Preller, K., Schleifer, C., Stämpfli, P., Krystal, J., Vollenweider, F., & Anticevic, A. (2017). 951-Changes in Resting-State Global Brain Connectivity in LSD-Induced Altered States of Consciousness are Attributable to the 5-HT2A Receptor. Biological Psychiatry, 81(10), S385. 10.1016/j.biopsych.2017.02.677
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All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 day later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.
Liechti, M. E. (2017). Modern Clinical Research on LSD. Neuropsychopharmacology. 10.1038/npp.2017.86
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Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (P<0.05, family-wise error). Notably, there was a significant negative correlation between LSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (P<0.05). These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing.
Mueller, F., Lenz, C., Dolder, P. C., Harder, S., Schmid, Y., Lang, U. E., … & Borgwardt, S. (2017). Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Translational Psychiatry, 7(4), e1084. 10.1038/tp.2017.54
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Over a third of the world’s population is infected with parasitic worms. One of the most burdensome infections underpins the neglected tropical disease schistosomiasis (Bilharzia) caused by parasitic flatworms of the genus Schistosoma, which afflicts ~200 million people worldwide. Consequently, there is a need to discover and develop next generation anthelmintics, active against a broad spectrum of parasitic helminths.
Flatworm musculature is regulated by bioaminergic signalling: addition of exogenous 5-HT to isolated flatworm muscle fibres causes contraction. This effect is likely mediated by engagement of serotonergic G protein coupled receptors (GPCRs). For example, in free living planarians, knockdown of a serotonergic GPCR (S7.1) impairs worm motility. Here, we demonstrate that the psychoactive agent, lysergic acid diethylamide (LSD) acts as a agonist at the planarian S7.1 receptor (EC50 = 1.3±0.5nM, Emax 99±5% of 5-HT response). LSD evoked contraction inhibited the motility of free living planarian worms (distance moved 16±2% versus control worms) and potently blocked bipolar regeneration evoked by praziquantel (IC50 = 0.5±0.2nM). These data raises the possibility that other psychoactive drugs, including psychotropics with known activity at human 5-HT2 receptors, could serve as efficacious lead compounds to disrupt flatworm mobility.
Therefore, we screened a variety of psychoactive agents on the motility of free living planarian flatworms, as well as the functionality of heterologously expressed S7.1 using a real time cAMP biosensor. Agents were discovered that modulated flatworm movement and regeneration, and efficacy of the screened molecules provided information about structural features necessary for activity at this abundant flatworm serotonergic GPCR. These data also identify features of ligands conveying activity at flatworm 5-HT GPCRs.
Woodhouse, K., Chan, J. D., & Marchant, J. (2017). Psychoactive Drugs as a Route to Development of Novel Anti-parasitic Agents. The FASEB Journal, 31(1 Supplement), 1002-2.
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Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic-associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.
Johnson, M. W., Garcia-Romeu, A., Johnson, P. S., & Griffiths, R. R. (2017). An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. Journal of Psychopharmacology, 0269881116684335. 10.1177/0269881116684335
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Observation: We report a case of a 25-year-old man crushed by a train while he was returning from a rave party. The consumption of 25I-NBOMe was rapidly evoked by people who had participated at the party.
Materials and methods: In this context, the post-mortem toxicological expertise was completed by a broad screening using high-resolution mass spectrometry detection (LC-HRMS). Three hundred NPS and metabolites (including 25B, 25C and 25I-NBOMes) can be found with this method. A targeted screening in MRM mode was also performed on a smaller number of hallucinogens.
Results: The toxicological analyses were performed on blood and urine samples. Amphetamines, cocaine, cannabinoids and opiates were not detected. Ethanol was measured at 0.71 g/L and 1.59 g/L in blood and urine samples, respectively. The screening by LC-HRMS did not reveal the presence of NPS, including NBOMes. The targeted screening in MRM mode revealed the presence of LSD and its metabolite, the 2-oxo-3-hydroxy-LSD. LSD was quantified at 0.2 ng/mL in blood.
Conclusion: This case alerts on the frequent confusion between NBOMes and LSD and on the renewed interest for LSD due to the popularity of NBOMes. This case therefore encourages the prudence and research of all hallucinogenic substances, even when the context is evocative.
Bodeau, S., Bennis, Y., Régnaut, O., Fabresse, N., Richeval, C., Humbert, L., … & Lemaire-Hurtel, A. S. (2017). LSD instead of 25I-NBOMe: The revival of LSD? A case report. Toxicologie Analytique et Clinique, 29(1), 139-143. 10.1016/j.toxac.2016.12.007
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LSD induces profound psychedelic effects, including changes in the meaning of percepts. The subjective effects of LSD are fully blocked by a 5-HT2A receptor antagonist. LSD may alter meaningfulness by increasing activity in cortical regions responsible for processing personal attribution.
Halberstadt, A. L. (2017). Hallucinogenic Drugs: A New Study Answers Old Questions about LSD. Current Biology, 27(4), R156-R158. 10.1016/j.cub.2016.12.058
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