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Caine
lab rat



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Peptide psychedelics?
#14411132 - 05/06/11 04:19 PM (12 years, 8 months ago) |
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So I was reading about peptide toxins, and noticed that some of them have ridiculously low LD50's. Botulinum toxin's was in the nanogram range in monkeys (1/1000th of a microgram) which is insane. I am curious to know whether or not it would be possible to (bio)synthesize some incredibly powerful 5-HT2A agonist peptides? Seems like that would be an interesting field to do some work in, if not incredibly difficult since peptides can be massive molecules...
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2Cents



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Re: Peptide psychedelics? [Re: Caine]
#14411173 - 05/06/11 04:26 PM (12 years, 8 months ago) |
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....what the fuck is a peptide psychedelic?
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
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Re: Peptide psychedelics? [Re: Caine]
#14411180 - 05/06/11 04:28 PM (12 years, 8 months ago) |
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What's the mechanism of action for Botulinum toxin? In other words, how can it kill you at such low doses?
Cba to Wikipedia.
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Caine
lab rat



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Re: Peptide psychedelics? [Re: Mad_Larkin]
#14411187 - 05/06/11 04:29 PM (12 years, 8 months ago) |
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Paralysis, but I'n not sure what about it makes it so potent.
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Samuel L Jackson
Bad Motherfucker


Registered: 12/10/09
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Re: Peptide psychedelics? [Re: 2Cents]
#14411189 - 05/06/11 04:29 PM (12 years, 8 months ago) |
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Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
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2Cents



Registered: 12/04/08
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Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
Posts: 18,606
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Re: Peptide psychedelics? [Re: Caine]
#14411212 - 05/06/11 04:36 PM (12 years, 8 months ago) |
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Quote:
The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for vesicle fusion that releases neurotransmitters from the axon endings (in particular Acetylcholine).[58] Botulinum toxin specifically cleaves these SNAREs, and so prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.
Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin's mechanism of toxicity[citation needed]. Attacks involving botulinum toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.

Interesting that atropine is mentioned as an enhancer of the toxic effects.
Edited by Mad_Larkin (05/06/11 04:37 PM)
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Salomon
ಠ︵ಠ balance ಠ_ಠ weaver ಠ‿ಠ

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Re: Peptide psychedelics? [Re: Mad_Larkin]
#14411218 - 05/06/11 04:37 PM (12 years, 8 months ago) |
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shroomery: creating the next LSD one day at a time
-------------------- EVERYTHING EVENTUALLY BECOMES A DESERT
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Caine
lab rat



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Re: Peptide psychedelics? [Re: 2Cents]
#14411223 - 05/06/11 04:38 PM (12 years, 8 months ago) |
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Quote:
2Cents said:
Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
Crazed ramblings? It's not really that complicated  I'm just asking if anyone's heard of peptides that affect the 5-HT2A receptors.
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2Cents



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Re: Peptide psychedelics? [Re: Caine]
#14411232 - 05/06/11 04:41 PM (12 years, 8 months ago) |
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No offense mate, just curious.
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
Posts: 18,606
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Re: Peptide psychedelics? [Re: 2Cents]
#14411241 - 05/06/11 04:42 PM (12 years, 8 months ago) |
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Crazed ramblings up in this motherfucker. 
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The Whale

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Re: Peptide psychedelics? [Re: Caine]
#14411293 - 05/06/11 04:52 PM (12 years, 8 months ago) |
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Quote:
Caine said:
Quote:
2Cents said:
Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
Crazed ramblings? It's not really that complicated  I'm just asking if anyone's heard of peptides that affect the 5-HT2A receptors.
I could find the article if you'd like, but newer research suggests tryptamines involve more than just the 2A receptors (DMT was used in their lab). Additionally, some 2A agonists - including some medicines - don't even produce psychoactive effects. Peptides are pretty dense in the body and have widespread distribution as neurotrasmitters. Check out: Substance P. But they seem mostly to be involved in hormone behavior, so tinkering with these guys will likely grant control of the autonomic nervous system but not so much cerebral cognitive functions (I don't imagine). Although the behavior of ketamine, surprisingly, is subjectively "heady" despite focusing on NMDA. Meaning, we could target things like peptide-hormones and still end up tripping.
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: The Whale]
#14411327 - 05/06/11 04:59 PM (12 years, 8 months ago) |
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Quote:
The Whale said: I could find the article if you'd like, but newer research suggests tryptamines involve more than just the 2A receptors (DMT was used in their lab). Additionally, some 2A agonists - including some medicines - don't even produce psychoactive effects. Peptides are pretty dense in the body and have widespread distribution as neurotrasmitters. Check out: Substance P. But they seem mostly to be involved in hormone behavior, so tinkering with these guys will likely grant control of the autonomic nervous system but not so much cerebral cognitive functions (I don't imagine). Although the behavior of ketamine, surprisingly, is subjectively "heady" despite focusing on NMDA. Meaning, we could target things like peptide-hormones and still end up tripping.
Yeah, that's what I'm wondering, just because we really know nothing about mechanisms of psychedelic drugs, but there certainly are peptides with activity at neural receptors, like endorphins.
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mellowparty
legitimate researcher


