ETH-LAD is slightly more potent than LSD in both animals and humans.[4][6][5][13][8] It is about 1.6- to 2.3-fold more potent than LSD in rodent drug discrimination tests.[6][5][8] The drug's human dose range is 20 to 150μg orally, compared to a range of 50 to 200μg given for LSD, and it is said to be roughly twice as potent as LSD in humans.[1][2][4][7][8] As such, ETH-LAD is one of the most potent serotonergic psychedelics in humans known, if not the most potent known psychedelic.[5][4][6][7][8] Moreover, it has been said that LSD can no longer be considered the most potent psychedelic.[14] ETH-LAD's duration is 8 to 12hours as with LSD.[1]
The qualitative effects of ETH-LAD are similar to those of LSD.[6][1] In a limited number of anecdotal reports collected and published by Alexander Shulgin in TiHKAL however, ETH-LAD was described as more gentle and as less pushy, demanding, and aggressive than LSD, but also as having less of LSD's sparkle.[1] ETH-LAD was said to have a greatly modified degree of visual distortion relative to LSD as well.[1]
On June 10, 2014, the United KingdomAdvisory Council on the Misuse of Drugs (ACMD) recommended that ETH-LAD be specifically named in the UK Misuse of Drugs Act as a class A drug despite not identifying it as ever having been sold or any harm associated with its use.[19] The UK Home office accepted this advice and announced a ban of the substance to be enacted on 6 January 2015.[20]
1 2 3 4 5 Halberstadt AL, Geyer MA (2013). "[Chapter 61:] Neuropharmacology of Lysergic Acid Diethylamide (LSD) and Other Hallucinogens". In Miller PM, Blume AW, Kavanagh DJ, Kampman KM, Bates ME, Larimer ME, Petry NM, De Witte P, Ball SA (eds.). Biological Research on Addiction: Comprehensive Addictive Behaviors and Disorders. Vol.2. Elsevier. pp.625–635. doi:10.1016/b978-0-12-398335-0.00061-3. ISBN978-0-12-398335-0. The semisynthetic lysergamide LSD (N,N-diethyllysergamide; Fig. 61.9) is one of the most potent hallucinogens, with typical doses ranging from 60–200 μg. LSD contains two chiral centers and its action is highly stereospecific, with 5R,8R being the only active configuration. The diethyl amide group in LSD is optimal for activity, and potency drops by an order of magnitude if other alkyl groups or heterocyclic rings are substituted. It has been reported, however, that derivatives of LSD in which the N(6) methyl group is replaced by other alkyl groups are active, with the 6-ethyl compound (N(6)-ethyl-nor-LSD, ETH-LAD) being slightly more potent than LSD.
1 2 3 4 5 Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited". NIDA Research Monograph. 146: 52–73. PMID8742794. The DD data indicate that the n-propyl is slightly more active than LSD, although not significantly so, but the ethyl and allyl compounds were significantly more potent than LSD. [...] This was an area of the structure-activity relationships (SAR) that had been unfilled, and there is now some knowledge of the effect of the N(6) alkyl group on activity of lysergamide hallucinogens. If the animal data are used as a criterion, it is known that LSD is, in fact, not the most potent LSD-like agent; the ethyl and allyl compounds are more potent. Clinical data presented by Jacob and Shulgin (this volume) seem to corroborate this observation.
1 2 3 4 5 6 Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol.36. pp.1–43. doi:10.1007/7854_2017_475. ISBN978-3-662-55878-2. PMID28401524. One other structural modification that has led to potent psychedelics is replacement of the N(6)-methyl of LSD with a variety of other alkyl groups (Hoffman and Nichols 1985). In a rat drug discrimination assay, in animals trained to discriminate LSD from saline, the N(6)-allyl derivative had about twice the potency of LSD itself. The N(6)-ethyl was about 1.6-fold more potent than LSD, with the N(6)-npropyl being essentially comparable in potency to LSD. The N(6)-isopropyl had about 40% of the potency of LSD, with the N(6)-n-butyl having approximately 10% of the potency of LSD. Neither norLSD (N(6)=H), or N(6)-2-phenethyl-norLSD gave full substitution in the rats. Anecdotal human experiments then confirmed that the N(6)-allyl (AL-LAD) and N(6)-ethyl (ETH-LAD) congeners were psychoactive in man at doses that were not all that different from LSD itself, but the two compounds had psychopharmacology that was different from that of LSD (Shulgin and Shulgin 1997). The same source reported that the N(6)-n-propyl was much less active, with an oral dose in the range of 100–200 μg. The N(6)-propynyl (pargy-LAD) had some activity at 160 μg, and the N(6)-n-butyl was reported to do "something" at 500 μg. The N(6)-2-phenethyl congener was inactive up to 500 μg. These human reports, although anecdotal, do generally parallel the results obtained in the drug discrimination tests.
