Chapter 6 LSD and Other Hallucinogens. Definition of Hallucinogen Hallucinogens distortions of perception altered sense of reality, transported to new

Chapter 6

LSD and Other Hallucinogens

Definition of Hallucinogen

Hallucinogens distortions of perception altered sense of reality, transported to new reality

also called psychedelics (“mind-expanding”) drugs

produce these effects at low or moderate doses other drugs may produce hallucinations at high doses

Classifying Hallucinogens

• Four basic groups by pharmacologyserotoninergic (5-HT systems)noradrenergic (NE systems)cholinergic (ACh systems)miscellaneous

synthetic hallucinogense.g. phencyclidine (PCP) and ketaminelittle resemblance to any known neurotransmitter

Classifying Hallucinogens

Groups based on effectspsychedelicsdissociative anestheticsdeliriants

produce side effects that are very unpleasanttherefore generally not used recreationally

Figure 6.1

Claviceps tulasne(ergot)

Amanita muscaria(ibotenic acid)

Atropa belladonna (atropine)

Datura stramonium(atropine,scopolamine)

LSDA. is one of the most toxic of abused drugsB. was used by the CIA in experiments in the

1950sC. users show little tolerance to the drug,

even if used over long periodsD. like cocaine and the opiates, is abused

because it is a potent activator of DA reward systems

E. led to a surge in admissions to psychiatric admissions during its height of popularity as evidenced by DAWN statistics

Lysergic Acid Diethylamide (LSD)

Lysergic acid diethylamide (LSD-25)serotonergic drugsynthetically derived from ergot

toxic rye fungusresponsible for thousands of deaths over the centuries.

LSD itself has an extremely large safety marginunclear what the LD50 is


1938LSD synthesized by Albert Hofmann

1947

Sandoz marketed LSD (Delysid)

for treating psychiatric disorders

1950sCIA experiments for use in mind control

and chemical warfare

given to unsuspecting enlisted men


1960sLSD popularized by Timothy Leary

1990sresurgence in LSD abusebegan to reverse in 1997

Taken orally, experience lasts about 12 hours


LSD experienceunpredictable but certain features are commonly observed:

colorful hallucinations

synesthesia in which sounds often appear as visions

a distortion of perceptual reality

emotional swings

feeling of timelessness

illusory separation of mind from body

Lysergic Acid Diethylamide (LSD-25)

LSD affects a subtype of serotonergic receptors 5-HT-2A

receptorsdoes not result in addiction or dependencecraving is absenttolerance is extremely rapid; one dose

serves to prevent abuse

Facts and Fiction about LSD LSD does not

produce psychological or physical dependenceinduce a panic or psychotic state

(providing that there is a supportive setting fortaking of LSD; “set” is very important)*

elevate one’s level of creativitydamage chromosomes promote violent behavior

LSD abuse MAYcause birth defects if used during pregnancyresult in flashback experienceshallucinogen-induced persisting perceptual disorder (HPPD)

* Panic attacks are much more likely if the individual has an existing psychiatric condition than if not, or if the person is unsuspecting or is emotionally troubled at the time.

8th Grade 10th Grade 12th Grade

Lifetime*** 1.9% 2.6% 4.0%

Past Year 1.3 1.8 2.7

Past Month 0.5 0.7 1.1

Prevalence of LSD Use

Source: 2008 Monitoring the Future Survey,NIDA.


LSD is classified as a Schedule I drug.

LSD should be classified as a Schedule Idrug.

LSD closely resembles the molecular structure of __________.

A. dopamineB. serotoninC. endorphinsD. acetylcholine

Other Hallucinogens Related to Serotonin

Other serotonergic hallucinogens psilocybin

mushrooms (0.5% psilocybin, trace psilocin) oral delivery: tea or added to foods

20 min latency, 6 hr durationlysergic acid amide (LAA)

dimethyltryptamine (DMT)DMT the “businessman’s hallucinogen”often used with harmine, a MAO inhibitor

ayahuaskabufotenine“bufo” is a genus of toad; toad-licking

indole serotonin LSD

psilocybin harmine bufotenine

Hallucinogens Relatedto Norepinephrine

Mescalinefrom crown of peyote cactus (button)used in native American religious ceremonies

chemically related to norepinephrineactions at 5-HT-2A receptors are responsible hallucinogenic effects

