Psychedelic drugs work by entering the central nervous system and altering synaptic transmission. It is unclear what effect they may have on peripheral nerves, because people's perceptions overall are too screwed up to notice.

Antihistamines are similar, in a way. People take them because of desired effects on peripheral nerves - decreased runny nose, open lung passages, less itching etc. Some antihistamines also have considerable central nervous system effects - they make you sleepy.

Drugs cna be altered to more easily enter the central nervous system by adding lipophilic groups - such as a methyl group. Methamphetamine is more potent in the CNS because of addition of a methyl group. The addition of hydrophilic groups (a carboxy in the case of zyrtec) makes these molecules less likely to enter the brain, and thus less sedating - thus the nonsedating antihistamines.

I propose alteration of LSD and psilocybin by adding hydrophilic groups. This will limit access to the brain, but allow access to peripheral nerves. I am not really too sure what will happen, but at least you will be thinking clearly when it does. My hope is that these new drugs will alter nerve impulses in people who suffer chronic neuropathic pain, making this more tolerable. Alternatively, it might just change how perceptions are felt. Maybe Mescalito will still visit, but only on the outside.
-- bungston, Aug 29 2003

Marijuana-like molecule http://www.sciencen...0030816/fob2ref.asp
This is what inspired my thinking. What these folks have done is more complex than what I propose - figuring out a site of action by marijuana then making a custom molecule to activate only that site. Sorry, only subscribers can get full text. [bungston, Oct 04 2004, last modified Oct 06 2004]

baked #1 http://www.erowid.o...pihkal/pihkal.shtml
Virtually every analog/homolog/derivative of pschedelic phenethylamines (l-tyramine based), like: MDA, mescaline, etc... Actually, there are 1,000s more (see Chemical Abstracts) [Speed Razor, May 28 2009]

baked #2 http://www.erowid.o...tihkal/tihkal.shtml
Virtually every analog/homolog/derivative of pschedelic tryptamines (l-tryptophan based), like: LSD, pcilocybin, Harmine, etc... Actually, there are 1,000s more (see Chemical Abstracts) [Speed Razor, May 28 2009]

Hmm. Since receptor sites are extremely molecula shape dependant, you're going to have to be very careful where on the molecule you attach the hydrophillic group; and there's no way of determining how it will affect the activity of the molecule. Since the drugs are essentaially psychotropic, animal models may not be very useful. But a (+) anyway for good intentions.
-- 8th of 7, Aug 29 2003


Oh, so now it all just sort of makes sense now, doesn't it. I always thought of medical practice as more of an art than a science, but perhaps maybe not. I know someone who does do shrooms, and this person claims to have a feeling of extreme relaxation after all of the hallucinatory effects wear off. Perhaps this is the benefit of the natural psilobyn on periphery nerves.... eh, this kind of research probably couldn't hurt anything when there are so many willing participants to test it on.
-- quantum_flux, Jun 27 2007


/extreme relaxation after all of the hallucinatory effects /

Thanks for looking at this old one, [quantum]. That is exactly what I intended. Maybe shrooms relax some sort of neural damper in the brain and thus the hallucinations - but relaxing this damper in the peripheral body could be relaxing or beneficial.
-- bungston, Jun 27 2007


<nibbles on mushroom> GETS BIGGER

OOPs!
-- po, Jun 27 2007


All the fun is on the inside, so there would not be that many takers.
-- loonquawl, May 27 2009


effects on the nervous system outside the brain can harm the brain, they can cause dangerous behavior, and they are frequently addictive. Since the brain is essentially an integrative device, when supplied with junk data, or no data, the brain will try to make (false) sense of the data (hallucinations). I'm relatively sure that the effect on memory would be minimal but the potential for "loss of clear thinking" is very present. Without accurate feedback from the body the brain quickly goes somewhat nuts. In time you might be able to normalize this (think drunk goggles) but the immediate effect of wide spread sensory distortion would not likely leave you "in your right mind". Taking a drug that causes you to be so stimulated that you have a prolonged orgasm is going to have the same biochemical and addictive effects as taking a drug that only simulates the rush of orgasm.
-- WcW, May 27 2009


/effects on the nervous system outside the brain can harm the brain, they can cause dangerous behavior, and they are frequently addictive./

Examples, please. I cannot think of any addictive chemical that does not penetrate the brain. Imagine some chemical alteration in the peripheral nervous system of your foot. The foot will relay back what is happening insofar as it can. Your brain will try to make sense of the signals it receives, which will be in foot language since that's all you can get from the foot: hot, cold, buzzing, pressing etc. The foot cannot tell you "orange" or "loud". Likewise, signals from the bladder are in bladder language, which is pretty much "Got to pee!" regardless of whether the stimulus is fullness, inflamaation, foreign body or what have you.

