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Psilocybin
Mescaline
Lysergic acid diethylamide
Lysergic acid
Abstract Mescaline, lysergic acid diethylamide (LSD), and psilocybin are classic serotonergic psychedelics. A valid, direct comparison of the effects of these substances is lacking. The main goal of the present study was to investigate potential pharmacological, physiological and phenomenological differences at psychoactive-equivalent doses of mescaline, LSD, and psilocybin. The present study used a randomized, double-blind, placebo-controlled, cross-over design to compare the acute subjective effects, autonomic effects, and pharmacokinetics of typically used, moderate to high doses of mescaline (300 and 500 mg), LSD (100 µg), and psilocybin (20 mg) in 32 healthy participants. A mescaline dose of 300 mg was used in the first 16 participants and 500 mg was used in the subsequent 16 participants. Acute subjective effects of 500 mg mescaline, LSD, and psilocybin were comparable across various psychometric scales. Autonomic effects of 500 mg mescaline, LSD, and psilocybin were moderate, with psilocybin causing a higher increase in diastolic blood pressure compared with LSD, and LSD showing a trend toward an increase in heart rate compared with psilocybin. The tolerability of mescaline, LSD, and psilocybin was comparable, with mescaline at both doses inducing slightly more subacute adverse effects (12–24 h) than LSD and psilocybin. Clear distinctions were seen in the duration of action between the three substances. Mescaline had the longest effect duration (mean: 11.1 h), followed by LSD (mean: 8.2 h), and psilocybin (mean: 4.9 h). Plasma elimination half-lives of mescaline and LSD were similar (approximately 3.5 h). The longer effect duration of mescaline compared with LSD was due to the longer time to reach maximal plasma concentrations and related peak effects. Mescaline and LSD, but not psilocybin, enhanced circulating oxytocin. None of the substances altered plasma brain-derived neurotrophic factor concentrations. In conclusion, the present study found no evidence of qualitative differences in altered states of consciousness that were induced by equally strong doses of mescaline, LSD, and psilocybin. The results indicate that any differences in the pharmacological profiles of mescaline, LSD, and psilocybin do not translate into relevant differences in the subjective experience. ClinicalTrials.gov identifier: NCT04227756.
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This chapter highlights the similarities in chemical structure and physiologic effects of hallucinogens, as well as their metabolism, therapeutic uses and potential for misuse or abuse. Special attention is given to the testing process, with an emphasis on interpretation of test results. Hallucinogens are drugs that alter an individual's perception of reality. The classic hallucinogens include lysergic acid diethylamide (LSD), psilocybin, and mescaline. LSD is a derivative of lysergic acid, an alkaloid that occurs naturally in the fungus Clavicepspurpurea . LSD, psilocybin, and mescaline exert their perception-altering effects by acting on neural circuits in the brain that use serotonin as the neurotransmitter. Phencyclidine (PCP) and ketamine produce their effects by interfering with the activity of the neurotransmitter glutamate. PCP is hydroxylated to form inactive metabolites, which are then conjugated to glucuronic acid and excreted in urine. The chapter provides dissociative drugs phencyclidine and ketamine.
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Our use of drug-facilitated psychotherapy has been to aid repressed material to become conscious and to increase insight. Any method or tool which facilitates these processes has the possibility of being a valuable psychotherapeutic tool. Certain drugs on which we have done research, such as mescaline, ALD-52, ibogaine, psilocybin, Ditran (N-ethyl-3-piperidyl cyclopentylphenyl glycolate HC1), and lysergic acid diethylamide (LSD-25), have the capacity to broaden the patient’s spectrum of awareness. If a patient uses this enhanced capacity to look inward, he is often enabled, particularly in the case of LSD-25, to see and experience many affects, childhood memories, conflicts, and impulse strivings which were previously blotted out by the repressive forces. The present study was conducted in an attempt further to evaluate the use of LSD-25 as an aid to psychotherapy and to develop procedures and techniques for its most effective utilization with
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Psychedelic or hallucinogenic drugs such as lysergic acid diethylamide (LSD), 3, 4, 5-trimethoxy-β-phenethylamine (mescaline), psilocybin, 3, 4-methylenedioxymethamph-etamine (MDMA), N, N-dimethyltrypta-mine (DMT) and their relations occur in abundance throughout the natural world, and have been used by humankind for thousands of years.
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The effects of mescaline and lysergic acid were studied in schizophrenic patients. It was found that physiological changes were produced in these patients and that their mental symptomatology was markedly aggravated. The observations made with the above-mentioned drugs on normal individuals were compared with those seen in schizophrenic patients. Mescaline and lysergic acid are drugs that disorganize the psychic integration of a person. This disorganization is much more apparent in schizophrenics than in normals. The diagnostic, prognostic, and therapeutic use of these drugs is also discussed.
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D-lysergic acid diethylamide (LSD) displays (1) the phenylethylamine pattern present in mescaline, cyclazocine and catecholamines and (2) the 4-substituted tryptamine structure of psilocybin which is a serotonin analog. Hence (a) Naloxone--a blocker of the LSD-like side effects of cyclazocine--should (and does) block effects of LSD, and (b) cross-tolerance may be present between LSD and cyclazocine but not between mescaline and psilocybin. Even though LSD binds subcortically, its effect on regional perfusion of the brain and, presumably, function is primarily cortical and, since the perfusion shifts evoked by psilocybin are confined to subcortical regions, we assume that other compounds with the phenylethylamine structure such as mescaline, also may selectively affect cortical activity.
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