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Re: Peptide psychedelics? [Re: Caine]
#14411331 - 05/06/11 04:59 PM (12 years, 8 months ago) |
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Sweet idea
Endorphines are extremely potent compared to opiates so I dont see (at least in theory) whats stopping the possible existence of a protein that would form very cohesive non-covalent interactions with the hydroxytryptamine receptor.
Hit folding@home for some help with the protein engineering. Once you get that I'll write the gene for you, clone it in an adenoviral/exosome vector carrying vehicle and inject you in the brain with a pressurized syringe.
Balls will be tripped. I guess you'll have to forget about your 5HT receptors afterwards as these will be heavily endocytosed but it will be the ultimate psychedelic journey
Is there a pdb entry for any 5TH receptor. That will be your starting point
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Beanhead
IS IRONIC PARADOX


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Re: Peptide psychedelics? [Re: The Whale]
#14411341 - 05/06/11 05:02 PM (12 years, 8 months ago) |
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Enkephalins sounds cool aswell
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Caine
lab rat



Registered: 01/25/10
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I'll check the PDB and update this post in a minute...
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: Caine]
#14411414 - 05/06/11 05:18 PM (12 years, 8 months ago) |
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This is as close as I could get it seems, cool nonetheless
http://pubs.acs.org/doi/abs/10.1021/ci100402f
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mellowparty
legitimate researcher


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Re: Peptide psychedelics? [Re: Caine]
#14411418 - 05/06/11 05:20 PM (12 years, 8 months ago) |
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I hate structural biology but I like this paper  
Good post man
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The Whale

Registered: 11/01/10
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From the abstract: "The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies." Interesting.
You would have more success posting this at Bluelight. There are informed chemists afoot.
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Beanhead
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Re: Peptide psychedelics? [Re: Beanhead]
#14411429 - 05/06/11 05:22 PM (12 years, 8 months ago) |
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Log in to view attachment
You'll discover more reading this...
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: The Whale]
#14411447 - 05/06/11 05:26 PM (12 years, 8 months ago) |
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Quote:
The Whale said: From the abstract: "The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies." Interesting.
You would have more success posting this at Bluelight. There are informed chemists afoot.
I dunno if informed chemists are what I'm looking for, usually they can speak for hours on end about various organic chem techniques and are very handy when you want a small molecule in a pinch but peptide synthesis is a whole different ballgame.
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mellowparty
legitimate researcher


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Re: Peptide psychedelics? [Re: Beanhead]
#14411458 - 05/06/11 05:30 PM (12 years, 8 months ago) |
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Quote:
Beanhead said: You'll discover more reading this...
neat
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Caine
lab rat



Registered: 01/25/10
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Quote:
mellowparty said:
Quote:
Beanhead said: You'll discover more reading this...
neat
I downloaded it, I'll start the reading before I go to sleep later, looks really interesting. I made a thread in here maybe 3 or 4 months ago about omega conotoxin, which is a peptide in a certain snail's venom that's on the order of 1000 times more potent than morphine. Peptides seem to be really promising in the medical field, I don't know why there aren't more studies being done on this stuff.
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badchad
Mad Scientist

