EFFECT OF MARIHUANA ON INTRAOCULAR AND BLOOD PRESSURE IN GLAUCOMA

Ophthalmology, March 1980, Vol. 87, No. 3, pp. 222-228.

John C. Merritt, MD, William J. Crawford, PhD, Paul C. Alexander, MD,
Alfred L. Anduze, MD, Solomon S. Gelbart, MD

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 Univrsity
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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