Beyond LSD: The Enigmatic World of Lysergamide Psychedelics
Beyond LSD: The Enigmatic World of Lysergamide Psychedelics
LSD is just the tip of the psychedelic iceberg.
LSD (acid) is the third most popular drug in the United States — with approximately 8% of the population believed to have tried it at least once in their lifetime (according to data from 2020).
This is true despite the fact that LSD has been listed as a Schedule I drug since 1966.
There are many good reasons for acid’s widespread popularity:
It's often credited as the inspiration behind the works of countless musicians and artists
It’s proving to be a valuable tool for solving tough mental health problems (like existential anxiety, depression, and PTSD)
It’s one of the best solutions currently available for managing stubborn cluster or migraine headaches
It’s very safe — the toxic dose of LSD still hasn’t been clearly identified
On top of its capacity to transform your visual and auditory experience, LSD produces feelings of euphoria, unlocks deep personal insight, and is a reliable inducer of the so-called “mystical state of consciousness,” which allows room for profound healing and personal growth.
LSD is exceptionally strong, too — just 100 micrograms (1/10 of a milligram) is enough to propel users into the full depths of the psychedelic experience. It’s one of the only psychedelics potent enough to be delivered on tiny blotter squares (a few others include the DOX compounds and N-Bombs).
What many people don’t know is that LSD is just one of over a dozen other closely-related compounds collectively referred to as lysergamides.
Some are milder; some stronger; some are described as more visual; some longer lasting; and some are totally beyond comparison.
Welcome to the enigmatic world of lysergamide psychedelics.
What is a Lysergamide?
“Lysergamide” specifically refers to compounds that feature a lysergic acid base with an amide group attached. They’re a subgroup of the larger tryptamine family of compounds that all share a similar structure to serotonin.
Lysergamides mimic the effects of serotonin by binding to its receptors in the brain. Lysergamides also interact with dopamine and norepinephrine to produce changes in mood, mental stimulation, and executive functioning.
All lysergamides feature a carboxamide group on the eighth carbon and can feature any number of chemical groups on the R1, RN1, RN2, and R6 positions. The effects vary depending on which functional groups are attached.
Some, such as ETH-LAD, appear to have a stronger potency than LSD, while others, such as 2-Bromo-LSD may actually have the opposite effect and may even be anti-psychedelic.
Examining 33 Lysergamide Substances
There are dozens of lysergamides in existence today, but only a small sample of them have any actual research behind them.
After LSD was introduced to the world in the early 60s, researchers at Harvard, Stanford, and several other universities began studying it in detail. The results at the time were nothing short of astounding — suggested uses ranged from treating depression and psychiatric disorders to enhanced creativity and even mind control.
After LSD was banned in 1966, research came to a screeching halt. For the next few decades, only people like Alexander Shulgin, who had an exemption from the DEA to conduct research on various tryptamine and phenethylamine psychedelics, or underground chemists like Nick Sand and Tim Scully continued the important work in further developing the lysergamide class.
Later, in the 1980s, David E. Nichols and his team at Purdue University published a series of reports on lysergamides created in their lab. Dr. Nichols and his team are credited with inventing roughly 30 new lysergamides from 1984 to 1997 and are largely responsible for quantifying and classifying the effects of over a dozen others.
There are 2 main functional groups of lysergamides:
A) The psychedelic lysergamides — this includes compounds like 1B-LSD, 1cP-LSD, 1P-ETH-LAD, 1P-LSD, 1V-LSD, AL-LAD, ALD-52, ETH-LAD, ETFELA, IP-LAD, LAE-32, LSA, LSD, LSM-775, LSP, LSZ, PARGY-LAD, and PRO-LAD.
B) The vasoconstrictive lysergamides — Most of the non-psychoactive, as well as a few psychoactive lysergamides, possess powerful vasoconstrictive action (drugs that cause blood vessels to constrict). These compounds are generally either toxic or reserved for medical use in the treatment of migraines and excessive bleeding after childbirth. These include compounds such as ergotamine, ergonovine (ergometrine), or methylergometrine.
