From Jeffrey Hergenrather, MD, February 8, 2015
2.1.4. Rectal. Several different suppository formulations were evaluated in monkeys to determine the matrix that maximizes bioavailability and reduces first-pass metabolism  ; THC-hemisuccinate provided the highest bioavailability of13.5%. Brenneisen et al. evaluated plasma THC concentrations in two patients who were prescribed THC-hemisuccinate suppositories or MarinolM for spasticity . THC did not accumulate in the blood following 10 –15 mg daily doses. THC concentrations peaked within 1 – 8 h after oral administration, and ranged between 2.1 to 16.9 ng/ml. Rectal administration of 2.5– 5 mg of THC produced maximum plasma concentrations of 1.1– 4.1 ng/ml within 2 – 8 h. The bioavailability of the rectal route was approximately twice that of the oral route due to higher absorption and lower first-passmetabolism.
Int J Clin Pharmacol Ther. 1996 Oct;34(10):446-52.
The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients.
Brenneisen R1, Egli A, Elsohly MA, Henn V, Spiess Y.
Multiple doses of delta 9-tetrahydrocannabinol (THC) capsules (Marinol) and THC hemisuccinate suppositories were administered in 24-hour intervals to 2 patients with organically caused spasticity. After oral doses of 10-15 mg THC, peak plasma levels from 2.1 to 16.9 ng/ml THC and 74.5 to 244.0 ng/ml 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH, major THC metabolite) were measured by GC/MS within 1-8 h and 2-8 h, respectively. After rectal doses of 2.5-5 mg THC, peak plasma levels from 1.1 to 4.1 ng/ml THC and 6.1 to 42.0 ng/ml THC-COOH were measured within 2-8 h and 1-8 h, respectively. The bioavailability resulting from the oral formulation was 45-53% relative to the rectal route of administration, due to a lower absorption and higher first-pass metabolism. The effect of THC on spasticity, rigidity, and pain was estimated by objective neurological tests (Ashworth scale, walking ability) and patient self-rating protocols. Oral and rectal THC reduced at a progressive stage of illness the spasticity, rigidity, and pain, resulting in improved active and passive mobility. The relative effectiveness of the oral vs. the rectal formulation was 25-50%. Physiological and psychological parameters were used to monitor psychotropic and somatic side-effects of THC. No differences in the concentration ability, mood, and function of the cardiovascular system could be observed after administration of THC.
Cannabinoids and appetite stimulation
Appetite stimulation by cannabinoids is highly variable. Four within-subject design studies explored the effects of age, gender, satiety status, route of drug administration, and dose on intake. One study involved a single oral administration of active drug (15 mg males, 10 mg females) or placebo to an age and gender stratified sample of 57 healthy, adult light marijuana users. Eleven subjects received single doses by oral, sublingual, and inhaled routes in a second study. In the third study, 10 subjects ingested a single oral dose in fasted and fed states. A 2.5 mg dose was administered b.i.d. for 3 days by oral and rectal suppository routes in the fourth study. Mean daily energy intake was significantly elevated following chronic dosing by rectal suppository, but not oral capsule, relative to all acute dosing regimens except inhalation. Total daily energy intake was comparable on fed and fasted days, suggesting satiety mechanisms were not impaired by the drug. Subject age, gender, reported “high”, and plasma drug level were not significantly associated with drug effects on food intake.
Pharmacology Biochemistry and Behavior
Volume 49, Issue 1, September 1994, Pages 187–195