3. Umbruch 4.4..2005 - Online Pot

154 S.M. Huang and J.M. Walker
Studies of cannabinoid agonists on clinical pain in humans
The studies discussed in this section are the most compelling, because the subject
population was drawn from patients suffering from significant chronic
clinical pain. Chronic pain differs from acute pain due to neural changes that
occur with prolonged noxious stimulation. These changes lower the threshold
for pain (allodynia) and heighten the painfulness of noxious stimulation
(hyperalgesia). The mechanisms underlying different classes of pain (e.g.
inflammatory pain versus neuropathic or nerve injury pain) differ.
Consequently, different analgesics exhibit different degrees of efficacy in
chronic pain of different etiologies. For example, morphine is an excellent
analgesic for inflammatory pain, whereas it frequently lacks efficacy in neuropathic
pain [68]. Therefore, studies of different types of clinical pain are necessary
precursors to drawing sound conclusions about the efficacy of cannabinoids
for pain pharmacotherapy.
Positive results of cannabinoids have been found in the studies of cancer
pain conducted by Noyes and colleagues [69, 70]. The patients in the study
(n = 36) reported continuous pain of moderate intensity. In a double-blind random
pattern, patients received on successive days placebo, 10 and 20 mg of
∆ 9 -THC, and 60 and 120 mg of codeine. Pain ratings by the patients were used
to estimate pain-relief and pain-reduction scores. The results indicated that
20 mg of ∆ 9 -THC was roughly equivalent to 120 mg of codeine. Five of the 36
patients experienced adverse reactions to ∆ 9 -THC, one following 10 mg of
∆ 9 -THC, four following 20 mg. The effectiveness of cannabinoids on cancer
pain has also been observed in animal models [71].
Neuropathic pain is a potential target for cannabinoid pharmacotherapies,
which has been validated in preclinical as well as clinical studies. A
double-blind study evaluated the effect of intramuscular administration of various
doses of the ∆ 9 -THC analog levonantradol in moderate to severe postoperative
or trauma pain. Levonantradol provided pain relief at all four doses
studied (1.5–3.0 mg) compared to placebo. More than half of the patients
reported side effects, the most frequent being drowsiness with other symptoms
such as dizziness, mild hallucinations and nervousness occurring less frequently.
Recently, ∆ 9 -THC was evaluated in multiple sclerosis patients with
central neuropathic pain in a double-blind, placebo-controlled crossover
design [72]. Orally administered ∆ 9 -THC (10 mg daily for 3 weeks) lowered
median spontaneous pain-intensity scores and increased the median pain-relief
scores relative to placebo treatment. The modest but clear therapeutic effect
was associated with improvements on the SF-36 quality-of-life scale with no
change in the functional ability of the multiple sclerosis patients. During the
first week of treatment, adverse side effects of ∆ 9 -THC treatment (dizziness,
light-headedness) were more frequent with ∆ 9 -THC than placebo, but the
adverse effects decreased over the therapeutic course, possibly due to tolerance
[72]. In agreement with positive results from clinical data, a substantial number
of preclinical studies have found cannabinoids to be effective in models of