Trends in use of narcotic compounds
Trends in use of narcotic compounds
Estimates of money volumes in the "retail" market of
Europe
• Year 2013
– In total 24.3 miliard Euro (21-31)
– Cannabis 38 % (9.8 miliard)
– Heroin 28 % (6.8 miliard)
– Cocain 24 % (5.7 miliard)
– Amphetamines 8 %
– MDMA 3 %
• „Catching“
– Cannabis, cocain, MDMA
• Thujon
– Natural mixture of
isomers α,β (33% α,
67% β)
– Artemisia absinthium,
Artemisia vulgaris
Salvia officinalis,
Salvia sclarea
– Tanacetum vulgare
– Thuja occidentalis
– Folk medicine:
• Abortive, emenagogue,
digestive, carminative,
antiphlogistic,
anthelmintic
O
CH3
CH3
CH3
H
– Analgesic, analeptic, antidepressive
– Toxicity:
• CNS effect
– Tonic-clonic convulsions, cumulative effect
– Absinthism
» hyperexcitability, hallucinations
• Nephrotoxicity (degenerative changes)
• Hepatotoxicity
– Dependent on dosage and sensitivity
– Mechanism of effect:
• Blocker of GABAA chloride channel (similar to picrotoxine)
• α-thujon 2.3 times more effective than β-thujon
• Low affinity to cannabinoid receptor
• Metabolism:
– Reduction of keton to hydroxyl, excretion via urine
– 7-OH-thujon, dehydrothujon – also active
– Absinthism
– Oscar Wilde:
• „After the first glass [of absinthe] you see things as you wish they were.
After the second, you see things as they are not. Finally, you see things as
they really are, and that is the most horrible thing in the world.“
French method
Bohemian method
Blanche
Verte
Absenta
Hausgemacht
Bohemian-style
Cannabis spp.• Cannabis indica Lam., C. sativa L., C. ruderalis
Janisch.
• Shen-nung (2737-2697 B.C.)
– malaria, constipation, rheumatism,
Gynecologic problems
• Vine with hemp resin
– Surgical anaesthetic
• European folk medicine
– asthma, cough therapy
– epilepsy, sleep disorders, convulsions
– pain, rheumatism
– Externally
– Skin inflammations and infections
• Todays application
– glaucoma
• Lowering of intraoccular pressure
– nausea, vomiting, anorexia
– cancer (in vitro and in vivo start of apoptosis –
malignant gliom, breast cancer)
– Parkinson disease, sclerosis multiplex
– Immunomodulation – Crohn disease
– Antibiotic and antiviral effect
AK-47 Skunk n.1
Sensi Star
Nothern Lights
Jack Herer
R5
R4
OH
R1
R2OR3 O
R3
OH
R1
R2
OH
R1
R2
O R3
O
OH
R1
R2
H
H
R3
O
OH
R1
H
H
O
OH
R1
R2
H H
H
R1
R2
O
OH
R3
OH
H
H
O
O
R2
R3
R1
OH
R1
OH
OH
R4O
OR2
R1 R3
O
O
OH
OH
OH
O
O
OH
OH
OH
OMe
CBG-type cannabinoids CBC-type cannabinoids CBD-type cannabinoids delta9-trans-THC-type cannabionoids
delta8-trans-THC-type cannabionoids CBL-type cannabinoids CBE-type cannabinoids CBN-type cannabinoids
CBND-type cannabinoids CBT-type cannabinoids
• Cannabis as drug – THC content
– Marihuana (female inflorescence) cca 1% THC
– Hašhish (resin obtained by chipping or munching of female inflorescence cca 5 %
– Hashish oil (extract) 20% THC
• Main contain THC (levorotary form), CBD (canabidiol) – sedative and antibiotic effect,
canabinol (CBN) – high amount of CBN - effect similar to THC, but with feeling of fatigue and
drowsiness
• THC is oxidized by air oxygen (higher temperature increases effect) to non-active
compounds
– Should be stored in cold and hermetically closed wessels
• THC soluble in fat and alcohol (lipophilic), non well in water
• Biotransformation
– Cumulation in organism
– Half-time 27 days
Distribution of THC in the body.
