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Abstract: Marihuana inhalation was
accompanied by increased heart rate and decreased
intraocular and blood pressure in 18 subjects with
heterogenous glaucomas. The hypotensive effects appeared in
60 to 90 minutes as the decrease in intraocular pressure
(IOP) appeared to follow the decrease in blood pressure. In
addition to any local effect, the mechanism of lowered IOP
may also involve the decreased pressure perfusing the
ciliary body vasculature as a result of the peripheral
vasodilatory properties of marihuana. Postural hypotension,
tachycardia, palpitations, and alterations in mental status
occurred with such frequency as to mitigate against the
routine used in the general glaucoma population. Our data
indicate that further research should be directed to local
means of delivering the ocular hypotensive cannabinoid to
the glaucomatous eye. [Key words: blood pressure, glaucoma,
heart rate, intraocular pressure, marihuana,
delta-9-tetrahydrocannabinol.] Ophthalmology 87: 222-228,
1980
In 1971, Hepler (1) observed that marihuana smoking was
accompanied by decreases in ocular tension in normal males.
Later Lockhart et al (2) demonstrated an ocular hupotensive
effect in Jamaicans with raised intraocular tension. These
ocular effects, although of potential therapeutic benefit,
have not been fully documented. Our study investigates the
effect of marihuana inhalation on the intraocular pressure
in various forms of glaucoma.
MATERIAL AND METHODS
The patients were attending the glaucoma clinic at
Howard University Hospital, Washington, DC. Those with
evidence of cardiac, neurologic, or psychiatric
dys-function were excluded, as were all women in the
child-bearing years. After obtaining informed consent, 18
glaucoma patients (31 eyes) were selected for this study.
Eight were hypertensive, four diabetic, and one asthmatic.
Forty operative procedures had been performed on 17 eyes of
11 patients (Table 1). The visual acuities in the 31
glaucoma eyes are shown in Fig. 1. Nine patients had used
marihuana at least once, while the remaining nine patients
had not.
The marihuana cigarettes were a blend of Mexican
varieties grown at the Research Institute for
Pharmaceutical Studies at the University of Mississippi and
made available through the National Institute on Drug
Abuse, Rockville, MD. Each 900 mg marihuana cigarette
contained approximately 2% delta-9-tetrahydrocannabinol by
weight. Placebo therapy consisted of marihuana cigarettes
that had the alcohol extractable cannabinoids removed
leaving essentially a sugar and cellulose residue. Placebo
cigarettes retained the same characteristic smell and taste
as natural marihuana.
Glaucoma medications were discontinued in each patient
48 hours prior to testing. Initially blood pressure (BP)
and heart rate (HR) were measured every five minutes while
patients were sitting quietly for 15 to 20 minutes for
baseline values. Intraocular pressures were then measured
with a Goldmann applanation tonometer mounted onto a
Haag-Streit slit lamp. One cigarette (placebo or marihuana
randomly determined) was smoked over 10 to 20 minutes and
the blood pressure (BP), heart rate (HR), and intraocular
pressure (IOP) were measured at 15, 30, 60, 90, 120, 150,
180, and 240 minutes. Our results represent the mean +
standard error of the 31 glaucoma eyes. Statistical
significance for these data was selected at P <0.05
(paired t-test).
RESULTS
Marihuana inhalation was invariably accompanied by
significant increases in the heart rate. This tachycardia
was present within two to three minutes and was maximum
(X=123.0 +3,4 beats/minute) at 15 minutes. Heart rates
returned to control values within 90 to 120 minutes.
Insignificant changes in heart rate occurred after
inhalation of placebo (Fig 2). The IOP decreased 4.1 +1.5
mm Hg within the first 30 minutes after inhalation. The
maximum decrease of 6.6 + 1.5 mm Hg occurred at 90 minutes.
There was no difference in pressure-lowering effects in
those individuals whose angles were closed by synechiae
when compared to those with open angle glaucoma. Control
IOP was usually reached in four hours, although a longer
hypotensive effect was demonstrable in several subjects.
Insignificant changes in IOP occurred after placebo therapy
(Fig 3). The systolic blood pressure was decreased (X= 11.4
+ 3.0 mm Hg) and diastolic BP (X= 5.1 + 1.0 mm Hg) 60
minutes after marihuana therapy. In several patients the
maximum decrease in blood pressure occurred within 10 to 15
minutes and was accompanied by postural hypotension in five
cases. Blood pressures were not altered after placebo
therapy (Fig 4).
SIDE EFFECTS
Table 2 lists the side effects observed after marihuana
therapy in 18 subjects. Postural hypotension, occurring in
five subjects, was the most serious complication
encountered.
