Cannabis sativa L. - Botany and Biotechnology

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pathways are induced which alter the content of bioactive secondary metabolites
(Gorelick and Bernstein 2014 ). This is especially true for compounds which are
well known for pharmacological activity, such as terpenoids (Trapp et al. 2001 ),
alkaloids (Facchini 2001 ), and phenylproponoids (Dixon et al. 1995 ). Contact with
fungal pathogens has been shown to increase by orders of magnitude the levels of
phytoalexins, a group of bioactive defense compounds, found in plants (Dixon
1986 ). The levels of these compounds may be undetectable in non-stimulated
plants.
While the variability and lack of reproducibility in medicinal plants has hindered
their widespread development as botanical drugs, the interest in plants as alternative
treatments has only increased with time. Many of the modern ailments are not
adequately remedied with conventional medicine. As patients become dissatisfied
with conventional treatments, there is increasing demand for alternative therapies.
Currently, the medicinal plant gaining the most renewed interest and demand to be
integrated into mainstream medicine isCannabisspp.
Cannabis has been used traditionally for thousands of years however its phar-
macological mode of action remained a mystery for most of history. The mystery
began to be revealed with the identification of the major psychoactive compound
found inCannabis sativa,D^9 -tetrahydrocannabinol (THC) (Gaoni and Mechoulam
1964 ). Later on, it was discovered that the psychotropic effects of THC were the
result of its binding to, and activation of, specific plasma membrane bound,
G-protein coupled receptors, the cannabinoid CB1 and CB2 receptors (Matsuda
et al. 1990 ). The existence of the cannabinoid receptors led to the discovery of
endogenous compounds capable of binding to and activating them. Known as
endocannabinoids, the two most studied are N-arachidonoylethanolamine (anan-
damine) and 2-arachidonolyglycerol (2-AG) (Mechoulam 2005 ). These endo-
cannabinoids, their associated cannabinoid receptors, and the proteins involved in
their synthesis and degradation constitute the endocannabinoids system (ECS) (Di
Marzo et al. 2004 ). The ECS is involved in many of the basic biological processes
including gastrointestinal, cardiovascular, and respiratory function (Di Marzo et al.
2004 ). While the CB1 receptor is expressed primarily in the central nervous system
and is responsible for Cannabis’psychoactivity, the CB2 receptor, expressed in
many peripheral areas of the body, is not associated with psychoactive effects but
rather is involved in many other important physiological responses including bone
formation (Ofek et al. 2006 ), inflammation (Gertsch et al. 2008 ), immune regulation
(Cabral and Griffin-Thomas 2009 ), and energy homeostasis (Bermudez-Silva et al.
2007 ).
Because the ECS is involved in such a wide array of distinct pathophysiologies,
it is a prominent target for the treatment of many disorders. Natural and synthetic
cannabinoids have demonstrated potential therapeutic activity in many areas
including pain relief (Anand et al. 2009 ), mental disorders (Bambico et al. 2007 ),
gastrointestinal and liver diseases (Izzo and Camilleri 2008 ), and inflammatory and
inflammation related diseases (Gertsch et al. 2008 ). However, in many cases, usage
of plant material produced a much greater therapeutic response than treatment with
individual cannabinoids (Whiting et al. 2015 ). This is likely due to a synergistic or


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