Neuropathic pain syndromes probably are cases of unusual signals coming from a region and being interpreted as pain or discomfort by the brain, because the pain category is deemed the best fit.

Looking at this old posting - beanangel has since posted many more of this ilk: lets attach hydrophobic/hydrophilic groups to a bioactive molecule and alter its specificity.
-- bungston, May 27 2009


food. sex. self mutilation. gambling.

None of these activities "passes into the brain" and yet they have the potential to cause you to behave in an irrational fashion. A drug which causes you to perceive a sensation of satiation when you are hungry, freedom from all pain when some pain is normal, a sensation of extraordinary wellness or ease of movement, the inhibition of pain due to over exertion, unlimited sex drive and enjoyment, even hallucinatory sensations. All of these are clearly correlative with the danger of non-drug yet still brain harming behaviors. Any extreme stimulation has the potential to modify behavior and impair normal function. Sometimes using the mind altering potential of extreme stimulation can be very beneficial, and yet there are many examples of it causing harm.
-- WcW, May 28 2009


[WcW]: 'activities' passing into the brain pose semantic problems. 'gambling' outside the brain is just some movements performed, some sensory inputs about red objects with white dots on it or whatever. the problematic thing about gambling is all in the brain.

Drugs that cause the pain receptors in the skin to be silent (local anaesthetics) have no detrimental effect on the brain. Falling asleep in a weird pose, so an arm or a leg gets cut off perceptually, leading to the perception of an 'alien' arm at your side. All this alters the perception massively (as does wearing red tinted spectacles - the green receptors can take a day off) by just affecting peripheral mechanisms.

A drug just affecting peripheral nerves would never be able to give me the feeling of lying in warm grass - it might seem somewhat warm, or tingly, but the 'warm grass' perception is built by the brain from very specific input constellations. Getting addicted to strictly local anesthetics is akin to getting addicted to wearing gloves - it might happen once in a blue moon, but not as readily as with drugs that alter the substrate that makes addiction happen : the brain.
-- loonquawl, May 28 2009


// effects on the nervous system outside the brain can harm the brain//

I'd agree with this. Peripheral mechanisms can induce permanent changes in the CNS. Pain itself is a good example. At the heart of chronic nociceptive or neurogenic pain are central (spinal cord) neurons that have altered responses to afferent sensory impulses as well as descending inhibitory neurons, as a result of continuous peripheral impulses.

What (I think) [Bungston] is proposing is a method to determine the peripheral effects of LSD. Although this is probably unlikely to be of benefit in the management of chronic pain (most new drugs in this field target central transmission, and I don't think any of the receptors that LSD has any affinity for are involved in the peripheral mechanisms), his proposal certainly isn't going to make the brain go //quickly...nuts//. Our CNS isn't *that* plastic!

//food. sex. self mutilation. gambling// probably aren't the best examples to use in this case. The idea is about drug-receptor interaction, and I know of no drug that has purely peripheral actions that is addictive. All addictions on the other hand have a central mechanism.

The semantic problems are probably of our own making, in arbitrarily defining the peripheral and central nervous systems for our convenience, when they are both part of the same continuous system.
-- shudderprose, May 28 2009


I don't see your distinction. Sensory inputs cause regulatory changes in the brain. It doesn't matter if these changes are triggered by behavior (exercise, self induced pain, masturbation, eating) or by external conditions. The brain IS pretty plastic, take away or modify sensory data and the brain is going to try to make it fit back into the normal parameters. Acting outside the brain is an attempt to defeat the natural system of regulation which is essentially normative and so plastic that it can fake convincing data when none is present.

Phantom limb pain, need I say more.
-- WcW, May 28 2009


I thought it was a [beanangel] tribute idea.
-- normzone, May 28 2009


//Phantom limb pain, need I say more.//

I've already stated that pain is an example where a peripheral stimulus can result in central changes. Not too difficult to understand given the peripheral and central nervous systems are connected, and prolonged painful/nociceptive stimuli produce well researched changes in wide dynamic range neurons in the spinal cord.
How is this example a point in favour of you saying that a purely peripherally acting *drug* can result in harmful effects on the //brain//?

You're assuming, firstly, that the psychotropic/psychedelic effects of LSD are a peripheral phenomenon, which they're not.
And secondly, that LSD binds to receptors in the PNS that has a harmful effect on the CNS. Dopamine and serotonin receptors are hardly dominant features of peripheral nerves.

[Bungston] has already addressed the first assumption, but perhaps you didn't read his anno.
-- shudderprose, May 29 2009


//None of these activities "passes into the brain" and yet they have the potential to cause you to behave in an irrational fashion//

Food, sex, self mutilation and gambling are poor examples because they *do* pass into the brain. Food has a pretty direct route through taste buds, sex and pain through multiple sensory inputs, and gambling through sympathetic afferents, to name one.
-- shudderprose, May 29 2009



random, halfbakery