Case 1. The patient is a 28 year-old man who had never
used marihuana. The visual acuity in the normal right eye
was 20/15 and light perception in the left eye. Poor visual
function in left eye was the result of a tractional retinal
detachment, band keratopathy and glaucoma secondary to
complete angle closure by a fibrovascular membrane. The IOP
varied from 40 to 50 mm Hg on epinephrine 2%, diamox 500 mg
twice daily, and previous cryotherapy. The subject was
tested with marihuana seven days after receiving his last
glaucoma medication. He successfully smoked a 900 mg
cigarette in the sitting position over 10 to 15 minutes.
Ten minutes after completion, the heart rate fell to 60
beats/minute with the blood pressure becoming inaudible. He
became pale, cold, and sweaty as a result of the sudden
decrease in blood pressure. During this period the IOP was
1 to 2 mm Hg in the right eye and 16 mm Hg in the left eye.
The subject was immediately placed in the reclining
position with the blood pressure rising to 110 mm Hg and
IOP increased to 5 mm Hg in the right eye and 41 mm Hg in
the left eye as measured with a hand-held applanation
tonometer (Fig ). Case 2. The patient is a 31 year old man
whose glaucoma stemmed from multiple surgical procedures
for primary congenital glaucoma. The visual acuities were
bare light perception in the right eye and counting fingers
at two to three feet in the temporal field in the left eye.
Previous medical therapy included timolol maleate 0.5% in
both eyes twice daily, epinephrine 2% in both eyes twice
daily, and pilocarpine 6% in the left eye four times a day.
Carbonic anhydrase inhibitors were associated with kidney
stones and the patient admitted that he had become a
frequent (daily) user of marihuana for the past five to six
years. On test day 1, he smoked a 900 mg marihuana
cigarette over a 10-minute period. There were insignificant
changes in IOP and virtually no change in blood pressure
(Fig ^). Because of this poor response, and his previous
experience with marihuana, he was tested on another day
with two marihuana cigarettes which he inhaled over 25
minutes in the sitting position. Ten minutes after
completion, he became nauseous, light-headed, cold, sweaty,
and his blood pressure became inaudible. The heart rate
decreased to 60 beats/minute and the IOP fell to 14 mm Hg
(right eye) and 3 mm Hg (left eye). The subject was placed
in the reclining position with a resulting rise in both the
blood pressure and intraocular pressure (Fig 7).
DISCUSSION
Our study verifies that marihuana lowers both
intraocular pressure and blood pressure in a heterogenous
glaucoma population. The magnitude of these hypotensive
effects depends on the initial pressure levels, as greater
decreases in BP and IOP were evidenced in subjects with
essential hypertension after single dose administration of
marihuana. (4,5) The exact mechanisms by which cannabinoids
effect ocular tension in man are poorly understood. In
rabbits, topical (6) and intravenous (7,8) THC alter
aqueous dynamics primarily through the central nervous
system although intact peripheral adrenergic receptors are
necessary for the full expression of the THC's effect.
Intravenous delta-9-THC in rabbits with unilateral superior
cervical ganglionectomy causes a 25% pressure reduction in
the normal eye, with a significantly reduced effect in the
eye on the side of the ganglionectomy. Similarly the beta
adrenergic blockers, propranolol and sotalol, attenuate the
THC pressure-lowering effect while the alpha blockers
(phentolamine and Regitine) have been reported to inhibit
the THC-induced increase in total outflow facility by 25%
in rabbits. (9) Obvious species differences and lack of
pharmacologic evidence for adrenergic receptors in the
human eye preclude meaningful comparisons with the present
study.
In addition to any local effect, the systemic effects of
marihuana must be considered. Acute alterations in systolic
blood pressure, a major modulator of IOP, (10-12) could
account for the directional changes observed in IOP, as was
documented in the two subjects described with postural
hypotension. The marihuana-induced tachycardia may result
from stimulation of beta adrenergic receptors in the heart.
Although this tachycardia has been attenuated by
propranolol in normal males, (13-16) Benowitz et al (17)
have shown that delta-9-THC exerts both a beta stimulatory
and parasympathetic inhibitory effect on the heart.
Pretreatment of marihuana-experienced males with atropine
and propranolol, completely abolished the effect of
Delta-9-THC on the heart rate and blood pressure.
Similarly, bronchodilatory effects which occurred in one
asthmatic patient after marihuana corroborated other
studies (18) that suggest beta agonist properties of
delta-9-THC on lungs. The observed side effects in the
patients who never used marihuana were more severe than in
subjects who had previously experienced these effects.
Anxiety concerning the tachycardia, palpitations, and
postural hypotension predominated rather than euphoria: It
is because of the frequency and severity with which the
untoward events occurred that marihuana inhalation is not
an ideal therapeutic modality for glaucoma patients.
ACKNOWLEDGMENTS
The authors thank Roger Grimson, PhD, UNC School of
Public Health for statistical analysis of these data as
well as Ms. Donna Farrow and Mrs. Betty Lloyd (Medical
Illustrations) for preparation of this manuscript.
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