NATIONAL TOXICOLOGY PROGRAM Technical Report Series No. 446 (1996)

[Michael Komorn]

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.