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humankind. Pioneering clinical research in the last quarter of the twentieth cen-
tury has given some support to these anecdotal reports, but the methodological
challenges to human research involving a pariah drug are formidable. Studies have
tended to be small, imperfectly controlled, and have often incorporated unsatis-
factory synthetic cannabinoid analogues or smoked herbal material of uncertain
composition and irregular bioavailability. As a result, the scientific evaluation of
medicinal cannabis in humans is still in its infancy. New possibilities in human
research have been opened up by the discovery of the endocannabinoid system,
a rapidly expanding knowledge of cannabinoid pharmacology, and a more sym-
pathetic political environment in several countries. More and more scientists and
clinicians are becoming interested in exploring the potential of cannabis-based
medicines. Future targets will extend beyond symptom relief into disease modifi-
cation, and already cannabinoids seem to offer particular promise in the treatment
of certain inflammatory and neurodegenerative conditions. This chapter will begin
with an outline of the development and current status of legal controls pertaining
to cannabis, following which the existing human research will be reviewed. Some
key safety issues will then be considered, and the chapter will conclude with some
suggestions as to future directions for human research.
KeywordsCannabinoids · Medicinal cannabis · Human research · Therapeutic
potential
1
Introduction
The pariah status of cannabis is a relatively modern phenomenon. Cultivation of
the plant for hemp extends back to the Stone Age, and medicinal use dates back at
least 4,000 years (reviewed by Mechoulam 1986). In China a medical treatise dating
from around 2600b.c.e.recommends its use for relieving the symptoms of malaria,
constipation, rheumatic pains and dysmenorrhoea (Grinspoon and Bakalar 1993).
There are subsequent records of medicinal use throughout Asia, the Middle East,
Southern Africa and South America. Known to European physicians as Indian
hemp until christenedCannabis sativaby Linnaeus in 1753, it was not until the
mid-nineteenth century that it emerged as a mainstream medicine in Britain. The
Irish scientist and physician W.B. O’Shaughnessy had observed its use in India as
an analgesic, anti-spasmodic, anti-emetic and hypnotic. After testing its safety on
dogs, goats and himself he went on to administer cannabis resin in an ethanolic
solution to patients with a range of maladies. His report (O’Shaughnessy 1843) of
these experiments generated considerable interest, and medicinal use expanded
rapidly. By 1854 it had found its way into the U.S. Dispensatory, and “over-the-
counter” preparations were soon available in pharmacies throughout England
and Scotland. Establishment status was fully achieved through the enthusiastic
endorsement of one of Queen Victoria’s physicians (Reynolds 1890), but by the
end of the century cannabis had passed its zenith as a prescribed medicine and
home remedy. Although Sir William Osler was still recommending it for migraine