Pharmacokinetics — THC vs. Ethanol Detection Windows: 04-BS-12, December 2017, Q2

Question 2: Pharmacokinetics — THC vs. Ethanol Detection Windows (20 marks)

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Solubility is the whole story. Structurally, THC (tetrahydrocannabinol, C₂₁H₃₀O₂) is an almost entirely hydrocarbon molecule: a fused tricyclic ring system carrying a long unbranched pentyl side chain, with only a single phenolic –OH and one ring oxygen as polar functionality. Ethanol (CH₃CH₂OH), by contrast, is a tiny two-carbon molecule that is essentially all polar –OH relative to its size.

THC is highly lipophilic (fat-soluble). The large hydrophobic pentyl/tricyclic surface area vastly outweighs the one polar –OH, so THC (and its metabolites, e.g. 11-nor-9-carboxy-THC) partitions strongly into adipose (fat) tissue rather than staying in the aqueous blood/urine compartment. It is stored there and released back into the bloodstream only slowly over days to weeks as fat is mobilised, giving a long, low-level "tail" that standard immunoassays can still detect long after the original dose.
Ethanol is fully water-miscible (hydrophilic). Its small size and high polarity relative to its size mean it distributes uniformly through the body's water compartment and does not partition into fat at all. There is no slow-release depot.
Metabolic rate and route differ. Ethanol is oxidised rapidly and completely by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) at a roughly constant zero-order rate (about one standard drink per hour) all the way to CO₂/acetate, so it is essentially eliminated from the body within hours of the last drink. THC, by contrast, is metabolised by cytochrome P450 enzymes into more polar (still detectable) carboxy-metabolites, but this hepatic processing can only act on the fraction of THC currently in circulation — the fat-stored reservoir keeps re-supplying trace amounts for weeks in a chronic user.

Property	THC	Ethanol
Polarity / logP	very lipophilic (large hydrocarbon skeleton)	fully water-miscible
Tissue distribution	stored in fat, slow release	uniform in body water, no depot
Elimination	slow (weeks) via fat mobilisation + CYP450 metabolism	fast (hours) via ADH/ALDH, ~zero-order
Detection window	days–weeks (chronic use)	hours

Concept & Theory

Topic. Lipophilicity and tissue partitioning as the determinant of a drug's detection/elimination half-life.

Key relations. "Like dissolves like": a molecule's octanol/water partition coefficient (logP) predicts whether it accumulates in fatty tissue (high logP, like THC) or stays in aqueous compartments and is rapidly cleared (low logP / fully miscible, like ethanol).

Why this works. Fat acts as a slow-release reservoir only for molecules lipophilic enough to partition into it in the first place; a fully water-soluble small molecule has nowhere to "hide" from first-order/zero-order hepatic clearance.

Common pitfall. Attributing the difference only to "metabolism speed" without mentioning fat storage — the storage/redistribution step is the mechanistic reason THC's apparent elimination half-life is so much longer than a simple single-compartment model would predict.

Source. McMurry, Organic Chemistry, Ch. 27/30 (biomolecules, drug design; lipophilicity and logP).

Question 2 of 13: Pharmacokinetics — THC vs. Ethanol Detection Windows

Question 2: Pharmacokinetics — THC vs. Ethanol Detection Windows (20 marks)