Cannabinoids and Cystic Fibrosis - International Association for ...

64 JOURNAL OF CANNABIS THERAPEUTICScreas and ileum (Freedman et al. 1999). Thus, further decreasing DHAlevels in cftr / mice worsened pathological manifestations, whileelevating DHA levels by oral supplementation corrected the lipid imbalanceand reversed the pathology of the affected organs. As a consequenceit has been postulated that the mutated CFTR gene product isresponsible for the lipid imbalance and the ensuing pathogenesis (Greener2000).Endocannabinoids and Cystic FibrosisIs it possible that the synthesis of endocannabinoids, being fatty acidderivatives, is also modulated by CFTR proteins? There are a number ofstriking parallels between the clinical manifestations of CF and the domainsof cannabinoid and endocannabinoid influence, including lack ofappetite, nausea, diarrhea, and lung disease. Low endocannabinoid levelscould explain the appearance of these symptoms. However, even inthe absence of a causative role, it is proposed here that by stimulatingthe cannabinoid system, some of the CF pathology symptoms may bealleviated. The potential for cannabinoids to enhance appetite, therebypossibly preventing malnutrition in CF has been described above. Below,a number of additional manifestations of CF and a possible therapeuticrole for cannabinoids are described (Figure 2).Antiemetic EffectsVomiting induced by coughing (Blecker et al. 2000) often exacerbatesthe development of malnutrition in cystic fibrosis. Antiemeticbenefits of THC have been demonstrated in its effective relief of chemotherapy-inducednausea and vomiting (Mechoulam et al., 1998b;Abrahamov et al. 1995). Therefore the antiemetic potential of cannabinoidswould be expected to contribute to appetite enhancement inducedby cannabinoids in CF patients.DiarrheaDiarrhea appears in CF as a result of inadequate digestion due to pancreaticinsufficiency (Rolles 1998). Cannabinoids inhibit intestinal motilityvia local CB 1 (Colombo et al. 1998; Tyler et al. 2000) and/or viaCB 2 (Fride 1995; Hanus et al. 1999) receptors. Therefore administrationof cannabinoids to CF patients may counteract diarrhea and therebyhelp prevent loss of nutrients.