Human Studies of Cannabinoids and Medicinal Cannabis 737carried out a pilot study of smoked marijuana and oral THC (15 mg) in 11 patients.
IOP reductions averaging 30% were seen in 7, whilst 4 had no response.
Two small placebo-controlled studies of smoked and topical THC confirmed
a significant IOP reduction in glaucoma patients. Merrit and colleagues (1980)
compared smoked THC (2%) with placebo in a double-blind parallel-group study
in 18 patients. IOP was significantly reduced in comparison with placebo between
1.5 and 2.5 h after dosing. Unfortunately, these effects were accompanied by reduc-
tions in blood pressure, increases in heart rate, and “alterations in mental status”
which were not propitious for clinical utility. Merritt (1981) went on to investigate
THC eye-drops in a double-blind, placebo-controlled study in 8 patients. Dose-
related reductions in IOP were recorded using 0.05% and 1% drops with minimal
unwanted effects. Parallel reductions were noted in the untreated eye, suggesting
asystemicratherthanalocalmodeofaction.
It is now apparent that raised IOP is not the only pathological mechanism in
glaucoma. Impaired auto-regulation in arteries supplying the optic nerve head
may interfere with perfusion and cause neural damage (Prunte et al. 1998). The
discovery that CB 1 receptors are present in micro-vasculature (Sugiura et al. 1998)
and the ability of endogenous cannabinoids to produce vasodilation (Sugiura et
al. 1998) suggests the possibility that exogenous cannabinoids may alleviate this
deficit. Antioxidant andN-methyl-d-aspartate (NMDA) receptor neuroprotective
properties of cannabinoids (Hampson et al. 1998) raise the hope that they might
improve survival of ischaemic retinal ganglion cells. Future prospects have been
reviewed by Jarvinen et al. (2002). Non-irritant local delivery using cyclodextrins
and non-psychoactive cannabinoids offers considerable promise.
2.8
Epilepsy
Epilepsy afflicts around 1% of the world’s population, and historically was an
important target for medicinal cannabis (O’Shaugnessy 1843; Reynolds 1890).
Modern anti-epileptic drugs fail to provide satisfactory control in up to 30% of
patients, and all can produce disabling or even life-threatening unwanted effects.
A confusing picture emerges when cannabinoids are evaluated in animal models
of epilepsy (Karler and Turkanis 1981; Consroe and Snider 1986). CBD has anti-
convulsant properties with a spectrum distinct from standard anticonvulsants, ap-
parently not hampered by the development of tolerance but with a varying profile
according to the species tested. THC can produce seizures in some circumstances
but is anticonvulsant in others. In a recent study, THC (10 mg/kg) completely abol-
ished spontaneous seizures in the rat pilocarpine model of epilepsy (Wallace et al.
2003). The results also indicated that endogenous cannabinoid tone may modulate
seizure termination and duration via the CB 1 receptor.
Human research data are almost non-existent. There are anecdotal reports of
beneficial effects of cannabis in human epileptics (Grinspoon and Bakalar 1993)
and a couple of published single case reports. A man with grand mal epilepsy
stopped taking his anticonvulsants and suffered no fits for 6 months. He then