Pharmacokinetics and subjective effects of 1P-LSD in humans after oral and intravenous administration

Pharmacokinetics and subjective effects of 1P-LSD in humans after oral and intravenous administration
Buy 1P-Lsd online, 1-Propanoyl-lysergic acid diethylamide (1P-LSD) appeared as a non-controlled alternative to LSD a few years ago. Although evidence is beginning to emerge from in vitro and animal studies that 1P-LSD might serve as a prodrug for LSD, an equivalent evaluation in humans is unavailable. Controlled oral and intravenous self-administrations of 100 μg 1P-LSD hemitartrate are reported in two human volunteers followed by analyses of urine and serum samples using a fully validated LC–MS/MS method. Psychometric evaluations included assessment of selected subjective drug effects and administration of the Five-Dimensions of Altered States of Consciousness rating scale (5D-ASC). In serum and urine, oral administrations of 1P-LSD only led to the detection of LSD reflecting biphasic elimination with a terminal elimination half-life of approx. t1/2 = 6.4 h. 1P-LSD could be detected for only up to 4.16 h in serum and 2.7 h in urine following intravenous administration, whereas LSD was detected in all serum samples (last sampling after approx. 24 h) and up to 80 h in urine. LSD showed first order elimination kinetics with an approx. t1/2 = 5.7 h, whereas 1P-LSD showed a rapid decrease in concentration within the first hour followed by a slower decrease, most probably due to hydrolysis. The bioavailability of LSD after oral ingestion of 1P-LSD was close to 100%. The psychosensory effects of 1P-LSD and their time course were comparable to those seen after uptake of LSD in other studies which further supports the prodrug hypothesis. The 5D-ASC scores were higher after oral compared with intravenous administration of 1P-LSD.

Lysergic acid diethylamide (LSD) soon became a widely used experimental drug after Albert Hofmann discovered its psychoactive effects in 1943. The ability to induce psychoactive effects at low doses (< 100 μg) and the finding that it interacted with the serotonergic system, triggered wide-ranging research into the neurotransmitter system at the time.1 LSD induces a wide spectrum of psychotropic effects, including euphoria or dysphoria, hallucinatory phenomena, synesthesia, perceptual alterations, remembrance of significant life events, mystical experiences, ego-dissolution, and cathartic experiences. Deep-reaching insightful experiences, but also anxiety-producing experiences were described by users.2 LSD was also used in psychotherapy.3 Nearly ten thousand scientific papers on experiments with LSD have been published since the 1950s (cf.4). In the mid-1960s, LSD became a major drug of abuse. Since the 1970s, its recreational use became more widespread internationally without loss of popularity ever since (cf.5). Buy 1P-Lsd online

Several analogs of LSD have been explored in scientific research6–8 and in more recent years, a number of LSD derivatives have emerged on the market that did not appear to have any established history in the scientific literature. One of these LSD derived “designer drugs” is 1-propanoyl-LSD (1P-LSD) that was first reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in 2015.9 Anecdotal reports published on various Internet forums suggested 1P-LSD to show LSD-like effects but formal studies were not available. However, 1P-LSD was shown to display LSD-like effects in mice when using the head-twitch response (HTR) assay and it was confirmed that pretreatment with the selective 5-HT2A antagonist M100,907 blocked the HTR.10 The binding affinity of 1P-LSD to cloned human 5-HT1A and 5-HT2A receptors dropped 67- and 13-fold but increased by a factor of 3.5 at the human 5-HT2C receptor when compared with LSD. Furthermore, when measuring 5-HT2A receptor activation (Gq-mediated Ca2+ flux in HEK cells), it was revealed that 1P-LSD (and two other 1-acyl-LSD derivatives) only functioned as very weak partial agonists and antagonists, whereas no agonist activity was observed at 5-HT2B and 5-HT2C receptors.11

In vitro studies assessing the metabolic stability of 1P-LSD and other 1-acyl substituted lysergamides showed the formation of LSD12 which suggested that 1P-LSD and other lysergamides acylated at the indole nitrogen atom might function as a prodrug. Consistent with this observation, the subcutaneous administration of 1P-LSD (0.1 or 0.3 mg/kg) to male Sprague–Dawley rats led to the detection of LSD and LSD metabolites when plasma samples were analyzed taken 15 min later which suggested the appearance of rapid hydrolysis in vivo.11

Although the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LSD in humans have been thoroughly investigated,2, 13–16 data of this kind are still missing for 1P-LSD. Moreover, within the context of forensic toxicology, PK data will provide important information on casework. For example, in a recent intoxication case reportedly involving the ingestion of a 1P-LSD blotter, the implementation of