Dimethylheptyl-THC-11 oic acid: a nonpsychoactive antiinflammatory agent with a cannabinoid template structure.
OBJECTIVE
To assess the antiinflammatory activity of dimethylheptyl-THC-11 oic acid (DMH-11C), a nonpsychoactive synthetic derivative of tetrahydrocannabinol.


METHODS
Acute inflammation was induced by injection of interleukin-1beta and tumor necrosis factor alpha into subcutaneous air pouches formed on the backs of mice. Inflammation was quantified 6 hours later by pouch fluid leukocyte counts. Adjuvant-induced polyarthritis in rats was used as a model of chronic inflammation and joint tissue injury. Animals were either untreated, treated with safflower oil, or treated with DMH-11C in safflower oil. Arthritis was assessed by clinical observation and by histomorphologic evaluation of tibiotarsal joints.


RESULTS
Oral administration of DMH-11C reduced the accumulation of pouch fluid leukocytes and significantly reduced the severity of adjuvant-induced polyarthritis. Histopathologic studies of tibiotarsal joints showed that DMH-11C treatment attenuated pannus formation and joint tissue injury.


CONCLUSIONS
DMH-11C suppresses acute inflammation in the subcutaneous air pouch in mice and chronic joint inflammation characteristic of adjuvant disease in rats. These results demonstrate the potential use of this nonpsychoactive cannabinoid as an antiinflammatory agent.
Zurier
R B
RB
University of Massachusetts Medical Center, Worcester 01655-0335, USA.
Rossetti
R G
RG
Lane
J H
JH
Goldberg
J M
JM
Hunter
S A
SA
Burstein
S H
SH
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D005620:Freund's Adjuvant; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007375:Interleukin-1; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha
D000893:Anti-Inflammatory Agents; D015777:Eicosanoids; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C033189:dimethyl-heptyl tetrahydrocannabinol; D013759:Dronabinol; D005620:Freund's Adjuvant; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat