Lysergic acid diethylamide micro dosing
221192087
Psychedelics as a Treatment for Alzheimer's Disease Dementia
Currently, there are no disease modifying treatments for Alzheimer's disease (AD) or any other dementia subtype. The renaissance in psychedelic research in recent years, in particular studies involving psilocybin and lysergic acid diethylamide (LSD) coupled with anecdotal reports of cognitive benefits from micro dosing, suggests that they may have a therapeutic role in a range of psychiatric and neurological conditions due to their potential to stimulate neurogenesis, provoke neuroplastic changes and reduce neuroinflammation. This inevitably makes them interesting candidates for therapeutics in dementia. This mini review will look at the basic science and current clinical evidence for the role of psychedelics in treating dementia, especially early AD, with a particular focus on micro dosing of the classical psychedelics LSD and psilocybin.
Frontiers in Synaptic Neuroscience
Simon Vann Jones Allison O'Kelly
222137725
Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review
Microdosing psychedelic drugs that is, taking sub behavioral doses of lysergic acid diethylamide (LSD) or psilocybin is a growing practice in Western societies. Taken mainly for creative or mood enhancing purposes, thousands of users are increasingly being exposed to (micro)doses of psychedelic drugs. In this systematic review, we searched the available evidence from human studies, focusing our results in terms of three main axes: efficacy, safety, and the influence of the placebo effect in microdosing practices. While the available evidence has some strengths (e.g. large sample sizes, robust methodologies) there are also remarkable limitations (e.g. gender bias, heterogeneity of dosing schedules and drugs used) Highly contradictory results have been found, showing both the benefits and detriments of microdosing in terms of mood, creative processes, and energy, among other regards. This review provides a general overview of the methods and approaches used, which could be useful for improving future studies.
Neuroscience Biobehavioral Reviews
Genis Ona Jose Carlos Bouso
173189055
Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers
BACKGROUND Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD) known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100 200 mg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0 26 mg) on mood and behavior in healthy volunteers under double blind conditions. METHODS Healthy young adults (N 20) attended 4 laboratory sessions during which they received 0 (placebo) 6.5, 13, or 26 mg of LSD in randomized order at 1 week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed. RESULTS LSD produced dose related subjective effects across the 3 doses (6.5, 13, and 26 mg) At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected. CONCLUSIONS Single microdoses of LSD produced orderly dose related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 mg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.
Biological Psychiatry
Anya K Bershad Scott T Schepers Michael P Bremmer Royce J Lee Harriet de Wit
221326692
A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers
Background: Lysergic acid diethylamide (LSD) is an ergot alkaloid derivative with psychedelic properties that has been implicated in the management of persistent pain. Clinical studies in the 1960s and 1970s have demonstrated profound analgesic effects of full doses of LSD in terminally ill patients, but this line of research evaporated after LSD was scheduled worldwide. Aim: The present clinical study is the first to revisit the potential of LSD as an analgesic, and at dose levels which are not expected to produce profound mind altering effects. Methods: Twenty four healthy volunteers received single doses of 5, 10 and 20 ug LSD as well as placebo on separate occasions. A Cold Pressor Test was administered at 1.5 and 5 h after treatment administration to assess pain tolerance to experimentally evoked pain. Ratings of dissociation and psychiatric symptoms as well as assessments of vital signs were included to monitor mental status as well as safety during treatments. Results: LSD 20 ug significantly increased the time that participants were able to tolerate exposure to cold (3degC) water and decreased their subjective levels of experienced pain and unpleasantness. LSD elevated mean blood pressure within the normal range and slightly increased ratings of dissociation, anxiety and somatization. Conclusion: The present study provides evidence of a protracted analgesic effect of LSD at a dose that is low enough to avoid a psychedelic experience. The present data warrant further research into the analgesic effects of low doses of LSD in patient populations.
