White matter integrity after cannabidiol administration for treatment resistant epilepsy.

OBJECTIVE: The effects of individual cannabinoids on white matter integrity are unclear. Human studies have shown white matter maturation alterations in regular recreational cannabis users with the magnitude of these effects dependent on the age of exposure. However, studies have yet to determine which phytocannabinoids are most responsible for these changes. In the current study, we analyzed the effects of pharmaceutical grade cannabidiol oral solution (CBD; Epidiolex® in the U.S.; Epidyolex® in the EU; 100 mg/mL oral solution) on white matter integrity using diffusion MRI in patients with treatment resistant epilepsy (TRE). METHODS: 15 patients with TRE underwent 3 T diffusion MRI prior to receiving CBD and then again approximately 12 weeks later while on a stable dose of CBD for at least two weeks. DTI analyzes were conducted using DSI Studio and tract-based spatial statistics (TBSS). RESULTS: DTI analysis using DSI Studio showed significant increases in fractional anisotropy (FA) in the right medial lemniscus (p = 0.03), right superior cerebellar peduncle (p = 0.03) and the pontine crossing tract (p = 0.04); decreased mean diffusivity (MD) in the left uncinate fasciculus (p = 0.02) and the middle cerebellar peduncle (p = 0.04); decreased axial diffusivity (AD) in the left superior cerebellar peduncle (p = 0.05), right anterior limb of the internal capsule (p = 0.03), and right posterior limb of the internal capsule (p = 0.02); and decreased radial diffusivity (RD) in the middle cerebellar peduncle (p = 0.03) and left uncinate fasiculus (p = 0.01). The follow-up ANCOVA also yielded significant results when controlling for covariates of CBD dosage, age, sex, change in seizure frequency, and scanner type: FA increased in the pontine crossing tract (p = 0.03); RD decreased in the middle cerebellar peduncle (p = 0.04) and left uncinate fasciculus (p = 0.04). Subsequent TBSS analysis controlling for the same variables yielded no significant white matter differences between groups. CONCLUSION: These findings indicate relatively minor short-term effects of highly-purified plant-derived CBD on white matter structural integrity in patients with TRE.

Absence of DAZ gene mutations in cases of non-obstructed azoospermia.

Sequenced-tagged site (STS) analysis of the Y chromosome long arm (Yq) of azoospermic males has identified a minimum common deleted region of several hundred kilobases in approximately 13% of cases. A candidate azoospermia gene, DAZ (deleted in azoospermia), has been isolated from this region. DAZ has also been shown to be absent in severely oligozoospermic males albeit at a much lower frequency. These data, although highly suggestive, do not constitute formal proof that DAZ actually plays a role in azoospermia, as no small intragenic deletions, rearrangements or point mutations in the gene have been found. In this study we report the screening of DNA from 168 azoospermic/oligospermic males for the presence of the DAZ gene. Deletions involving DAZ were detected in five out of 43 (11.6%) azoospermic males whereas none were found in the remaining 125 oligospermic patients. We present the genomic structure of the 5' end of the DAZ gene together with its sequence analysis in 30 non-obstructed azoospermic males. No mutations in DAZ were found in any of the patients sequenced. These data provide no formal proof that DAZ is AZF. Thus the possibility is still valid that another gene(s) mapping to the deletion interval may be responsible for, or contribute to, the observed phenotypes. Alternatively, if DAZ is AZF, they suggest that the most frequent cause of gene inactivation is via large deletions possibly mobilized by Y chromosome repetitive sequences.