Cannabinoids and Cystic Fibrosis: A Novel Approach to Etiology and Therapy

I finished the research paper, I wasn't able to get access to the full paper but quite a few key pages that made a great read. I have a much more thorough idea of how cannabis, more specifically cannabinoids, affect the body and how this in turn would greatly help alleviate the symptoms of Cystic Fibrosis and give me and others a better quality of life.

Here are a few key sections from the paper, which can be accessed by clicking my post title. I have highlighted main points with green text, for those looking for a quick overview.

Cannabinoids and Cystic Fibrosis:
A Novel Approach to Etiology and Therapy
Ester Fride

"Pulmonary dysfunction has long been considered the
primary cause for morbidity and mortality in CF (Pilewski and Frizell
1999), with malnutrition appearing as a compounding detrimental factor
(Borowitz 1996). More recently however, malnutrition is being recognized
as playing a primary role in disease progression (Borowitz
1996; Schoni and Casaulta-Aebischer 2000) possibly even being responsible
for lung pathology and infections (Yu et al., 2000).
(...)
Fatty Acid Balance
A fatty acid imbalance is observed in CF patients, including elevated
levels of arachidonic acid and reduced levels of DHA. (...) the low DHA levels
have been shown to play a fundamental role in the pathogenesis in the organs
affected by the CF disease: lungs, pancreas and ileum (Freedman et al. 1999).
Thus, further decreasing DHA levels in cftr-/- mice worsened pathological
manifestations, while elevating DHA levels by oral supplementation corrected
the lipid imbalance and reversed the pathology of the affected organs."

**This is where it gets interesting**

"Is it possible that the synthesis of endocannabinoids, being fatty acid
derivatives, is also modulated by CFTR proteins? There are a number of
striking parallels between the clinical manifestations of CF and the domains
of cannabinoid and endocannabinoid influence, including lack of
appetite, nausea, diarrhea, and lung disease. Low endocannabinoid levels
could explain the appearance of these symptoms. However, even in
the absence of a causative role, it is proposed here that by stimulating
the cannabinoid system, some of the CF pathology symptoms may be
alleviated."
(...)
Antiemetic Effects
Vomiting induced by coughing (Blecker et al. 2000) often exacerbates
the development of malnutrition in cystic fibrosis. Antiemetic
benefits of THC have been demonstrated in its effective relief of chemotherapy-
induced nausea and vomiting (Mechoulam et al., 1998b;
Abrahamov et al. 1995). Therefore the antiemetic potential of cannabinoids
would be expected to contribute to appetite enhancement induced
by cannabinoids in CF patients.

Diarrhea
Diarrhea appears in CF as a result of inadequate digestion due to pancreatic
insufficiency (Rolles 1998). Cannabinoids inhibit intestinal motility
via local CB1 (Colombo et al. 1998; Tyler et al. 2000) and/or via
CB2 (Fride 1995; Hanus et al. 1999) receptors. Therefore administration
of cannabinoids to CF patients may counteract diarrhea and thereby
help prevent loss of nutrients.

Inflammation
Most destruction of lung tissue in CF is now thought to be secondary
to a very aggressive neutrophilic inflammatory response (Konstan &
Berger 1997; Wagener et al. 1997). This ultimately leads to respiratory
failure. The antiinflammatory potential of cannabinoids is well documented
(Klein et al. 2000; Straus 2001) and is thought to occur by interference
with the arachidonic acid-eicosanoid synthetic pathways
(McPartland 2001). We have demonstrated in a mouse model of arachidonic
acid-induced ear inflammation that cannabinoids and endocannabinoids
are effective antiinflammatory agents acting via CB
receptors (Hanus et al. 1999; Fride et al. unpublished observations).
Since cannabinoid receptors are present in lungs (Calignano et al.
2000), THC may be of additional benefit for CF patients, by reducing
inflammatory processes in the lungs.

Lungs
It has been demonstrated recently that bronchodilating and cough-reducing
activity of endocannabinoids in irritated lungs are mediated by
local CB1 receptors (Calignano et al. 2000). Therefore cannabinoids
may also benefit CF patients by their bronchodilating and cough suppressing
effects.

Pain
CF patients suffer pain from a variety of sources (Ravilly et al. 1996)
including abdominal pain related to steatorrhea and malabsorption
(Zeltzer et al. 1996), chest pain due to impacted sputum, pleuritic involvement
with lung inflammation and infection, or chest wall pain
associated with developing kyphoscoliosis and decreased chest wall
mobility (Massie et al. 1998). Pain may also occur from gall bladder or
kidney stones or from osteoporosis (Haworth et al. 1999; Lambert
2000; Ravilly et al. 1996). Cannabinoids are analgesics effective in a
variety of conditions (Mechoulam et al. 1998b; Martin and Lichtman
1998), acting via cannabinoid receptors within as well as outside the
brain and spinal cord and suppressing both acute and chronic pain
(Pertwee 2001).
(...)
CONCLUSIONS
In this paper a novel therapeutic target for cannabis is proposed,
based on recent developments in research on cannabis on one hand, and
on research on cystic fibrosis on the other. Recent findings suggest that
the primary factors in the pathogenesis of CF includes fatty acid imbalance,
possibly leading to such major manifestations of CF as chronic
inflammation of the lungs and pancreatic disease (Greener 2000; Freedman
et al. 1999). In the final stages of the disease malnutrition accompanied
by a lack of appetite is frequently seen (Anthony et al. 1999;
Schoni and Casaulta-Aebischer 2000). Additional symptoms of the disease
may include pain due to a variety of sources (Ravilly et al. 1996),
diarrhea (Rolles 1998) and nausea (Blecker et al. 2000).
Intriguingly, the therapeutic effects of cannabinoids include the potential
to counteract each of these conditions. Thus appetite enhancement
(Beal et al. 1997) and a critical role in food ingestion (Fride et al.
2001), analgesic, antiemetic, antiinflammatory, inhibition of intestinal
motility and bronchodilating effects have been demonstrated (Calignano
et al. 2001; Colombo et al. 1998; Fride 1995; Mechoulam et al. 1998b;
Hanus et al. 1999; Tyler et al. 2000).
(...)
It is proposed here, that CFTR not only regulates fatty acid balance
but also endocannabinoid biosynthesis. Such mechanism predicts that
low levels of endocannabioids in CF patients and in cftr-/- mice will be
found, which could be responsible for many symptoms. It is hoped that
affirmative data will eventually lead to the use of cannabinoids at more
initial stages of cystic fibrosis (Figure 2)."

Hopefully you all found that as interesting as I did. This not only shows that cannabinoids would aid in malnutrition and eating habits, but also alleviates just about every other symptoms of CF.

Again, if you would like the link to the available portion of this research paper click on the title on this post. Don't forget to leave any comments/suggestions for future blog posts.

Breathe easy,
-Ryan