treatment of dermatological conditions such as acne and dermatitis. https://botanixpharma.com
  3. Levitee Labs: Using psychedelics in the treatment of mental health conditions, pain management, and addiction. https://leviteelabs.com/about
  4. Lobe: By using psychedelics in combination with NAC (a treatment traditionally used in paracetamol overdose), Lobe are targeting treatment of neurological disorders including traumatic brain injury.  https://www.lobesciences.com/
  5. Beckley Psytech: Using psychedelics for managing neuropsychiatric disorders such as alcohol addiction and depression. https://www.beckleypsytech.com/
  6. COMPASS Pathways: COMPASS are bringing the work of Dr Ronald Sandison to the 21st century. With their own personal experiences of navigating depression within their own families, COMPASS are pioneering psilocybin-based psychotherapy. https://compasspathways.com/
  7. Eleusis: A cutting-edge biotech company transforming psychedelics into evidence-based drug therapies. https://www.eleusisltd.com/approach/
  8. Viridia Life Sciences: Recognising the power of combined psychedelic treatment with psychotherapy, Viridia Life Sciences are, in their own words, bridging “the gap between what the mental healthcare system can provide and what people really need.” https://www.viridia.life/
  9. Delix: Delix are employing truly groundbreaking methodology to bring their ‘psychoplastogen’ drugs to market. https://delix.netlify.app/
  10. Gilgamesh: AI-powered, revolutionary, psychedelic drug development. https://www.gilgameshpharmaceutical.com/
  11. GH Research: Focused on 5a naturally-occurring psychoactive substance from the tryptamine class. https://www.ghres.com/
  12. MindMed: Developing psychedelic inspired medicines that seek to treat underlying causes of distress in the brain https://mindmed.co/
  13. Cybin: Lead investigational molecule, CYB003, is derived from psilocybin https://cybin.com/
  14. Delix: Discovering a novel class of neuroplasticity-promoting therapeutics known as psychoplastogens https://www.delixtherapeutics.com/

Our mission at Lindus Health is to accelerate clinical trials, so patients can benefit from new treatments sooner. We are a next-generation CRO helping biotech pioneers run radically faster, more reliable clinical trials. We do this by marrying a world class clinical team with an end to end technology platform, including EDC, database, site and feasibility products. We also have unique access to over 5m electronic health records. We can recruit participants and execute a trial efficiently, from capturing trial endpoints, managing screening and patient visits.

Our products have been used to recruit, onboard and handle data from thousands of patients and Lindus Health has helped run over 70 studies up to 3x faster than traditional CROs. Get in touch to see how we could help solve your next clinical trial!

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