[www.rhodium.ws] [] [Chemistry Archive]

Discussions on the synthesis of LSD

Taken from the Hive & Usenet
Plus some reference Lists at the end

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Kaff (posted 05-16-98)

It just occurred to me that noone ever mentions acid. I have Fester's book Practical LSD Manufacture but that's about as practical as buying a wheat farm just to make acid. Yeah right Hawaiin Baby woodrose seeds and morning glory seeds have some lysergic acid, but why aren't there any new methods?

drone 342 (posted 05-16-98)

I agree, Fester's LSD book was a major disappointment -- yet one more reason to loath the guy. There is an advancement, one which Fester didn't include, which is the use of POCl3 as a dehydrating reagent in the condensation of lysergic acid with diethylamine. Check out Rhodium's page, as well as hyperreal for more info on this new developement.

The wierdest part about it is that it was developed by our friends over at the Edgewood Arsenal in Maryland during the mid-seventies -- the good people who lead the world in cutting-edge chemical warfare technology and supply the intelligence community with all the wierd shit they use. These are the same folks who stockpiled QNB in multi-kilo quantities right into the eighties, as well as the freaky things they don't tell anyone about. Some day, I want a tour of that place.

Anyways, the important thing to keep in mind, which really shows yet again how much Fester talks out of his ass, is that all the seeds, fungi, and other biomass is NOT the way to allocate your lysergic compounds for this reaction. Anybody who makes it on a big scale is using most liekely ergot alkaloids from a commercial source -- foreign pharmacy companies, etc. Its not that hard to get your hands on an ounce or two of ergotamine or ergonovine if you put your noggin to it. Hell, even bromocryptine will work (remove the bromine by maing the grignard out of it, then hydrolyzing it. As long as its done gently, no funky additions, olgermizations or whatever, will happen.)

I've been waiting for someone to bring this subject up. Ask and you shall recieve.

KrZ (posted 05-17-98)

Whats wrong with Hawaiin Baby Woodrose? When your making something where 1 dose=50 micrograms a pound of HWBR goes a long ways... Does fester talk about culturing as a source in an incubator?

Fan of Shulgin (posted 05-17-98)

IMHO culturing the ergot fungus in the best method by far for producing LSD. Even someone with absolutely no knowledge of microbiology can culture ergot. And as to obtaining the fungus, it can be found in most large fields of rye. This is no joke, wait just until harvest time and go out and have a look for the 'heads'. The beauty of growing the Claviceps is that you can keep it alive for ever if you are careful, and thus have an almost never ending supply of raw material.

It is worth noting, that this is the method that most illegal acid labs operate (look up operation Julie in the UK!). Even producing acid on a small scale requires you to prepare shit loads of the precursors, because even working under red light at low temperatures and low humidity does not have that great an effect on keeping yields high (a 20% yield in LSD manufacture is considered a great success). Remember LSD is inherantly unstable!

Anyway - LSD synthesis, Claviceps cultivation etc are one of the most talked about drug manufacturing methods on the net. Have a good long search around!

drone 342 (posted 05-17-98)

I'm telling you guys, mushroom cultivation IS NOT where its at! As far as I can tell, this is not as common of a procedure as people believe. Why? Ever look at the amount of solvents entailed in extracting the stuff? This is a way too involved process that uses far too many resources. MAYBE there's some lab that does this, but it's just not practical. Besides, this bioproduction entails the chemist mastering a whole bunch more skills than the tricky ones already required.

I stand by my procedure as THE ONE TRUE WAY(tm), or at least the best of the one true ways. Think about it: Bromocryptine into bromolysergic acid. Bromolysergic acid into bromolysergic acid diethylamide. Bromolsyergic acid diethylamide into its respective grignard reagent. Grignard reagent decomposition into LSD. Add a dash of tartaric acid, and chromatograph it. All pretty simple procedures -- relatively speaking.

Bromocryptine is easy to get in reasonable quantities. Other ergot alkaloids are also available, and would alow the chemist to skip a debromination step or two as well.

While some believe that LSD is only worthwhile on a mega-huge scale of ounces at a time, I contend that using the sources I suggest, that a gram-size batch would still be a very attractive endevor.

HBWR seeds might be a decent way to go, I agree, but I prefer pill extracting any day. Considering also the price and notriousness of this as a source, other sources should be investigated more thotoughly. How much does a kilo of seeds go for nowadays?

Still, here's another source. Grain companies have a lot of fancy-shmancy equiptment I've been told, soley to remove claviceps from our food supply. This means that every harvest season, your local grain elevator has got pounds of ergot-ladden grain that they normally throw away. This I heard from a friend of mine who worked in a grain elevator -- lost contact with him since my chemical skills were upgraded. This is worth some investigating.

Anyways, I agree that far too little research is being done into these matters, and I'd like to see more discussion of the chemistry of Hoffmann's baby. The chemistry IS above kitchen production conditions, but not out of reach for the semi-elite of The Hive's Chemical Guard. By eliminating the riduculous, over-complicated bullshit procedures out there, and replacing them with simpler, more practical means, the small circle of people willing-and-able to perform this most sacred of chemistry is widended considerably.

KrZ (posted 05-18-98)

Drone, c'mon, we are not talking about mushrooms here, wake up son... Mushrooms growing right on top of rye plants, that would look prety silly.. All you need is a sample, some .2% agar plates and some sterile technique, not exactly skill-requiring stuff..

drone 342 (posted 05-18-98)

KrZ said: Drone, c'mon, we are not talking about mushrooms here, wake up son... Mushrooms growing right on top of rye plants, that would look prety silly. All you need is a sample, some .2% agar plates and some sterile technique, not exactly skill-requiring stuff.


Sorry, I suffer from a mild case of irony deficiency, and so its hard for me to tell when folks are pulling my leg. I wholeheartedly aprove of and endorse mushroom cultivation -- provided it is of my favorite basidiomycetes genus that starts with the letter "p".

However, I think you'll discover claviceps is harder than you think. Ever try to get a pure culture of that stuff? If you go through any of the research collections or biotech companies, you're going to have to fill out more paperwork than you'd believe -- not because its laden with ergot goodness, but because its considered a agriculturally harmful organism. It's about as involved as filling out forms for the purchasing of an encapsulating machine. If you choose to isolate your own strain from the field, good luck. You got a 2-month or so window of time to collect it, and then comes the isolation process. Then once you have pure claviceps, you're going to have to isolate a decent-producing heterokaryote from your collection, which you may or may not have. Once you manage THAT, then comes the petri dish phase, followed by the initial submerged culture for producing seed stock, then finally the large-scale submerged culture to yield a a sludge of filaments you gotta strain out, dry, then extract.

Yuck. There are a lot of professional folks out there who's entire days, nay, entire careers relovle around ergot production. I rather rely on the fruits of their labor and save all the schmassle that this project would otherwise entail.

Think about it. I honestly feel the main detractor from more people producing LSD is this ergot culturing myth. Yeah, everyone says "Boy, I sure wish I could make some good acid. All I gotta do is get a chemistry degree under my belt, get a good lab space, and on top of that, raise a culture of some fucked-up saprophytic fungus that'll give me gangrene in the process." This is obviously daunting. If you disagree and say its not too much of a bother, then why aren't more people kicking out kilos of "L"? What I'm proposing is that this fungus cultivation idea is more of a detriment to acid production than an advantage. Just extract the shit from pills, or go to the third world where the stuff is cheap, and you can buy it in its straight uncut powder form for pharmaceutical outlets (there are several countries where you can do this when you know a good pharmacist and have the cake to do some bribing; believe me, I've looked.)

