Reviewing the Potential of Psychedelics for the Treatment of PTSD

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search for and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, 2 psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses 4 types of compounds: 3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics (e.g., psilocybin and lysergic acid diethylamide), and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

Abstract A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted

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

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. 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

Return of the lysergamides. Part VI:Analytical and behavioural characterization of 1-cyclopropanoyl-d-lysergic acid diethylamide (1CP-LSD)

Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1-acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1-Cylopropanoyl-LSD (1CP-LSD) has recently emerged as a new addition to the group of lysergamide-based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP-LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC–MS also revealed the detection of artificially induced degradation products. Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1-acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP-LSD also induces the head-twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD-like behavioural profile. 1CP-LSD induced the HTR with an ED(50) = 430.0 nmol/kg which was comparable to 1P-LSD (ED(50) = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP-LSD in humans