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Chapter 12 Psychedelic Drugs: Mescaline, LSD, and other Hallucinogens What is a psychedelic drug? Any agent that causes alterations in perception, cognition, and mood as its primary psychological actions in the presence of an otherwise clear sensorium. (Abraham, Aldridge, and Gogia) 4 Classes of Psychedelic Drugs Anticholinergic Catecholamine-like Serotonin-like Psychedelic anesthetics-(affect a specific subclass of glutamate receptors- NMDA receptors). Difference between Mescaline and LSD Mescaline (more commonly known as peyote) is a catecholamine-like psychedelic drug. It produces an acute psychotomimetic state with prominent effects on the visual system when taken. Effects can last for about 10 hours. LSD is a serotonin-like psychedelic drug. It produces an alteration in thinking, emotion, arousal, and self-image. Time is slowed down. Visual alterations are the characteristic phenomenon. Effects last for about 6 to 8 hours. More about LSD The LSD-induced psychedelic experience typically occurs in three phases: 1. The somatic phase occurs after absorption of the drug & consists of CNS stimulation & autonomic changes that are predominantly sympathomimetic in nature. 2. The sensory (or perceptual) phase is characterized by sensory distortions and pseudohallucinations, which are the desired effects by the drug user. 3. The psychic phase signals a maximum drug effect, with changes in mood, disruption of thought processes, altered perceptions of time, depersonalization, true hallucinations, and psychotic episodes. Experiencing this phase is called a “bad trip”. Psychedelic Syndrome Hallucinations manifest their impressive alterations of mood, perception, and thought.The sorting process of the pontine raphe, a major center of serotonin activity which filters stations for incoming sensory stimuli, is disrupted by such drugs and a surge of sensory data and an overload of brain circuits is caused. Problems associated with LSD use: Chronic or intermittent psychotic states Persistent or recurrent major affective disorder (depression) Exacerbation of preexisting psychiatric illness Disruption of personality or chronic brain syndrome known as “burnout” Post-hallucinogenic perceptual disorder or “flashbacks” characterized by the periodic hallucinogenic imagery months or even years after the immediate effect of LSD has worn off. How Phencyclidine (PCP) works: Effects result of binding as noncompetitive antagonists of the NMDA glutamate receptors. Acute doses of PCP can induce a toxic psychosis. Repeated doses induce a more persistent schizophrenic symptomatology, including psychosis, hallucinations, flattened affect, delusions, formal thought disorder, cognitive dysfunction, and social withdrawal. Properties that characterize the clinical usefulness of PCP and ketamine: PCP is an open channel blocker of the NMDA receptor, transiently occluding the pore. It has a promising strategy to prevent glutamate-mediated neuronal cell death & associated disorders such as stroke, epilepsy, and Huntington’s disease. NMDA antagonists have also been proposed as potentially advantageous as neuroprotective agents, potentially useful for the treatment of CNS ischemia & head trauma. MDMA MDMA (a.k.a. ecstasy, XTC, and Adam) is a synthetic amphetamine derivative. Cross between stimulant and hallucinogen Enhanced mood, sense of well being, increased emotional sensitiveness, little anxiety, mild depersonalization and derealization phenomena (mildly hallucinogenic), changes in sense of space and time, heightened sensory awareness, increased psychomotor drive MDMA problems and toxicities MDMA may be too dangerous for human use Potent neurotoxin in animal studies Memory impairment in humans Fatalities during periods of intense activity/ skiing, dancing, etc. hyperthermia, tachycardia, disorientation, dilated pupils, convulsions, rigidity, breakdown of skeletal muscles, kidney failure, and death. MDMA 1.5% to 3.5% of 15 to 30 year olds have used ecstasy within previous year Early studies found generally self-limiting patterns of use, low levels of intravenous use, and few adverse health effects Now extensive polydrug use the norm, high rates of intravenous use, many physical, psychological, financial, relationship, occupational problems Combined use of MDMA with LSD (candyflipping) appears to be increasing