On Sat, 1 Apr 2000, Jeff Bartel went:
> While we were covering hunger in my General Psychology course, a
> student asked me if smoking marijuana somehow influences your
> (lateral) hypothalamus, his implication being that if the LH is one
> cause of hunger and if smoking marijuana causes people to be hungry,
> the two might be related.
[...]
> While we're on this subject, maybe whoever knows the answer to that
> question can answer another question about marijuana and hunger. How
> does marijuana reduce nausea associated with chemotherapy
In both cases--appetite stimulation and antinausea/antiemetic effects
--the answer appears to be "Well, we have THC receptors in the right
places." For example, there's a light sprinkling of THC receptors in
various hypothalamic nuclei, including the lateral hypothalamus. But
I can't find any studies in which lab animals were given
microinjections of THC into the lateral hypothalamus to determine
whether that would induce hyperphagia (overeating). Similarly, the
presence of THC receptors in various brainstem regions provides nice
_circumstantial_ evidence for brainstem mediation of marijuana's
antiemetic effect (along with its tachycardic effect and its tendency
to produce dry mouth)--but again, I can't find microinjection studies
that directly test any of that. (Of course, rats can't vomit anyway,
so there'll be no testing of antiemetic effects in them.)
> Is the mechanism involved affected by the route of administration
> (i.e., smoking vs. eating)?
The mechanism is thought to involve the CNS (and presumably the same
_part_ of the CNS) regardless of how the drug was administered; at
least, I've never seen speculation to the contrary. But if the
patient can't hold anything down, smoking may work better--so goes
one line of argument for medical use of smoked marijuana.
A couple of vaguely relevant abstracts are below.
--David Epstein
[EMAIL PROTECTED]
Romero J, Wenger T, de Miguel R, Ramos JA, and Fernandez-Ruiz JJ.
Cannabinoid receptor binding did not vary in several hypothalamic nuclei
after hypothalamic deafferentation.
Life Sciences. 63(5):351-6, 1998.
Abstract
Cannabinoid receptors are sparsely distributed in the hypothalamic nuclei,
although they seem to be located on key neurons because their activation
produces important neuroendocrine effects. In the present study, we have
examined whether cannabinoid receptor-containing hypothalamic neurons are
intrinsic or extrinsic to this brain region. To this end, we have examined
whether the hypothalamic deafferentation was followed by a general loss of
cannabinoid receptor binding, thus suggesting that cannabinoid
receptor-containing neurons would have their cell bodies outside the
hypothalamus, or whether this was followed by no changes in binding, thus
suggesting that cannabinoid receptors would be located on intrinsic
neurons. Three experimental groups were then analyzed: (i) animals with
complete hypothalamic deafferentation in both sides; (ii)
hemideafferentated animals; and (iii) sham-operated animals. In the three
cases, cannabinoid receptor binding did not vary among these three groups
in any of the hypothalamic nuclei analyzed. These were the arcuate
nucleus, ventromedial hypothalamic nucleus, lateral and dorsal
hypothalamic areas, paraventricular nucleus and medial preoptic area. This
clearly supports the view that cannabinoid receptor-containing neurons
into the hypothalamus are all intrinsic to this brain region.
Glass M, Dragunow M, and Faull RL.
Cannabinoid receptors in the human brain: a detailed anatomical and
quantitative autoradiographic study in the fetal, neonatal and adult human
brain.
Neuroscience. 77(2):299-318, 1997 Mar.
Abstract
The anatomical distribution and density of cannabinoid receptors in the
human brain was studied in one fetal (33 weeks gestation), two neonatal
(aged three to six months) and eight adult (aged 21-81 years) human cases
using quantitative receptor autoradiography following in vitro labelling
of sections with the synthetic cannabinoid agonist [3H]CP55,940.
Cannabinoid receptors were distributed in a heterogeneous fashion
throughout the adult human brain and spinal cord. The allocortex contained
very high concentrations of cannabinoid receptor binding sites in the
dentate gyrus, Ammons's horn and subiculum of the hippocampal formation;
high concentrations of receptors were also present in the entorhinal
cortex and amygdaloid complex. Cannabinoid receptor binding sites were
also present throughout all regions of the neocortex, where they showed a
marked variation in density between the primary, secondary and
associational cortical regions: the greatest densities of receptors were
present in the associational cortical regions of the frontal and limbic
lobes, with moderate densities in the secondary sensory and motor cortical
regions, and with the lowest densities of receptors in the primary sensory
and motor cortical regions. Relatively high concentrations of cannabinoid
receptors were consistently seen in cortical regions of the left
(dominant) hemisphere, known to be associated with verbal language
functions. In all of the cortical regions, the pattern and density of
receptor labelling followed the neocortical laminar organization, with the
greatest density of receptors localized in two discrete bands--a clearly
delineated narrow superficial band which coincided with lamina I and a
deeper broader, conspicuous band of labelling which corresponded to
laminae V and VI. Labelling in the intervening cortical laminae (II-IV)
showed lower densities, with a well delineated narrow band of label in the
middle of laminae IV in the associational cortical regions. The thalamus
showed a distinctive heterogeneous distribution of cannabinoid receptors,
with the highest concentration of receptors localized in the mediodorsal
nucleus, anterior nuclear complex, and in the midline and intralaminar
complex of nuclei, i.e. in thalamic nuclei which have connectional
affiliations with the associational cortical areas. The basal ganglia
showed a distinctive heterogeneous pattern of receptor binding, with the
very highest concentrations in the globus pallidus internus, moderate
concentrations in the globus pallidus externus and ventral pallidum, and
moderately low levels of binding throughout the striatal complex. In the
midbrain, some of the highest levels of cannabinoid receptor binding sites
in the human brain were present in the substantia nigra pars reticulata,
with very low levels of labelling in all other midbrain areas. The highest
densities of cannabinoid receptor binding in the hindbrain were localized
in the molecular layer of the cerebellar cortex and the dorsal motor
nucleus of the vagus, with moderate densities of receptors in the nucleus
of the solitary tract. The spinal cord showed very low levels of receptor
binding. Studies on the distribution of cannabinoid receptors in the fetal
and neonatal human brain showed similar patterns of receptor distribution
to that observed in the adult human brain, except that the density of
receptor binding was generally markedly higher, especially in the basal
ganglia and substantia nigra. The pattern of cannabinoid receptor
labelling in the striatum showed a striking patchy pattern of organization
which was especially conspicuous in the fetal brain. These results show
that cannabinoid receptor binding sites in the human brain are localized
mainly in: forebrain areas associated with higher cognitive functions;
forebrain, midbrain and hindbrain areas associated with the control of
movement; and in hindbrain areas associated with the control of motor and
sensory functions of the autonomic nervous system.
