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  1. NIDA in 1996 knew that THC is not addictive and does not induce physical dependence. https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr446.pdf November 1996 NTP TR 446 NIH Publication No. 97-3362 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health NATIONAL TOXICOLOGY PROGRAM Technical Report Series No. 446 TOXICOLOGY AND CARCINOGENESIS STUDIES OF THC IN F344/N RATS AND B6C3F, MICE (GAVAGE STUDIES) THERAPEUTIC EFFECTS THC has been shown to have antiemetic properties. The antiemetic effect may result from actions affecting the vomiting center in the brain stem or affecting connected structure such as the amygdala and neocortex that modulate the activity of the vomiting center (Howlett et al., 1990). Because the mechanism of action by which THC exerts its effect is not understood, the use of THC as an antiemetic is problematic. There are questions about its efficacy against a broad range of therapeutic regimens, and there are reservations about its neuro behavioral side effects. Recently, interests on the antiemetic properties of THC are waning as use of antagonists to the 5hydroxytryptamine receptor, 5-HT3, has become more widespread (Iversen, 1993). THC has been used to reduce intraocular pressure in the treatment of glaucoma. However, no definitive evidence is available to explain the alteration of intraocularpressure by THC (Martin, 1986). THC may act as a vasodilator and cause a decrease in capillary pressure within the ciliary body, or the effects may be related to reduction of prostaglandins in the eye (Martin, 1986). The use of THC to treat glaucoma is impractical because it cannot be applied topically due to its insolubility in water and because of its psychoactive properties when given systemically. The use of B-adrenoceptor blockers or pilocarpine to treat glaucoma has diminished the interest in THC as a therapeutic agent for reducing intraocular pressure (Iversen, 1993). THC has been shown to have bronchodilating action, but very little is known about its mechanism of action. Inhibition of prostaglandin synthesis has been suggested (Martin, 1986). THC has been shown to be antinociceptive in experimental animals in the tail flick, hot plate, Nilsen, acetic acid or phenylquinone writhing tests, andpinch tests (Segal, 1986), but the effect is less potent than that of morphine (Dewey, 1986). The interest in the antinociceptive effect of THC is because the chemical does not induce physical dependence. Reports on the anti-inflammatory, analgesic, and antipyretic activity of THC are confusing (Dewey, 1986). THC appears to interact with a prostaglandin receptor coupled to adenylate cyclase to inhibit CAMP formation while producing the antinociceptive effect. The anti inflammatory and antinociceptive effects of THC may be mediated via a prostaglandin pathway. However, further studies are needed to determine its action. THC depresses feed consumption in rats in a dose related manner (Dewey, 1986), but tolerance develops after repeated exposure. Conversely, THC has been recommended for stimulating appetite in cancer and acquired immune deficiency syndrome patients (Plasse et af., 1991). The mechanism of appetite stimulation by THC is not clear. THC induces convulsions in rabbits and mice (Martin and Consroe, 1976; Karler et al., 1986; Turkanis and Karler, 1984). However, THC has also been shown to be an anticonvulsant (Fried and McIntyre, 1973; Karler et al., 1974, 1986; Corcoran et al., 1978). Pertwee (1988) has postulated that the anticonvulsant property of THC is due to its inhibition of depolarization-dependent Ca++ uptake into brainstem synaptosomes.
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