Cannabinoids

Human Studies of Cannabinoids and Medicinal Cannabis 739

during sleep. Effects on sleep architecture were modest, but some effects of both
cannabinoids on slow wave sleep were reported. Overall, these results suggest that
the improvement in sleep quality frequently reported in clinical trials is mainly
due to nocturnal symptom relief rather than a primary hypnotic effect.
THC (0.1 mg/kg) was reported to have anti-depressant properties in cancer
patients (Regelson et al. 1976). There are anecdotal reports that cannabis may act
as a mood stabiliser in bipolar affective disorder (Grinspoon and Bakalar 1998).
The discovery that the endogenous cannabinoid system has a central function
in extinction of aversive memories (Marsicano et al. 2002) raises the fascinating
possibility that CB 1 agonists may prove therapeutic in phobias or post-traumatic
stress disorder.

2.10

Asthma

Although cannabis was used as a bronchodilator in the nineteenth century, modern
human research seems to have been limited to a brief period in the 1970s. Small
controlled studies in asthmatic volunteers (Tashkin et al. 1974; Williams et al.
1976; Tashkin et al. 1977) showed that oral, smoked and aerosolised THC had
significantbronchodilatoractivitycomparabletothatofsalbutamol,thoughslower
in onset. Dose-related tachycardia and intoxication occurred at higher doses. An
inhaled aerosol avoided systemic absorption of THC but induced cough and chest
discomfort, which limited its usefulness.

3

Safety Issues with Cannabis-Based Medicines

Cannabis is known to demonstrate very low acute toxicity. To the best of this
author’s knowledge, it remains the case that no human death has been reliably
ascribed to cannabis toxicity alone. It has been estimated, based on extrapolation
from mouse to man, that the lethal dose to effective dose ratio is around 40,000:1
(Grinspoon and Bakalar 1993, p 138). Minor adverse events (AEs) including intoxi-
cation, dizziness and dry mouth occur frequently with THC-containing medicines,
but are generally mild or moderate in intensity and well tolerated by patients. In
a recent large study (Zajicek et al. 2003), out of 417 patients allocated to THC or
cannabis extract, only 9 patients discontinued treatment because of intolerable
AEs, and serious or life-threatening AEs were no more frequent following active
treatments than placebo.
Cannabis and THC are known to increase heart rate, cardiac output and supine
blood pressure, and can cause orthostatic hypotension (Jones 2002). Because of the
resulting increase in cardiac work, cannabis and THC are probably best avoided by
patients with clinically significant cardiovascular disorders. Cardiovascular effects
tend to tolerate out over chronic dosing (Benowitz and Jones 1981). A survey of
myocardial infarction survivors set out to investigate whether smoking marijuana