Download 2/10/2015 Tetrahydrocannabinolic acid (THCA) – Plant Precursor to THC

2/10/2015
Tetrahydrocannabinolic acid (THCA) – Plant Precursor to THC
H
OH
COOH
H
O
THCA
Non‐psychoactive
THC
Psychoactive
“THC” present in Cannabis exists mostly as THCA – assumed self‐defense role for plant
Drying or heating the plant material (smoking or vaporizing) converts THCA to THC.
Extensive heat and/or drying over time further converts THC to CBN (weakly psychoactive).
THC, CBD and CBN – Most Extensively Studied Phytocannabinoids
Tetrahydrocannabinol (THC)
Cannabidiol (CBD)
Cannabinol (CBN)
Concentration ranges from 1 ‐ 40% of plant extract
Up to 40% of plant extract
(variable)
Trace amounts though increases over time (THC degradation product)
Pi
Primary psychoactive h ti
component in Cannabis
Non psychoactive
Non‐psychoactive, anti‐convulsant, anxiolytic
activity
Weakly psychoactive
What is the thermodynamic driving force for conversion of THC to CBN?
Which compounds are chiral?
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2/10/2015
Endocannabinoids – Compounds Produced In Vivo That Bind to CB Receptors
Anandamide most studied endocannabinoid. Sanskrit for “bliss”. O
HO
Anandamide
Endocannabinoid that binds CB1 and CB2 receptors
N
H
THC
Phytocannabinoid that binds CB1 and CB2 receptors
Compare molecular shape and polarity of anandamide and THC.
THC Chemical Properties
• Glassy solid / sticky solid depending on temperature
• Low water solubility
Low water solubility
• Soluble in organic solvents – can be extracted by various methods
• Boiling point 250 °C 2
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THC Pharmacokinetics
Absorption
Smoked/vaporized, oral, transdermal, sublingual, rectal suppository
Effects last 2 3 hours or less if smoked longer if taken orally
Effects last 2‐3 hours or less if smoked –
longer if taken orally
Smoking/vaporizing allows titration of desired dose
Distribution
Accumulates in lipophilic tissues
THC Pharmacokinetics
Metabolism
Primarily occurs in liver – lesser extent in intestines, brain, heart, lung, other tissues
Primarily occurs in liver lesser extent in intestines, brain, heart, lung, other tissues
>100 metabolites formed
Primary route – oxidative metabolism followed by conjugation to more water‐soluble metabolite
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THC Metabolism – Primary Route
OH
H
OH
H
O
11‐OH‐THC
Psychoactive metabolite
THC
HO
O
H
Biphasic effects may be attributed to active metabolites.
OH
11‐OH‐THC potentially causes increased appetite.
H
O
THC‐COOH
Inactive metabolite
Drug screens analyze inactive metabolite THC‐COOH
Excretion of THC and Its Metabolites
HO
O
H
OH
H
O
THC COOH
THC‐COOH
THC COOH glucuronide
THC‐COOH‐glucuronide
Predominately THC‐COOH and THC‐COOH‐glucuronide excreted in urine.
Trace THC excreted in urine, and some 11‐OH‐THC excreted in feces.
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Outline Mechanism for Conversion of CBD to THC (Laboratory Reaction)
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