Suppository

⚠️⚠️ Claims frequently outrun the evidence. A suppository is a solid unit-dose preparation designed for insertion into the rectum or vagina, where body temperature melts or dissolves the base to release cannabinoids. Typical bases include cocoa butter, coconut oil, Witepsol H15, hydrogenated palm oil, or glycerinated gelatin, shaped into "bullets" of roughly 2 grams containing 25–100mg of cannabinoid. The anatomical rationale offered in marketing — that rectal venous drainage through the inferior and middle rectal veins bypasses the portal circulation and avoids first-pass metabolism — is pharmacologically plausible, but published human pharmacokinetic data for plain cannabinoid suppositories are strikingly negative. ElSohly and colleagues found plain Δ9-THC administered rectally produced no detectable plasma THC in human subjects, attributed to poor dissolution and mucosal transfer of the highly lipophilic parent molecule. Systemic absorption has been demonstrated only for THC-hemisuccinate, a patented water-soluble prodrug — not the plain cannabinoid used in essentially all commercial dispensary suppositories. ⚠️ The common claim that rectal cannabis "delivers therapeutic effect without psychoactivity" is more plausibly explained by minimal systemic absorption than by a first-pass bypass. Vaginal suppositories are best understood as localized topicals acting on pelvic tissue cannabinoid receptors; systemic PK data are sparse. Legitimate use cases exist in palliative care and for patients who cannot tolerate oral administration. → See also: Topical, onset and bioavailability (Part 5). ---