Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) Improves Symptoms of Rett Syndrome: An Open-Label Study.

Aim: The aim of this Phase I/II open-label study was to assess the safety and efficacy of NTI164, a novel full-spectrum medicinal cannabis plant extract 0.08% Δ-9-tetrahydrocannabinol (THC), in Rett syndrome (RTT).

Methods: Eleven female participants (5-16 years) with a pathogenic variant in the MECP2 gene were recruited to this study, receiving NTI164 twice daily for 12 weeks. The primary outcome measure was the Clinical Global Impression-Improvement (CGI-I) Scale, with secondary outcomes measured using the CGI-Severity (CGI-S), RTT Behaviour Questionnaire (RSBQ), RTT-Symptom Index Score (RTT-SIS), RTT-Domain-Specific Concerns-Visual-Analog Scale (RTT-DSC-VAS), Impact of Childhood Neurological Disability/Quality of Life (ICND+QoL), and RTT-Caregiver Burden Inventory (RTT-CBI). Paired-samples t-test was used to assess significance between baseline and Week 12.

Results: Improvements were seen in the total CGI-I score (p = 0.028), with improvements in communication skills (p = 0.003), mental alertness (p = 0.033), socialisation/eye contact (p = 0.0004), attentiveness (p = 0.001), and anxiety (p = 0.004). CGI-S also demonstrated better outcomes after NTI164 administration (p = 0.008). RSBQ showed improvements in total score (p = 0.0005), general mood (p = 0.0003), breathing problems (p = 0.041), repetitive face movements (p = 0.004), and fear/anxiety (p = 0.006). RTT-DSC-VAS showed positive developments in abilities to communicate choices (p = 0.041). ICND total score was improved (p = 0.003), as well as cognition (p = 0.027) and Quality of Life (p = 0.0002). Total score on the RTT-CBI was improved (p = 0.006).

Conclusion: NTI164 demonstrated safety and improved some clinical and functional outcomes in RTT. These improvements justify ongoing research into NTI164, which may be a potential adjunct therapy in RTT.