Lysergic acid diethylamide (LSD) is one of the most widely abused hallucinogens, which can alter consciousness, produce mental disorder, and cause harmful behavior. 1-Propionyl-LSD (1 P-LSD), a novel ...derivative of LSD, has the similar hallucinogenic effect. It is a control substance in several countries. 1 P-LSD can act as a prodrug for LSD and is rapidly hydrolyzed to LSD in humans. Therefore, LSD use should be confirmed by the absence of 1 P-LSD and in the detection of LSD. Here, we describe a LC–MS/MS method for the simultaneous extraction of LSD, iso-LSD, 2-oxo-3-hydroxy-LSD, and 1 P-LSD from hair. Hair samples (25 mg) were pulverized by cryogenic grinding in methanol. The limits of detection were 0.2–1 pg/mg and the limits of quantification were 0.5–2 pg/mg. This method was validated and applied to hair samples from 18 suspects who may have used LSD. Segmental hair analysis revealed a decrease in the LSD concentrations from the proximal to the distill end, while 1 P-LSD was not detected in any hair segments. The interpretation of hair analysis results of LSD still remains difficult. Nevertheless, concentrations of LSD and iso-LSD in human hair from 18 LSD users were reported. LSD concentrations were from <LOQ to 4.0 pg/mg (n = 18, median 1.5 pg/mg) in the proximal 0–3 cm segment, from <LOQ to 1.8 pg/mg (n = 8) in the 3–6 cm segment, and from <LOQ to 0.6 pg/mg (n = 4) in the 6–9 cm segment. Iso-LSD ranged from <LOQ to 1.4 pg/mg (n = 4) in the 0–3 cm segment and was detectable only in one 3–6 cm segment. To our knowledge, this is the first study to monitor LSD together with 1 P-LSD in hair.
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•Method provides determination of LSD, iso-LSD, 2-oxo-3-hydroxy-LSD, and 1 P-LSD in hair.•LSD concentrations reported in hair from 18 LSD users.•Low hair concentrations of LSD (up to 4 pg/mg) detected in LSD users.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
The aim of the present study was to characterize the pharmacokinetics and exposure–subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was ...developed for clinical use in research and patients.
Method
LSD (100 μg) was administered in 27 healthy subjects using a placebo‐controlled, double‐blind, cross‐over design. Plasma levels of LSD, nor‐LSD, and 2‐oxo‐3‐hydroxy‐LSD (O‐H‐LSD) and subjective drug effects were assessed up to 11.5 hours.
Results
First‐order elimination kinetics were observed for LSD. Geometric mean maximum concentration (Cmax) values (range) of 1.7 (1.0–2.9) ng/mL were reached at a tmax (range) of 1.7 (1.0–3.4) hours after drug administration. The plasma half‐life (t1/2) was 3.6 (2.4–7.3) hours. The AUC∞ was 13 (7.1–28) ng·h/mL. No differences in these pharmacokinetic parameters were found between male and female subjects. Plasma O‐H‐LSD but not nor‐LSD (< 0.01 ng/mL) concentrations could be quantified in all subjects. Geometric mean O‐H‐LSD Cmax values (range) of 0.11 (0.07–0.19) ng/mL were reached at a tmax (range) of 5 (3.2–8) hours. The t1/2 and AUC∞ values of O‐H‐LSD were 5.2 (2.6–21) hours and 1.7 (0.85–4.3) ng·h/mL, respectively. The subjective effects of LSD lasted (mean ± SD) for 8.5 ± 2.0 hours (range: 5.3–12.8 h), and peak effects were reached 2.5 ± 0.6 hours (range 1.6–4.3 h) after drug administration. EC50 values were 1.0 ± 0.5 ng/mL and 1.9 ± 1.0 ng/mL for “good” and “bad” subjective drug effects, respectively.
Conclusion
The present study characterized the pharmacokinetics of LSD and its main metabolite O‐H‐LSD. The subjective effects of LSD were closely associated with changes in plasma concentrations over time.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background:
Meta-analysis of randomized studies using lysergic acid diethylamide (LSD) for alcohol use disorder (AUD) showed large, significant effects for LSD efficacy compared to control ...conditions. Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders.
