3. Umbruch 4.4..2005 - Online Pot

236 G.W. Guy and C.G. Stott
∆ 9 -THC, seen as symptoms of dysphoria, depersonalization, anxiety, panic
reactions and paranoia [36].
It is possible that the observed difference in side-effect profiles may also be
due, in part, to differences in routes of administration: orally administered
∆ 9 -THC undergoes ‘first-pass metabolism’ in the small intestine and liver, to
11-OH-THC; and the metabolite has been reported to be psychoactive, albeit
on the basis of limited evidence [37]. Inhaled ∆ 9 -THC undergoes little
first-pass metabolism, so less 11-OH-THC is formed [38, 39]. The effect of the
route of administration on tolerability has been known for years. Walton, in
1938, remarked that “smoking cannabis is a satisfactory expedient in combating
fatigue, headache and exhaustion, whereas the oral ingestion of cannabis
results chiefly in a narcotic effect which may cause serious alarm” [40].
The other classes of compounds present in cannabis also have their own
pharmacology (e.g. terpenoids, flavonoids) [31, 32]. The potential for interaction
and synergy between compounds within the plant may play a role in the
therapeutic potential of cannabis as a medicine. This may explain why a
cannabis-based medicine using extracts containing multiple cannabinoids, in
defined ratios, and other non-cannabinoid fractions, may provide better therapeutic
success and be better tolerated than the single synthetic cannabinoid
medicines currently available.
CBD, as a non-psychoactive cannabinoid, is currently the cannabinoid of
considerable interest. CBD, along with ∆ 9 -THC, has been demonstrated to
have a wide range of pharmacological activity, with the potential to be developed
for a number of therapeutic areas [41]. It is likely that other cannabinoids,
present in small amounts in Cannabis sativa L., may also have interesting
pharmacological properties, for example tetrahydrocannabivarin (THC-V),
cannabichromene (CBC) and cannabigerol (CBG) [31, 32, 39].
Regulatory requirements
The pharmaceutical development of cannabis-based medicines is well documented
[42, 43]. For cannabinoids to be made into pharmaceuticals, licensed
by the regulatory bodies around the world, they must reach strict requirements
laid down in terms of the product’s quality, safety and efficacy and increasingly
the healthcare industry requirement of cost-effectiveness. Such standards
are achieved by adhering to the industry and regulatory standards of Good
Laboratory Practice (GLP), Good Manufacturing Practice (GMP) and Good
Clinical Practice (GCP), according to the guidance documents provided by the
International Conference on Harmonisation [44]. All requirements are now
implemented through European Union and national legislation. In the case of
plant-based medicines they must also adhere to Good Agricultural Practice
(GAP) standards.
As a result, quality control is required throughout the whole of the manufacturing
chain, including the production of raw materials. For pharmaceuti-