1. 1B-LSD
1B-LSD (1-butyryl-lysergic acid diethylamide) is an acetylated version of LSD. There isn’t much research available on this compound, but preliminary studies suggest it to be around 15% of the strength of LSD. Aside from being less potent, the effects are practically indistinguishable from both LSD and 1P-LSD.
1B-LSD was popular in Europe and Canada for a while as a “legal acid,” but new laws have since been imposed to ban this research chemical.
2. 1cP-LSD
1cP-LSD (1-(cyclopropylmethanoyl)-lysergic acid diethylamide) is an acylated derivative of LSD with similar potency to 1P-LSD. 1cP-LSD is believed to be a prodrug for LSD.
Like many research chemicals, 1cP-LSD was created to avoid laws that banned known psychedelics. This particular compound first entered the market in Germany and the Netherlands in 2019, shortly after the government banned 1P-LSD.
3. 1P-ETH-LAD
1P-ETH-LAD (1-Propionyl-6-ethyl-6-nor-lysergic acid diethylamide) is believed to serve as a prodrug for ETH-LAD — one of the stronger members of the lysergamide family. The experience is considered more visual than LSD and has less of an impact on emotion and mood.
This compound was made to avoid regulation but has since been banned in most European countries, Canada, the US, and Australia.
4. 1P-LSD
1P-LSD (1-propionyl-lysergic acid diethylamide) is a modified version of LSD. It features a propionyl group attached to the nitrogen molecule in the indole portion of LSD. This makes the molecule inactive but is quickly metabolized by the liver into LSD.
Because of the prodrug status of 1P-LSD, the potency tends to vary for each user and has a slower onset time than LSD. For most people, the subjective effects are on-par with LSD.
This was one of the first research chemicals developed to provide “legal LSD” to the market sometime around 2012. Most countries have since banned the substance or enacted analog laws that ban psychoactive isomers of banned substances by default. Currently, 1P-LSD is listed as legal in Canada.
5. 1V-LSD
1V-LSD (1-Valeroyl-d-lysergic acid diethylamide) — sometimes referred to as Valerie — is a modified version of 1P-LSD. While there’s virtually no research available on this compound, it’s believed to act as a prodrug for LSD and exhibits near-identical effects.
This compound is the latest invention in a series of chemicals invented in response to various bans in Europe. First, LSD was banned, so analogs like 1P-LSD were invented. Then 1P-LSD was banned, so 1cP-LSD was made. After 1cP-LSD was banned, too, 1V-LSD was designed to take its place. This game of cat and mouse continues to this day.
Places with analog laws, like the US, UK, and Austria, consider 1V-LSD explicitly illegal because it’s a psychoactive derivative of LSD. Switzerland recently added the substance to its prohibited substance list, but the compound remains in a legal grey area throughout most of Europe, Canada, and Australia.
6. 2-Bromo-LSD
2-Bromo-LSD (2-Bromolysergic acid diethylamide) — sometimes called BOL-148 — is believed to block the effects of LSD. It binds to the same receptors but does not exert any psychedelic activity.
This compound was one of many ergotamine derivatives invented by Albert Hofmann and his team in the late 1950s. The goal of creating these compounds was to find a new treatment for migraine headaches. This eventually led to the accidental discovery of the lysergamide family of psychedelics.
2-Bromo-LSD has been shown to offer some support for cluster headache attacks, and due to the lack of psychoactivity compared to LSD, it may prove useful for this application in the near future. However, more research is needed to confirm the safety and efficacy of this compound for this application.
It’s also possible this compound could be used to dull the effects of LSD.
7. AL-LAD
AL-LAD (N6-allyl-6-norlysergic acid diethylamide) is one of the more common lysergamide derivatives. Compared to LSD, AL-LAD is favored for its slightly milder but more visual effects. It also tends to be less introspective and more “recreational” than LSD — which can often lead users to feel deeply introspective and philosophical.
