A considerable number of human and animal studies indicate that Cannabidiol (CBD) exerts therapeutic effects in a wide range of health disorders. These include anxiety disorders, neuropathic pain, epilepsy, cancer treatment-related symptoms, and possibly schizophrenia, psychosis, depression and obsessive compulsive disorder.
Considering CBD’s general safety, it is somewhat surprising that it has not yet been marketed as a stand-alone drug (Sativex, which is available in Canada and some European countries, contains a 1:1 ration of THC and CBD). A reason for this might be due to its low potency, which requires that large doses be administered to achieve significant therapeutic effects. For instance, in human studies of anxiety, doses of 300 to 600 mg of CBD are needed to achieve effects comparable to those of 10 mg of diazepam (source).
In an attempt to overcome this hurdle, an international team of researchers from Israel and Brazil has been trying to create more potent molecules derived from CBD. The team focused on fluorination, a method employed by pharmacists worldwide to enhance endogenous and synthetic drugs, which is applied in nearly 20% of the new drugs released in the market. Using this method to add a fluorine atom to the “aromatic ring” of the CBD molecule, the researchers obtained a new and much more potent molecule (HUF-101). Their successful finding was published this July in the journal PLOS ONE.
After the chemical synthesis of HUF-101, different concentrations of the compound were tested in mice under four behavioral assays. These testrd for the presence of any protective effects against anxiety, depression, schizophrenia and compulsive behavior.
Overall, the experiment revealed strong protective effects of HUF-101 in the four assays. More importantly, when the data were compared to previous studies, it was obvious that similar effects to those of CBD were being achieved at much lower concentrations of HUF-101. In the anxiety and depression tests, comparable effects were observed at a tenth of the concentration; while in the schizophrenia and compulsive behavior tests, concentrations ranging from a twentieth to a third were holding the same effects.
In a subsequent manipulation, the researchers found that when they blocked CB1 or CB2 receptors, both CBD and the derivative HUF-101 lost their efficacy in preventing compulsive behavior. This suggests that an indirect activation of these receptors by both drugs was likely mediating the behavioral effect. The authors did not attempt to test what mechanisms were responsible for the remaining behaviors due to logistical limitations. Considering the many mechanisms of action known for CBD and the fact that none is likely to singlehandedly explain all the effects observed, such an endeavor would have been prohibitively long.
Several other issues remain to be tackled in future research, including the tracing of HUF-101 toxicity profile in different animal models, the study of its pharmacodynamic parameters, and assessing how well these effects generalize to other types of assays that measure similar aspects of behavior. Only after addressing these issues will any prospects of clinical human trials be feasible. For now, this new compound remains an interesting scientific finding with potential applications in the development of more effective cannabis-based medicines.