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Appetite Stimulation/Cachexia
What research has been done and what is known about the possible medical
uses of
marijuana?
It has been shown that there is a strong relationship between smoking
marijuana and increased
frequency and amount of eating.
Survey data on appetite stimulation (Haines and Green 1970) (N = 131) showed
that 91 percent
of marijuana users eat every time they smoke. Tart (1970) found that 93 percent
of marijuana
users (131) reported that marijuana made them enjoy eating very much and that
they consequently
ate a lot more. Foltin and colleagues (1986) reported that marijuana users eat
more often. A
study by Farrow and associates (1987) reported no hematologic changes or signs of
nutrient
deficiencies in marijuana users.
Marijuana is reported to enhance the sensory appeal of foods. Taste does not
seem to be altered
as measured by indexes of sourness (citric acid in lemonade), saltiness (NaCl in
tomato juice),
sweetness (sucrose in cherry-flavored drink), and bitterness (urea in tonic
water). There does not
appear to be impairment in the normal satiety mechanisms following marijuana
ingestion.
Foltin and colleagues (1988) saw signs of a general increase in food intake on
smoked marijuana
days versus placebo days. The effect may not persist over an extended period of
time, but long-term studies have not been done. Setting is important in appetite
enhancement and social
settings contribute heavily. Williams and associates (1946) did a chronic dosing
study. They
found that body weight went up and stayed up, possibly due to an effect of
marijuana on fluid
retention. Greenberg and colleagues (1976) saw a sharp increase in food intake
followed by a
leveling off. The increase in body weight may reflect a reduction in energy
expenditure.
Food intake was greater after smoking, compared to oral and sublingual
administration, but there
was much individual variability. Marijuana seems to enhance appetite in the
evening, whereas
many cancer patients report having most of their appetite in morning. This would
suggest a
potential complementary use of marijuana.
Cachexia or wasting due to HIV infection is increasingly prevalent in the era
of effective
prophylaxis for Pneumocystis carinii pneumonia (Hoover et al. 1993).
Significant weight loss,
more than 20 percent of ideal body weight, is associated with shortened survival
of HIV-infected
patients (Kotler et al. 1989). The major causes of weight loss in HIV-infected
patients are
opportunistic infections, enteric infections associated with malabsorption, and
reduced caloric
intake. The latter is the most important cause of wasting in the absence of
opportunistic
infections and malabsorption (MacCallan et al. 1995).
Administration of the appetite stimulants megestrol acetate (VonRoenn et al.
1994) and dronabinol
(Gorter et al. 1992) is associated with weight gain in HIV-infected patients.
Anabolic steroids
and recombinant human growth hormone produce an increase in lean body mass
(Mulligan et al.
1993). In published studies, the weight gain produced by appetite stimulants or
hormonal therapy
has not been shown to be associated with an improved immunologic status or
clinical outcome.
All investigations, however, have been relatively short, 12 to 24 weeks in
length. Although there
is much anecdotal evidence of weight gain produced by use of smoked marijuana, no
objective
data relative to body composition alterations, HIV replication, or immunologic
function in HIV-infected patients are available. An epidemiologic study
demonstrated no alteration in the natural
history of HIV infection with use of smoked marijuana (Kaslow et al. 1989),
although other
investigations in uninfected volunteers and animal models indicated that there
are effects on
components of the immune system. There have been no recent published studies of
the impact of
smoked marijuana on the immune system in HIV-infected patients using
state-of-the-art
immunologic assays.
Megestrol acetate (Oster et al. 1994, VonRoenn et al. 1994) produces weight
gain that is
predominantly fat, with very little increase in lean body mass. Dronabinol
(9-THC) has been
studied in patients with cancer (Nelson et al. 1994; Plasse et al. 1991) and AIDS
(Gorter et al.
1992), who showed increased weight gain.
Beal and colleagues (1995) studied dronabinol as treatment for anorexia
associated with weight
loss in patients with AIDS. A significant increase in appetite was seen with a
decrease in nausea,
and a mood increase that was not significant. The 6-week study may have been too
short to fully
capture the effects of dronabinol.
In a survey looking at physicians' choice of drugs to treat wasting, the first
line choice of
80 percent of the care providers was megestrol with dronabinol being used by 54
percent.
Dronabinol was also the second line choice of most providers.
Problems that have been identified with dronabinol are that patients feel "too
stoned"; are unable
to titrate their dose properly; note delayed onset of effect, prolonged duration
of effect, or problems
with malabsorption; and "not the same feeling as smoked marijuana."