C. HEATHER ASHTON BJP 2001;178:101-106
©2001 by The Royal College of Psychiatrists
• Cannabis as a drug
– Way of application
• Inhalation, smoking
• Peroraly
• Cannabis as drug – effects
– Psyche – effect on CNS
• Canabinoid receptors
– THC
– Endogennous canabinoids
– Lungs – smoking
• Similar to tabacco
• Little bit different style of smoking
• 1 joint – 9 cigarettes
– Fertility
• Effect on spermias
– Effect on foetus
• Slower development of children
– Risk of higher occurence of schizophrenia?
Syntethic cannabinoids
O
N
CH3
Naftoylindol
JWH-018, AM-678
N
O
CH3
OCH3
CH3
Fenylacetylindol
JHW-250
OH
OH
CH3
CH3
CH3
Cyklohexylfenol
CP-47,497
MDMA-CHMICA
– Salvinorin A
• Diterpen of clerodadiene type
• Salvia divinorum Lamiaceae
• Hallucinogenic
• Shamanic plant, Hierba de la
Pastora
O O
O
O
OO
O
O
HH
– Salvia divinorum
• 100 grams of drug
• Chewing
• Maceration
• Smoking of dry leaves and
extracts
• Effect
• Euphoric states
• Colored visions and
hallucinations
• Rush
– Salvinorin A
• Selective inhibitor kappaopiod
receptors
• Agonist of D2 receptors
• Do not affect 5-HT2A
receptor
• Anabasine
– Nicotiana spp.
Solanaceae
– Anabasis aphylla
Chenopodiaceae
– Similar to nicotine
– Highly toxic
– Often intoxications
– Teratogen
• Poultry, cattle, pigs
• So called arthrogryposes
• Anabaseine
– Aphaenogaster rudis
N
N
N
N
• Nicotine
– Nicotiana spp. Solanaceae
– Highly toxic
– Common intoxication
– N-receptors – parasympatomimetic
Acute intoxication
– Smoking: headache, pallenes, cold sweat, tremor,
vertigo, nauzea and vomiting
– Perorally: higher doses produce starting nausea with
deep breathing, vomiting, furthermore tremor,
convulsions, death caused by paralysis of respiratory
muscles. Dose of 40-60 mg of nicotine is deadly up
to 10 minutes
N
N
• Arecoline
– Areca catechu betel Arecaceae
– Muscarine effect
– Higher doses can affect also
nicotinic receptors
– Salivation, perspiration, miosis
N O
O
• Cocaine
• Erythroxylon cocca,
Erythroxylaceae
– History
• Indians for tribe of Chibcha
• Inkas
• Spanish
• Coca-cola till 1904
• 1860 Albert Niemann – pure
cocaine
• Sigmund Freund, Carl Coller
–Metabolism
– Formation of ethylderivate during ethanol intoxication
Kokain
O
O
N
CH3
O
O CH3
Benzoylekgonin
O
O
N
CH3
OH
O
OHN
CH3
O
O CH3
Ekgonin methylester
Nor-kokain
O
O
NH
O
O CH3
O
O
N
CH3
OH
O
OH
m-hydroxybenzoylekgonin
O
O
N
CH3
O
O
CH3
Kokaethylen
N
CH3
O
O CH3
Methylester anhydroekgoninu
O
O
N
O
O CH3
OH
Nor-kokain nitroxid
Přítomnost ethanolu
Trans-esterifikace
CYP34A
CYP34A
– Mechanismus účinku
• Indirect sympatomimetic
(inhibitor reuptake of
noradrenaline)
• Block of ion channels of neurons
(disorder of signal transmission)
• Adrenergic stimulation
– Peripheral effects
• Vazoconstriction, hypertermia,
mydriasis
• Low doses - ↓ of heart rate
• High doses - ↑ of heart rate,
cardiac arrest
– Central stimulation
• Euphoria, exhaustion of
neurotransmiteres (NA), short
depressive effect
• Rise of psychic dependence
– Does not trigger physical
dpendence
• Intelectual stimulation,
hyperactivity, hyperlucidity
• Self-delusion, paranoid psychosis
N
O
O
O
O
H
• Cocaine
– Complication during
usage
• Cardiovascular arrest
– Way of administration
• As chlorid or base
• Chlorid
– Snuffling, i.v.