As simple as ergot cultivation sounds, there's plenty of reasons its not done commonly.

drone 342 (posted 05-18-98)

Oh yeah, and I almost forgot. With bromocriptine, you can do that grignard degredation process as your first couple steps; this wil cut down on the amounts of POCl3 and Et2N required in the amidation and save you precious resources. Grignards don't readily add to amides, so you can take advantage of that.

drone 342 (posted 05-20-98)

Okay, so of available precursors for acid, we got:

Seems to me the chemistry and methodology is pretty cut-and-dry -- the main problem is precursor aquisition. So what other exciting sources might be out there for the ergoloid ring?

drone 342 (posted 05-20-98)

Actually, I just stumbled across the articles I was looking for:

Commodium (posted 05-20-98)

Yeah, looks like (according to that Journal of the AOAC article) Hawaiian Baby Wood Rose is 0.04 to 0.30 % LSA, by weight.

drone 342 (posted 05-20-98)

Incidentally, I looked into the possible utilization of sleepy grass, butit looked like it was full of all sorts of other alkaloid garbage aside from lisergic acid and its amides. Chanoclavines, Pyridines, etc. This might be a good source if anybody knows a good way of separating the wheat from the chaff in this case. What else besides HPLC will do the trick? (I have an HPLC machine for my amusement, but I can only do tiny volumes; besides, half the point of this research is figuring out ways of doing this kind of stuff successfully garage-style rather than just in the lab.)

Also, does anybody else harbor the same loathing for Fester and his piece-o-shit-excuse-for-an-acid-book as I do? I mean, he completely missed the POCl3 method, and left "method X" a mystery (even though its probobly just as full of shit as the rest of the book.) In addition, he mistakenly thought propionic anhydride had something to do with acid chemistry, and then didn't even give a particularily meaningful synthesis for it. All his methods looked like rehashes of patents from the earlier part of this century (available in half a dozen other publications already,) and the only lysergic acid source he offers is buying a goddam wheat farm and raising a crop of moldy rye grain! Even his claviceps raising would take over a year to accomplish!

So, his book only would be practical for a farmer with a couple years on his hands, a few 55-gallon barrels of tech-grade solvents, a lab full of large-scale equiptment for advanced organic chemical procedures, and some rather extensive training in organic chemistry. If a person had all those resources available to them at the same time, they'd be an idiot if they couldn't find a better way of going about things than that.

buzzz (posted 05-20-98)

I haven't looked over it a great deal but, the book Psychedelic Chemistry by Michael Valentine Smith gives detailed info on lysergic acid and extractions for ergot extraction from HBWS and states that the seeds yield 7mg alkaloids/100 g of seeds and that thru the usual steps to reach the end point of lsd that you get roughly 1g LSD / kg of seed. the book can be ordered from Loompanics.

drone 342 (posted 05-20-98)

Got a copy of that one already; what library would be complete without MVS's book? Nothing too earth-shattering, but still I like it; there's an aura of honesty to it that you don't see in many other underground drug books. MVS is sure no formally-trained chemist, but at least he knew how to operate a copying machine and give credit where it was due.

Your numbers don't add up. (7mg ergot/100g HBWR)×(1000g/1kg) does not equal even 1g of ergot, but I get the general gist of it. I'll give it a look-see. Thanks for the tip. Considering that a kilo can be boughten for around $300-$400 dollars, it looks like it would almost be a good investment (I prefer the chemistry of drugs where the profit margin is closer to 95-99% rather a mere 75-80%, but hey, its acid.)

KrZ (posted 05-21-98)

LSD Manufacture: Illegal LSD Production

LSD has been manufactured illegally since the 1960's. A limited number of chemists, probably less than a dozen, are believed to be manufacturing nearly all of the LSD available in the United States. Some of these manufacturers probably have been operating since the 1960's.

LSD manufacturers and traffickers can be separated into two groups. The first, located in northern California, is composed of chemists (commonly referred to as 'cooks') and traffickers who work together in close association; typically, they are major producers capable of distributing LSD nationwide. The second group is made up of independent producers who, operating on a comparatively limited scale, can be found throughout the country. As a group, independent producers pose much less of a threat than the northern California group inasmuch as their production is intended for local consumption only.

Drug law enforcement officials have surmised that LSD chemists and top echelon traffickers form an insider's fraternity of sorts. They successfully have remained at large because there are so few of them. Their exclusivity is not surprising given that LSD synthesis is a difficult process to master. Although cooks need not be formally trained chemists, they must adhere to precise and complex production procedures. In instances where the cook is not a chemist, the production recipe most likely was passed on by personal instruction from a formally trained chemist. Further supporting the premise that most LSD manufacture is the work of a small fraternity of chemists, virtually all the LSD seized during the 1980's was of consistently high purity and sold in relatively uniform dosages of 20 to 80 micrograms.

LSD commonly is produced from lysergic acid, which is made from ergotamine tartrate, a substance derived from an ergot fungus on rye, or from lysergic acid amide, a chemical found in morning glory seeds. Although theoretically possible, manufacture of LSD from morning glory seeds is not economically feasible and these seeds never have been found to be a successful starting material for LSD production. Lysergic acid and lysergic acid amide are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate is regulated under the Chemical Diversion and Trafficking Act.

Ergotamine tartrate is not readily available in the United States, and its purchase by other than established pharmaceutical firms is suspect. Therefore, ergotamine tartrate used in clandestine LSD laboratories is believed to be acquired from sources located abroad, most likely Europe, Mexico, Costa Rica, and Africa.11 The difficulty in acquiring ergotamine tartrate may limit the number of independent LSD manufacturers. By contrast, illicit manufacture of methamphetamine and phencyclidine is comparatively more prevelant in the United States because, in part, precursor chemicals can be procured easily.

Only a small amount of ergotamine tartrate is required to produce LSD in large batches. For example, 25 kilograms of ergotamine tartrate can produce 5 or 6 kilograms of pure LSD crystal that, under ideal circumstances, could be processed into 100 million dosage units, more than enough to meet what is believed to be the entire annual U.S. demand for the hallucinogen. LSD manufacturers need only import a small quantity of the substance and, thus, enjoy the advantages of ease of concealment and transport not available to traffickers of other illegal drugs, primarily marijuana and cocaine.

Cooking LSD is time consuming; it takes from 2 to 3 days to produce 1 to 4 ounces of crystal. Consequently, it is believed that LSD usually is not produced in large quantities, but rather in a series of small batches. Production of LSD in small batches also minimizes the loss of precursor chemicals should they become contaminated during the synthesis process.

LSD crystal produced clandestinely can be as much as 95- to 100-percent pure. At this purity-and assuming optimum conditions during dilution and application to paper-1 gram of crystal could produce 20,000 dosage units of LSD. However, analysis of LSD crystal seized in California over the past 3 years revealed an average purity of only 62 percent. Moreover, LSD degrades quickly when exposed to heat, light, and air and is most susceptible to degradation during the application process and once it is in paper form. As a result, under less than optimal, real-life conditions, actual yields are significantly below the theoretically possible yield: 1 gram of LSD crystal genarally yields 10,000 dosage units of LSD, or approximately 10 million dosage units per kilogram.

Over the past 30 years, the traditional dilution factor for manufacturing LSD has been 10,000 doses per 1 gram of crystal. Therefore, dosage units yielded from high-purity (95- to 100-percent pure) LSD crystal would contain 100 micrograms. However, dosages currently seen contain closer to 50 micrograms. This discrepancy stems in part from production impurities: during the sythesis process, manufacturers generally fail to perform a final 'clean-up' step to remove by-products, thereby lowering the crystal's purity. Further, though average purity of tested LSD crystal samples is, as noted, 62 percent, the average potency of doses analyzed is approximately 50 micrograms rather than 62 micrograms, as would be expected. The diminished potency can be attributed to distributors who, when applying the crystal to paper, often 'cheat' by diluting 1 gram of crystal to produce up to 15,000 or more dosage units.