Several panelists pointed out that the weight gain is primarily an
accumulation of water
(sometimes of fat), but not of lean body mass. On the other hand, oncologists
heard from
patients with advanced cancer that increased appetite and weight gain are
psychologically
helpful, regardless of the nature of the added weight, and regardless of the
impact (if any) on
survival. Panelists also commented that very likely weight loss is an indicator
rather than a
cause of impending death.
2. What are the major unanswered scientific questions?
Some questions that need to be answered in future studies are:
Does smoking marijuana increase total energy intake in patients with catabolic
illness?
Does marijuana use alter energy expenditure?
Does marijuana use alter body weight, and to what extent?
Does marijuana use alter body composition, and to what extent?
So far, it has not been shown that reversing wasting changes mortality risk.
Another question is
whether weight gain is associated with positive changes in psychological status.
It seems related
but has not been systematically addressed.
3. What are the diseases or conditions for which marijuana might have
potential as a treatment
and which merit further study?
Areas of study for the potential appetite-stimulating properties of marijuana
include the cachexia
of cancer, HIV/AIDS symptomatology, and other wasting syndromes. With an
appropriate
delivery system designed to minimize the health risks of smoking, studies of the
appetite-stimulating potential of cannabinoids are justified. Such
investigations should be designed to
assess long-term effects on immunologic status, the rate of viral replication,
and clinical
outcomes in participants as well as weight gain.
In therapeutic trials for cachexia, research should attempt to separate out the effect of marijuana on mood versus appetite. Complex interactions likely are involved.
References
Beal, J.E.; Olson, D.O.; Laubenstein, L.; et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10:89-97, 1995.
Farrow, J.A.; Rees, J.M.; and Worthington-Roberts, B.S. Health, developmental, and nutritional status of adolescent alcohol and marijuana abusers. Pediatrics 79:218, 1987.
Foltin, R.W.; Brady, J.V.; and Fischman, M.W. Pharmacol Biochem Behav 25:577-582, 1986.
Foltin, R.W.; Fischman, M.W.; and Byrne, M.F. Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 11:1-14, 1988.
Gorter, R.; Seifried, M.; and Volberding, P. Dronabinol effects on weight in patients with HIV infection. AIDS 6:127, 1992.
Greenberg, I.; Kuehnle, J.; Mendelson, J.H.; and Bernstein, J.G. Effects of marijuana use on body weight and caloric intake in humans. Psychopharmacology 49:79-84, 1976.
Haines, L., and Green, W. Marijuana use patterns. Br J Addict 65:347, 1970.
Hoover, D.R.; Saah, A.J.; Bacellar, H.; et al. Clinical manifestations of AIDS in the era of Pneumocystis prophylaxis. Multicenter AIDS Cohort Study. N Engl J Med 329:1922-1929, 1993.
Kaslow, R.A.; Blackwelder, W.C.; Ostrow, D.G.; et al. No evidence for a role of alcohol or other psychoactive drugs in accelerating immunodeficiency in HIV-1-positive individuals: A report from the Multicenter AIDS Cohort Study. JAMA 26:3424-3429, 1989.
Kotler, D.P.; Tierney, P.R.; Wang, J.; and Pierson, R.N., Jr. The magnitude of body cell mass depletion determines the timing of death from wasting in AIDS. Am J Clin Nutr 50:444-447, 1989.
MacCallan, D.C.; Noble, C.; Baldwin, C.; et al. Energy expenditure and wasting in human immunodeficiency virus infection. N Engl J Med 333:83-88, 1995.
Mulligan, K.; Grunfeld, C.; Hellerstein, M.K.; et al. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab 77:956-962, 1993.
Nelson, K.; Walsh, D.; Deeter, P.; and Sheehan, F. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia (Review). J Palliat Care 10(1):14-18, Spring 1994.
Oster, M.H.; Enders, S.R.; Samuels, S.J.; Cone, L.A.; et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med 121:400-408, 1994.
Plasse, T.F.; Gorter, R.W.; Krasnow, S.H.; Lane, M.; Shepard, K.V.; and Wadleigh, R.G. Recent clinical experience with dronabinol. Pharmacol Biochem Behav 40:695-700, 1991.
Tart, C.T. Marijuana intoxication: Common experiences. Nature 226:701, 1970.
VonRoenn, J.; Armstrong, D.A.; Kotler, D.P.; et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 121:393-399, 1994.
Williams, E.G.; Himmelsbach, C.K.; Wikler, A.; and Rudle, D.C. Studies on marihuana and pyrahexyl compound. Publ Health Rep 61(29):1059, July 19, 1946.
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