Substances and mechanisms with Dr Charles Nichols

My unofficial Vital Study Zine #16 with observations from Vital Psychedelic Training and recent happenings in the space

Pamela Simard, ‘BDL’

Dr Charles Nichols – son of canonical chemist Dr David Nichols – puts forward a single very good reason for extracting the profound components from psychedelics.

“These drugs are taking so long to develop because the FDA wants much more rigorous testing,” he informs us from the front line of medical authorisation.

One particular medicine on his to-do list Charles found by isolating the properties of mescaline, synthesised from the peyote cactus.

Turns out psychedelics interact with cells in the soft muscle tissue around the heart, as well as the brain. He’s already registered a patent.

While LSD for example “isn’t a very strong anti-inflammatory” Charles says, mescaline has an “extremely potent” effect on inflammatory-based issues like, for example, breathing condition asthma.

The discovery could have major implications for psychedelic healing of previously unconsidered issues. Not just physical struggles like asthma but also schizophrenia, Parkinson’s and Alzheimer’s which are all connected with inflammation.

“So much has to do with inflammation and the over-active immune system right now,” says Charles, pharmacology professor at LSU Health Sciences in New Orleans with a background at Purdue and Vanderbilt universities.

Charles on the job. Embroidered lab coats FTW

‘Inflammation’ is shorthand here for ‘chronic inflammation’. Oxidants produced in the aftermath of a stress hormone spike for example, linger around and screw stuff up over time.

“I never intended to follow my father into psychedelics actually”

It’s a cause of cancer, psoriasis, arthritis, asthma, allergies, Chron’s Disease, hepatitis, neurodegenerative diseases like Parkinson’s, and more. In younger folks chronic inflammation is mostly caused by stress, bad diets and poor sleep.

The chemical aspect in question has nothing to do with the ‘psychedelic’ properties of mescaline. It has the same anti-asthmatic effect on its own sans tripping when tested on Charles’ elite lab rats bred for psychometric testing.

The intrepid rodents tested it out against 25 other designer psychedelics from the drug cupboard Charles inherited from his father David: the pharmacologist who synthesised DMT for Rick Strassman, MDMA for MAPS and psilocybin for PsiloDep 2.

“I never intended to follow my father into psychedelics actually,” says Charles coyly when I ask in the Q&A if he’d ever noticed the hand of fate guiding his work – like it did when Albert Hoffman felt compelled to re-examine the LSD that’d sat on his shelf un-investigated for seven years.

Charles tried to evade his cosmic destiny in vain. Two separate freaky coincidences nudged him towards a career in consciousness expansion.

The eventual pharmacologist initially studied genetics. Even now Charles’ ‘animal models’, creatures bred for testing purposes, are much envied in scientific circles.

Exhausted by the minutiae of fruit fly genetics after finishing a Phd, the younger Charles was restless for change. Twirling absent-mindedly on his lab stool wondering how to enter the world of employment, Charles spied a promo ad for a new book from Vanderbilt University scientist Elaine Sanders-Bush, who he’d heard his father mention.

He called up and asked about assistant roles.

“It turned out the job involved studying the effects of LSD on mouse and rat brains,” says Charles, “it was one of only a handful of labs doing so at the time. They’d run out of budget for now and couldn’t hire anyone. But a few months later Elaine called and asked if I was interested.”

Charles met Sanders and showed her his resumé featuring his education at Perdue University. “Elaine said she knew a Dr David Nichols there, at which point I had to tell her,” confesses Charles.

“Eventually we might isolate the qualities of peak experience, ego dissolution and breaking stuck thinking”

The next turning point came as Charles was working at New Orleans University in the chaotic aftermath of Hurricane Katrina. Struggling to find researchers he took a chance on a visiting Chinese scientist who needed facilities. By 2013 Charles and collaborator Bangning Yu had isolated the effects of mescaline-derived DOI on inhibiting tumour necrosis factor (TNF)-a mediated inflammation, which is associated with asthma, Parkinson’s Disease and many more conditions not previously part of psychedelic research.

‘Our data suggests,’ reads the modest blurb, ‘that sub-behavioural levels of certain psychedelics represents a new, steroid-sparing, small molecule strategy for the treatment of peripheral inflammatory related diseases.’

Targeting diseases on the fringe of psychedelic potential is not where Charles’ quietly vast ambition ends, though.

The basic neuro-scientific explanation of how psychedelics do their thing is the chemicals interact with receptors in the body’s cells. In particular ones given the code ‘5-HT2a’ usually given over to the neurotransmitter serotonin.

LSD contains serotonin in its chemical make-up. It latches on to receptors; hence the lengthy trip. Serotonin certainly isn’t simply ‘the happiness chemical’. It’s related to memory, learning, imagination, sexual arousal, appetite, anxiety and ‘diseases with complex etiologies.’