Journal of psychopharmacology
Johannes G Ramaekers Nadia Hutten Natasha L Mason Patrick C Dolder Eef L Theunissen Friederike Holze Matthias E Liechti Amanda Feilding Kim P C Kuypers
222838681
Acute dose dependent effects of lysergic acid diethylamide in a double blind placebo controlled study in healthy subjects
Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well defined doses of LSD. We used a double blind, randomized, placebo controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 ug) and 200 ug LSD 1 h after administration of the serotonin 5 hydroxytryptamine 2A (5 HT2A) receptor antagonist ketanserin (40 mg) Test days were separated by at least 10 days. Outcome measures included self rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic subjective response relationship was evaluated. LSD showed dose proportional pharmacokinetics and first order elimination and dose dependently induced subjective responses starting at the 25 ug dose. A ceiling effect was observed for good drug effects at 100 ug. The 200 ug dose of LSD induced greater ego dissolution than the 100 ug dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25 200 ug. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 ug LSD. The LSD dose response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 ug. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5 HT2A receptor activation.
Neuropsychopharmacology
Friederike Holze Patrick Vizeli Laura Ley Felix Muller Patrick C Dolder Melanie Stocker Urs Duthaler Nimmy Varghese Anne Eckert Stefan J Borgwardt Matthias E Liechti
221915244
Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants
"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 ug) and placebo were administered in a double blind, randomized, placebo controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration subjective effect relationships were described using pharmacokinetic pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127 181) 279 pg/mL (243 320) and 500 pg/mL (413 607) after 5, 10, and 20 ug LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half life was 2.7 hours (1.5 6.2) The 5 ug dose of LSD elicited no significant acute subjective effects. The 10 ug dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 ug LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 ug dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose proportionally increased at doses as low as 5 20 ug and decreased with a half life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 ug.
Clinical pharmacology and therapeutics
Friederike Holze Matthias E Liechti Nadia Hutten Natasha L Mason Patrick C Dolder Eef L Theunissen Urs Duthaler Amanda Feilding Johannes G Ramaekers Kim P C Kuypers
229109850
Lysergic Acid Diethylamide Toxicity
D lysergic acid diethylamide, or LSD, is a compound of the lysergamide class known for its powerful psychedelic effects on humans. Although first synthesized in 1938 by Albert Hofmann in an attempt to create a central nervous system stimulant, it was not until 1943 when Hofmann discovered the molecule's subjective effects on the human body after accidental absorption through the skin. Only a few days later, on the 19 of April 1943, reports suggest Hofmann ingested around 250 micrograms of the drug, marking the very first intentional "LSD trip." While Hofmann, and countless others afterward, who report ingesting the drug at various dosages, indicate a wide variety of effects, a common denominator of sorts is the absolute profundity of the experience that the drug seems to elicit in users.A substance of significant pharmacological and clinical interest, LSD remains as the most researched hallucinogen. It was famously examined by the CIA in the 1950s when the research program MK ULTRA was implemented to investigate potential methods and pharmacological agents to aid in the development of "truth serums." Further research centered on the substance's mechanism of action in the body was conducted, and the early belief that it had serotonergic properties was eventually confirmed. Specifically, the drug acts as a partial agonist at the 5 HT1A, 5 HT2A, 5 HT2B, 5 HT2C, and 5 HT6 receptors. The threshold dose of LSD is commonly accepted to be 15 micrograms, while a relatively heavy dose at the opposite end of the accepted spectrum is around 300 micrograms. As the dosage increases beyond this arbitrary setpoint, reports suggest an increase in the intensity of the drug's effects. This dosing brings up an all important question that applies to any substance under scrutiny: pharmacologically speaking, what is the drug's toxicity? Interestingly, in the case of LSD, no deaths can be attributed to its direct effects.