Pure, high-potency LSD is a clear or white, odorless crystalline material that is soluble in water. It is mixed with binding agents, such as spray-dried skim milk, for producing tablets or is dissolved and diluted in a solvent for application onto paper or other materials. Variations in the manufacturing process or the presence of precursors or by-products can cause LSD to range in color from clear or white, in its purest form, to tan or even black, indicating poor quality or degradation. To mask product difficiencies, distributors often apply LSD to off-white, tan, or yellow paper to disguise discoloration.

At the highest levels of the traffic, where LSD crystal is purchased in gram or multigram quantities from wholesale sources of supply, it rarely is diluted with adulterants, a common practice with cocaine, heroin, and other illicit drugs. However, to prepare the crystal for production in retail dosage units, it must be diluted with binding agents or dissolved and diluted in liquids. The dilution of LSD crystal typically follows a standard, predetermined recipe to ensure uniformity of the final product. Excessive dilution yields less potent dosage units that soon become unmarketable.

LSD crystal usually is converted into tablet form ('microdots' that are 3/32 inch or smaller in diameter), thin squares of gelatin ('window panes'), or applied to sheets of prepared paper (blotter paper-initially used as a medium-has been replaced by a variety of paper types). LSD most frequently is encountered in paper form, still commonly referred to as blotter paper or blotter acid. It consists of sheets of paper soaked in or otherwise impregnated with LSD. Often these sheets are covered with colorful designs or artwork and are usually perforated into one-quarter inch square, individual dosage units.

KrZ (posted 05-21-98)

Taken from Michael Valentine Smith: Psychedelic Chemistry, pages 105-107:

The Culture and Extraction of Ergot Alkaloids

Sucrose .................................... 100 g
Chick pea meal .............................. 50 g
Calcium nitrate .............................. 1 g
Monopotassium phosphate ...................... 250 mg
Magnesium sulphate ........................... 250 mg
Potassium chloride ........................... 125 mg
Ferrous sulphate heptahydrate ................ 8.34 mg
Zinc sulphate heptahydrate ................... 3.44 mg

Make up a culture medium by combining the following ingredients in about 500 milliliters of distilled water in a 2 liter, small-neck flask:

Add water to make up one liter, adjust pH 4 with ammonia solution and citric acid. Sterile by autoclaving.

Inoculate the sterilized medium with Claviceps purpurea under sterile conditions, stopper with sterilized cotton and incubate for two weeks periodically testing and maintaining pH 4. After two weeks a surface culture will be seen on the medium. Large-scale production of the fungus can now begin.

Obtain several ordinary 1 gallon jugs. Place a two-hole stopper in the necks of the jugs. Fit a short (6 inch) glass tube in one hole, leaving 2 inches above the stopper. Fit a short rubber tube to this. Fill a small (500 milliliter) Erlenmeyer flask with a dilute solution of sodium hypochlorite, and extend a glass tube from the rubber tube so the end is immersed in the hypochlorite. Fit a long, glass tube in the other stopper hole. It must reach near the bottom of the jug and have about two inches showing above the stopper. Attach a rubber tube to the glass tube as short or as long as desired, and fit a short glass tube to the end of the rubber tube. Fill a large, glass tube (1 inch x 6 inches) with sterile cotton and fit 1-hole stoppers in the ends. Fit the small, glass tube in end of the rubber tube into 1 stopper of the large tube. Fit another small glass tube in the other stopper. A rubber tube is connected to this and attached to a small air pump obtained from a tropical fish supply store. You now have a set-up for pumping air from the pump, through the cotton filter, down the long glass tube in the jug, through the solution to the air space in the top of the jug, through the short glass tube, down to the bottom of the Erlenmeyer flask and up through the sodium hypochlorite solution into the atmosphere. With this aeration equipment you can assure a supply of clean air to the Claviceps purpurea fungus while maintaining a sterile atmosphere inside the solution.

Dismantle the aerators. Place all the glass tubes, rubber tubes, stoppers and cotton in a paper bag, seal tight with wire staples and sterilize in an autoclave.

Fill the 1-gallon jugs 2/3 to 3/4 full with the culture medium and autoclave.

While these things are being sterilized, homogenize in a blender the culture already obtained and use it to inoculate the media in the gallon jugs. The blender must be sterile. Everything must be sterile.

Assemble the aerators. Start the pumps. A slow bubbling in each jug will provide enough oxygen to the cultures. A single pump can, of course, be connected to several filters.

Let everything sit a room temperature (25 C) in a fairly dark place (never expose ergot alkaloids to bright light - they decompose) for a period of ten days.

After ten days adjust the culture to 1% ethanol using 95% ethanol under sterile conditions. Maintain growth for another two weeks.

After total of 24 days growth period the culture should be considered mature. Make the culture acidic with tartaric acid and homogenize in a blender for one hour.

Adjust to pH 9 with ammonium hydroxide and extract with benzene or chloroform/iso-butanol mixture.

Extract again with alcoholic tartaric acid and evaporate in a vacuum to dryness. The dry material in the salt (i.e., the tartaric acid salt, the tartrate) of the ergot alkaloids, and is stored in this form because the free basic material is too unstable and decomposes readily in the presence of light, heat, moisture and air.

To recover the free base for extraction of the amide of synthesis to LSD, make the tartrate basic with ammonia to pH 9, extract with chloroform and evaporate in vacuo.

If no source of pure Claviceps purpurea fungus can be found, it may be necessary to make a field trip to obtain the ergot growths from rye or other cereal grasses. Rye grass is by far the best choice. The ergot will appear as a blackish growth on the tops of the rye where the seeds are and are referred to as "heads of ergot." From these heads of ergot sprout the Claviceps purpurea fungi. They have long steams with bulbous heads when seen under a strong glass or microscope. It is these that must be removed from the ergot, free from contamination, and used to inoculate the culture media. The need for absolute sterility cannot be overstressed. Consult any elementary text on bacteriology for the correct equipment and procedures. Avoid prolonged contact with ergot compounds, as they are poisonous and can be fatal.

The whole part with the pump is unecessary, you can get micropore 1-gallon jugs from http://www.fungi.com and alot of the gear you would need, obtaining a pure strain sounds like the tricky part, culturing and selection of pure-looking samples a couple times should do it. LSD must be synthesized, it's such a beautiful molecule...

Piglet (posted 05-21-98)

Fan of Shulgin: I checked out the 'Operation Julie' book and it says that the Ergot compounds were ALL bought. Initially by simply driving to Switzerland and paying cash (those were the days!) and later using fake companies and from underground sources (Brotherhood of Eternal Love with Leary et all).

I have never read of any large LSD manufacturers making there own. It is quite a skill & is quite dangerous (ergot IS classed as a poison, do you like your extremeties? Do you want them to go black and drop off? Don't try growing ergot without knowing the safety rules)

Someone I know was in prison with Kemp (the Julie main-man) and Kemp is a 1 in a million brainiac.

Ergot compounds appear in certain prescription migraine medications (all made by Sandoz, fancy that!)

