of marihuana on intraocular and blood pressure in glaucoma
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
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.
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.
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.
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
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).
2 lists the side effects observed after marihuana therapy in 18 subjects. Postural
hypotension, occurring in five subjects, was the most serious complication encountered.
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).
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.
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.
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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