• Base
– Smiking (crack),
inhalation
• Mixture with heroine
– snowball
• Mixture with alcohol
– Cardiotoxic
– Highly euphorizing
• Tropane alkaloids
– Azabicyclo[3,2,1]octan
– Apoatropin, atropin,
hyoscyamin, scopolamin
– Solanaceae
– Parasympatolytics
• Competitive antagonists
of acetylcholinergic
receptors
• Muscarine type
– Intoxication
• Red pigmentation of face,
dry mucose, thirst
• Tachycardia, mydriasis
• Hypertermia, central
excitation, hallucination
• Coma, respiratory failure
N
O
O
OH
•Morphine, codeine, heroine
–Morphinan alkaloids
–Effective levorotary form
–Morphinan type of alkaloids
• Typical for Papaver spp. Papaveraceae
• Morphine
–P. somniferum, P. setigerum Papaveraceae
–Stereospecific, reversibile linkage to opioid receptors
• At diiferent levels of CNS
–Agonist at presynaptic receptors of myelinized fibers of
small diameter
• Nociception, inhibition of substance P release
• Uprise of physical dependance
–Inhibition of enkephaline production and
simultaneous occupation of receptors
–Insufficiency of natural ligands and morphinans
» Withdrawal syndrome
–Effect on respiration
• Depression of respiratory centre
–Decrease of sensitivity to hypoxia and pCO2
–Dependent on dose
–Tempo of onset dependent on way of
administration
–Miosis of central origin
–Depression of centre for cough
–Complex effect on centre for vomiting
• Nausea and vomiting
–Influence on hypophysis
• ↓secretion of FSH, LH, ACTH
–Influence on hypothalamus
• ↑secretion of ADH
–Influence on fibers of smooth muscles
• Constipation and urinary retention
• Metabolism of morphine
• Symptoms of withdrawal
– Chronic users
• Nasal bleeding, perspiration, lachrymation,
anxiety
• Mydriasis, myalgia and pain of joints
• Insomnia, tachycardia, arrhythmias,
polypnoe, dispnoe
• Nausea, diarrhea
• Acute intoxication
– Usually overdose from different reasons
– High dosage
• Immediate depression of CNS
– Lower dosage
• Initial short stimulation
• Successive malaise, fatigue, somnolence
• Heart rate decreases and tends to fade
• Respiration slow and shallow
• Loss of consciousness
• Relaxation of muscles, extinction of
reflexes
• Cold, pale, wet skin
– If the dose high enough
• Coma, relaxation of muscles
• Circulatory failure, cyanosis
• Death caused by CNS depression
– Respiratory arrest
• Chronic intoxication
– Morphinism
• Short time of uprise
– Strong analgetic
– Experiments with drug
• Tolerance to dosage
• Combination of health
problems
– Social excomunication
» Psychical and
physical dilapidation
– Criminality
– Prognosis adverse
» Accompanying
diseases
» Suicidal tendences
http://www.mujweb.cz/www/jpdepot/danger/Drugs.htm
http://www.mujweb.cz/www/jpdepot/danger/Drugs.htm
• Tryptamines
– Bufotenine
• In water poorly soluble compounds
• Piptadenia peregrina Mimosaceae
– Cojoba Tree
• Arundo donax Poaceae
• Several fungi and frogs
• Intoxication
– Halucinogennic efect, influence on psychic
» Similar to LSD and mescaline
– Frame of mind: anxiety, percetion disorders
– Mydriasis, hypertension
– High dosage
» Respiratory paralysis
» Motoric paralysis
– N,N-dimethyltryptamine (DMT)
• Prestonia amazonica Apocynaceae
• Piptadenia peregrina Mimosaceae
• Shortly effective halucinogennic compound
– 0,7-1mg/kg
• Model psychosis
– Vegetative symptomatology
– Emocional and perception disorders
– Illusions and visions
– Space-time distortions
NOH
N
CH3
CH3
• Psilocyne, psilocybine
– Psylocibe, Conocybe, Stropharia
– Psilocybe
• 0,2 % to 0,6 % of psilocybine
• 10 mg p.o. dose
• Chewing – better absorption from oral cavity
• 8 hours for excretion cca 80 %, 5-6 hours of effect
• Starting symptoms
– Headache, anxiety and weariness, unwitting yawning (often without drowsiness),
extraordinary convulsions, balance disorders, tremor and sweating.
