Cannabinoids in rehabilitation medicine: From controversy to clinical potential

For many years, cannabinoids have been regarded less as a scientific therapeutic option and more within the context of social stigma, political debate, and legal restrictions. However, contemporary neuroscience and clinical research increasingly indicate that this perspective is gradually changing.^{[1, 2]} Today, the central question in rehabilitation medicine is no longer whether cannabinoids should be discussed, but rather how these agents can be integrated in a safe, rational, and evidence-based manner to support functional recovery in chronic neurological conditions requiring long-term rehabilitation, such as multiple sclerosis (MS), spinal cord injury, stroke, cerebral palsy, and traumatic brain injury (TBI). The success of rehabilitation is not defined solely by pain reduction but by improvements in mobility, activities of daily living, social participation, and overall quality of life. Two key considerations emerge in this context. First, whether cannabinoids can support patients’ engagement in rehabilitation beyond providing symptomatic relief warrants direct investigation. Second, this potential role must be weighed against current uncertainties in clinical practice and important safety concerns.

At the core of this emerging approach lies the endocannabinoid system (ECS), which functions as a neuromodulatory bridge between the central nervous system, peripheral nervous system, and immune system. The ECS regulates key processes relevant to rehabilitation, including pain perception, inflammation, motor control, emotional balance, sleep, and neuroplasticity.^{[3, 4]} In particular, cannabinoid receptor type 1 (CB1), distributed throughout the basal ganglia, cerebellum, cortex, and spinal cord, plays a key role in mechanisms underlying spasticity and neuropathic pain. In contrast, cannabinoid receptor type 2 (CB2) is associated with anti-inflammatory effects and neuroimmune modulation, suggesting a potential neuroprotective role.^{[4, 5, 6, 7]} This biological framework helps explain the increasing interest in cannabinoids within rehabilitation practice.

This interest largely stems from the limited efficacy of conventional treatments for refractory neuropathic pain and spasticity. In MS and spinal cord injury, pain and increased muscle tone do more than reduce quality of life; they can also limit patients’ engagement in rehabilitation.^{[8, 9]} This concept is consistent with a facilitator model: not a cure, but the removal of an obstacle. Indirect support for this view comes from clinical observations in MS, although rehabilitation engagement itself has not yet been used as an outcome measure. Preparations containing a combination of tetrahydrocannabinol and cannabidiol have been reported to reduce spasticity and its associated symptoms, whereas the effect on formal disability measures such as the Expanded Disability Status Scale is small and of uncertain clinical relevance.^{[10, 11, 12, 13]}

One of the most compelling developments in neurorehabilitation is the potential synergy between cannabinoids and neuroplasticity-based rehabilitation technologies. Robot-assisted gait training (e.g., Lokomat) and task-oriented rehabilitation approaches aim to promote cortical reorganization. Some neurophysiological studies in patients with MS suggest that cannabinoids may modulate cortical excitability and plasticity, a mechanism potentially relevant to motor learning.^[14] A non-randomised trial coupling nabiximols with robot-assisted gait training reported greater gains in functional independence and gait performance.^[2] However, definitive confirmation from randomised trials is still awaited. If such future studies demonstrate meaningful synergistic effects, cannabinoids may indeed be redefined not only as symptomatic agents but as active neuromodulatory tools within rehabilitation strategies; at present, however, this remains a hypothesis rather than an established finding (Figure 1). TBI rehabilitation represents another important area of expanding cannabinoid research. Preclinical studies demonstrate that CB2 receptor activation reduces neuroinflammation in animal models of TBI, potentially limiting white matter damage.^{[5, 6]} While these findings are encouraging, clinical translation of neuroprotective effects to human TBI rehabilitation remains limited. Although current evidence is primarily derived from preclinical studies, cannabinoids warrant further investigation as potential biological modulators of neuroplasticity and responses to rehabilitation interventions.

Figure 1.

Proposed framework: cannabinoids as potential rehabilitation facilitators in neurological conditions. Some mechanisms and outcomes await further confirmation.

Despite these promising developments, clinical enthusiasm must be balanced with scientific caution. The integration of cannabinoids into rehabilitation practice remains challenged by significant methodological and clinical limitations. The heterogeneity of existing studies, small sample sizes, short follow-up periods, and lack of standardization hinder the development of robust clinical protocols. Standardized dosing regimens are still lacking, and most formulations require individualized titration. Furthermore, the impact of side effects such as euphoria, sedation, and dizziness on rehabilitation outcomes has not been sufficiently investigated. Limited knowledge among clinical experts regarding both the therapeutic benefits and potential adverse effects contributes to hesitancy in prescribing cannabinoids. While global advancements in cannabinoid research are evident, their clinical application remains heavily dependent on regional regulations. In the context of Türkiye, a legal framework for the controlled medical use of cannabinoid-containing products has been established; however, their integration into routine clinical practice remains limited by the absence of standardized guidelines and large-scale studies.^[15]

In conclusion, cannabinoids should neither be regarded as a miraculous therapy nor dismissed due to historical biases. Current evidence supports their adjunctive role, particularly in carefully selected patients with MS-related spasticity and refractory neuropathic pain. Their potential effects on neuroplasticity, neuroinflammation, and rehabilitation engagement are promising, although not yet sufficiently substantiated. Future research should focus on standardized dosing protocols, long-term functional outcomes, and patient selection criteria in neurorehabilitation populations. Large multicenter randomized trials are needed to determine whether cannabinoids can meaningfully enhance rehabilitation participation and functional independence beyond symptomatic relief.

Declaration of Generative AI Use: Artificial intelligence tools were used during the preparation of this editorial article to assist with language editing and figure preparation.