Maximo Baquiran Yasir Al Khalili
221863586
Re evaluation of the discriminative stimulus effects of lysergic acid diethylamide with male and female Sprague Dawley rats
Recent discoveries from clinical trials with psychedelic assisted therapy have led to a resurgence of interest in the psychopharmacology of lysergic acid diethylamide (LSD) Preclinical drug discrimination is an invaluable tool to investigate the neurochemical mechanisms underlying subjective drug effects. The current study extends previous drug discrimination research by including both sexes. Adult female (n 8) and male (n 8) Sprague Dawley rats were trained to discriminate 0.08 mg/kg LSD from saline under a fixed ratio 20 schedule of food reinforcement. Substitution tests were conducted with several substances, including other serotonergic hallucinogens, psychostimulants, mixed psychedelic stimulants and synthetic cathinones. Stimulus antagonist tests were conducted with selected serotonin and dopamine antagonists. LSD substitution with serotonergic hallucinogens was comparable between sexes. Modest but intriguing differences were observed between male and female rats in the extent of partial substitution by 3,4 methylenedioxymethamphetamine and 3,4 methylenedioxyamphetamine enantiomers and the synthetic cathinones, 3,4 methylenedioxypyrovalerone and 4 methylmethcathinone. Dopamine antagonists failed to block the LSD cue in both sexes and exerted stronger rate suppressant effects in male rats. The 5 hydroxytryptamine antagonist, (R) a (2,3 dimethoxyphenyl) 1 [2 (4 fluorophenyl) ethyl] 4 piperidinemethanol (MDL 100 907) blocked LSD discrimination in both sexes, although complete blockade was evident at lower doses in male rats. These results support previous findings regarding the prominent role of serotonergic activities underlying LSDs discriminative stimulus effects in male rats and generalize these findings to female rats. In consideration of the rising popularity in psychedelic assisted psychotherapy, further research may be warranted to evaluate possible sex differences in the behavioral and subjective effects of LSD.
Behavioural pharmacology
Keli A Herr Lisa E Baker
211136396
Lysergic acid diethylamide causes mouse retinal damage by up regulating p JAK1/p STAT1
Abstract Purpose: Lysergic acid diethylamide (LSD) is a powerful hallucinogen with high potential for abuse. There is far less known about its effects on the retina, especially the underlying mechanisms. This study was to investigate the acute toxicity of LSD on the retina of C57 mice and its mechanisms of action. Methods: C57 mice were treated with LSD at progressively increasing doses (0.2 1.2 mg/kg) intraperitoneally two times daily for 5 days, mice treated with saline served as negative control. Electroretinography (ERG) was used to test the function of the retina. Toluidine blue staining was used to detect the morphology of the retina. Enzyme linked immunosorbent assay (ELISA) was used to measure the apoptosis related factors. Real time PCR and western blot techniques were used to measure expression changes of genes and proteins, respectively. Results: LSD treatment caused retinal damage, as shown by a decrease in ERG response and the loss of photoreceptor cells. LSD treatment also increased apoptosis through up regulating the expression of p JAK1/p STAT1. Conclusions: Our study indicated that intraperitoneal administration of LSD induced retinal damage of C57 mice, at least partially through regulating the JAK/STAT pathway.
Cutaneous and ocular toxicology
Kang Chen Xiangyun He Chen Li Yangjin Ou Yiru Li Jia Lai Meng Lv Xuqing Li Ping Ran
227257508
Acute Lysergic Acid Diethylamide Does Not Influence Reward Driven Decision Making of C57BL/6 Mice in the Iowa Gambling Task
While interest in psychedelic drugs in the fields of psychiatry and neuroscience has re emerged in recent last decades, the general understanding of the effects of these drugs remains deficient. In particular, there are gaps in knowledge on executive functions and goal directed behaviors both in humans and in commonly used animal models. The effects of acute doses of psychedelic lysergic acid diethylamide (LSD) on reward driven decision making were explored using the mouse version of the Iowa Gambling Task. A total of 15 mice were trained to perform in a touch screen adaptation of the rodent version of the Iowa Gambling Task, after which single acute doses of LSD (0.025, 0.1, 0.2, 0.4 mg/kg) serotonin 2A receptor selective agonist 25CN NBOH (1.5 mg/kg) d amphetamine (2.0 mg/kg) and saline were administered before the trial. 25CN NBOH and the three lowest doses of LSD showed no statistically significant changes in option selection or in general functioning during the gambling task trials. The highest dose of LSD (0.4 mg/kg) significantly decreased premature responding and increased the omission rate, but had no effect on option selection in comparison with the saline control. Amphetamine significantly decreased the correct responses and premature responding while increasing the omission rate. In conclusion, mice can perform previously learned, reward driven decision making tasks while under the acute influence of LSD at a commonly used dose range.
Frontiers in Pharmacology
Lauri Elsila Nuppu Korhonen Petri Hyytia Esa R Korpi