• Psychic symptoms
– Deformation of reality perception, warm colored visions, caleidoscopic effect
– Changes of mood, euphoria, happyness, extraordinary depression and irritation
– Psychoses connected with depersonalisation, disorders of time perception, direction
and distance, false imaginations
• Acute toxicity
– Relatively low (deadly dossage of psylocybine for human is approx. 17 gramů)
– Risk of hasty decisions
– Latent psychic dideases (for example schizophrenia)
OP
OH
O
O
N
N
+
CH3
CH3
H
• β-carboline indol alkaloids
• Harmane, harmaline, harmine
• Peganum harmala, Zygophylum
fabago, Tribulus terrestris
Zygophyllaceae
• Passiflora incarnata Passifloraceae
• Inhibitory MAO
– Elevated levels of neuromediators
» Serotonine, noradrenaline
– Especially in brain
» Central effect
– Early symptoms of intoxication
» Nausea, vomiting, pale skin
» Signs of aggression
– Further progression
» Half-sleep with dreaming
» Hallucinations
N
CH3
N N
N
CH3
O
CH3
N
N
CH3
O
CH3
Peganum harmala
• Ergolines
– Hlavně čeleď Convolvulaceae
• Rivea corymbosa, Ipomoea spp.
– Ergine (lysergamide)
• Toxic dose 1 μg/kg p.o.
• Mexican ceremonial drugs
– Ololiuqui, coaxihuitl and
further
– Ergosine
• Similarly to ergine
• Inhibition of prolactine secretion
– Chanoclavin
– Agroclavine
– Lysergol
N
N
CH3
O NH2
H N
O
O
N
N
O
CH3
CH3
CH3
O
N
CH3
N
H
H
N
N
CH3
CH3
OH
H
N
N
CH3CH3
H
H
N
N
CH3
OH
H
– Ibogaine, tabernathine
• Tabernanthae iboga, Voacanga
spp. Apocynaceae
• Activity in CNS
– Inhibitor of neronal nicotine
receptors
– Lower dosage
» Central stimulation
» Tremor, bristlin hair
» Salivation, mydriasis
» Anxiety, aggression
– High doses
» Hallucination serotonine
effect
» Deep depression and
anxiety
• Cardiovascular system
– Negative ionotropic and
chronotropic effect
N
N
O
H
H
N
N
O
H
• Other indol alkaloids
– Mezembrenone,
mezembrine, mezembrinol
• phenyloxyindols
• Sceletium alkaloids
Aizoaceae
• Narcotic, coca-like effect
• Addictive drug
– channa
N O
O
O
H
Kosmatec
• Amines
– Ephedrine
• Aromatic amine
• Ephedra spp. Ephedraceae
• Sympathomimetic activity
– Increase of blood pressure and
peripheral vasoconstriction
– Penetration to CNS
• Acute intoxication
– Sweating, headache, anxiety
– Muscular weakness and tremor
– Mydriasis
– Palpitation
– Insomnia
– Galegine
• Galega officinalis Fabaceae
• Derivative of guanidine
• Damage of mitochondrial function
• Convulsions, breath difficulties,
pulmonary edema
– Khatamines
• Arylalkylamines
• Catha edulis, Maytenus crucorii
Celestraceae
• Ephedra spp. Ephedraceae
• Khatine and khatinone the most
important
• Khatinone
– Similar properties to amphetamine
– During drying converts to
norpseudoephedrine and norephedrine
• Drug is used via chewing
– North-East Africa
– Fast decomposition prevents large
transportation and business
– Suppression of sleep, stimulation, against
fatigue
• Intoxication
– Anorexia, hyperthermia, stimulation of
respiratory centre
– Mydriasis, arrhythmia, hypertension
– Psychic symptoms
» Anxiety, panic attack, aggresivity