From: p****@po.CWRU.Edu (Peter B*********)
Newsgroups: alt.hemp
Subject: Pharmacol. Biochem. Behav. 49:187-195, 1994.
Date: 12 Oct 1994 19:45:50 GMT
Message-ID: <37hede$9n8@usenet.INS.CWRU.Edu>


Some interesting (and humorous) excerpts from a recent issue of Pharmacology
Biochemistry and Behavior.  I would tend to dispute some of their findings,
conclusions and experimental design, however I give you these selected out-
takes to draw your own conclusions.

Tttle:  Cannabinoids and Appetite Stimulation
  by Richard D. Mattes, Karl Engelman, Leslie M. Shaw and Mahmoud A. Elsohly

Research conducted in Philadelphia, PA and sponsored by the Federal
Government.

Summary of conclusions:  ...the present data demonstrate an appetite-
stimulating action of THC in healthy, adult, light marijuana users only when
administered at a dose of 2.5 mg b.i.d. by rectal suppository.  Comparable
oral dosing was less effective.  Acute administration of the drug by various
routes at levels often used to control nausea and emesis did not elicit an
increment in energy intake.  Under the conditions of these studies, subject
age, gender, hunger status, reported "high", and plasma drug level were not
significantly associated with drug effects on food intake.  However, different
results may be obtained under varying conditions (i.e., a social setting
conducive to positive drug-related effects on psychological and behavioral
measures) or with selected clinical populations."

Just what WERE the conditions?

Method--Study Protocols (4)
  "Data are presented from four studies, all of which had within-subject
designs.  The first was a double-blind, placebo-controlled, single oral dose 
study involving an age and gender stratified study population (acute oral
study).  In the second, subjects were monitored after single oral, sublingual,
and smoked doses (multiroute study).  The third involved administration of the
THC either PO or PR b.i.d. for 3-day periods (chronic study), and a fourth
assessed food intake following single oral dosing of subjects in fasted and
fed states (satiety study).  Different individuals were enrolled in each study.
All subjects were recruited by public advertisements and received monetary
compensation for their participation.  Subjects were informed that each
study's aim was to document the physiological actions of the drug; dietary
effects were never mentioned.  The studies were approved by the Committee on
Studies Involving Human Beings at the University of Pennsylvania.

1.  Acute Oral Study

  This study was designed to determine whether ingestion of the currently
FDA-approved formulation of THC stimulates energy intake and alters the type,
nutrient composition, or taste properties of selected foods.

Protocol.  Participants reported to the hospital at 0800 h after an
overnight fast.  Vital signs were collected, a dietary questionnaire was
completed, and a battery of chemosensory tests (described elsewhere (27))
was administered.  A standard breakfast (421 kcal) comprised of one buttered
(5 g) English muffin (57 g), orange juice (240 ml), and 2% milk (240 ml) was 
consumed in its entirety.  Immediately afterwards, a single dose (15 mg for
males, 10 mg for females) of delta-9-THC in sesame oil (Marinol, Unimed, Inc,
Somerville, NJ) or matched placebo was swallowed.  At 1000 h a tray of pre-
weighed foods (sandwhich cookies, cupcakes, chocolate candies, bananas, red
apples, pudding, carrots, fruit punch, potato chips, corn chips, peanuts,
cheese, crackers, dill pickles, V-8 juice, plain yogurt, green apple, sour
hard candies, grapefruit, cranberry juice, bittersweet chocolate, radishes, 
walnuts, celery, raw broccoli, orange marmalade, bitter lemon drink) was made
available for the rest of the test day.  This array of foods provided options
that were rated by other subjects in previous studies as primarily sweet, sour
salty, or bitter.  Vital signs were taken and the dietary questinnaire was
completed at this time and hourly for the duration to the day. Sensory testing
and blood draws were repeated at 1100, 1300, and 1500 h.  Lunch was self-
selected from a menu containing about 60 items plus condiments at 1100 h and
the preweighed items were were presented at 1200 h.  Between scheduled acti-
vities, subjects were free to engage in quiet recreational activities on the
hospital floor.  Only one subject was tested per day.  Following subject 
release (at approximately 1800 h), all foods were reweighed to determine the
amounts consumed (i.e., no food was given to the other patients or hoarded for
later consumption).  A minimum of 3 weeks was interposed between sessions to
ensure that any drug administered during a study day was cleared before
subsequent testing.

2.  Multiroute study

  This study explored the acute appetite stimulating effects of THC following
different routes of administration.