The book 'Operation Julie' has a few pictures of the chemistry setup. It was pretty involved stuff. One small hilight was a brown bottle featured slap-bang in the middle of one picture. It said 'NaNO2'. Fester says that this 'might' be a replacement for acetyl-acetone. It is. THAT was the Method-X bit. It's not even a secret.

drone 342 (posted 05-21-98)

Here's a thought:

What about using DCC as your dehydrating reagent for forming an amide bond? High yields and low temps means better product in larger quantities.

Ref: Encyclopedia for Organic Synthesis, Paquett, L.A., Ed; Wiley, 1995; vol. 3, p. 1731

also check your Merck (of course)

Much of the fancy-schmancy technology devoted to peptide synthesis is equally applicable in this situation as well. There's a ton of ways to go from an acid to an amide, and its good to have as many as possible in one's repetoire.

oh yeah, DCC is "DiCyclohexylCarbodiimide".

Structure: (C6H12)-N=C=N-(C6H12)

The reaction converts this to dicyclohexylurea.

KrZ posted (05-22-98)

JLF sells pure claviceps purpea 1 gm for 10.00.

drone 342 (posted 05-22-98)

Re: Claviceps. That doesn't sound like too good of a deal. Do they have better prices when you buy in bulk? Even at half the price, that really isn't too good a deal. Considering the tiny percentage of ergot alkaloids in a gram, then considering how much less you have after hydrolyzing off those useless peptides, and how much less you have still after the dehydration of the acid with ethylamine, ten dollars is way more than street prices. This isn't even counting in labor as a cost (most chemists I know like to get paid.)

josh (posted 05-22-98)

Hey drone, would you post a synth. for lsd using bromocryptine.This synthesis that you have briefly described is very interesting.This bee would greatly appreciate it.

Ritter (posted 05-22-98)

I'm no expert on Grignards, however do you really feel you could get the -Br to react w/ Mg to make the Grignard? My experience has been that its pretty freakin' difficult to make tender complicated multi-cyclic molecules such as bromocryptine undergo Grignard formation. I only skimmed your comments above and may be reiterating what you stated but I think the best way to go about this would be to hydrolyze off the peptide garbage leaving bromo lysergic acid and then subject this to Grignard's reaction. I think the appropriate time to form the amide is after the Grignard because a carboxyl group will probably be less reactive than an amide group towards the Grignard.

drone 342 (posted 05-24-98)


Yes, Grignard will work wonders in this case, and no, it actually is easy to get it to do it. All that multicyclic studd simply doesn't appeal to the grignard substituent -- its looking for an electron-deficient site labile and with nowhere to run to. Amides are surpisingly sturdy to these condsitions, and will not readily react at all. As far as I see it, that would really be the only concern (regarding the carbonyls found therin.)The reason for this is that the nitrogen is electron donating, whereas in any other carbonyl, it doesn't have this luxury, and will react readliy with a Grignard. Conditions are a snap, just a nice dry ether soultion or Benzene solution (with light being thoroughly eliminatined from the envronment around the flask) of the free base of your ergot caompound in question will do. If you're still worried about that reaction affecting the peptide, just save it for the last step -- make bromo-LSD, then do it. I guaruntee that the amide will be safe.


Thank you. This is the useful type of information we need buckets of if we want to end the war on drugs (my strategy: an all-out assault; a psychedelic blitzkrieg. Hey, now that's a catchy phrase!)

drone 342 (posted 05-24-98)

Fan of Shulgin,

Where can you get a living 1-gram clean specimen of claviceps purpurea? Are you sure its alive? How do you know this works, or is this strictly speculation?


Tell you what; I'll give the ref's, and anybody with the resources to actually perform this should also have plenty of access to the library. Actually, all you need is a copy of a decent lab manual describing the synthesis of grignard reagents, and follow the general guidelines for producing a Grignard intermediate. Then, add water. You now have ergocriptine. Hydrolyze it and condense with diethylamine according to the proceedures listed in TiHKAL.

Alternatively, one could use DCC. From the Encyclopedia of Reagents for Organic Synthesis:

Typically, DCC (1.1 equiv) is added to a concentrated solution (0.1-1.0M) of the carboxylic acid (1.0 equiv), amine (1.0 equiv), and catalyst (when used) in methylene chloride or acetonitrile at 0°C. The hydrated DCC adduct, dicyclohexylurea (DCU), quickly precipitates and the reaction is generally complete within 1 h at rt..."

Downsides: THF and DMF screw things up by slowing things down and ecouraging the production of side-products, as well as racemizing the carboxylic acid. The other downside is in some solvents, a trace of DCU can disolve in with your product, requiring purification (nothing flash chromatography wouldn't take care of quite easily, which you have to do anyways if you want to be a good person.)

Further refs:

Piglet (posted 05-26-98)

Fan Of Shulgin: When I typed about the dangers of ergot, I meant to to guy producing it. The actual amount of ergot needed to produce 'St. Antonys Fire' immediately seem quite low. It was estimated from the last outbreaks (after WW2 when people were starving and would eat ANYTHING including infested rye) that about 30mg causes SEVERE reactions. I know you would never ingest such amounts of ANY substence in a lab, but growing your own ergot is not a lab technique. I did check out that old chestnut about growing in culture. Most of the researchers had little success. I think it CAN be produced in culture, but only by someone who REALLY knows there stuff. Sandoz grow rye to this day!

drone 342 (posted 06-10-98)

Piglet, where did you get this information about Sandoz? As far as I know, Claviceps is one of those organisms that researchers have spent a lot of time, money, and energy in getting it to grow in submerged culture on a large scale -- and have come up with a successful means of doing so. I've heard some similar things in publications from times past, but I suspect that in modern industry, the transition has been made.

Cherrie Baby (posted 06-11-98)

"Where can you get a living 1-gram clean specimen of claviceps purpurea?"

During late summer have a look at the Rye grass in the local park. You'll notice a purple-brown "ear" growing on the rye seeds - this stuff is Claviceps purpurea. It grows in my back garden. If you have some experience with shrooms this is easy to grow. The big catch is that nearly all the LSA producing ergot has been from particular strains which you'll have to get from a lab that stocks pure cultures. I don't think wild ergot would work when making LSA's. I've been told that you can grow the ergot (easily) but it won't make LSA unless it's the right strain!

Are there any biochemists out there who know the answer to this one way or another?

Forest Gump (Posted Dec. 24, 1997)

The book that you refer to "Practical LSD Manufacture" by Uncle Fester, now in its 2nd Ed. isn't completely about LSD, although from the title one could get that impression. The first edition contianed 115 pages, of which only about 70 pages actually had anything to do with LSD synthesis, the rest mostly about Fester's pet project: TMA-2 synthesis. The second edition contains 142 pages, almost all the extra pages going to his pet project -- which now consumes about halve the book -- while the LSD portion remains virtually unchanged (all the errors and mistakes of the first edition were remarkably well preserved into the second). A naive person could be forgiven for mistakenly thinking the book of being just a vehicle for his pet project -- but of course we know better.

Before I list just some of those errors let me preface it with this: it is obvious that not only does Fester not have any practical experience with Lysergic chemistry, but that he is also confused by it.

  1. Isomer Confusion. In chapter 4 Fester makes repeated mistakes as to chirality. On page 24, in reference to the anhydrous hydrazine degradation method, he tells us that this procedure produces very little iso- compound, when in fact it produces predominately iso- material. On page 25 he informs us of the importance of maintaining anhydrous conditions to avoid getting racemic product -- on further reading it is obvious that by "racemic" he means iso/normal mixtures, as nowhere is there to be found any reference to the l (levo) compound.

