The Leaf THE LEAF November-December 2019 | Page 15

Introduction
Cannabis
(marijuana,
hashish,
or
cannabinoids) has been used for medical and
recreational purposes for many centuries and
is likely the only medicine or illicit drug that
has constantly evoked tremendous interest or
controversy within both the public domain
and medical research.
Cannabinoids appear to be able to modulate
pain, nausea, vomiting, epilepsy, ischemic
stroke, cerebral trauma, multiple sclerosis,
tumours, and other disorders in humans
and/or animals.
However, marijuana has been the most
commonly used illicit drug in developed
countries,
producing
acute
memory
impairment and dependence/withdrawal
symptoms in chronic users and animal
models.
Cannabis acts on 2 types of cannabinoid
receptors, the CB1 and CB2 receptors, which
are distributed mainly in the brain and
immune system, respectively.
In the brain, CB1 receptors are also targeted
by
endogenous
cannabinoids
(i.e.,
endocannabinoids) such as anandamide
(AEA),
2-arachidonylglycerol,
and
arachidonoylethanolamide.
The recent discovery that the hippocampus is
able to generate new neurons
(i.e., neurogenesis) throughout the lifespan of
mammals, including humans, has changed the
way we think about the mechanisms of
psychiatric disorders and drug addiction.
The sub granular zone of the dentate gyrus
(SGZ) in the adult brain contains neural
stem/progenitor cells (NS/PCs) capable of
producing thousands of new granule cells per
day.
We, and others, have shown that these
newborn
hippocampal
neurons
are
functionally integrated into the existing
neuroanatomical circuitry and are positively
correlated with hippocampus-dependent
learning and memory processes and the
developmental mechanisms of stress and
mood disorders. …
Chronic administration of the major drugs of
abuse including opiates, alcohol, nicotine, and
cocaine has been reported to suppress
hippocampal neurogenesis in adult rats,
suggesting a potential role of hippocampal
neurogenesis in the initiation, maintenance,
and treatment of drug addiction.
The recent finding of prominently decreased
hippocampal neurogenesis in CB1-knockout
mice suggests that CB1 receptor activation by
endogenous, plant-derived, or synthetic
cannabinoids may promote hippocampal
neurogenesis.
However, endogenous cannabinoids have
been reported to inhibit adult hippocampal
neurogenesis.
Nevertheless, it is possible that exo- and
endocannabinoids
could
differentially
regulate hippocampal neurogenesis, as exo-
and endocannabinoids act as full or partial
agonists on CB1 receptors, respectively.
The goal of the present study was to test the
hypothesis that the potent synthetic
cannabinoid HU210 is able to promote
hippocampal neurogenesis, leading to the
anxiolytic and antidepressant effects of
cannabinoids.