“Pressing different 5-HT2a receptors, and others, creates the various effects,” says Charles. Identifying medical properties could be just the beginning, he insists: “Eventually we might isolate the qualities of peak experience, ego dissolution and breaking stuck thinking.”

That’s not all. A new testing system Charles has designed examines the long terms effects of a single dose, identifying ‘persistent normalisation of stress-induced hippocampal dysfunction relevant to depression and other psychiatric conditions’

Find out more about Charles’ astonishing findings and their implications in this issue’s contents just below. You can also see Charles present his findings here, talk about inflammation and more with Mind and Matter here, and his thoughts on psychedelics and genetics plus more over on the New Psychonaut YouTube lecture channel. Follow Charles on Twitter at @lab_nichols.

If you want to go deep on neuroscience may I recommend Tokyo-based, Cambridge-educated neuroscientist Dr Andrew Gallimore’s extensive guide.

Here’s what’s in this week’s issue of your multi-syllabic Vital Student Zine, themed along Vital Psychedelic Training’s core pillars of study:

These five items I pulled from the week’s research are themed along Vital’s natural element-themed structure. Air provides an overview of psychedelic use, Fire concerns therapeutic applications, Water covers ‘space holding’ – the art of keeping it together, Earth is where you’ll find medical matters, and Ether discusses integration, the process of bringing psychedelic power into regular life. Click straight through to your pet subject.

Wicked Wheeze

Medical

A chemical component of mescaline can treat asthma, perhaps many more physical problems. And it’s not even the bit that makes you trip

Keith Coventry, ‘Inhaler’ in the permanent collection at the Southbank

Dr Charles Nichols’ major research breakthrough is the isolation of anti-inflammatory properties from the active agent in peyote.

Mescaline, in 1917 the first psychedelic ever synthesised, could treat conditions ranging from asthma to psoriasis and complex neurodegenerative disorders.

Dr Nichols’ lab has isolated anti-inflammatory properties within a designer drug variant of mescaline called DOI.

Mescaline enjoyed significantly better results than steroidal treatments when tested on Charles’ premium lab rats. And mice.

It’s almost certainly down to 5-HT2a receptors in the soft muscle around the heart becoming activated by psychedelics too.

Charles’ experiments showed mescaline/DOI prompted ‘extremely potent inhibition of tumour necrosis factor (TNF)-α-mediated inflammation.’

I hope you’re sitting down to take in what happens after that, ‘cos it might be a bit much to get your head around straight away:

‘5-HT2A receptor stimulation with the agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(R)-DOI] rapidly inhibits a variety of TNF-α-mediated proinflammatory markers,’ says the report barely managing to contain its enthusiasm. That’s not all.

‘Including intracellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), and interleukin (IL)-6 gene expression, nitric-oxide synthase activity, and nuclear translocation of nuclear factor κB, with IC50 values of only 10 to 20 pM.’

Unbelievable.

Importantly, these anti-inflammatory aspects of mescaline/DOI are chemically separate to its psychedelic properties. Any medicines derived from them wouldn’t prompt a psychedelic experience.

This isn’t just good news for any asthma sufferers who don’t fancy turning themselves on each time they need a blast of their inhaler. 

“We analysed 25 different psychedelics and revealed no correlation between behavioural potency and their ability to cure asthma”

It’s also a boon for folks who could do with help for their conditions as soon as possible. 

“One reason for isolating non-psychoactive components is the Federal Drug Association,” says Charles, “Even a minute psychoactive component requires much more rigorous testing.” New medicines derived from psychedelics that don’t blow the patient’s mind, make it to market much faster.

“Pretty much every everything nowadays seems to involve some aspect of of inflammation,” comments Charles, “the neuro-immune network hypothesis has become a really hot field. It underlies a lot of psychiatric disorders,” he says, citing depression, schizophrenia plus Parkinson’s and Alzheimer’s diseases. 

This doesn’t mean that someone on the wrong end of Alzheimer’s should be obliged to trip balls. Or kids with asthma.

“Inflammatory cells exist in the lungs, that affect asthma, and all over the body,” says Charles, “the brain has a primitive immune system too. Biopsies have revealed inflammation in the brains of a subset of depressed patients: cytokines and microglia are increased. Unmedicated schizophrenics have a significant amount of neuro-inflammation, plus it’s associated with drug abuse.”

“LSD is actually a poor anti-inflammatory and DMT has none of the properties at all,” says Charles when I ask him about his asthma breakthrough.

It only came about when he was left without a researcher after Hurricane Katrina, and took a chance on visiting professor Bangning Yu who needed a lab and complimented his own research.

“We analysed 25 different psychedelics and revealed no correlation between behavioural potency and their ability to cure asthma,” says Charles, “We will be able to engineer drugs that have less psychedelic activity, potentially even no psychedelic activity, but full anti-inflammatory properties.” 

He’s already honed a version of lab psychedelic DOI that has two-thirds less of the mind-expanding effects, but offers the same relief from asthmatic wheezing.