Psychedelic Drugs
description
Transcript of Psychedelic Drugs
produce visual hallucinations and out of body experiences
alterations in cortical functioning
Also affect mood, thinking and physiologicalprocesses
At least 90 different species of plant and many synthetic agents can produce these effects
Distinguish them by the NT system that they work on (primarily)
many occur in nature; other newer ones are synthetically produced
Prior to 1960 (or so) – these were primarily restricted to religious rituals and most people were not even really aware of them
Most psychedelics resemble one of 4 NT◦ ACh, catecholamines (NE, DA) and 5HT
ANTICHOLINERGIC◦ Scopolamine
CATECHOLAMINERGIC◦ Mescaline◦ DOM, MDA, DMA, MDMA (ecstasy), etc◦ Myristicin, elemicin
5HT like◦ Lysergic acid diethylamide (LSD)◦ Dimethyltryptamine (DMT)◦ Psilocybin, psilocin, bufotenine, Ololiuqui,etc
GLUTAMINERGIC NMDAR ANT◦ Phencyclidine (Sernyl) (PCP)◦ Ketamine (Ketalar)◦ Dextromethorphan
OPIOID KAPPA R AG◦ Salvinorin A
from Salvia plants
Serotonin-like drugs – includes lysergic acid diethylamide (LSD) psilocybin, psilocin dimethyltryptamine (DMT) bufotenine
◦ 5HT acting psychedelics produce characteristic syndrome disturbances in thinking, illusions, elementary
and complex visual hallucinations
believe that these psychedelics interact with 5-HT2A receptors
LSD – agonist DMT, bufotenine – partial agonist
?? why doesn’t 5HT have psychotomimetic effects? What about SSRIs?
naturally occurring compounds exist that resemble the indole ring
investigating therapeutic use of compounds obtained from ergot fungus
LSD belongs to class of agents called ergot alkaloids
Grew on rye (and some other grain) when weather conditions were right
Types of ergot poisoning
convulsive ◦ characterized by twisting and contorting body in
pain, trembling and shaking, muscle spasms, confusions, seizures, delusions and hallucinations
gangrenous ergotism ◦ Due to decreased blood flow, infections occur in
the extremities, accompanied by burning pain and loss of extremities.
explanation for witch trials….
Joan of Arc
Saint Anthony’s Fire
On August 15, 1951 one in twenty of the 4000 inhabitants of a village in France called Pont Saint Esprit (Bridge of the Holy Spirit) went mad. They had hallucinations, writhed in agony in their beds, vomited, ran crazily in the streets and suffered terrible burning sensations in their limbs.
Joan of Arc
Saint Anthony’s Fire◦ dreaded illness in the Middle Ages
LSD – ◦ during mid 1960’s – 1970’s – LSD –
History◦ synthesized in 1938; ◦ Albert Hoffman (Sandoz)- swiss chemist◦ looking for possible therapeutic uses of ergot fungus◦ early animal studies – not much
◦ first human experience 1943 although arguments can be made for a much earlier time
LSD 25 had strong uterine effect and animals became stuporous but restless◦ nothing of special interest – set back on shelf……◦ 5 years later – made new batch and must have
gotten tiny amount on fingers◦ tried it again under a more controlled condition
using a 0.25 mg dose (10X the dose for most to show an effect)
most potent drug in existence◦ 10 – 300 ug
Uses of LSD – 1953 - 1966◦ LSD used as adjunct to psychotherapy◦ possible treatment for alcoholics◦ treating cancer patients◦ possible truth serum
1966- Sandoz recalled LSD and withdrew sponsorship for work with LSD
NIMH – stopped LSD research (in house) in 1968; stopped funding in 1974
NIAAA – stopped supporting psychedelic research in 1975
Recreational Use of LSD◦ early to mid 1960’s
Pharmacology of LSD – ◦ drug is odorless, colorless, tasteless◦ extremely potent (25 – 100 ug) but no OD
death reported in humans rats – behavioral effects at 0.04 mg/kg and LD50
~ 16 mg/kg (400X the behaviorally effective dose)
Pharmacokinetics◦ absorption rapid – oral route most common◦ ½ life ~ 3 hrs◦ Effect usually lasts ~ 8-12 hours◦ metabolized in liver
tolerance – develops very rapidly recovery is also usually rapid (so weekly
use of same dose is possible) Cross tolerance – LSD with psilocybin,
mescaline Sympathomimetic (activates sympathetic
NS) and so autonomic signs are often first to appear◦ dilated pupils, elevated temperature, BP and
salivation
LSD experience-◦ mostly visual/perceptual changes◦ altered sense of time◦ synethesia – mixing of senses◦ depersonalization◦ typical lasts 6 – 9 hours
Adverse Reactions◦ panic reaction◦ flashbacks
quite variable and unpredictable
