Alexander Shulgin's Greatest Psychedelic Hits
Alexander Shulgin created hundreds of psychedelic compounds — 6 of them stood out as his all-time favorites. He dubbed these his “magical half-dozen.”
Alexander Shulgin was the most prolific psychedelic chemist in history — earning him the nickname “the godfather of psychedelics.”
Few people have changed the course of psychedelic drug development and research the way he did.
Of course, Albert Hofmann — the man who first synthesized LSD and identified psilocybin from magic mushrooms — comes to mind too.
Alexander and his wife, Ann Shulgin, developed and cataloged well over 200 psychoactive substances — several of which have gone on to become some of the most well-known and well-researched psychedelics in the world.
Shulgin’s work directly led to the field of designer drugs which is now a pervasive field of interest consisting of thousands of psychoactive substances.
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How it All Started: DEA-Approved Psychedelics
Shulgin was working for Dow Chemical in the 1960s, where he quickly made a name for himself after inventing the first biodegradable chemical pesticide, Zectran — which earned the company millions.
It was around this time that Shulgin first started experimenting with psychedelics — particularly mescaline — the active ingredient in a series of psychoactive cacti (Peyote, San Pedro, and Peruvian Torch Cactus).
Shulgin worked out a deal with Dow where he could construct his own lab at home and work part-time as a consultant for the company. In his spare time, he would work on something much more interesting…
Shulgin was good friends with DEA officer Bob Sager, who was the head of the DEA’s Western Laboratories. Through this connection, he held pharmacology seminars for DEA agents and supplied the DEA with samples of psychoactive compounds. He even served as an expert court witness in exchange for permission to conduct experiments with restricted substances.
All of this led to the culmination of Shulgin’s laboratory — which he dubbed “The Farm.”
Shulgin had the expertise, equipment, and go-ahead from the DEA to invent, manufacture, and test psychedelics nobody else on Earth had access to.
Shulgin never sold any of his creations, and everything he did was legal. He even authored a reference book for law enforcement and received several awards from the DEA for his service.
It All Came Crashing Down in 1994
For two and a half decades, Shulgin was living the dream. He was earning good money working for Dow Chemical and giving lectures and spent most of his time working on what he loved.
I think deep down, Shulgin knew it wasn’t going to last forever.
He was always troubled by the accounts of a renegade psychoanalyst and creator of the “free love” movement, Wilhelm Reich. Reich had invented a device he called the orgone energy accumulator, which he claimed had healing abilities for those who lay inside it.
After the FDA asked Reich to stop advocating for his box, he refused and was thrown in jail, where he later died. All his research and writings on the orgone machine were destroyed.
Shulgin refused to share the same outcome and decided to stop publishing his works in academic literature. Instead, he began accumulating his research into a book co-authored by his wife called PIHKAL: A Chemical Love Story — which is part love story between the duo and part recipe book for over 200 psychedelic phenethylamines.
In 1994, just two years after the publication of his book, the DEA decided to raid his lab and stick him with $25,000 in fines. He then had to rescind his licenses for violating its terms — or else adhere to stipulations he considered “unreasonable.”
Shulgin didn’t stop working after that, but he was forced to change his focus to remain within the confines of the law. This later work led to the publication of his second book, TIHKAL: The Continuation — which is the second part to the couple’s love story and a recipe book focused on tryptamine-based psychedelics.
Shulgin’s Stance on Psychedelics
Shulgin’s entire life’s work was dedicated to identifying and documenting new psychedelic substances.
He claimed that mescaline made him aware of the existence of a world buried in our spirit, whose “availability” was “catalyzed” by chemicals.
He was a self-identified libertarian and believed there is no place for the government to control what people decide to take into their bodies.
He’s been quoted saying:
“Our generation is the first, ever, to have made the search for self-awareness a crime if it is done with the use of plants or chemical compounds as the means of opening the psychic doors.”
Shulgin believed psychedelic substances:
“must be not only allowed but encouraged. It’s essential that our present negative propaganda regarding psychedelic drugs be replaced with honesty and truthfulness about their effects, both good and bad.”
Staying true to his belief, Shulgin always offered a completely unbiased depiction of the substances he was using — both the good and the bad.
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What Drugs Did Alexander Shulgin Discover?
Shulgin was prolific when it came to inventing new drugs. As any good chemist, he was meticulous in his process.