Aims:
To supplement clinical studies, reports of psychedelic use in naturalistic settings can provide further data regarding potential effects of psychedelics on alcohol use.
Methods:
An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non-clinical settings.
Results:
343 respondents, mostly White (89%), males (78%), in the USA (60%) completed the survey. Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption, with 72% meeting retrospective criteria for severe AUD. Most reported taking a moderate or high dose of LSD (38%) or psilocybin (36%), followed by significant reduction in alcohol consumption. After the psychedelic experience 83% no longer met AUD criteria. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in alcohol consumption, controlling for prior alcohol consumption and related distress.
Conclusions:
Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many ...neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions—both therapeutic and hallucinogenic—are not understood, although activation of the 5-HT2A serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH—a prototypical hallucinogen—in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders.
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•Cryo-EM 5-HT2A serotonin receptor structure complexed with hallucinogen and Gαq•The hallucinogen 25CN-NBOH displaces “toggle switch” tryptophan•Interactions essential for Gαq-specific signaling identified•X-ray crystal structure of LSD complexed with 5-HT2A elucidated
Roth et al. reveal structurally how psychedelics, including LSD, psilocin, mescaline, and various N-BOH analogs, mediate their therapeutic and hallucinogenic effects by binding to and activating their molecular target, the serotonin (5-HT) 2A receptor coupled with G-protein Gαq.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rationale
Previous research demonstrating that lysergic acid diethylamide (LSD) produces alterations in time perception has implications for its impact on conscious states and a range of ...psychological functions that necessitate precise interval timing. However, interpretation of this research is hindered by methodological limitations and an inability to dissociate direct neurochemical effects on interval timing from indirect effects attributable to altered states of consciousness.
Methods
We conducted a randomised, double-blind, placebo-controlled study contrasting oral administration of placebo with three microdoses of LSD (5, 10, and 20 μg) in older adults. Subjective drug effects were regularly recorded and interval timing was assessed using a temporal reproduction task spanning subsecond and suprasecond intervals.
Results
LSD conditions were not associated with any robust changes in self-report indices of perception, mentation, or concentration. LSD reliably produced over-reproduction of temporal intervals of 2000 ms and longer with these effects most pronounced in the 10 μg dose condition. Hierarchical regression analyses indicated that LSD-mediated over-reproduction was independent of marginal differences in self-reported drug effects across conditions.
Conclusions
These results suggest that microdose LSD produces temporal dilation of suprasecond intervals in the absence of subjective alterations of consciousness.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was ...used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.
With the emergence of new psychoactive substances (NPSs) over the years, the substances detected on stamps (also known as blotter papers) have also evolved from the traditional drug—lysergic acid ...diethylamide (LSD) to the multiple variants of lysergamides such as ALD‐52 and 1P‐LSD. The analysis of such blotter papers is usually done by solvent extraction followed by identification using gas chromatography–mass spectrometry (GC‐MS). This study has shown that hydrolysis to form LSD was observed in GC‐MS analysis when ALD‐52 was extracted with methanol. The extraction of ALD‐52 using other solvents such as acetonitrile, ethanol, isopropyl alcohol, ethyl acetate, and acetone, followed by GC‐MS analysis, was investigated. It is shown that alcoholic solvents such as methanol and ethanol will result in the conversion of ALD‐52 to LSD during GC‐MS analysis, whereas the sterically hindered isopropyl alcohol will prevent this conversion. Investigation also shows that the hydrolysis of ALD‐52 to LSD occurs at the GC injector port. It was also observed that the degree of hydrolysis was more pronounced at a lower concentration (0.1 mg/mL). The study was extended to a close analog—1P‐LSD, and the results showed that 1P‐LSD similarly hydrolyzes to LSD. However, 1P‐LSD was observed to be more stable than ALD‐52 due to steric hindrance because of the propanoyl group.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rationale
Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on ...subjective well-being and personality.
Methods
We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI).
Results
On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found.
Conclusions
In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects.
Trial registration
Registration identification number: NCT01878942.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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