This compound isn’t new. It’s been around since the 70s and has been formally studied several times already. Dr. David E. Nichols and his team at Purdue University have focused on this chemical in at least one study, and the compound earned a mention in Alexander Shulgin’s book, TIHKAL.
8. ALD-52
ALD-52 (1-acetyl-N,N-diethyllysergamide) is a homolog of 1P-LSD — the two are identical aside from 1P-LSD containing one additional carbon atom.
Unsurprisingly, the effects of ALD-52 and 1P-LSD are virtually identical. ALD-52 serves as a prodrug for LSD, only becoming active after it’s processed by the liver. This can delay the onset of effects by as much as one additional hour compared to LSD — though most people start to experience the effects within about 60 minutes of taking it.
This lysergamide was first synthesized in Hofmann’s lab in the 1950s. It was believed to be the active ingredient in a particularly strong batch of LSD called Orange Sunshine (produced by Nick Sand), but this was later debunked by Sand himself. The effects of ALD-52 are considered equivalent, if not slightly weaker than LSD.
9. Amesergide
Discovered by Eli Lilly and Company. It was explored as a potential treatment for depression, anxiety, schizophrenia, male sexual dysfunction, migraine, and thrombosis. It reached phase II clinical trials but was discontinued and never marketed. Psychedelic properties are unknown.
10. BU-LAD
BU-LAD (6-butyl-6-nor-lysergic acid diethylamide) was one of several lysergamide compounds invented by Alexander Shulgin. It was published in his book, TiHKAL, but hasn’t received much attention since this because of its weak effect profile. Shulgin reportedly consumed a dose of 500 micrograms of BU-LAD and reported only mild psychoactive effects.
11. Cabergoline
This compound shares close structural resemblance with AL-LAD, but possesses none of the psychedelic qualities. It acts as a dopamine (D2) antagonist rather than serotonin (5HT2A) agonist like other lysergamides. It’s sometimes prescribed as medicine under the trade name, Dostinex, for treating high prolactin levels and managing Parkinson's disease. It also has the unique ability to reduce refractory time in males.
12. DAL
This lysergamide was invented by Alexander Shulgin and is listed in his and his wife’s book, TiHKAL. Shulgin suggests DAL (diallyllysergamide) is “an order of magnitude less potent than LSD itself.”
13. ECPLA
ECPLA (N-ethyl-N-Cyclopropyllysergamide) was invented by Synex Synthetics. Research from 2019 suggests it has roughly 40% potency compared to LSD, but no further research has been published.
14. Ergometrine
Ergometrine is one of the many naturally-occurring lysergamides produced by the Claviceps purpurea fungus as well as the hair clystervine (Jacquemontia tamnifolia) and lavender moonvine (Ipomoea muricata). It’s sold under the trade names Ergotrate, Ergostat, and Syntometrine. It’s used for treating contractions of the uterus and heavy bleeding after childbirth. It’s psychedelic in high doses but also quite toxic.
15. Ergotamine
This compound is produced in the Claviceps purpurea fungus. It’s currently sold under the trade names Cafergot (ergotamine and caffeine) and Ergomar as a treatment for migraine headaches.
16. ETFELA
This compound was first discovered by the team working under David E. Nichols at Purdue University. Jason C. Parrish is credited with its synthesis. The effects of ETFELA (N-ethyl-N-(2,2,2-trifluoroethyl) lysergamide) have not been well studied, but early research suggests slightly higher potency than LSD.
17. ETH-LAD
ETH-LAD (6-ethyl-6-nor-lysergic acid diethylamide) is one of the most popular lysergamides aside from LSD. Its popularity is likely the result of its slightly stronger effect profile. The threshold dose of this compound is only 20 micrograms. For comparison, the threshold of LSD is closer to 30 micrograms.
Despite its popularity, there’s limited information regarding safety or qualitative effect differences.