Bufo Marinus, also known as the cane toad,
skin and glandular secretions toad secretions have been used since
ancient time……
Psilocybin◦ long history in religious and ceremonial use◦ indole isolated by Abby Hoffman and then
synthesized
Morning Glory Seeds
-Hoffmann analyzed seeds-found several active alkaloids as well as d-lysergic acid amide
-dangers: pesticides, substances coated on seeds in US; coatings on seeds can cause nausea, vomiting, headaches, increased BP, probably need 100s for species common in US
Heavenly Blue
NE and DA receptors important site of action for a large group of psychedelic drugs structurally similar to catechol NT and amph
differ from nt by one or more methoxy group (-OCH3)
exert amphetaminelike psychostimulant actioons; can enhance energy, endurance, sociability and sexual arousal
psychedelic actions probably due to augmentation of 5HT neurotransmissions (5HT2A)
Peyote – common plant in southwest US and Mexico
Spineless cactus with small crown or button
mescal buttons (not mescal liquour from agave cactus, mescal beans)
dates back 5000 or more years◦ Aztecs
used in spiritual ceremonies (Native American Church)◦ Members of Native American Church exempt
from federal criminal penalities for religious use (predates CSA)
mescaline identified in 1918
pharmacokinetics:◦ mescaline rapidly absorbed orally
levels increased in brain 1-2 hrs acute psychotomimetic state 3.5 – 4 hrs
◦ effects can persist for ~ 10 hrs◦ does not appear to be metabolized◦ imaging studies – hyperfrontal pattern of activity
(right hemisphere)
Synthetic amphetamine derivatives◦ large group of synthetic hallucinogens
chemically related to amphetamines;◦ structurally related to mescaline and
methamphetamine◦ exs. DOM –dimethyoxymethamphetamine
100X more potent than mescaline (but less potent than LSD)
high incidence of OD – use not common – toxic
MDMA – Ecstasy- methlenedioxymethamphetamine◦ potent and selective serotonin neurotoxin◦ neurotoxic – issues re raves
nutmeg and mace◦ common household spices◦ ingestion of large amounts – confusion
disorientation, impending doom, depersonalization
◦ structural resemblance to mescaline◦ many unpleasant side effects including vomiting,
nausea and tremors◦ if people try it once – they don’t usually try again
PCP (phencyclidine)◦ developed as an IV anesthetic- Sernyl – Parke Davis◦ monkey studies suggested that it was a good
analgesic but did not produce muscle relaxation OR sleep –
◦ a dissociative anesthetic◦ several patients were unmanageable as they
emerged from the anesthetic; ◦ studies showed patients becoming angry or
uncooperative; reduction in sensitivity to pain in combination could contribute to violent behavior
PCP (phencyclidine)◦ few reports of intense visual experiences
and many more reports of body image changes
◦ reports of disorganized thinking, suspiciousness and lack of cooperation
Recreational Use of PCP◦ early 1970’s – PCP crystals sprinkled onto
oregano, parsley, etc and sold as marijuana◦ can be made inexpensively and relatively
easily PCP receptor – discovered in 1979
◦ appears to antagonize GLU ◦ endogenous ligand – as yet unknown
Other PCP like drugs◦ Ketamine ◦ related veterinary product
Other PCP like drugs◦ Ketamine ◦ related veterinary product◦ 1999 – widespread reports of ketamine abuse
resulted in ketamine receiving Schedule III designation
◦ not as strong an effect as PCP
an analgesic and a drug of abuse common ingredient in more than 140 OTC
cough suppressants high doses produce hallucinations highest age group for abuse potential -
from salvia plant (magic mint, diviner’s sage, Sally-d)
potato family contains all naturally occurring agents in this category◦ atropine, scopolamine
◦ atropine – belladonna – active ingredient in deadly nightshade.
ACh antagonist –
comes from belladona (Deadly nightshade) Jamestown weed, jimsonweed, stinkweed,
devil’s apple, moonflower, mandrake
scopolamine containing plants have been used and misused for centuries
Professional and amateur poisoners used deadly nightshade as a source of poison
Ibogaine - psychoactive indole alkaloid from roots of Tabernanthe iboga
Howard Lotsof-
Preclinical data reduces self-administration of bothcocaine and morphine, as well as attenuates symptoms of morphine WD
mechanism of anti-addictive action of ibogaine not well defined
NMDA R antagonist; kappa agonist; mAChR activityhas hallucinogenic effects in humans