After creating a new compound, he would begin the testing process — here’s how it worked:
He would start with an extremely low dose of the new drug first and increase slowly each day until he noticed psychoactive effects (AKA a threshold dose). Sometimes this would involve taking the drug for several weeks until it reached a dose high enough to exhibit effects.
Understanding that some compounds, such as LSD, are active at incredibly low doses (~50 micrograms), Shulgin would often start here in the 50–100 microgram range and build slowly over time. Some drugs, like mescaline, aren’t active until closer to 200 mg — over 1000 times that of LSD. (Needless to say, it sometimes took quite a while to find the safe active dose).
The problem with new, untested compounds is that there‘s no way of knowing what the dose could be until you test it.
This kind of testing was risky, but Alexander Shulgin was patient and cautious — the substance would present itself when it was ready.
Once the threshold was discovered, he and his wife would meet with his team of psychonaut friends to properly test the substance at his realized effective dose. They would all take what Shulgin believed to be a reasonable dose for each person, and work together to characterize the effects of the new drug.
Once a drug was mapped out, Shulgin would move on to the next one — rarely repeating any of the substances he created once the process was complete.
Here are some of his most notable discoveries:
MDMA
Alexander Shulgin is often credited with inventing MDMA (3,4-Methylenedioxymethamphetamine), but this isn’t exactly true.
MDMA was actually invented in a laboratory at Merck Pharmaceuticals in 1912, and the method of synthesizing it was patented in 1913. Merck conducted no formal studies on the substance after this, and it was shelved for decades.
After hearing about the substance, Shulgin set out to develop a new synthesis method to get around the patent. As a master of his craft, it took Shulgin no time to figure out another method to synthesize MDMA, which he published in his book PiHKAL.
Shulgin played an indirect (but significant) role in popularizing psychedelic-assisted psychotherapy. He introduced his newly-created MDMA to Leo Zeff — a psychologist in Oakland, California.
Zeff used MDMA with his patients in small doses and introduced the practice to hundreds of other psychotherapists around the country.
Now, as we’re in the middle of 2023, MDMA-assisted psychotherapy is on the verge of entering the mainstream once again.
The 2C-X Family
There are over 70 known 2C-X compounds in existence today — most of which were created by Shulgin but others, such as Aaron P. Monte, Johannes S. Buck, and Daniel Trachsel, have also contributed to this list.
2C substances are modeled after mescaline and are thought to work through similar mechanisms. They mimic the effects of dopamine and serotonin to alter regions of the brain involved with consciousness and sensory perception.
Some studies have found that 2C-B, the most studied member of the family, also affects the adrenergic receptors. This action is likely the cause of the stimulating effects that differentiate this group from other psychedelics like LSD or DMT.
The DOX Family
The DOX family of psychedelics is a series of highly potent, long-lasting psychedelic stimulants. The most popular member of the family is DOM (2,5-Dimethoxy-4-methylamphetamine) — more on this compound later.
Several members of this class approach similar potency as lysergamides like LSD or AL-LAD. The effects of these drugs are a distinct blend between the visual aspects of LSD and the empathogenic qualities of MDMA.
Unfortunately, this class has a high incidence of side effects and has proven difficult for users with less experience using psychedelics.
5-MeO-DALT & 5-MeO-MALT
Prior to his death, Shulgin was reportedly working on a series of N-allyated tryptamines — such as 5-MeO-DALT and 5-MeO-MALT. He never ended up getting through his rigorous testing protocol before sharing the recipe with a user on Reddit — who promptly blasted the recipe on his own website.
Within a few weeks, 5-MeO-DALT was available online, leading to the first overdose.
Someone in Florida took a dose 100 times higher than what Shulgin estimated the safe dose to be.
This is a prime example of why an expert like Shulgin is a necessary step in drug development. While taking unknown substances is inherently risky, there are ways to do it safely.
Shulgin would start with extremely small doses and build up very gradually over time until he felt the effects.
The user who overdosed took what he felt would be a strong enough dose to get him high and nearly died from it.
NBOMes
The NBOMe class of drugs (namely, 25-I-NBOMe) has effects very similar to LSD — but with some nasty downsides.
In PiHKAL, Shulgin referred to this substance with a positive sentiment — he enjoyed this compound a lot — but we now know this drug is extremely dose-dependent and can be lethal.
There have been deaths associated with this NBOMEs, and many people who narrowly escaped overdose experience lasting side effects from using the drug. It’s the only other psychedelic class potent enough to be administered via blotter paper — the same way LSD and other lysergamides are delivered.
