Lecture 31 Street Drugs

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23 Apr 2012
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Lecture 31 Street Drugs
Marijuana Δ9Tetrahydrocannavinol (THC)
Pharmacodynamics
oTHC binds to CB1, CB2 receptor
CB1 in CNS
Activation of presynaptic CB1 receptor (inhibits Glutamate, GABA
release)
oMimics endogenous ligands
Anadamide, 2-arachidonylglycerol (synthesized on cellular
depolarization, calcium influx)
Retrograde synaptic messengers
Cannabis Pharmacokinetics depends on route of administration
oBioavailability: oral vs. inhaled
oLipid soluble
oBiliary excretion of metabolites
Extended half life
Active metabolite 11-OH-THC
Effects:
oTHC powerful psychoactive compound
Euphoria, relaxation, drowsiness
Large doses: grandeur, change perception of time passage, sensation
distortion, hallucination
oChronic exposure results in dependence
oTherapeutic Use
Appetite, nausea, glaucoma, analgesia of chronic pain (CB1 Ag),
smoking cessation (CB1 ANT)
Cocaine
Alkaloid from leaves of Erthroxylon Coca in Andes
oLevamisole
Highly addictive
oInhaled, immediately absorbed with instant “rush”
Secondary effect similar to amphetamines
Pharmacodynamics
CNS
oBlocks reuptake transporter of dopamine, norepinephrine, serotonin
oReward pathway effects
Peripheral
oBlock voltage gated sodium channel
Intranasal Pharmacokinetics
Readily enters CNS
Onset, duration increases addiction propensity
Metabolism via hydrolysis (esterase), CYPs
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