3. Umbruch 4.4..2005 - Online Pot

Cannabinoid targets for pain therapeutics 153
istration of doses that are ineffective; (2) the oral route of administration adds
variability owing to the unpredictable absorption of ∆ 9 -THC; (3) smoked marijuana
contains additional constituents that modify its actions; and (4) studies
of experimental pain in healthy subjects provide information on the spectrum
of the effects of cannabinoids in humans and initial indications with regard to
the feasibility of their use in humans, while clinical trials on specific pathological
pain syndromes are more relevant in assessing the effectiveness of
cannabinoids on particular pain conditions.
Studies of cannabinoid agonists on experimental pain in humans
Several investigators have studied the effects of cannabinoids on pain perception
in humans by administering controlled painful stimuli to healthy volunteers.
One such study [63] found that an oral dose of 5 mg of ∆ 9 -THC given to
healthy volunteers decreased their ability to distinguish between various intensities
of painful heat stimuli with a time course that was distinguishable from
the effects on memory and psycholinguistic measures. This effect is consistent
with a pain-suppressive effect of the compound. Using sensory decision theory,
they separated this effect from response bias, which refers to the tendency
to respond either positively or negatively and is influenced by non-sensory factors
such as the subject’s culture, temperament and mood. Another study that
used sensory decision theory reached the opposite conclusions [64], but in this
study the large amount of ∆ 9 -THC that was consumed by the volunteers (an
average of 19.4 marijuana cigarettes per day for high consumption and 13.1 for
moderate users) almost certainly produced drug tolerance, which develops rapidly
with cannabinoids, and may have confounded the results, making the data
very difficult to interpret.
Raft and colleagues [65] demonstrated in healthy subjects that intravenously
administered ∆ 9 -THC (0.022 and 0.044 mg/kg) increased pain threshold
(the lowest intensity of stimulation that gives rise to pain) but not pain tolerance
(the intensity at which pain becomes unbearable) to mechanical and electrical
stimulation. Hill and colleagues [66] also measured pain thresholds and
tolerance. In this study, healthy volunteers inhaled marijuana smoke.
Marijuana smoking lowered the pain threshold as well as pain tolerance. A
drawback of this study is the inability to state the dose with any accuracy, a
possible basis for the fact that it is at variance with the results of Raft and colleagues
[65].
A recent study employing topical administration of the cannabinoid agonist
HU-210 has demonstrated its effectiveness in reducing the magnitude of pain
produced by capsaicin as well as mechanical and thermal hyperalgesia and
allodynia in human volunteers [67]. This was a particularly intriguing finding
because topical application led to reduced pain sensation with no observable
psychotropic effects.