NBOMe drugs are another good example of the inherent risk of research chemicals (compounds with little to no formal study). Without a large pool of data to draw information from regarding safety, it’s hard to know how you’re going to react to a certain compound.
Introducing Shulgin’s Magical Half-Dozen
Out of all the compounds Shulgin created, he and his wife dubbed just 6 of them as their so-called “magical half-dozen.”
1. Mescaline
(3,4,5-trimethoxyphenethylamine)
Mescaline was the first psychedelic drug Alexander Shulgin used, and it changed the course of his life forever.
His early work largely relied on manipulating the chemical structure of mescaline by adding new chemical groups in order to find new psychedelics. This directly led to the creation of the 2CX psychedelics, which dominate the list of Shulgins’ magical half-dozen.
Shulgin describes the effects of mescaline in PIHKAL as follows (400 mg dose):
“During the initial phase of the intoxication (between 2 and 3 hours) everything seemed to have a humorous interpretation. People’s faces are in caricature, small cars seem to be chasing big cars, and all cars coming towards me seem to have faces. This one is a duchess moving in regal pomp, that one is a wizened old man running away from someone. A remarkable effect of this drug is the extreme empathy felt for all small things; a stone, a flower, an insect. I believe that it would be impossible to harm anything—to commit an overt harmful or painful act on anyone or anything is beyond one’s capabilities. One cannot pluck a flower—and even to walk upon a gravel path requires one to pick his footing carefully, to avoid hurting or disturbing the stones. I found the color perception to be the most striking aspect of the experience. The slightest difference of shade could be amplified to extreme contrast. Many subtle hues became phosphorescent in intensity. Saturated colors were often unchanged, but they were surrounded by cascades of new colors tumbling over the edges.”
Dosage: 200–400 mg (Sulfate Salt)
Duration: 10–12 hours
2. DOM
(2,5-dimethoxy-4-methylamphetamine)
DOM was the only DOX to make this list — most of them are deemed too powerful and carry uncomfortable side effects, which are especially strong for the psychedelic-naive.
This psychedelic can easily produce negative “eerie” feelings, as well as beautiful vibrant, and jubilant sensations depending on the surroundings — it’s extra important to be wary of set and setting, including who joins you on the journey.
The effects of DOM remain active for nearly a full day, with some tapering-off effects felt throughout the following day as well.
Shulgin described the effects of DOM as follows (10 mg):
“If on this page I shall have expressed it to you then it is true that DOM has the glory and the doom sealed up in it. All that’s needed to unseal it is to surround it with a warm living human for a few hours. For that human for those hours all the dark things are made clear.”
Dosage: 3–10 mg
Duration: 14–20 hours
3. 2C-B
(2,5-dimethoxy-4-bromophenethylamine)
2C-B is the most popular of the 2C family. It’s widely used in rave subculture for its blend of entactogen and psychedelic qualities. The best way to describe the effects of this compound is that it’s somewhere in between MDMA and LSD.
Shulgin described 2C-B as follows (20 mg):
“The drug effect first became known to me as a shift of colors toward golden and rose tones. Pigments in the room became intensified. Shapes became rounder, more organic. A sensation of lightness and rivulets of warmth began seeping through my body. Bright lights began pulsing and flashing behind my closed lids. I began to perceive waves of energy flowing through all of us in unison. I saw all of us as a gridwork of electrical energy beings, nodes on a bright, pulsating network of light. Then the interior landscape shifted into broader scenes. Daliesque vistas were patterned with eyes of Horus, brocades of geometric design began shifting and changing through radiant patterns of light. It was an artist’s paradise—representing virtually the full pantheon of the history of art.”
Dosage: 12–24 mg
Duration: 4–8 hours
4. 2C-E
(2,5-dimethoxy-4-ethylphenethylamine)
2C-E is the third-most-popular member of the 2C psychedelic group. Its popularity is surprising due to its more “challenging” nature — but even Shulgin himself considered it one of his favorites.
The 2C-E experience tends to follow an EBB and flow with increasing intensity, followed by periods of deep introspection.
2C-E can be euphoric and pleasantly introspective — but also dark and depressing.
The experience is completely unreliable from one person to the next or one trip to the next. This one is recommended for more experienced psychonauts familiar with fundamentals like set and setting, and know how to get themselves out of a psychedelic funk.