    The older hydrazine hydrate method produced a 1/1 mixture of d and l compounds; the l compounds are inactive and represent a total loss, as there is no convenient method to convert them into the desired d compound. The anhydrous hydrazine method is a newer improvement upon this which avoids the l compound, but it still gives about 2/3 of the iso- compound which is also inactive; 2/3 inactive product sounds real bad, but it's not nearly as bad as the older method because the iso- compound is easily isomerized into the active compound in about 2/3 yield. When Hofmann refers to this new method as not producing any "racemic" material what he means is that it doesn't produce any of the useless l compound, not that it doesn't produce iso- compound.

    Also, the amidation procedure he gives in the same chapter produces some iso- compound, although nowhere does he mention that. Indeed, from reading the purifacation procedure, he seems to think that this amidation method also preserves chirality.

  2. Continuum Error. The first paragraph on page 27 (i.e., "Both of these choices are really very poor, ...") picks up from nowhere, and we're left to wonder what he's refering to. Chalk this one up to bad proofreading (this is Loompanics we're talking about after all).

  3. Outdated Methods. The four amidation methods in the book have long since been superseded by the phosphorus oxychloride in chloroform method, which is not in the book.

  4. Method X. In the book a big deal is made about his erroneous discovery of a "superior" LSD method which he calls "method x". I'll spare you all the convoluted details and inane logic of how he came about this "discovery" except for this one statement of his: "Note that propionic anhydride is a listed chemical under the Chemical Diversion Act, with a reporting threshold of 1 gram. There is only one substance in the field of clandestine drug manufacture where 1 gram is a significant amount -- LSD"

I'm sure not a few DEA chemists must have laughed there ass off after having read that. Propionic anhydride is used to make fentanyl and its analogues. Some fentanyl analogues are 10 times more potent than LSD!!!!

And that is just some of the errors contained within that book. And with that I'll leave you, hopefully a little bit more knowlegable.

FX (Posted Dec. 25, 1997):

Hey, thanks a lot. You seem to know quite a bit about LSD chemistry. I'm sure that Fester's book has some errors, but I am not aware of any other book in existence on practical LSD manufacture. Are you? It is amazing how few people know anything about LSD synth, apparently it is the hardest recreational drug to manufacture of them all, much much harder than ectacy or meth. Why is this? How should someone go about learning about LSD manufacture assuming that they don't have PhDs in chemistry? According to DEA, almost all of the LSD made in the United States is made but just a handful of chemists in california! Can you believe that? A half a dozen people make amost 100 million hits per year, and they have been doing it since the 1960s! This almost blows the mind!

Forest Gump (Posted Dec. 25, 1997):

Below are all the books that are in print that I know of which contain LSD synthesis procedures:

So, which ones do I recomend for someone serious about LSD chemistry? Well, all of them! But not for the reasons you might think at first.

Most of these books contain serious errors. The Anarchist Cookbook for example has a method of "Making LSD in the kitchen" which is incorrect of course, although it does give an accurate procedure which is merely a reprint of the first part of Pioch's patent method. The Book of Acid calls to use sodium nitrate in one method, when in fact it is sodium nitrite which is used in that procedure. Recreational Drugs doesn't really contain anything that wasn't already in Psychedelic Chemistry, although it does give an incorrect LSD structure. All these books can go a long way in developing one's critical faculties though -- which is an important attribute for an LSD researcher to have, considering the B.S. factor that surrounds LSD.

So, which of these books do I think are the most important to have? All the books listed below, in order of importance:

  1. Psychedelic Chemistry
  2. Practical LSD Manufacture

Again, not for all the obvious reasons. Number 1 and 2 contain many journal references, and so can be a good step-off point to the real gold mine: the chemical journals at your nearest university science library. TIHKAL and #1 both have the most up-to-date method, although that's the only method TIHKAL has.

Believe it or not, you can probably start learning about LSD chemistry right now if you have a chemistry text-book or are near any library. Just look-up the following (numbered in order of importance):

  1. carboxyl group;
  2. carboxylic acids;
  3. amides;
  4. amines;

also, look-up:

and of course, alkaloids.

You see, LSD is an amide. LSD is usually made from lysergic acid which is a carboxylic acid and diethylamine which is an amine. Lysergic acid is in turn usually made by degradation of an amide, such as ergotamine.

All of these procedures involve the changing of one functional group: the carboxyl group. A good LSD chemistry researcher will devote much (MUCH) study to this group.

I hope that this has been helpful.

Forest Gump:

CB: (2) Another dodgy thing about Fester's "Practical LSD Manufacture" is his recommendation to make LSAs by growing ergot on rye and to plant your own rye field in order to do this! Is the man mad? Fester appears to be ignorant of the existence of C. paspali.

FG: Yes, Fester is a bit loopy to think that prospective LSD chemists are going to become Farmer for a Year. Although the method certaintly works, the labor and amount of solvents required make it impractical for one or two people.

Some more references:

CB: (4) In D. M. Perrine's book "The chemistry of mind-altering drugs" pages 274-278 outline syntheses of LSD. He includes both modern total synthetic methods and clandestine methods [he figures that lysergic acid is made from either growing C. paspali to produce paspalic acid OR by diverting LSA from medicines]

Some of Perrine's references are:

CB: (5) In M. V. Smith's "Psychedelic Chemistry" growth of C purpurea on synthetic media is described. Just about everyone claims that C purpurea will only grow on grain in a field. What's Up Doc?

FG: Getting species of Claviceps to grow in culture is easy. Getting species of Claviceps to grow in culture and produce lysergamides' is what's hard. I'm sure M. V. Smith's method in said book will work just fine for growing Claviceps species, but it will all be for nought, as no lysergamides' will be produced by it.

Successful culture methods have been developed which use specific strains of both C. paspali and C. purpurea to produce as much as 2 to 5 g of lysergamides per liter of culture!!!!

I direct you to "Biosynthesis of Ergot Alkaloids and Related Compounds", Tetrahedron, Vol. 32, pp. 873-912 (1976). On page 883 under the heading "Industrial production of ergolines" it gives a brief overview of what I just mentioned, and gives references to those procedures.

I hope that this has been helpful for you.

Subject: Lysergic Acid references as promised...
From: aankrom@blackfoot.ucs.indiana.edu (aankrom)
Date: Thu, 7 Apr 1994

FN Johnson et al, J. Med. Chem. 16, 532 (1973), "Emetic Activity of Reduced Lysergamides"

(LSAs using amine and POCl3) JACS 76, 5256; Tet. Lett. 1569 (1969)

Biosynthesis of ergot in submerged culture:
Arcamone et al,
Proc. Roy. Soc. B155, 26 (1961)

Stoll & Hofmann - In "The Alkaloids" - ed Manske & Holmes, vol 8, 725-83.

Fetoclavine & fumigaclavine in Aspergillus fumigatus
Fres, Spilsbury & Wilkinson
Fumigaclavine in Rhizopus nigricans - Yamano et al, 1962, 1961

KrZ - posted 06-21-98


CA: 71:P69351y : Describes mutants of strain NRRL 3027 producing 2270mg/l of ergoline compounds of which 85% were amides of lysergic and isolysergic acids. (Swiss patent application)

CA: 77:P156333n : Describes a method used to get 9.75g pure lysergamides from a 10 litre fermentation originally containing an estimated 15g.

CA: 94:13992r : Reference Indian Drugs; 1980; 17(8) 228-31 (Eng.)

CA: 90:118108c : Reference Indian Drugs; 1979; 16(4) 88-93 (Eng.)

CA: 102:219574y : Serbo-Croat areticle describing 2.2g/l prod. by C. paspali Stevens and Hall (1984).