2,5-dimethoxy-4-methylampetamine (DOM)more euphoric, less hallucinogenic than LSD

may produce “amphetamine psychosis” with prolonged use


DOM

DOM and MDMAsynthetic variations of the amphetamine molecule

MDMA (Ecstasy) popular club drugneurotoxic to 5-HT neurons

synthetic, taken orally in tablet or capsule form(3,4 methylenedioxymethamphetamine (MDMA)

structurally similar to 5-HTblocks 5-HT, NE reuptake

may also enter terminals via5-HT transporter

MDMA


http://en.wikipedia.org/wiki/Image:Ecstacy_monogram.jpg


MDMA (Ecstacy, XTC, etc)Sometimes used in combination with other drugs

e.g. LSD, psilocybin, marijuana, ketamine


MDMA (Ecstacy, XTC, etc)mental stimulationemotional warmthenhanced sensory perceptionincreased physical energy.

Has been used in psychotherapy for its

empathy-enhancing effectsPTSD, other anxiety disorder

Popular club drug


MDMA (Ecstacy, XTC, etc)nauseachillssweatingteeth clenchingmuscle crampingblurred visionhyperthermia

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2,5-dimethoxy-4-methylampetamine (DOM)more euphoric, less hallucinogenic than LSDslower onset than LSD, effects last 7-24 hourslike LSD, DOM is a 5-HT-2A partial agonist

may produce “amphetamine psychosis” with prolonged use

DOM

Your text includes DOM and MDMA as hallucinogens often classified as stimulants

potent effects on NE and DA reuptake, much like “classical” stimulants

arousal effects are much greater than those of psychedelics.

Hallucinogenic effectsmuch milder than those of true psychedelics


dopamine norepinephrine

mescaline

MDMA DOM

amphetamine

Mescaline is derived from __________.A. psilocybin mushroomsB. the bark of a South American treeC. substances created in a laboratoryD. the peyote cactus

Toxicity of MDMA (Ecstasy) involves __________.A. hyperthermiaB. dehydrationC. agitation and confusionD. all of the above

Hallucinogens Relatedto Acetylcholine

Anticholinergic (ACh antagonist) hallucinogensblock muscarinic ACh receptors

cause extreme confusion, temporary psychosis“deliriants”amnesiaautonomic effects includeblurred visionextreme dilation of pupilsrapid heart rateall of which are unpleasant to the userpreclude becoming drugs of abuse

.

Hallucinogens Relatedto Acetylcholine

Sources includedeadly nightshade (belladonna)mandrake rootshenbane seedsdatura family (jimsonweed)

involved in sorcery andwitchcraft since the MiddleAges (“hexing drugs”)

combination of atropine,scopolamine, and/or hyoscyamine

Phencyclidine and Ketamine

dissociative anestheticsNMDA (glutamate) receptor antagonistshallucinogenic properties make them unsuitable for use in humansketamine is a standard component of a commonly used veterinary anesthetic

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine,

and Salvia divinorum

Salvinorin A (Salvia divinorum)analgesic as well as hallucinogenic propertiesselective κ-opioid receptor agonist


and Salvia divinorum PCP (angel dust)

1950sdeveloped as an anesthetic

1960sappeared as a psychedelic street drugdeveloped a reputation for adverse reactionsaggression, acute schizophrenia-like behaviorslost favor

1970sreappeared smokable forms

alone or in combination with marijuana


and Salvia divinorum PCP (angel dust)

snorted, smokedduration of effect, 4-6 hrs

Chronic Effectsmemory lossdifficulties with speech and thinkingdepressionweight lossAddictive—users engage in drug-seekingSymptoms may persist up to one year after

stopping PCP abuse.

The principal reason anticholinergic drugs have little or no street appeal is that they produce __________.

A. nausea and headachesB. powerful hallucinationsC. a feeling of flying out of controlD. amnesia


Table 6.2


and Salvia divinorum

Ketaminepopular club drugproduces a dream-like intoxicationinability to move or feel painamnesiapotentially hazardous depression in breathing


and Salvia divinorum Salvia divinorum

Mexican leafy herbsmokedchewedbrewed as a tea

Hallucinogenic effectsshort-lived (1 min onset, 30 sec duration)altered visual perception, perception of realitymood and body sensationsemotional swingsfeelings of detachmentindividual experimentation, not a club drug

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Chapter 6 LSD and Other Hallucinogens. Definition of Hallucinogen Hallucinogens distortions of perception altered sense of reality, transported to new