Here’s what Shulgin had to say about 2C-E (20 mg):
“The view out of the window was unreal. The garden was painted on the window, and every petal of flower and tuft of grass and leaf of tree was carefully sculptured in fine strokes of oil paint on the surface of the glass. It was not out there; it was right here in front of me. The woman who was watering the plants was completely frozen, immobilized by Vermeer. And when I looked again, she was in a different place, but again frozen. I was destined to become the eternal museum viewer.”
Dosage: 10–25 mg
Duration: 8–12 hours
5. 2C-T-2
(2,5-dimethoxy-4-ethylthiophenethylamine)
The 2C-T-X compounds are a subgroup of the 2C family. Only about half of these compounds are psychoactive; the other half appear to be inactive.
2C-T-2 is known for its potent euphoric qualities — very similar to MDMA. It’s euphoric and empathogenic but also features a powerful visual component similar to LSD.
The catch is that this compound is very dose-dependant. The psychedelic effects will only increase to a certain point before the sentiment of the experience shifts. Hallucinations then become much darker and malevolent — mimicking the effects of delirium more than that of a classical psychedelic.
Here’s what Shulgin had to say (12 mg):
“I don’t feel this for fully an hour, but when I do it is quite a weight. It feels good to work it through. It is OK to be with pain. You can’t eliminate it. And it is OK to contact your deep pools of anger. And all of it stems from the lack of acknowledgment. All the macho carrying on, the fights, the wars, are ways of demanding attention, and getting even for not having had it in one’s life. I am experiencing more deeply than ever before the importance of acknowledging and deeply honoring each human being. And I was able to go through and resolve some judgments with particular persons.”
Dosage: 12–25 mg
Duration: 6–8 hours
6. 2C-T-7
(2,5-dimethoxy-4-propylthiophenethylamine)
2C-T-7 is the other “popular” 2C-T-X compound — best known for its long-lasting effects (~15 hours) and consistent euphoria.
This compound is strong, but it’s less likely to result in “challenging” or “uncomfortable” experiences than other 2C compounds.
Here’s Shulgin’s report (20 mg):
“I lay down with music, and become engrossed with being as still as possible. I feel that if I can be totally, completely still, I will hear the inner voice of the universe. As I do this, the music becomes incredibly beautiful. I see the extraordinary importance of simply listening, listening to everything, to people and to nature, with wide open receptivity. Something very, very special happens at the still point, so I keep working on it. When I become totally still, a huge burst of energy is released. And it explodes so that it takes enormous effort to quiet it all down in order to be still again. Great fun.”
Dosage: 10–30 mg
Duration: 8–15 hours
The Shulgin Rating Scale
Shulgin and his rag-tag group of psychonaut friends would regularly test his creations to explore their effects. They even developed a rating scale to describe the visual, auditory, and physical sensations induced by the substance.
This system was described in detail in PiHKAL.
The rating was designed to describe the intensity of the psychedelic experience. There were six different options:
(-) = No effect noticed whatsoever.
(±) = Consciousness shifted away from the baseline, but it wasn’t strong enough to clearly be the result of the chemical
(+) = It’s clear the shift away from baseline is due to the substance, but it isn’t particularly strong.
(++) = This level of intensity is undeniable, but the experienced psychonaut will be able to decide whether they want to engage with the experience or continue as usual with their daily activities.
(+++) = This level describes the maximum intensity. the strength of the experience is strong enough that ignoring or repressing its effects is no longer possible.
(++++) = This level was considered separate from the others; only used to describe substances with an intensity that matched a level three (+++), but included the rare “peak experience” where transcendental or “bliss” states were experienced.
Here are some examples of how the Shulgins used this scale in their research:
1. DOB (1 mg)
"By the 4th hour I am absolutely a +++ & am searching the kitchen for food. But what I eat is only so-so... The next day I was still hungry for altered spaces & successfully challenged the residual + with LSD to which allowed direct shot up to a +++ again"
2. Ganesha (32 mg)
"... Towards the end of the experiment, I looked at a collection of photos from a recent trip to Europe, and the visual enhancement was wonderful. A rolling +++ "
3. DOEF (3 mg)
"At 13 hours, I am still too alert to sleep, but a couple of hours later, OK. In the morning there is still a trace of something going on. This was a valid +++."
→ Check out our recent thread about this topic
Read Alexander & Ann Shulgins’ Books
Tihkal: The Continuation (1997)
The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds (2011)
Further Reading
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