Cannabis Pharmacokinetics
THC plasma concentration model for smoked and oral (edible) routes. The difference between the two curves is the most important harm reduction message for cannabis — especially for edibles.
Personal details
Fatty food dramatically increases oral THC bioavailability. This is why edibles from a restaurant hit harder than homemade ones.
Driving limits
Dose schedule
Smoked vs oral — why they feel so different: Smoked THC reaches the brain in seconds and peaks in minutes. Oral THC undergoes extensive first-pass metabolism, converting to 11-OH-THC — an active metabolite that is more potent and crosses the blood-brain barrier more readily. This is why edibles produce a qualitatively different, more intense, and longer-lasting effect.
The long tail matters for driving: THC is highly lipophilic and accumulates in fat tissue. Regular users can test positive for THC days after last use. The driving limit can be exceeded without any acute impairment, but also — impairment can persist after THC drops below the legal limit.
Tolerance significantly affects the curve: Regular users have substantially different PK and PD responses. The concentration zones are calibrated for occasional users — regular users may feel little at concentrations that would overwhelm a first-time user.
Dangerous combinations
The most common dangerous combination. Alcohol increases THC absorption and the combination produces multiplicative — not additive — impairment. Driving ability is severely compromised at doses of each that seem manageable alone. Strong nausea and vomiting risk ("greening out").
Additive CNS and respiratory depression. GHB combination is particularly unpredictable with a narrow therapeutic window. Opioid combination increases sedation and respiratory risk.
Both are CNS depressants. Combined sedation can be excessive. Respiratory depression risk increases, particularly at high doses of either. Benzodiazepines are sometimes used to treat cannabis-induced anxiety — but recreational combination is risky.
Cannabis strongly intensifies psychedelic effects. Can cause overwhelming experiences, loss of control, and paranoia in people who thought they knew their psychedelic dose. Many difficult psychedelic experiences are cannabis-triggered.
Cannabis can dramatically intensify ketamine dissociation. Unpredictable threshold shift — amounts of ketamine that would normally produce mild effects can trigger full dissociation when combined with cannabis. Many difficult ketamine experiences involve cannabis.
Cardiovascular strain from stimulant combined with cannabis-induced tachycardia. Anxiety and paranoia significantly amplified. Heart rate elevation can be concerning in people with underlying conditions.
Cannabis is strongly contraindicated if you have or are at risk of psychosis. For people taking antipsychotics, cannabis can destabilise symptom control. Cannabis use is associated with triggering first psychotic episodes in genetically vulnerable individuals.