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Chapter 13

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Suzanne Erb

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Dissociative Anaesthetics, Psychedelics, and Hallucinogens Chapter 13 Notes Qualitative and quantitative effects of drugs dependant on dose Lower doses: alter mood and thought content (no hallucination) Somewhat higher doses: clear perceptual distortions (not true hallucination) High doses: cause hallucinations Because of this effect, theses drugs are also called hallucinogens. Psychotomimetic (psychosis mimicking) or psychotogenic (psychosis-generating) are also used to describe theses drugs because at only at high doses hallucinations occur, at low doses : gross distortion or disorganizations of mental capacity, emotion, capacity to recognize reality, communicate may occur. These two terms are not accurate as 1) many drugs induce a condition that mimics a natural psychosismania and schizophrenia) 2) doses of some drugs that do mimik natural psychotic states (cocaine/amphetamine) are not taken for this reason Psychedelic (mind altering) is another term, but the meaning isnt clearreferred to as P/P/Hs (psychotomimetic/psychedelic/hallucinogenic substances) Aboriginals used P/P/Hs (iboga, mescaline, psilocybin) containing plants in rituals, healing, and promote group cohesiveness. 1960s: psychotherapists recommend using these drugs for mental illness GENERAL CHARACTERISTICS OF P/P/Hs Four major classes of P/P/Hs: 1. Monoamine-related subs: effects are mediated by differences in activity of seretonin (5HT), DA, and NE in CNS 2. Cannabiniods: derivatives of marijuana plant (or similar synthetics) 3. Anticholinergics: block Ach activity in brain 4. Dissociative aesthetic: analgesic-aesthetic drugs with P/P/Hs effects Ibogaine: drug with pharmacological properties so unique that doesnt fit in any 4 classes Most of these drugs are rein forcers for humans because of their ability to alter consciousness, visual processes, rather than causing effect son reward centres of brain Euphoria is common effect, but is highly context-specific. It may cause a dysphoric reaction (panic/paranoid) in some cases. Nonhumans wont self-administer many P/P/Hs in their pure form, whereas they will with psychotics/sedative-hypnotics, and narcotics. When pure LSD/mescaline used in catheter, animals avoid administering Three types of P/P/Hs are readily administered by nonhumans: Delta 9thc (in marijuana), PCP, MDMA. Research over past 30 years with P/P/Hs on humans is limited because 1) lack of funding, 2) Schedule 1 drugs, 3) earlier research lacked controls so people suffered adverse effect, 4) ethical limitationscan only be used in animals Drug Discrimination Paradigm: a powerful tool for assessing subjective effects of P/P/Hs animals are trained to tell difference b/w the effects of a placebo and those produced by particular drug E.g., rat conditioned to respond to lever if injected with placebo, and again if injected with LSD. Rats learn to respond to correct lever and is rewarded with a drug that mimics LSDto see how it reacts: will it press the same lever associated with LSD or the one associated with the placebo This procedure can be used to see which neurotransmitter systems are involved in drugs subjective effects This paradigm is useful in that drugs unknown effects on CNS can be compared, and specific sites at which drugs act MONAMINE-RELATED P/P/Hs Similar basic molecular structure to 5HT, DA and NE 5-HT type P/P/Hs: LSD, psilocybin, psilocin, bufotenine, DMT, and DET Catachoamine type P/P/Hs: mescaline, DMMA, MDA, MMDA Ideolamine and catecholamine type P/P/Hs are similar, but potency varies LSD 100x more potent than psilocybin, and 4000x more potent than mescaline in humans Duration LSD:several hours DMT: 1 hours Mescaline, psilocin, psilocybin: duration is between LSD and DMT\ Effects range from being similar to amphetamine to those very similar t oLSD In some cases the effects depend on which isomer of compound is administered. Dextro isomer of MDA- amphetamine like- symptoms; levi isomer induces LSD effects Drugs in this category have very rapid tolerance both mental and physical Tolerance is complete after 3-4 days exposure Mono P/P/Hs are cross tolerant, with each other but dont show cross tolerance with other classes of P/P/Hs No tolerance developed to LSD transfer to DMT (can be because DMT has ~30 min short duration) Human and animals are reported as having similar subjective effects at the same dose All mono- P/P/Hs do not have abstinence syndrome following chronic exposure Mono- P/P/Hs effects on body: pupil dilation, increase hr and bp and body temperature LSDs HISOTRICAL SIGNIFICANCE LSD is a derivative of ergot fungi Albert Hofmann synthesized LSD One of most potent drug agents knowncan exert detectable effects at 50 micograms (weight of grain of salt) Interest in LSD went through 3 phases: Phase 1) Interest in LSDs potential for finding out the biochemical basis for psychosis Phase 2) In 1953, proposed to be potentially useful in psychthereapies (Freuds influence) Often used to open therapy process, was used to treat disorders: alcoholism, drug addiction, emotional and physical distress, cancer pain. However LSD therapy began to wane in mid-60s because a) its purpose of use could not be decided upon in the psychiatry community, b) it had become a social hippie problem Phase 3) LSD became a class of abused drugs that mainstream culture attempted to suppress (also became a Schedule 1 drug) NEUROCHEMICAL EFFECTS OF LSD AND RELATED COMPOUNDS LSD is absorbed within 30/60 minutes after oral administration (highly lipid-soluble) can stay in body up to 15 hours Its especially potent as the drug is distributed throughout the whole body, with low levels in the brain LSDs mechanisms and precise sites of action are difficult to determine as a very small dose is need to cause effects Only 2 cases of death by LSD reported LSD and other mono- P/P/Hs induce their effects through mechanism linked to the serotonergic system LSD inhibits spontaneous firing of serotonergic neurons of the reticular activating system and so LSD was hypothesizes to induce the intense emotions and vivid imagery of the dream state (while awake)however evidence was found to be incompatible with this view: tolerance to its psychotomimetic effects occurred with chronic LSD exposur
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