Purists sneer at scientific tinkering. But lab studies showed Dr Nichols how psychedelics heal the body. Could he uncover the secret of profundity too?

Neuroscience is different to other aspects of psychedelic study, ‘since it is so spectacularly and usefully right over so many things.’

Raymond Tallis wrote those semi-satirical words in Aping Mankind: Neuromania, Darwinitis and the Misrepresentation of Humanity. Neuroscience ‘is often given authority where it has none’ warns Tallis.

Grudgingly I admit all those long words and graphs might come across well in a formal context. During a presentation to drug legislators, for example. Certainly compared to showing a clip of Tales from the Trip on the the meeting room’s wall-mounted LCD screen. 

So it’s sweetly satisfying for heads to beat bureaucrats at their own game with the slew of pro-psychedelic neuroscience stats flooding out of respected institutions.

Granted, the arcane apparatus of the psychedelic experience itself remains beyond even the grasp of they who have mastered the most multisyllabic words from this incomprehensible, in-style, inculcation. 

“That’s still a wide open mystery,” confesses Dr Charles Nichols, eminent psychedelic pharmacologist and Vital neuroscience lecturer.

“Specific pathways may be involved in the psychedelic process”

Charles is the son of Dr David Nichols, chemist to the stars. David made the DMT for Rick Strassman, MDMA for MAPS and psilocybin for Johns Hopkins.

“Back in the 2000s my father’s lab looked at the cross talk downstream from when G-alpha-i protein interacts with a specific beta and gamma that activates a hormone called Src, which then activates a series of enzymes. That’s the very top effector.”

Right. No wonder nobody’s got to the bottom of it as yet. 

“Specific pathways may be involved,” Charles whispers conspiratorially to the cheap seats.

No talk of neuroscience in these pages is complete without a mention of Greatest Living Englishman Dr Robin Carhart-Harris.

Dr Carhart-Harris’ sympathetic yet rigorous research at scientific bastion Imperial College London brought the psychedelic experience its medical legitimacy. His REBUS, ‘relaxed beliefs under psychedelics’ model is widely considered the neatest summation of psychedelic neuroscience. (without wishing to damn it with faint praise). 

“My lab studies what psychedelics do that serotonin doesn’t”

For anyone too embarrassed to ask the scientific way to say ‘tripping’ is ‘Relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system.’ Obviously.

Dr Charles Nichols is a pharmacologist developing new drugs. Unlike his celebrated psychedelic chemist dad Dr David, Charles has the benefit of Carhart-Harris’ research, or its slipstream at least.

Charles uses his prodigious skill with the pestle, mortar and petri dish to identify, isolate and augment certain properties within his arsenal of exotic designer psychedelics.

Specifically, “The study is my lab now is around what psychedelics do that serotonin itself doesn’t,” says Charles. 

Which is a lot.

He’s already found that mescaline-derived DOI has a tremendously positive effect on inflammatory conditions including asthma. And, he’s worked out that it’s not even one of the bits that makes you trip. Which has implications aplenty for widespread use. And the sensitive conversation around non-psychedelic psychedelics.

(Ethnobotanist Richard Evans Schultes wrote in 1938, “Some of the ills listed as responding to peyote were tuberculosis, pneumonia, scarlet fever, intestinal ills, diabetes, rheumatic pains, colds, grippe, fevers and venereal diseases.” Cheers Mark Gunther of Lucid News).

Psychedelics possess less ‘inhibitory’ effects on brain receptors that might suppress ‘excitatory’ ones, compared to serotonin. They hit the accelerator while cutting the brakes: boosting neurotransmission while hindering the body’s autonomous attempts to bring body chemistry back to ‘normal’.

“The profound and mystical effect itself is still a mystery”

This initiates a ‘synaptic cascade’ of excitatory messages. Once that gets to the Raphe nuclei in the brain stem connected to the whole brain, it’s blast off.

The resulting “downstream cross talk” takes an unusual route through the nervous system. Precisely what is a little vague. Zen meditation buff Dr Bryan Roth is on it with a system he calls ‘TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome’. He’s also the guy making the non-psychedelic psychedelics for DARPA.

“All psychedelics have a surprisingly different set of reactions with the 5-hydroxytryptamine receptors associated with serotonin,” says Charles, “but they all work on 5-hydroxytryptamine receptor 2a.” 

Neuroscientists gave it with the catchy nickname ‘5-HT2a’. Relax, they’ve got loads more.

Mescaline for example only activates two other receptors besides 5-HT2a. LSD’s “complex pharmacology” on the other hand means it interacts with 17 different receptors in total.

‘The phrase 5-HT2a agonist has supplanted psychedelic, which still carries faint whiffs of hippie-era hedonism,’ tech bible Wired tipped us off in its recent feature The High-Stakes Race to Engineer New Psychedelic Drugs.