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HIV/AIDS
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Haney
M.: Effects of smoked marihuana in healthy
and HIV + marihuana smokers. J Clin Pharmacol
2002; 42: 34S-40S |
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This article presents data from two avenues
of marihuana research. First, the author shows
that daily marihuana smoking in healthy individuals
produces dependence, as demonstrated by withdrawal
symptoms such as increased irritability and
depression and decreased food intake. In addition,
two antidepressant medications were evaluated
to assess their potential effectiveness in the
treatment of marihuana withdrawal symptoms:
(1) sustained-release bupropion (0, 300 mg/day)
and (2) nefazodone (0, 450 mg/day). Research
participants were regular marihuana smokers
who lived in a residential laboratory in groups
of two to four. While inpatients, participants
smoked active marihuana (2.8%-3.1% THC) repeatedly
for 4 days, followed by 8 to 12 days of placebo
marihuana (0.0% THC). Results show that during
marihuana abstinence, (1) bupropion increased
ratings of irritability, depression, and stomach
pain and decreased food intake and sleep quality
compared to placebo maintenance, and (2) nefazodone
decreased anxiety during marihuana withdrawal
but did not alter ratings of irritability and
misery. Thus, neither medication showed promise
as potential treatments for symptoms of marihuana
withdrawal. The second avenue of research focused
on the effect of cannabinoids in individuals
with muscle mass loss, an indicator of wasting
in HIV illness. Given that there are little
scientific data contributing to the debates
concerning medical marihuana, this study directly
compared the effects of oral delta9-THC (0,
10, 20, 30 mg PO) to smoked marihuana (0.0%,
1.8%, 2.8%, 3.9% THC) in HIV + marihuana smokers
with muscle mass loss (< 90% body cell mass/height).
Multiple dimensions of human behavior were measured,
including food intake, mood, and cognitive performance.
Drugs were administered using a within-subject,
double-blind, staggered, double-dummy design.
Participants were free to self-select from a
variety of foods throughout most of the session.
Preliminary data (n = 9) suggest that oral THC
was more effective at increasing food intake,
but the volunteers "liked" the effects
of smoked marihuana more than the effects of
oral THC.
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Beal
J.E. et al: Dronabinol as a treatment for
anorexia associated with weight loss in
patients with AIDS. Journal of Pain and
Symptom Management 1995; 10(2): 89-97 |
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The effects of dronabinol on appetite and weight
were evaluated in 139 patients with AIDS-related
anorexia and > or = 2.3 kg weight loss in
a multi-institutional study. Patients were randomized
to receive 2.5 mg dronabinol twice daily or
placebo. Patients rated appetite, mood, and
nausea by using a 100-mm visual analogue scale
3 days weekly. Efficacy was evaluable in 88
patients. Dronabinol was associated with increased
appetite above baseline (38% vs 8% for placebo,
P = 0.015), improvement in mood (10% vs -2%,
P = 0.06), and decreased nausea (20% vs 7%;
P = 0.05). Weight was stable in dronabinol patients,
while placebo recipients had a mean loss of
0.4 kg (P = 0.14). Of the dronabinol patients,
22% gained > or = 2 kg, compared with 10.5%
of placebo recipients (P = 0.11). Side effects
were mostly mild to moderate in severity (euphoria,
dizziness, thinking abnormalities); there was
no difference in discontinued therapy between
dronabinol (8.3%) and placebo (4.5%) recipients.
Dronabinol was found to be safe and effective
for anorexia associated with weight loss in
patients with AIDS.
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Bredt
BM, et al: Short-term effects of cannabinoids
on immune phenotype and function in HIV-1-infected
patients. J Clin Pharmacol 2002;
42: 82S-89S. |
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Cannabinoids, including smoked marihuana and
delta9-tetrahydrocannabinol (THC) (dronabinol,
Marinol), have been used to treat human immunodeficiency
virus-1 (HIV)-associated anorexia and weight
loss. Concerns have been raised, however, that
these compounds might have adverse effects on
the immune system of subjects with HIV infection.
To determine whether such effects occur, the
authors designed a randomized, prospective,
controlled trial comparing the use of marihuana
cigarettes (3.95% THC), dronabinol (2.5 mg),
and oral placebo in HIV-infected adults taking
protease inhibitor-containing highly active
antiretroviral therapy (HAART). Assays of immune
phenotype (including flow cytometric quantitation
of T cell subpopulations, B cells, and natural
killer [NK] cells) and immunefunction (including
assays for induced cytokine production, NK cell
function, and lymphoproliferation) were performed
at baseline and weekly thereafter. On the basis
of these measurements and during this short
21-day study period, few statistically significant
effects were noted on immune system phenotypes
orfunctions in this patient population.
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Abrams
DI et al: Short-term effects of cannabinoids
in patients with HIV-1 infection: a randomized,
placebo-controlled clinical trial. Ann
Intern Med. 2003 Aug 19;139(4):258-66. |
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Cannabinoid use could potentially alter HIV
RNA levels by two mechanisms: immune modulation
or cannabinoid-protease inhibitor interactions
(because both share cytochrome P-450 metabolic
pathways).