Life History and Poisonous Properties of Claviceps paspali;
H. B. Brown (Mississippi Agricultural Experiment Station);
Journal of Agricultural Research, Vol. 7, No. 9, pp 401-405.
Describes on brief glance through it - germination of the yellowish-grey sclerotia found on Paspalum dilatatum Poir. observed in the region of the Mississippi Agricultural College. Also contains reference to Stevens and Halls' original article (1910).

Biotechnological Exploitation of the Ergot Fungus (Claviceps Purpurea);
Karl Esser and Andrea Duvell; Process Biochemistry, August 1984 pgs 142-149.
Synopsis: "The alkaloids of the ergot fungus C. purpurea and related species already known as drugs in the middle ages are still finding many uses in medical therapy (he he). Since the supply of natural grown ergots is not sufficient, the biotechnological production of ergot alkaloids has gained in importance. This requires not only an undestanding of physiological and environmental conditions, but also concerted breeding in order to increase and stabilize the production level".

Biology of Claviceps; Willard A. Taber; Chapter 15 (sorry - i don't remember which book this came from, but it should be indexed under Taber in Biological Abstracts) pgs 449-486.
"If one desires isolates of C. paspali (which are high producers of simple amides), one must go to paspalum grass. ... C. paspali differs from all other species in possesing a yellowish tan cauliflower- shaped sclerotium rather than the purplish banana-shaped sclerotium, and it has been suggested that this species be trasnsferred to the genus Mothesia."

The Ergot Alkaloids; A. Stoll and A. Hofmann (THE);
Chapter 21, The Alkaloids, Manske (ed. ?) vol. VIII, pgs 725-779+.
Describes lots and lots and lots of chemical detail regarding everything from biogenesis to complete chemical synthesis as a means of confirming structure. Also has a section completely devoted to "Derivatives of Ergot Alkaloids" in which the following processes for synthesizing amides are discussed:

Kobel, Schreier, Rutschmann. Helv. Chim. Acta, 47, 1052 (1964)

Subject: LSD in the Literature

Certainly making LSD from 'scratch' is not currently thought to be cost effective, however, a variety of publications exist describing how. I realize that this compilation may be above most of your heads however some of the more serious of you might be interested in some of the literature describing various LSD syntheses. If you know of others please post them.

A short synthesis of the 8-azaergoline ring system by intramolecular tandem decarboxylation-cyclization of the Minisci-type reaction
Doll MKH
J Org Chem 64, 1372-1374 (1999)

Enantiospecific synthesis of (R)-4-amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole, an advanced intermediate containing the tricyclic core of the ergots
Hurt CR, Lin RH, Rapoport H
J Org Chem 64, 225-233 (1999)

Practical synthesis of 8-alpha-amino-2,6-dimethylergoline: An industrial perspective
Baenziger M, Mak CP, Muehle H, et al.
Org Process Res Dev 1(6), 395-406 (1997)

New synthesis and characterization of (+)-lysergic acid diethylamide (LSD) derivatives and the development of a microparticle-based immunoassay for the detection of LSD and its metabolites
Li Zy, Gocszkutnicka K, McNally AJ, et al.
Bioconjugate Chem 8(6) 896-905 (1997)

Total synthesis of 2,6-dimethylergolin-8 alpha-amines
Waldvogel F, Engeli P, Kusters E
Helv Chim Acta 80(7), 2084-2099 (1997)

A new synthesis of indoles
Murphy JA, Scott KA, Sinclair RS, et al.
Tetrahedron Lett 38(41), 7295-7298 (1997)

An attempted total synthesis of lysergic acid via an alkene/N-sulfonylimine cyclization
Ralbovsky JL, Scola PM, Sugino E, et al.
Heterocycles 43(7), 1497-1512 (1996)

Enzymatic Synthesis Of Beta-N-Acetylhexosaminides Of Ergot Alkaloids
Kren V, Scigelova M, Prikrylova V, Et Al.
Biocatalysis 10(1-4), 181-193 (1994)

Synthesis Of Lysergic-Acid Derivatives By Tandem Radical Cyclization Reactions
Ozlu Y, Cladingboel De, Parsons Pj
Synlett (5), 357-358 (1993)

A New Synthesis Of (±)-Lysergic Acid
Kurihara T, Terada T, Yoneda R
Chem Pharm Bull 34(1), 442-443 (1986)

A New Synthesis Of Lysergic Acid
Rebek J, Tai Df
Tetrahedron Lett 24(9), 859-860 (1983)

A New Synthesis Of (±)-Lysergic Acid
Kiguchi T, Hashimoto C, Naito T, Et Al.
Heterocycles 19(12), 2279-2282 (1982)

Total Synthesis Of (±)-Lysergic Acid By An Intramolecular Imino-Diels-Alder Reaction
Oppolzer W, Francotte E, Battig K
Helv Chim Acta 64(2), 478-481 (1981)

Synthesis of LSD-25

Originally published in 1967 as "The Psychedelic Guide to Preparation Eucharist" by Robert E. Brown.

Preparatory arrangements

Starting material may be any lysergic acid derivative,from Claviceps purpures(ergot) on rye grain or from culture, from Ipomea (morning glory) seeds, or from synthetic sources. Preparation #1 uses any amide, or lysergic acid as starting material. Preparations #2 and #3 must start with lysergic acid only, prepared from the amides as follows:

10 g of any lysergic acid amide from various natural sources is dissolved in 200ml of mathanoic KOH solution and the methanol removed immediately in vacuum. The residue is treated with 200ml of an 8% aqueous solution of KOH and the mixture heated on a steam bath for one hour. A stream of N2 gas is passed through the flask during heating and the evolved NH3 in the gas stream may be titrated in HCL to follow the reaction. The alkaline solution is made neutral to congo red with tartaric acid,filtered,cleaned by extracting with ether, the aqueous solution filtered and evaporated. Digest with MeOH to remove some of the colored material from the crystals of lysergic acid.

Arrange the lighting in the laboratory similarly to that of a darkroom. Use photographic red and yellow safety lights since lysergic acid derivatives are decomposed by light. A weak, long wave ultraviolet source is conveniently made from the purple glass filter used in the 1950 ford dash lighting system. A small tungsten bulb will provide enough light.

Have plenty of aluminum foil handy to cover reagents and products when light is present. Rubber gloves must be worn due to the highly poisonous nature of ergot alkaloids. A hair dryer, or, much better, a flash evaporator, is necessary to speed up steps where evaporation is necessary.

Preparation #1

Step I - Use Yellow Light

Place one volume of powdered ergot alkaloid material in a tiny roundbottom flask and add two volumes of anhydrous hydrazine. An alternate procedure uses a sealed tube in which the reagents are heated at 112°C. The mixture is refluxed (or heated) for 30 minutes. With an open condenser, keep an inert atmosphere on the reaction. Add 1.5 volumes H2O and boil 15 minutes. On cooling in the refrigerator, isolysergic acid hydrazide is crystallized.

Step II - Use Red Light

Chill all reagents and have ice handy. Dissolve 2.82 g of the hydrazide rapidly in 100ml 0.1 N ice-cold HCl using an ice bath to keep the reaction vessel at 0°C. 100ml ice-cold 0.1 N NaNO2 is added and after 2 to 3 minutes vigorous stirring, 130ml more HCl is added dropwise with vigorous stirring again in an ice bath. After 5 minutes, neutralize the solution with NaHCO3 saturated sol. and extract with ether. Remove the aqueous solution and try to dissolve the gummy substance in ether. Adjust the ether solution by adding 3 g diethylamine per 39ml ether extract. Allow to stand in dark, gradually warming up to 20°C over a period of 24 hours. Evaporate in vacuum and treat as indicated in the purification section for conversion of iso-lysergic amides to lysergic acid amides.