Protocol.  
The testing protocol was identical to that used in the acute oral study
except multiple routes of drug delivery were tested.  After breakfast, a single
dose (15 mg for males, 10 mg for females) of delta-9-THC in sesame oil
(Marinol, Unimed, Inc, Somerville, NJ) was swallowed, allowed to dissolve
under the tongue or a single710-795 mg marijuana cigarette (2.57 +/- 0.06%
delta-9-THC) was smoked (supplied by the National Institute on Drug Abuse,
Research Triangle Park, NC).  Smoking entailed inhaling for 3 s, holding 12 s,
exhaling, waiting 15 s and repeating until the cigarette was burned down to a
2 cm stub.  Each test session was separated by at least 3 weeks.  Because of 
concern about lingering drug effects on behavior, subjects remained in the
hospital until 2300 h.  The snack tray was available until 2000 h.  Subjects 
were provided a self-selected dinner at 1800 h (the nutrient content of which
was measured).

3.  Chronic Study

  This study was designed to provide preliminary data on the appetite stimul-
ating effects of THC following repeated low (2.5 mg) doses by two (oral and
rectal suppository) routes.

Protocol.  The types of measures assessed (e.g., sensory function, blood
pressure, salivary function) were identical to those monitored in the acute
oral study, but the timing of the activities differed. Blood was drawn at 0800,
1200, 1600, 2000, and 2300 h each day.  Sensory testing was conducted at 
0800 and 1600 h the first day and only at 1600 h on the subsequent two days.
Eating opportunities included a self-selected breakfast (0800 h), lunch (1200
h), dinner (1730 h), and a snack tray (1000-2300 h) each day.  A 2.5 mg dose
of delta-9-THC was administered PO or PR (as the hemisuccinate ester, 
supplied by ElSohly Laboratories, Oxford, MS) at 0900 and 1700 h.  The two
3-day test sessions were separated by a minimum of 3 weeks.

4.  Satiety Study

In this study,the appetitive effects of THC administration to subjects in a fed
and fasted state were contrasted to determine whether the drug alters satiety.
Failure to compensate for the energy provided by the pretreatment breakfast 
would indicate a disruption of satiety mechanisms.

Protocol.  The testing protocol was identical to that used in the oral study
except subjects either received no morning meal or one containing 455 kcal
comprised of scambled eggs (87.3 g), bacon (14.3 g), half of an English
muffin (28 g) with 7.5 g of margarine, orange juice (120 cc), and milk (240 cc
of whole milk). Immediately after breakfast, a single dose (15 mg for males, 10
mg for females) of delta-9-THC in sesame oil (Marinol, Unimed, Inc, Somerville
NJ) was swallowed.  The 2 test days were separated by a minimum of 3 weeks.

Selected Results/Discussion

...There was a high level of variability in plasma drug levels,especially among
subjects after oral drug administration coincident with a small standard
breakfast.

...Snacks accounted for more energy than the self-selected lunch during both
active and placebo treatments.

...Intakes were also similar following acute administration of the drug by
oral, inhaled, and sublingual routes.

...Two of the subjects who reported experiencing a pronounced "high" 2 h
following inhalation of THC elected to sleep through lunch and had the lowest
daily intakes (830 and 482 kcal). Omitting these subjects, mean energy intake
after inhalation of THC was 2719 +/- 359 kcal; 481 kcal more than oral dosing 
and 603 kcal greater than sublingual dosing effects.  Due to the high variance 
and small sample size, these difference were not statistically significant.

...Snack items (e.g., sweet pastries, chocolate candy) were consistently the
largest contributors of energy.

...Energy intake was not significantly related to reported "high" under any
condition.  However, it should be noted that approximately 20% of participants
in the acute oral study who reported little of no "high" during the study day
volunteered information that they experienced a "high" later that evening and
ate large amounts of food.

...Analyses used intake scores computed as the difference between active and 
placebo treatment days.  No significant association was observed between age
and difference in total energy intake (r = 0.11), reported "high" (r = -0.11),
AUC for parent drug (r = 0.02), or AUC for metabolite levels (r = -0.06).

...Inhalation of THC led to more consistent elevations of plasma drug concent-
ration and tended, albeit not significantly, to promote intake.

...Anectodal reports indicate that marijuan may also alter eating patters and,
in particular, stimulate a desire for sweet items (12, 15, 20, 21).  More 
frequent intake of snack foods accounted for much of the noted increase in 
total energy intake in several controlled studies (12, 13, 15).

...Drug-induced behavioral changes resulting in decreased energy expenditure
have been hypothesized to account for increased energy intake (39).  Shifts of 
fluid balance do not account for the findings (17, 39).  Thus, our failure to
document a THC-related increment in food intake should not be interpreted as 
evidence that THC will be ineffective in the maintenance of adequate body 
weight in clinical populations.