OBJECTIVE: To determine the
short-term effects of smoked marihuana on the
viral load in HIV-infected patients.
DESIGN: Randomized, placebo-controlled,
21-day intervention trial.
SETTING: The inpatient General
Clinical Research Center at the San Francisco
General Hospital, San Francisco, California.
PARTICIPANTS: 67 patients
with HIV-1 infection.
INTERVENTION: Participants
were randomly assigned to a 3.95%-tetrahydrocannabinol
marihuana cigarette, a 2.5-mg dronabinol (delta-9-tetrahydrocannabinol)
capsule, or a placebo capsule three times daily
before meals.
MEASUREMENTS: HIV RNA levels,
CD4+ and CD8+ cell subsets, and pharmacokinetic
analyses of the protease inhibitors.
RESULTS: 62 study participants
were eligible for the primary end point (marihuana
group, 20 patients; dronabinol group, 22 patients;
and placebo group, 20 patients). Baseline HIV
RNA level was less than 50 copies/mL for 36
participants (58%), and the median CD4+ cell
count was 340 x 109 cells/L. When adjusted for
baseline variables, the estimated average effect
versus placebo on change in log10 viral load
from baseline to day 21 was -0.07 (95% CI, -0.30
to 0.13) for marihuana and -0.04 (CI, -0.20
to 0.14) for dronabinol. The adjusted average
changes in viral load in marihuana and dronabinol
relative to placebo were -15% (CI, -50% to 34%)
and -8% (CI, -37% to 37%), respectively. Neither
CD4+ nor CD8+ cell counts appeared to be adversely
affected by the cannabinoids.
CONCLUSIONS: Smoked and oral
cannabinoids did not seem to be unsafe in people
with HIV infection with respect to HIV RNA levels,
CD4+ and CD8+ cell counts, or protease inhibitor
levels over a 21-day treatment.
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Kosel
B.W. et al: The effects of cannabinoids
on the pharmacokinetics of indinavir and
nelfinavir. AIDS 2002; 16: 543-550 |
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BACKGROUND AND OBJECTIVES:
The use of cannabinoids for appetite stimulation
and the management of wasting and antiretroviral
side-effects has become a common practice in
the care of HIV-infected individuals. We present
pharmacokinetic data from a randomized placebo-controlled
study designed to evaluate the metabolic effects
of smoked marihuana and dronabinol in HIV-infected
patients receiving indinavir (IDV) or nelfinavir
(NFV).
METHODS: Subjects on stable
regimens containing IDV 800 mg every 8 h (n
= 28) or NFV 750 mg three time a day (n = 34)
were randomized to one of three treatment arms:
3.95% THC marihuana cigarettes, dronabinol 2.5
mg capsules or placebo capsules administered
three times daily. Serial blood sampling was
performed at baseline and on day 14 of treatment.
The changes in NFV and IDV pharmacokinetics
were measured as the median percentage change
from baseline.
RESULTS: At day 14, the 8-h
area under the curve (AUC(8)) changed by -10.2%
(P = 0.15), maximum concentration (C(max)) by
-17.4% (P = 0.46), and minimum concentration
(C(min)) by -12.2% (P = 0.28) for patients in
the NFV marihuana arm (n = 11). Similar decreases
had occurred by day 14 among patients in the
IDV marihuana arm (n = 9): AUC8 had changed
by -14.5% (P = 0.074), C(max) by -14.1% (P =
0.039), and C(min) by -33.7% (P = 0.65).
CONCLUSION: Despite a statistically
significant decrease in C(max) of IDV in the
marihuana arm, the magnitude of changes in IDV
and NFV pharmacokinetic parameters in the marihuana
arm are likely to have no short-term clinical
consequence. The use of marihuana or dronabinol
is unlikely to impact antiretroviral efficacy.
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Green
ST et al, Nabilone as effective therapy
for Intractable nausea and vomiting in AIDS.
Br. J. clin. Pharmac. 1989; 28 : 494-495 |
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In the scenario described here the patient was
fast approaching a terminal state. The rapid
relief of the patient’s distressing nausea
and vomiting (which was a paramount consideration)
following administration of nabilone suggests
that the drug is efficaceous in this situation.
Currently, the recommended daily dosage during
cancer chemotherapy is 1 mg or 2 mg twice daily,
but it can be used up to a maximum total daily
dose of 6 mg.
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Flynn
J, Nabilone for the Management of Intractable
Nausea and Vomiting in Terminally Staged
AIDS. Journal of Palliative Care 1992; 8(2),
46-47 |
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The author agrees with Green et al. that nabilone
is a viable therapeutic alternative in the treatment
of AIDS-related intractable nausea and vomiting.
Its use as a first-line therapy is somewhat
restricted by its cost and by its side effects
of hypotension and hallucinations. The amelioration
of existing hallucinations in the patient may
have been serendipitous and warrants further
documentation.
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