Preparation # 2

Step I - Use Yellow Light

5.36 g of d-lysergic acid are suspended in 125ml of actonitrile and the suspension cooled to about -20°C in a bath of acetone cooled with dry ice. To the suspension is added a cold -20°C solution of 8.82 g of trifluoroacetic anhydride in 75ml of acetonitrile. The mixture is allowed to stand at -20°C for about 1.5 hours during which time the suspended material dissolves, and the d-lysergic acid is converted to the mixture anhydride of lysergic and trifluoroacetic acids. The mixed anhydride can be separated in the form of an oil by evaporating the solvent in vacuum at a temperature below about 0°C. Everything must be kept anhydrous.

Step II - Use Red Light

The solution of mixed anhydrides in acetonitrile from Step I is added to 150ml of acetonitrile containing 7.6 g of diethylamine. The mixture is held in the dark at room temperature for about 2 hours. The acetonitrile is evaporated in vacuum, leaving a residue of LSD-25 plus other impurities. The residue is dissolved in 150ml of chloroform and 20ml of ice water. The chloroform layer is removed and the aqueous layer is extracted with several portions of chloroform. The chloroform portions are combined and in turn,washed with four 50ml portions of ice-water. The chloroform solution is then dried over anhydrous Na2SO4 and evaporated in vacuum.

Preparation # 3

The following procedure gives good yield and is very fast with little iso-lysergic acid being produced, however, the stoichometry must be exact or yields will drop.

Step I - Use White Light

Sulfur trioxide is produced in an anhydrous state by carefully decomposing anhydrous ferric sulfate at approximately 480°C. Store under anhydrous conditions.

Step II - Use White Light

A carefully dried 22 liter RB flask fitted with an ice bath, condenser, dropping funnel and mechanical stirrer is charged with 10 to 11 liters of dimethyformamide (freshly distilled under reduced pressure). The condenser and dropping funnel are both protected against atmospheric moisture. 2 lb. of sulfur trioxide (Sulfan B) are introduced dropwise, very cautiously with stirring, during 4 to 5 hours. The temperature is kept at 0-5 degrees throughout the addition. After the addition is complete, the mixture is stirred for 1-2 hours until some separated,crystalline sulfur trioxide-dimethylformamide complex has dissolved. The reagent is transferred to an air-tight automatic pipette for convenient dispensing, and kept in the cold. Although the reagent, which is colorless may change to yellow and red, its efficiency remains unimpaired for three to four months in cold storage. An aliguot is dissolved in water and titrated with standard NaOH to a phenolphthalein end point.

Step III - Use Red Light

A solution of 7.15 g of d-lysergic acid monohydrate (25 mmol) and 1.06 g of lithium hydroxide hydrate (25 mmol) in 200 L of MeOH is prepared. The solution is distilled on the steam bath under reduced pressure. The residue of glass-like lithium lysergate is dissolved in 400ml of anhydrous dimethyl formamide. From this solution about 200ml of the dimethyl formamide is distilled off at 15mm pressure through a 12- inch helices packed column. The resulting anhydrous solution of lithium lysergate left behind is cooled to 0 degrees and, with stirring, treated rapidly with 500ml of SO3-DMF solution (1.00 M soln). The mixture is stirred in the cold for 10 minutes and then 9.14 g (125.0 mmol) of diethylamine is added. The stirring and cooling are continued for 10 minutes longer, when 400ml of water is added to decompose the reaction complex. After mixing thoroughly, 200ml of saturated aqueous NaCl solution is added. The amide product is isolated by repeated extraction with 500ml portions of ethylene dicloride. The combined extract is dried and then concentrated to a syrup under reduced pressure. Do not heat the syrup during concentration. The LSD may crystallize out, but the crystals and the mother liquor may be chromatographed according to the instructions on purification.

Purification of LSD-25

The material obtained by any of these three preparations may contain both lysergic acid and iso-lysergic acid amides. Preparation #1 contains mostly iso-lysergic diethylamide and must be converted prior to separation. For this material, go to Step II first.

Step I - Use Darkroom and follow with Long Wave UV

The material is dissolved in a three to one mixture of benzene in chloroform. Pack a chromatography column with a slurry of basic alumina in benzene so that a one-inch column is six inches long. Drain the solvent to the top of the alumina column and carefully add an aliquot of the LSD-solvent solution containing 50ml of solvent and 1 g LSD. Run this solution through the column, following the fastest moving blue fluorescent band. After it has been collected, strip the remaining material from the column by washing with MeOH. Use the UV light sparingly during this procedure to prevent excessive damage to the compounds. Evaporate the second fraction in vacuum and set aside for Step II. The fraction containing the pure LSD is concentrated in vacuum and the syrup will crystallize slowly. This material may be converted to the tartaric acid and the LSD tartrate conveniently crystallized, mp 190-196°C

Step II - Use Red Light

Dissolve the residue derived from the methanol stripping of the column in a minimum amount of alcohol. Add twice that volume of 4 N alcoholic KOH solution and allow the mixture to stand at room temperature for several hours. Neutralize with dilute HCl, make slightly basic with NH4OH and extract with chloroform or ethylene dicloride as in preparations #1 or #2. Evaporate in vacuum and chromatograph as in the previous step.


Neutralize all leftover solutions and residues with NaHCO3 and evaporate in vacuum to low volume. Extract with ammoniacal chloroform and evaporate the extract to dryness. This residue may be run through the whole process again and more LSD will be produced.

Storage and use

Lysergic acid compounds (among them LSD) are unstable to heat, light and oxygen. In any form it helps to add ascorbic acid as an anti-oxidant, keeping the container tightly closed, light-tight with aluminum foil, and in refrigerator.

Packaging for use presents many possibilities, partially due to the incredibly small dosage involved. First a bio-assay of the solvent is made, then it may be measured by the volume of the solvent it is in. The solvent may be evaporated onto a weighed, calculated amount of some inactive powder such as chalk. sugar or baking soda. This bulky powder may be easily encapsulated in weightable portions. It is advantageous to add a trace of dry ascorbic acid to the dried powders. Sugar cubes offer a handy but extremely notorious method of dispensing. Other methods are without number, here being offered just a few occasionally used by the criminal element. Gelatin capsules are coated with the liquid solution and the capsules filled with an inert substance. Decoys such as this inert mixture might include a trace of brown color, a trace of quinine for fluorescence, and a trace of some relatively non-toxic compound which nearly mimicas the infra-red spectrum of LSD. For transport, a smuggler might evaporate a considerable amount onto a pocket handkerchief or onto a sheet of paper, providing the solution was properly decolorized before such treatment. These underhanded methods are used by criminals to avoid punitive action by law enforcement enthusiasts.

One gram of pure LSD, if used in a truly enlightened, careful manner can be the door to a magnificent experience to nearly 3,000 individuals. Used furtively and in ignorance, the same amount may bring terrible confusion and abject terror to nearly one-third of these.


