A Phase I/II clinical trial published today by the Journal of Paediatrics and Child Health has found that NTI164, a low-THC full-spectrum cannabis extract, can significantly improve the core symptoms associated with Rett syndrome (RTT), a rare neurodevelopmental disorder.
Conducted over 12 weeks, the open-label trial administered NTI164 to 11 girls between the ages of 5 and 16, each diagnosed with a pathogenic MECP2 gene variant.
The study observed statistically significant improvements across a range of key measures. Participants experienced better mental alertness, communication skills, attentiveness, eye contact, and reduced anxiety, as measured by the Clinical Global Impression-Improvement scale and other validated tools. Additional improvements were noted in breathing abnormalities, mood, repetitive facial movements, and overall quality of life. Caregivers also reported a reduction in their own burden.
Researchers believe the benefits may be due to NTI164’s anti-inflammatory and neuroprotective properties. Lab tests show that NTI164 can reduce microglial reactivity and the production of pro-inflammatory cytokines like TNF-α. This is particularly relevant for RTT, where immune dysfunction, oxidative stress, and neuroinflammation contribute to disease progression. Improvements in breath-holding—a common and distressing RTT symptom—may be linked to this anti-inflammatory action.
While the study did not include a placebo group and had a small sample size, the findings provide an early but promising foundation. A larger, placebo-controlled Phase II/III trial is in development in Australia and will incorporate RNA sequencing, proteomics, and cytokine analysis to explore NTI164’s mechanisms of action further.
Researchers conclude by saying:
RTT is associated with a range of complex clinical manifestations due in part to immune system dysregulation, aberrant cellular signalling, and chronic inflammation. This Phase I/II study of NTI164 in RTT provides an encouraging foundation for further studies in this population. The improvements observed in clinical outcomes and caregiver burden justify ongoing research and confirm NTI164 is a potential adjunct therapy for RTT.
