736 P. R o b s o n
2.6
Appetite Suppression in Obesity
A growing understanding of the role of central cannabinoid systems in the reg-
ulation of appetite (Williams and Kirkham 1999) has raised the possibility that
blocking CB 1 receptors might inhibit appetite (Kirkham 2003). Testing this hy-
pothesis has become a possibility with the development of the selective CB 1 recep-
tor antagonist SR141716A (rimonabant). Studies in various animal models have
demonstrated that this produces marked reduction of food intake, body weight
and adiposity (e.g. Ravinet et al. 2002).
At the time of writing, seven phase III clinical trials are in progress focusing on
rimonabant’s effect on weight loss and smoking cessation. None of these has yet
been published in peer-reviewed journals, but two have been completed and the
results presented at a U.S. cardiology conference in 2004. According to information
supplied by the manufacturer, overweight patients treated with rimonabant 20 mg
daily for 1 year lost significantly more weight than placebo patients (p<0.001).
Improvement in some associated cardiovascular risk factors (e.g. waist circum-
ference, HDL cholesterol and triglyceride plasma levels, C-reactive protein levels)
were also reported. Unwanted effects were described as consisting mainly of mild
and transient nausea and dizziness, though twice as many patients dropped out on
rimonabant 20 mg than placebo. A second study suggested that smokers seeking
abstinenceweretwiceaslikelytobesuccessfulwhentreatedwithrimonabant20mg
for 10 weeks in comparison with placebo (p= 0.002). Rimonabant also appeared
to protect against the weight gain commonly seen following smoking cessation.
Once again, however, there were twice as many dropouts on active treatment. It
must be noted that these results await peer review.
2.7
Glaucoma
Glaucoma is the commonest cause of blindness in the Western World. Raised intra-
ocular pressure (IOP) is usually due to an obstruction to the outflow of aqueous
humour at the front of the eye, and by far the commonest deficit is primary
open-angle (chronic simple) glaucoma. A range of topical and systemic drugs are
used to treat this, but efficacy is variable and there are many possible unwanted
effects.
The discovery that cannabis lowers IOP was first reported by Hepler and Frank
(1971), and the mechanism by which this is achieved still remains to be clarified.
Controlled studies in healthy subjects (Hepler et al. 1976; Perez-Reyes et al. 1976;
Jones et al. 1981) have shown that oral, injected or smoked THC produces dose-
related reductions of IOP as much as 30% below baseline, though tolerance may
occur on chronic dosing.
Inthe1970s,anecdotalreportsofsymptomreliefbysmokedmarijuanaappeared
and a small number of glaucoma patients successfully argued in the U.S. for legal
access to the drug (Grinspoon and Bakalar 1993). Hepler and colleagues (1976)