Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile

Since Albert Hofmann's first use of lysergic acid diethylamide (LSD) in 1943, many structurally related compounds have appeared (for example AL-LAD, 1P-LSD, ETH-LAD, LSZ). Coney and colleagues note that rapid legal changes and a synthesise-proscribe-synthesise dynamic have contributed to the emergence and online availability of these LSD analogues, and that most human information to date comes from animal models and user reports on websites. Animal data suggest these lysergide derivatives act as 5-HT2A agonists and can produce hallucinogenic effects in rodents, but relative potencies vary and reported human dosages differ from animal potency estimates. Ethical barriers and uncertainty about harms limit controlled human research on these compounds. This study aimed to describe self-reported patterns of use, sourcing and routes of administration, and perceived acute effects of selected LSD analogues (AL-LAD, 1P-LSD, ETH-LAD) in humans, and to compare those profiles with self-reports for LSD. The authors used an anonymous web-based survey to characterise user demographics and subjective effect ratings, emphasising rapid, population-level descriptive data where clinical or laboratory confirmation is not available.

Data were drawn from the Global Drug Survey (GDS) 2016, an anonymous, self-selected online survey run between November 2015 and February 2016. Ethical approval was obtained from King's College London. After excluding records for capture glitches, duplicates, non-use, fake drugs, and implausible ages, the analytic dataset comprised 96,894 respondents from many countries; the largest national contributions were Germany, Switzerland, New Zealand, the UK, and the United States. The subsample relevant to this paper included 3,678 respondents who reported LSD analogues or LSD as their last new drug tried; that group had a mean age of 23.4 years (SD = 5.7) and was 74% male. Respondents reported lifetime and last-12-month use of LSD and LSD analogues. The survey asked about specific analogues (AL-LAD, 1P-LSD, ETH-LAD) and grouped others under an "LSD analogues" category; for analysis the authors combined AL-LAD with the LSD analogues category and refer to these collectively as "LSD analogues." For each drug identified as the respondent's last new drug tried, profiling variables included route of administration, source, type of effect, duration, time to peak, and a set of subjective ratings scored 1–10 (strength, pleasurable high, comedown, urge to use more, negative effects while high, perceived risk of harm, and value for money). Prior to inferential testing the study team assessed missingness (no variable had more than 5% missing), multicollinearity, normality and homoscedasticity. Linearity appeared violated but the authors deemed multivariate analysis of variance (MANOVA) robust enough to proceed. Group comparisons used MANOVA to test differences across multiple subjective-rating outcomes between LSD and LSD analogue users (LSD n = 3,015; LSD analogues n = 306). Independent-samples t tests compared duration and time to peak. The significance threshold was set at alpha = .05 and only valid percentages were reported.

In the full GDS sample (N = 96,894), 27% (n = 25,953) reported lifetime LSD use versus 2% (n = 2,349) reporting lifetime use of LSD analogues. Recent (last 12 months) use was reported by 13% (n = 12,491) for LSD and by 1% (n = 1,431) for LSD analogues. High overlap existed between the two: of respondents who ever used LSD analogues and had available data (n = 2,202), 91% (n = 2,004) also reported lifetime LSD use; among those who used analogues in the last 12 months (n = 1,249 with data), 85% (n = 1,055) also reported recent LSD use. Comparisons of recent users showed that LSD analogue users were younger on average and more likely to be male than recent LSD-only users. A higher proportion of recent analogue users were from the UK and the United States. When respondents judged the last new drug they tried as an LSD analogue, 93% described the effects as psychedelic (LSD/ketamine-like); smaller proportions described stimulant, cannabis-like, empathogenic or other effects. Sources differed markedly: 56% of analogue users reported obtaining the drug online, 33% from a friend and 8% from a dealer; by contrast, LSD was more commonly obtained from a friend (68%) and less commonly purchased online (8%). Route of administration was predominantly oral for both groups (analogue users: 83% swallowed; 17% other oral forms such as sublingual or blotter); only isolated reports of snorting or injecting were recorded and overall ROA did not differ significantly between LSD and analogues. The modal duration of effect was 8 hours and the modal time to peak 2 hours for both LSD and LSD analogues, with no significant differences in mean duration (t(443) = 1.50, p = .134) or time to peak (t(3601) = .85, p = .398). The MANOVA comparing seven subjective ratings across the two groups was significant on the combined dependent variables, F(7, 3313) = 4.74, p < .001. Follow-up tests indicated no difference in negative effects while high (F(1, 3319) = 0.81, p = .368). However, LSD received significantly higher ratings than LSD analogues for pleasurable high (F(1, 3319) = 5.50, p = .019), strength of effect (F(1, 3319) = 5.51, p = .019), comedown (F(1, 3319) = 5.37, p = .021), urge to use more drugs (F(1, 3319) = 3.89, p = .049), value for money (F(1, 3319) = 10.78, p = .001), and perceived risk of harm following use (F(1, 3319) = 27.32, p < .001). The authors interpret these differences as indicating that, in this sample, LSD analogues were experienced as similar in time course but generally weaker and rated lower on both reward-related measures and perceived harm compared with LSD.

Coney and colleagues state this is the first study to characterise patterns of use and self-reported acute effects of selected LSD analogues in humans using a large, anonymous web survey. Typical analogue users in the sample were males in their mid-20s, commonly identifying as White and often students or employed, a profile similar to other reports of psychedelic users though potentially influenced by GDS sample bias. Notable differences between analogue and LSD users included a greater proportion of analogue reports from the UK and US and a substantially higher likelihood of sourcing analogues online, consistent with broader observations of new psychoactive substances moving through web vendors and cryptomarkets. In terms of subjective effects, respondents reported that analogues produced psychedelic effects and showed a similar time to peak and duration as LSD (modal time to peak 2 hours; modal duration 8 hours). The main quantitative differences were lower ratings for analogue drugs on pleasurable high, strength, comedown, urge to use more, value for money, and perceived risk of harm—findings the authors suggest are consistent with animal potency data indicating lower potency for some analogues (for example 1P-LSD) compared with LSD. Coney and colleagues emphasise several limitations: reliance on self-report and a self-selected survey sample, potential mislabelling or misclassification of substances by users (including the possibility that some reports relate to chemically unrelated compounds such as NBOMe substances), lack of chemical confirmation and dosage data, and limited information about concurrent drug use. They recommend future work include chemical verification, dose measurement, more detailed experience metrics, and investigation of short- and long-term harms to better understand these compounds' effects and risks.

The extracted Conclusion heading begins by restating that this is the first study to describe the self-reported effect profile of AL-LAD, 1P-LSD, and ETH-LAD in humans. The sentence in the provided extraction is incomplete and ends mid-phrase, so the remainder of the authors' concise concluding statement is not available in the extracted text. The Discussion earlier in the paper reports that analogues were described as similar to LSD in time course but generally weaker in subjective intensity and related ratings, and the authors call for replication with chemical confirmation and better dose measurement.