Use of phytocannabinoids and their analogs as negative allosteric modulators of the CB1 receptor

CBD analogs like H4-CBD and CBDP act as CB1 NAMs to reduce THC side effects while preserving its therapeutic benefits, addressing the scarcity of effective CB1 modulators for treating conditions such as obesity, drug abuse, pain, and CNS disorders.

WO2025171222A1 Publication Date: 2025-08-14UNIVERSITY OF MISSISSIPPI +1
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Patent Information

Application Number
PCT/US2025/014952
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-02-07
Filing Date
2025-02-07
Publication Date
2025-08-14

AI Technical Summary

Technical Problem

There is a scarcity of potent and selective negative allosteric modulators of the CB1 receptor that effectively mitigate the neuropsychiatric side effects of THC while preserving its therapeutic benefits for treating conditions like pain, anxiety, obesity, and neurodegenerative disorders.

Method used

The use of cannabidiol (CBD) analogs, such as H4-CBD and CBDP, as negative allosteric modulators (NAMs) that bind to specific sites on the CB1 receptor, reducing THC-induced side effects without impairing its therapeutic effects, combined with THC in pharmaceutical compositions.

Benefits of technology

H4-CBD and CBDP mitigate THC-induced memory impairment and other neurological side effects while maintaining the beneficial effects of THC, offering a more optimal pharmacological profile for treating conditions like obesity, drug abuse, pain, and CNS disorders.

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Abstract

In one aspect, the disclosure relates to the use of negative allosteric modulators (NAMs) of cannabinoid receptor 1 (CB1) and pharmaceutical compositions comprising the same in methods of treating or preventing diseases or disorders including substance abuse, anxiety, pain, obesity, cancers, neurodegenerative disorders, and central nervous system (CNS) disorders. In one aspect, the NAM can be selected from H4-CBD or CBDP. In some aspects, the pharmaceutical compositions additionally include Δ9-tetrahydrocannabinol (THC), and the NAMs of CB1 reduce or eliminate unwanted neurological side effects of THC while preserving its disease- and symptom-mitigating effects.
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