Psychotomimetics: Behavioral Pharmacology
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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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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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Abstract Chapter 16 of Addiction Medicine covers hallucinogens, dissociative drugs, and empathogens. Hallucinogens, also termed psychedelics, are a large and diverse group of substances, some of which occur in fungi and plants and some which are chemically synthesized. Some have psychostimulant properties as well. They include psilocybin, mescaline, dimethyltryptamine (DMT), ayahuasca, lysergic acid diethylamide (LSD), and NBOMes and tryptamines. Dissociative drugs include ketamine, phencyclidine (PCP), and nitrous oxide. The term empathogens covers MDMA and similar drugs. The prevalence and mode of use of these drugs are described together with their pharmacological effects. Clinical syndromes include acute intoxication and chronic use, flashbacks (characteristic of psychedelic use in particular), psychosis, acute anxiety state, and acute and chronic brain syndromes. The principles of diagnosis and management are then outlined. Dependence is uncommon with hallucinogens, although with regular consumption of microdoses of LSD, it is increasingly recognized. It is well recognized for ketamine and derivatives.
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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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Introduction Psychedelics - including LSD (lysergic acid diethylamide), psilocybin, DMT (N, N-dimethyltryptamine), ayahuasca and mescaline - have an ancient history across various civilizations. In 1950, after LSD’s discovery by Hofmann, psychedelics enjoyed a short-lived relationship with psychiatry, before prohibitive legislature emerging in response to the recreational use in the mid-1960s. However, the last decade has witnessed a renewed scientific interest in psychedelics - a phenomenon referred to as the ‘Psychedelic Renaissance’. Objectives Review the pharmacology of psychedelic drugs and the latest evidence of its therapeutic potentials in anxiety, mood and addictive disorders. Methods Literature review performed on PubMed and Google Scholar databases, using the keywords “psychedelics”, “hallucinogens”, “d-lysergic acid diethylamide (LSD)”, “psilocybin”, “ayahuasca”, “mescaline”, “DMT (N,N-dimethyltryptamine)”. Results The psychedelics or “classic hallucinogens” can be subdivided into three sub-classes: the plant-derived tryptamines (psilocybin and ibogaine) and phenethylamines (mescaline), and the semisynthetic ergolines (LSD). The therapeutic potentials are mediated by an agonist action on 5-HT2A receptors expressed in frontal and paralimbic structures involved in mood and emotion regulation, introspection, interoception and self-consciousness. Stimulation of 5-HT2ARincreases the glutamatergic tone and neuroplasticity and is accompanied by reduced amygdala activity, reducing anxiety. Experimental, open-label, and RCTs showed anxiolytic, antidepressive, and antiaddictive effects with psychedelics. As examples, psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression in treatment-resistant depression. Conclusions Despite the promising effects of psychedelics on anxiety, depression and addiction, the evidence is still preliminary, waiting for long-term studies with bigger samples. Conflict of interest No significant relationships.
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