1 2 3 4 5 Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs"(PDF). NIDA Res Monogr. 146: 74–91. PMID8742795. The last and by far most potent family of the tryptamine hallucinogens is found in the ergolines related to LSD. These are listed in table 9. Classically, the diethylamide has been considered the most potent of all and the prototype for comparison. [...] However, variations of the N-6 substitution have maintained the potency of LSD and in some cases enhanced it. [...] TABLE 9. LSD analogs.
1 2 3 4 5 6 7 Nichols DE (February 1986). "Studies of the Relationship Between Molecular Structure and Hallucinogenic Activity". Pharmacol Biochem Behav. 24 (2): 335–340. doi:10.1016/0091-3057(86)90362-x. PMID3952123. The ergolines can be viewed as rigid tetracyclic tryptamines. Within this class of compound is found the semisynthetic d-lysergic acid diethylamide (Fig 8) (d-LSD), the most potent of the hallucinogenic drugs. [...] Of the many structural modifications which have been made to the LSD structure, none had yielded a compound more potent than LSD itself. This report will briefly describe some derivatives of LSD which do appear to have somewhat higher potency than LSD. [...] The observations of potency comparable to, or greater than LSD [with N(6)-alkyl-substituted lysergamides] was of great interest. It seemed likely, based on the generalization in the drug discrimination assay and the high potencies of several of the derivatives, that these might well be more potent hallucinogens in man than LSD. Very recently, preliminary studies were carried out (A T Shulgin, personal communication) which indicated that indeed, the N(6)-ethyl and the N(6)-allyl-nor-LSD derivatives are somewhat more potent than LSD, by perhaps a factor of 2–3. Early results also indicated that N(6)-propyl-nor-LSD retains activity comparable to LSD, but with perhaps less visual distortion. These preliminary results were obtained after only a few experiments with each compound and further evaluation to define the potency and character of these lysergamides is underway.
1 2 Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". Br J Pharmacol. doi:10.1111/bph.17361. PMID39354889.
1 2 Julio de Carvalho P (2024). "The use of prodrugs as drugs of abuse". WIREs Forensic Science. 6 (3). doi:10.1002/wfs2.1514. ISSN2573-9468. Retrieved 27 March 2025. Other analogues of LSD, such as 6N substituted AL-LAD e ETH-LAD, do not degrade into LSD, but have their own prodrugs—1P-AL-LAD/1cP-AL-LAD (Brandt, Kavanagh, Westphal, Pulver, Morton, et al., 2022; Brandt, Kavanagh, Westphal, Pulver, Schwelm, et al., 2022; Kavanagh et al., 2023) and 1P-ETH-LAD (Brandt et al., 2017), respectively—that undergo diacylation resulting in the parent drug.
1 2 3 Hoffman AJ, Nichols DE (September 1985). "Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives". Journal of Medicinal Chemistry. 28 (9): 1252–1255. doi:10.1021/jm00147a022. PMID4032428.
1 2 Oberlender RA (May 1989). "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue e-Pubs. Purdue University. Of the many structural modifications to LSD that have been evaluated for their effect on activity over the last forty five years, very few have led to compounds with comparable potency. Only derivatives in which various alkyl groups replaced the methyl at the N-6 position of LSD seem to retain or even surpass the potency of the parent drug. Of these compounds, the n-propyl derivative was found to be equipotent to LSD, while the ethyl and allyl derivatives were more potent in the rat than the parent drug by factors of 1.6 and 2, respectively (Hoffman and Nichols, 1985). These DD-based estimates of potency were subsequently confirmed in preliminary studies with humans (A.T. Shulgin, cited in Nichols, [1986a]). Thus, LSD can no longer be considered the most potent hallucinogen. [...] Nichols DE (1986a) Studies of the relationship between molecular structure and hallucinogenic activity. Pharmacol Biochem Behav 24: 335-340.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