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Posts: 13,372
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If you got too large, you may not fit the receptor.
It may depend on how the peptide bond affects the final conformation of the protein.
-------------------- ...the whole experience is (and is as) a profound piece of knowledge. It is an indellible experience; it is forever known. I have known myself in a way I doubt I would have ever occurred except as it did. Smith, P. Bull. Menninger Clinic (1959) 23:20-27; p. 27. ...most subjects find the experience valuable, some find it frightening, and many say that is it uniquely lovely. Osmond, H. Annals, NY Acad Science (1957) 66:418-434; p.436
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: badchad]
#14411497 - 05/06/11 05:41 PM (12 years, 8 months ago) |
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Quote:
badchad said: If you got too large, you may not fit the receptor.
It may depend on how the peptide bond affects the final conformation of the protein.
True, that's what would be so difficult about its synthesis, but in theory there is nothing wrong with it. That's partially why (bio) was in the OP, because I know that botox has taken ages of evolution to be created. It would be crazy to be bitten by some animal only to find yourself tripping absolute balls ten minutes later to the point of immobilization. Crazy defense mechanism, I tell you what
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Beanhead
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Re: Peptide psychedelics? [Re: Caine]
#14413788 - 05/07/11 04:15 AM (12 years, 8 months ago) |
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Handbook of Biologically Active Peptides
EDIT: Abba Kastin Abba Kastin, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
Number Of Pages: 1640 Publication Date: 2006-08-29 Sales Rank: 990838 ISBN / ASIN: 0123694426 EAN: 9780123694423 Binding: Hardcover Book
Description: Peptides play a crucial role in many physiological processes including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The Handbook of Biologically Active Peptides presents, for the first time, this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine. The Handbook of Biologically Active Peptides is a definitive, all-encompassing reference that will be indispensable for individuals ranging from peptide researchers, to biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and to endocrinologists. Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas with which they would not ordinarily be familiar.*Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas that they would not ordinarily be familiar.*Fascinating relationships described in the book include the presence of some peptides originally found in frog skin that persist in the human human and brain where they can affect food intake and obesity.
If I get my hands on this i'll put the link up but haven't found it yet, i'm glad i'm non the only one interested in peptides. Althrough my pharmacology/chemistry knowledge isn't sufficient most of the time to understand everything, it's a gread read nontheless (I can register for chemistry education tommorow  FINALLY )
Edited by Beanhead (05/07/11 04:24 AM)
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: Beanhead]
#14413916 - 05/07/11 05:41 AM (12 years, 8 months ago) |
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Beanhead, you should try to do some research on possible peptide psychedelics once you have access to some good lab equipment and protein writing tools
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Beanhead
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Re: Peptide psychedelics? [Re: Caine]
#14413933 - 05/07/11 05:53 AM (12 years, 8 months ago) |
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Who knows?
I like chemistry, there is already so much research done about it that you can't possibly grasp everything... And then you realize we know barely anything at all . Lovely !
h**p://ifile.it/9j8zxy/ebooksclub.org__Handbook_of_Biologically_Active_Peptides.pdf
Edited by Beanhead (05/07/11 05:55 AM)
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Spiderbaby
?



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Re: Peptide psychedelics? [Re: Caine]
#14414279 - 05/07/11 08:53 AM (12 years, 8 months ago) |
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Psychoactive peptides are known, Dermorphin for example, its unusual as its sequence contains D-Alanine.
Unfortunately developing small peptide drugs would be difficult since small peptides can adopt a large number of conformations compared to a small organic molecules which have a well defined shape to "fit" a receptor. And add to that the difficulty or near impossibility of solving structures of integral membrane proteins like GPCRs. Structure based drug design would be extremely difficult for peptide drugs. The design approach would have to be assaying vast libraries of peptides for activity and then optimizing from there once you have a lead peptide.
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Mad_Larkin

Registered: 11/29/07
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Re: Peptide psychedelics? [Re: Spiderbaby]
#14414320 - 05/07/11 09:08 AM (12 years, 8 months ago) |
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Interesting shit. That dermorphin stuff is a constituent of the frog venom South American indians use when they go hunting.
Quote:
Dermorphin is about 30-40 times more potent than morphine but less likely to produce drug tolerance and addiction.
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Spiderbaby
?



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Re: Peptide psychedelics? [Re: Mad_Larkin]
#14414358 - 05/07/11 09:21 AM (12 years, 8 months ago) |
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i think they call it sapo or something,
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mellowparty
legitimate researcher


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Re: Peptide psychedelics? [Re: Spiderbaby]
#14953599 - 08/20/11 06:14 PM (12 years, 5 months ago) |
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Quote:
Spiderbaby said: Psychoactive peptides are known, Dermorphin for example, its unusual as its sequence contains D-Alanine.
What if you clone the nucleotide sequence of this peptide (corrected for codon bias in humans) and also put in an amino acid isomerase gene to give the enzyme that will create the geometrically unusual kink in the polypeptide backbone. Then stick a rabies virus promoter element and just for fun attach an N-terminal secretion signal. That last bit may perturb the properties of such a small and unusual peptide and probably the isomerase would have to be targeted to the endoplasmic reticulum 
So assuming you have your psychoactive peptide on a plasmid with all the molecular requirements for it to be active at the correct site (the synaptic interface). Then you inject yourself in the middle of the brain and subject your head to mediolateral electrostatic field so that the plasmid is electroporated towards the anode (which you point to the brain hemisphere of choice). The plasmid gets expressed and secreted and binds your receptor of choice. You trip ballz or die of a respiratory arrest 
In order to ensure the competence of the cells you can put your construct in a retrovirus or better yet in exosomes with recombinant surface proteins (since we said rabies then rabies virus glycoprotein that will bind acetylcholinergic neurons)
I just got back from work and I'm pretty baked atm so I might have made a mistake somewhere. If its correct then its gonna be a hell of a trip.
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