# Cannabinoid Therapies in Less-Common Disorders: Clinical Evidence and Formulation Strategies

## TL;DR

This review explores how cannabinoids may help treat rare disorders beyond their known uses, focusing on new clinical evidence and drug delivery methods.

## Contribution

The paper provides a critical synthesis of recent clinical evidence and formulation strategies for cannabinoids in less-common disorders.

## Key findings

- Cannabinoids show potential in treating rare conditions like refractory epilepsies and movement disorders.
- Advanced formulations like nanocarriers aim to improve bioavailability and patient response consistency.
- Negative outcomes in some trials highlight challenges in methodology and pharmacology.

## Abstract

Background/Objectives: Cannabinoids are increasingly recognised for their therapeutic potential beyond well-established indications such as chronic pain, multiple sclerosis, and specific epileptic syndromes. Recent advances have highlighted their possible role in less-common or orphan diseases, opening new avenues for pharmaceutical research and clinical application. Methods: This review provides a critical synthesis of the most recent evidence (2020–2025), available in PubMed and Scopus, regarding the use of cannabinoids in conditions including refractory epilepsies beyond Dravet and Lennox–Gastaut syndromes, movement disorders such as dystonia and Tourette syndrome, rare dermatological diseases like epidermolysis bullosa, and emerging data in Crohn’s disease. Results: Negative outcomes, such as those reported in Fragile X syndrome trials, are also discussed as instructive examples of methodological and pharmacological challenges. Particular attention is given to the optimisation of pharmaceutical formulations and advanced separation technologies, including oromucosal sprays, transdermal gels, and novel nanocarrier systems, which aim to overcome issues of bioavailability and variability in patient response. Finally, safety concerns, regulatory aspects, and the need for robust clinical trials are addressed. Conclusions: Overall, cannabinoids represent a promising yet underexplored therapeutic option in rare and complex disorders, warranting further investigation supported by innovative pharmaceutical approaches.