Onset

Onset is the latency from cannabis administration to first perceptible effect, dictated by the route-dependent absorption rate into systemic circulation and subsequent CNS partitioning. Because THC is highly lipophilic and crosses the blood-brain barrier rapidly, onset tracks plasma appearance closely. Inhaled cannabis (smoked or vaporized) produces detectable plasma THC within seconds and perceptible subjective effects within 5–10 minutes, with Tmax 3–10 minutes (Grotenhermen 2003; Huestis 2007). Oral/edible administration requires gastric absorption and hepatic first-pass metabolism to active 11-OH-THC, yielding delayed onset of 30 minutes to 2 hours (Vandrey et al. 2017 J Anal Toxicol; Newmeyer et al. 2017 Clin Chem). Sublingual/oromucosal products (e.g., nabiximols) bypass some first-pass, producing onset of ~15–45 minutes (MacCallum & Russo 2018 Eur J Intern Med). Onset varies with dose, formulation (lipid-based edibles onset faster than starch matrices), co-ingested food, and individual CYP variability. Citations: Grotenhermen F. Clin Pharmacokinet. 2003;42:327-360; Vandrey R et al. J Anal Toxicol. 2017;41:83-99; MacCallum CA, Russo EB. Eur J Intern Med. 2018;49:12-19.