Ergot Culture and Extraction of Lysergic Acid Derivatives

Synthesis of d-LSD maleate or tartrate from lysergic acid with POCl3

Emetic Activity of Reduced Lysergamides
Johnson, Ary, Teiger, Kassel. J
Journal of Medicinal Chemistry 16(5), 532-537 (1973)


Drug Discrimination and Receptor Binding Studies of N-Isopropyl Lysergamide Derivates
Huang, Marona-Lewicka, Pfaff, Nichols
Pharmacology, Biochmistry and Behavior 47(3), 667-673 (1994)

Stereoselective LSD-like Activity in d-Lysergic Acid Amides of (R)- and (S)-2-Aminobutane
Oberlender, Pfaff, Johnson, Huang, Nichols
Journal of Medicinal Chemistry 35(2), 203-211 (1992)

Synthesis and LSD-like Descriminative Stimulus Properties in a Series of N6-alkyl Nor-LSD Derivates
Hoffman-AJ, Nichols
Journal of Medicinal Chemistry 28, 1252-1255 (1985)

Note: JMC 35(2), 203-211 (1992) has some amazing stereoviews of LSD which might interest non-chemists who like to cross their eyes...

From: chrle@mursuky.campus.mci.net

As a public service to alt.drugs I have posted the following with some comments by myself. The following is a good example of the credo: A handful of refs does not a chemist make. I found this on one of the drug info sites. I've number the lines for commenting.

LSD Synthesis
  1. Under reduced light (or red light) a stirred solution of 3.15g (11mmol)
  2. of d-lysergic acid monohydrate and 4.45g (99 mmol) of diethylamine was
  3. brought to reflux by heating. Heat was removed, and reflux was maintained
  4. by the addition of 2 mL (3.4g, 22mmol) of phosphorous oxychloride (POCl3)
  5. over a 2 minute period. The mixture was then refluxed for an additional
  6. 4-5 mins until an amber-colored solution resulted. The solution was
  7. brought to room temperature and was washed with 200ml of 1M NH4OH.
  8. The CHCl3 solution was dried (MgSO4), filtered, and concentrated under vacuum
  9. (not allowing the solution to exceed 40°C). The last traces of the solvent were removed at 2-5 mmHg. The viscious residue was dissolved in a minimum amount of MeOH and acidified with a freshly prepared 20% solution of maleic acid in MeOH. Crystallization occured spontaneously. The needles were filtered, washed with cold MeOH and air-dried. Yield was 66% after further purification by column chromatography over alumina (Brockman) and elution with 3:1 benzene-chloroform. The chromatography takes appx 8-9 hours. Alternatively, it can be crystallized as the (+)-tartrate from MeOH. After crystallizing from cold MeOH, it is diluted with ethyl acetate, filtered and the the crystals are washed with ethyl acetate.

This procedure also works for primary amines and small dialkyl amines. LSD, however, probably remains the most worthwhile product. Other interesting amines might be the N-ethyl-N-propyl derivative (LEP) and the morpholide (LSM-775). 75µg of the morpholide have been reported to have been as effective as 50µg of d-LSD but with 45 min onset (vs 1 hour) and a 1 hour peak (vs 4 hours). The procedure would probably work well for LEP, but yields would be reduced for the morpholide. Other N20-alkyl-lysergic acid derivatives tend to be more than 10 times less potent than LSD if not effectively inactive. N6-ethyl- (and allyl/propyl) derivates of LSD may be more active than LSD itself, but synthetic routes to these chemicals presently start with LSD and yields would probably inhibit their appearance on the illicit market. (N6 is the other nitrogen on the ring structure in addition to the N1 pyrrole/indole nitrogen). Derivatives of LSD (besides LSA/LA-111 and lysergic acid) are not scheduled, but would be prosecutable under the designer drugs act after testimony from a DEA agent that in their opinion the defendant was planning to distribute them.


Line 1: suppose to be a refluxing slurry according to ref: [Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides." Journal of Medicinal Chemistry 16(5), 532-537 (1973)] Method B

Line 2: The 3.25g of d-lysergic acid monohydrate is suppose to be dissolved in 150ml of CHCl3. 96mmol of diethylamine is supposed to be used and 96mmol of this is ~7.1g, not 4.45g...(where's a good periodic chart when you need one?). The 7.1g of diethylamine is supposed to be dissolved in 25ml of CHCl3.

Line 3-4: To the 3.25g of d-lysergic acid monohydrate dissolved in 150ml of CHCl3 that is undergoing reflux is added the diethylamine/CHCl3 solution and 2 ml of POCl3. These are added simultaneously from separate dropping funnels over 2-3 minutes. Method B

Line 8: The CHCl3 is dried... What? Yes, it's dried but this is the first time that the procedure that was given in this "how to" even makes mention of it! Of course, all of this is made very clear in the ref: [Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides." Journal of Medicinal Chemistry 16(5), 532-537 (1973)]

It's pretty clear that this "how to" was posted by someone with little or no chemical expertise who had a couple of refs in hand, ran to the local college library, photocopied the papers, typed up this mess and posted it for the benefit (ha!) of others.

So, do you still want to attempt a synthesis of LSD? Yes? Well get the refs and get the whole story. A few chemistry classes wouldn't hurt either.

From: aankrom@blackfoot.ucs.indiana.edu
Subject: Re: How to Make LSD File 2
Date: Mon, 4 Apr 1994

When I saw the subjects relating to the synthesis of LSD, I knew the information would be outdated. It's humourous to see people who think they're in the know giving out info that was outdated even in the 70's.

Lysergic acid amides are commonly made by a simple and efficient procedure using POCl3 and the desired amine in CHCl3 solution. I doubt that this procedure is used by the majority of clandestine chemists, but since I don't know any, I wouldn't know. By the description of the procedure, it's simple and uses relatively safe reagents (I have a reference, but not handy...) And you won't find it in any obvious places even in the most recent Merck because LSD is not the product of focus in the article.

This is why I doubt that unsavvy clandestine chemists would be using this procedure. But according to the article, the method has a broad scope and has been used by Nichols and Oberlender for some other lysergic acid amides. (The article in question regards 9,10-saturated derivatives tested for emetic properties). It's time to stop turning to those stupid "how to make your very own drug" guides and learn how to read real chemsitry literature. If you can't, don't bother...

Even the synthesis of lysergic acid is outdated. Rebek has described an extremely elegant synthesis of methyl lysergate from L-tryptophan which gives only the natural isomer of lysergic acid. It's still a several step procedure, but most of the reagents are fairly common and the yields are greatly improved over past syntheses.

This brings me to an interesting side-note. Several years ago, analogues of LSD that were 2 and 3 times as potent as LSD were synthesized. These went largely unnoticed and would most likely prove of little interest to clandestine chemists because LSD was the precursor used and the loss in synthesis outweighed the gain in potency. But using Rebek's synthesis, one could simply alter the procedure slightly and intorduce the groups that make the compounds more potent. When the 6N-methyl group is replaced by ethyl or allyl, it becomes 2 and 3 times as potent respectively.

I am posting this for general information. I may post references if I decide it would be prudent. Requests will be ignored and I ask you not to send e-mail requesting references. But if you just want to chat about them and maybe speculate on subjective effects or other avenues of substitution... I don't know if I'll ever see the day that research in this area is open and legal, but I'd love to...

From: aankrom@blackfoot.ucs.indiana.edu
Subject: References as promised...
Date: Thu, 7 Apr 1994

OK. The references that I mentioned, here they come...

Synthesis of Ergot Alkaloids from Tryptophan
J Rebek Jr., et al,
J. Am. Chem. Soc. 106, 1813 (1984)

A New Synthesis of Lysergic Acid
J. Rebek Jr., et al,
Tet. Lett. 24(9), 859-860 (1983)
(and refs. therein.)

Emetic Activity of Reduced Lysergamides
FN Johnson et al,
J. Med. Chem. 16, 532 (1973)
(Lysergamides using s-amine and POCl3)

I still feel like making a disclaimer that I am not encouraging this information to be used to synthesize illegal compounds, but for personal enlightenment. It's time to pull chem-wannabe's out of the Dark Ages!