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ch 6

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Chapter 6 LSD and Other Hallucinogens Hallucinogens A wide variety of drugs that result in hallucinations do not exist Compare to illusion: distorted or inaccurate perception of stimuli that do exist Important consensus e.g. hearing voices definitely overestimates of motion? Hallucinogens Proposed as an alternative description Intended to convey idea that typically hallucinogens result in distorted perceptions A hallucination is not the same thing as a delusion: A belief held despite convincing contrary evidence, impossibility Does not mean that hallucinations cannot involve body) Hallucinogens Note two ways to classify drugs: Similar effects, e.g. stimulants Similar chemistry, e.g. opioids Hallucinogens as a description is based on the former, i.e. similar effects For our purposes, focus on psychoactive drugs that primarily produce hallucinations Keeping in mind that high dosage or chronic use of other drugs may result in hallucinations E.g. exclude cocaine, amphetamines despite possibility of formication hallucinations Types of Hallucinogens Large number of naturally occurring hallucinogens in addition to synthetic (derived from natural or completely synthetic) Can classify based on primary neurotransmitter Keeping in mind that almost all work on multiple systems Examples Serotonin: LSD, psilocybin Norepinephrine: mescaline (peyote), MDMA (Ecstacy) LSD (Lysergic acid diethylamide) Synthetic drug derived from lysergic acid Present in ergot, fungus that grows on rye bread, other grains Ergot poisoning / ergotism Among other things, convulsions, restricted blood flow, and hallucinations Research on lysergic acid was the result of trying to find drugs that could be used to reduce bleeding, relax muscles, without the high toxicity LSD (Lysergic acid diethylamide) Albert Hofmann: studied lysergic acid, and synthesized variations on it one was LSD Hoffman named it LSD-25: 25th derivative of lysergic acid (or 25th synthesized variation) lysergic acid LSD LSD (Lysergic acid diethylamide) Hofmann initially synthesized LSD in 1938, revisited is in 1943 first LSD (Lysergic acid diethylamide) Last Friday, April 16,1943, I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home, being affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away. To confirm this was the result of accidental exposure he later experimented on himself went home while still feeling the effects LSD - Effects LSD is an extremely potent chemical specifically, the response requires a very small dose an average 50-150 g (micrograms - millionth of a gram) assumed this was the smallest quantity that would have an effect Despite potency, very little toxicity: estimated LD50 for humans 300-600x ED50 therapeutic index ~1/300 1/600 compare to caffeine: ~ 1/100 generally oral administration: easily absorbed through mucous membranes LSD - Effects Acute Effects Initially, sympathetic NS activation dilation of pupils, elevated blood pressure and body temperature ~30 minutes 2 hours: Hallucinations: again, can involve distorted perception (illusions) Mood changes: euphoria, but also the potential for panic Synesthesia: sensations, e.g. seeing colors LSD - Physiology LSD acts on serotonin receptors like opioids, chemical structure is similar, and binds to serotonin receptors multiple serotonin receptors, but key is serotonin-2A (5HT2A) - agonist LSD Serotonin (5-HT) Important to note that specific mechanism is important SSRIs increase serotonergic activity by blocking reuptake do not result in hallucinations LSD Acute & Chronic Effects Tolerance, but no dependence does require increased dosage to achieve same effects, but no indication of physical or psychological dependence can be attributed to prolonged activity of the drug, unpredictable nature evidence for interaction with dopamine receptors associated with craving likely cause of euphoria, but euphoria is LSD Acute & Chronic Effects Panic & Psychotic Behavior panic is a feature constant one but not a by definition, experience is psychotic hallucinations, derealization, etc. however, features differ: e.g. primarily auditory, person tends to withdraw from others LSD Acute & Chronic Effects Flashbacks: estimated 5-30% of people remechanism unknown, though appears unique to LSD does not always involve panic DSM-IV-TR: hallucinogen persisting perception disorder keep in mind criteria are 1) it occurs and 2) causes distress LSD Acute & Chronic Effects Violence & Criminality not considered mainstream media tended to focus on and misrepresent negative events no evidence for any systematic patterns of violence associated with acute or chronic use important to keep in mind that it is psychoactive distorted perceptions, derealization may lead to acts of violence indirectly but so does alcohol (and to a much greater degree) Famous LSD Myths Readily absorbed through the skin not readily absorbed however - 1000x the amount Hofmann took and unclear whether it was the drugs or attempts to revive No one was ever permanently institutionalized because he thought he was an orange Causes damage to human chromosomes initial series of studies suggested damage to human chromosomes by 1971, after ~100 studies, no evidence time did not emphasize this media at the Things that perhaps should be LSD myths government experiments British experiment: Related: 2006 British government settles with several soldiers acknowledging uninformed testing CIA: MK-ULTRA Extensive, covert & illegal program of testing methods LSD one of the initial drugs used again, very little informed consent to lure subjects e.g. using brothels LAA Lysergic Acid Amide Hallucinogenic properties of chemical found in morning glory seeds Traditional use in ceremonies among some Native American cultures (still practiced today) For the US: seeds intentionally coated in pesticide or other toxin to prevent ingestion i.e. adding substance to prevent ingestion Mescaline / Peyote Mescaline is a norepinephrine-related hallucinogen found in the peyote cactus Classified as a Schedule I drug under federal law However, federal law (with some weaknesses) does allow usage in religious ceremonies for the Native American Church These laws also provide access to areas significant to religious practices in this case, (licensed) access to area where peyote is MDMA (Ecstasy) MDMA: Synthetic drug with effects on norepinephrine also on serotonin and dopamine 3,4-Methylenedioxymethamphetamine amphetamine-related hallucinogen: similar chemical structure d-amphetamine MDMA MDMA (Ecstasy) e.g. association with raves also considered a designer drug: however, despite prominent use starting in 1980s, first synthesized in 1912 Psychological effects: stimulant (similar to amphetamine) generally mild hallucinogenic empathy towards others MDMA (Ecstasy) Despite testimony of potential medical benefits, eventually classified as a Schedule I drug Toxicity: Acute: (one) elevated body temperature danger associated with use in clubs, combining physical exertion with already elevated body temperature Chronic: (include) cognitive impairments, anxiety, insomnia note these are not entirely dissimilar from chronic effects of licit psychoactive medications MDMA (Ecstasy) Potential medical benefits (2010): Findings from double-blind study involving psychotherapy and either MDMA or placebo: - Improvement in PTSD symptoms with MDMA compared to placebo - No adverse effects detected MDMA (Ecstasy) Potential cause of effects: MDMA releases oxytocin - Oxytocin is produced by the body, associated with inducing birth and lactation - Also associated with prosocial behavior (i.e. being excellent to one another)

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