The drug creator, Alexander Shulgin, claims ETH-LAD produces strong visual effects but is less likely to produce unwanted physical sensations compared to other tryptamine psychedelics.
18. IP-LAD
IP-LAD is short for 6-Isopropyl-6-nor-lysergic acid diethylamide. It was also discovered by David E. Nichols’ lab team who estimated it to have roughly 40% of the potency of LSD.
19. LAE-32
This compound is most closely-related to ergine. It’s effects are comparable to LSD but much milder and shorter-lasting. This compound was one of the substances the CIA tested as part of their MK-Ultra project, but no further research has been published on this compound and little is known about it’s specific effects.
20. LSA
LSA (d-lysergic acid amide) is a naturally-occurring lysergamide found in the ergot fungus as well as the seeds of morning glory and Hawaiian baby woodrose (both from the Convulaceae family).
LSA was discovered in 1932 and classified under the name “ergine” [8]. Other sources use the term LAE-111.
Compared to other lysergamides, LSA is much less potent and has a distinct sedative action. This combination gives LSA a distinct oneriogenic effect that’s absent from most of the other compounds in this category.
The conventional dose of LSA is around 500 micrograms to 1 gram, making it less than 10% as potent as LSD. Most LSA is derived from either morning glory or Hawaiian baby woodrose seeds in the form of tinctures, but isolated LSA is also available.
The effects of LSA are described as lucid and dreamy but come with some negative qualities as well. The body load from LSA can be uncomfortable and, in some cases, extreme, producing feelings of nausea, stomach cramping, tingling, and dizziness. These effects can be quite uncomfortable.
21. LSB
This compound was first developed by Eli Lilly in the 1950s, but wasn’t publicized until the 90s by David E. Nichols and team. LSB (lysergic acid 2-butyl amide) is unique in that it has a much higher potency than LSD on the 5HT1A receptors but lower potency at the 5HT2A receptors.
Since most of the psychedelic effects are involved with 5HT2A interaction, it’s believed this substance is a weaker psychedelic overall (but no research is available to prove/disprove this).
22. LSD
LSD (lysergic acid diethylamide) — AKA Lucy, LAD, and Acid — is hands down the most popular member of the lysergamide family of psychedelics. While LSD isn’t necessarily the strongest, it was the first to be explored scientifically. It provides long-lasting and profound effects while lacking any major safety risks.
Part of the reason this compound became so popular is because of advocates like Timothy Leary, Leo Zeff, Richard Alpert, and others throughout the 1960s and 70s.
LSD was supplied to Leary, Alpert, and the rest of their team by Sandoz Pharmaceuticals as part of the Harvard Psilocybin Project. At the time, LSD was perfectly legal, and Sandoz wanted researchers to conduct research on their new compound in order to find a potential use for it.
After LSD became a symbol for the 60s counterculture and hippie movement, then-president Ronald Regan banned the substance and declared war on drugs. This, of course, brought all research on LSD and other psychedelics to a halt for several decades.
The US government had a secret project called MK-ULTRA in the 60s, 70s, and 80s as well, which attempted to use LSD for more nefarious purposes like mind control and truth serums.
23. LSD-Pip
The Pip in LSD-Pip stands for piperidine, which is a naturally occurring molecule found in plants like black pepper and is a component of many important, pharmacologically-active (and sometimes toxic) alkaloids such as anabasine, lobeline, and coniine. LSD-Pip is not well-studied but is believed to possess much weaker psychedelic effects.
24. LSH
This compound is found in the Claviceps purpurea fungus in relatively high amounts.
Claviceps mainly infect rye grains but are also present in the fresh seeds of Hawaiian baby woodrose and morning glory vine. The seeds of both plants contain psychoactive doses of this chemical.
LSH (lysergic acid α-hydroxyethylamide) is unstable and quickly breaks down into another psychoactive lysergamide, LSA.
