Scientists re-engineered natural psychedelic drug as treatment for depression and addiction, without the trippy effects

Originally published at: https://boingboing.net/2020/12/10/scientists-re-engineered-natural-psychedelic-drug-as-treatment-for-depression-and-addiction-without-the-trippy-effects.html

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“… and sharply reduced both alcohol- and heroin-seeking behavior in mice and rats.”

I understand what is going on, but it sure does sound weird when it is phrased like that.

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That is a huge achievement, if it proves out in human trials!

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Westley could have used ibogaine (unrefined) in the battle of wits, and Vizzini could have spent the rest of the movie tripping balls rather than dying.

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I was just coming on here to make a Princess Bride joke, damn.

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Without the trippy effects? Where is the fun in that?

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Yeah, but presumably people suffering from clinical depression mainly want to be able to get on with their lives and not necessarily be tripping balls all the time.

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I always suspected that decriminalizing drugs would take away some of the fun, just never like this.

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Hard-pressed to imagine the “fun” effects of prohibition… :thinking:

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Shulgin and Naranjo studied tetrahydroharmine and other beta-carbolines in the '60s but abandoned them because too little was known to mitigate the potential risks of further study.

But for ‘N’-methylation, the novel and presumably unsynthesized tabernanthalog is very close to 6-methoxy tetrahydroharmine below.

Tetrahydroharmine_300px

Ibogaine, 5-methoxy analog, looks like a mashup of the cocaine nucleus with harmine and is clearly a more challenging synthesis.
Ibogaine_300px

Typically, what would be the 4- and 5-methoxy analogs in indoles are the ones with entheogenic activity so it’s not surprising that a 6-methoxy beta-carboline ain’t got no buzz.

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And also this week, there’s this, also from South America

DMT is found in several plants and is one of the active ingredients in ayahuasca, a bitter drink consumed during shamanistic rituals in South America and elsewhere.

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I tried DMT once. I had enough for three people, melted into a puddle on the couch, and spent 20 mins apparently passed out while actually speaking with god. Scared hell out of my friend.

The seemingly endless adolescent depression fucked off for several months.

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Heavy caution on extrapolating any pharmacological specificity from structures. Very easy to slide on anchoring bias when playing that game. When the brain is happily hotswapping 5HT2A variants with CB, D1R, NMDA, and other receptors in funky dynamic heteromers, I don’t put any stock in predictions of toxicity/safety, let alone psychedelic or other neuroactive effects.

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While certainly promising in terms of psychiatric benefit, there are multiple issues that jump out at me:

1.) The appropriation of indigenous medicines by western pharmacology is problematic at best, and part of systematic cultural genocide at worst.

2.) Taken out of cultural context, vision-inducing hallucinogenic medicine tends to bypass the healing aspect of social cohesion produced through facilitated shamanic experience and ceremony. Removing the vision-producng component of a medicine further diminishes and dilutes this aspect.

3.) Focusing on the pharmacological aspects of addiction helps us understand biochemistry, not human healing. It’s one aspect of many, in the complex systems that function together to create human personality, behavior, and culture.

4.) Patenting and profiting from indigenous medicines (by creating novel analogs and variants) erases the indigenous discovery and generations of refinement of these medicines, often playing into a Eurocentric view and perpetuating white supremacy.

5.) Traditional medicines “discovered” by scientists can lead to overharvesting of the plants, animals, or funguses containing prized molecules, leading to diminished availability in traditional contexts. This can reduce genetic diversity & resiliency, as sub-standard variants suitable to mono-crop agriculture and industrial chemistry become the norm.

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Mickey Rat! Whoop!!

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True enough. No one predicted that 3-naphthoyl indoles would bind to cannabinoid receptors.

While the absence of 6-methoxy tryptamines in Shulgin’s Tihkal is not dispositive, it’s a suggestion as to where one might look when doing the QSAR modeling and burning up some institutional-grade computer time.

One thing that stood out (to me) was early mention of improved neural plasticity, so there’s a possibility of improved therapies for stroke sufferers.

The UCDavis announcement is a teaser.

The UCD news release has more details.

The primary article is in Nature.
DOI link: https://doi.org/10.1038/s41586-020-3008-z

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I understand the desire to isolate the portions of a natural drug that focus specifically on a result - but it is my understanding that the use of ibogaine is more than just a chemical reaction that reduces, inhibits or eliminates the compulsive desire for opioids and/or alcohol - the “trippy” portion of the experience is a physical and emotional journey which allows underlying trauma to be confronted and ameliorated. This clinical method is more about selective chemistry than a true understanding of the complex interrelation between our minds, our bodies and the bark of this wonderful plant.

Also - don’t take the fun out of good shit.

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We already could have had the bulk of the benefit of doing this just by not making the psychedelic versions illegal in the first place.

I’m a bit skeptical about the ibogaine derivative in particular, as somebody who’s life was changed by a profoundly powerful psychological experience. I’m not so sure you can divorce the psychoactive effects from its efficacy.

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Way to fuck up a good thing, science! Way to fuck up a good thing.

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Method diversification or bullshit.

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