25. LSM-775
This compound is not well tested, but early reports suggest its effect profile is similar to that of LSA. It’s sedative, oneirogenic, and produces lucid “dream-like” hallucinations. It was tested by Alexander Shulgin and included in his book, TiHKAL, but his reports are conflicting, with one entry suggesting LSM-775 shared similar potency to LSD, while another claimed the active dose was nearly 10 times higher.
26. LSP
This compound was first researched by the Purdue Team operating under Dr. David E. Nichols.
The only research currently available for this drug is simple receptor potency assays. This research found that LSP (lysergic acid 3-pentyl amide) has 2 isomers with different potencies.
The (R) isomer is roughly 50% as potent as LSD, while the (S) isomer is inactive.
27. LSZ
LSZ (lysergic acid 2,4-dimethylazetidide) was first discovered by David E. Nichols at Purdue University in the 1980s. The effects are virtually identical to LSD but with slightly higher potency and longer-lasting effects. The come-up is also slower, taking up to 1.5 hours to begin feeling the effects.
Anecdotal reports suggest this compound has a higher emphasis on the emotional experiences of lysergamide psychedelics, less visual intensity, and a somewhat sedative nature in higher doses. Many people claim this to be the best psychedelic for use in the evenings because it’s easier to fall asleep afterward.
28. Methergine
This compound is listed on the WHO list of essential medicines. It’s sold under the brand name, Methergine, where it’s used for treating migraine headaches and to prevent or control excessive bleeding after childbirth.
29. Methysergide
Sold under the brand names, Deseril and Sansert, this compound was primarily used to treat migraine and cluster headaches but has since been removed from the market due to causing a high incidence of side effects.
30. MiPLA
This is one of the compounds originally created by Albert Hofmann while he was working at Sandoz in the late 1930s. It was explored in greater detail by David E. Nichols and his team at Purdue University, where they found MiPLA (lysergic acid methylisopropyl amide) possesses roughly 30–50% of the potency of LSD.
31. MLD-41
We know very little about this substance, but early research estimates roughly 1/3 the potency compared to LSD. The last-known report on MLD-41 (N1-Methyl-lysergic acid diethylamide) comes from 1983.
32. PARGY-LAD
PARGY-LAD (6-propynyl-6-nor-lysergic acid diethylamide) is a homolog of LSD with a similar effect profile. The potency of this compound is reportedly much lower than LSD, however — with the threshold dose around 160 micrograms. According to Alexander Shulgin, the psychoactive dose for this compound is somewhere in the ballpark of 500 micrograms — making this compound roughly 40% as strong as LSD.
33. PRO-LAD
PRO-LAD (6-propyl-6-nor-lysergic acid diethylamide) is another creation of the Purdue University team led by David E. Nichols in the 1980s. This compound shares the same structure as LSD, with the addition of just two extra carbons. This changes the potency and effect profile slightly — though most people probably wouldn’t be able to tell the difference.
Some users suggest PRO-LAD has a stronger body load than LSD — producing sensations like tingling in the fingers and toes, a sensation that one is either floating or sinking into the ground, and increased awareness of other bodily sensations.
What’s The Strongest Lysergamide Psychedelic?
Anecdotal reports suggest ETH-LAD is the strongest member of the lysergamide class, but not by much. The threshold dose of this compound is somewhere around 20 micrograms, compared to 25 for LSZ and 25–30 for LSD. Most people who take a tab of ETH-LAD won’t be able to tell the difference from a tab of LSD.
It’s difficult to assess the potency of these compounds through anecdotes because it’s impossible to know the exact dosage used. A blotter tab can hold anywhere from 25–200 micrograms of active ingredient, depending on how it was made and how long it’s been in storage.
One way to assess the potency of psychoactive compounds is to compare their binding capacity on target receptors such as the 5HT2A receptor. However, this doesn’t provide the whole picture either. Just because something binds more strongly to a receptor doesn’t mean the effects it produces are stronger.
All this aside, based on the information currently available, here’s an estimated ranking of the top 10 most potent lysergamides (strongest to weakest):
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