Non Pain Uses of Medical Marijuana in Rehabilitation

Overview and Description

Therapeutic cannabinoids first entered U.S. clinical use in 1985, when the synthetic Δ9-tetrahydrocannabinol capsule dronabinol was approved for chemotherapy-induced nausea and vomiting.¹ In 1992 the indication was expanded to cover anorexia with weight loss in HIV/AIDS,² and clinicians soon adopted the drug off-label for cancer-related cachexia.³ Nabilone, another synthetic analogue, received initial clearance in 1985 and was reintroduced to the U.S. market in 2006 for refractory CINV.⁴ These early synthetics paved the way for plant-derived agents such as nabiximols and purified cannabidiol, which are now studied for spasticity and are licensed for certain pediatric epilepsies.⁵

Against this historical backdrop, medical marijuana refers to the use of Cannabis sativa or its synthetic analogs to treat specific medical symptoms through cannabinoid-based modulation of neurologic, inflammatory, and metabolic pathways.⁶ The two most studied compounds are delta-9-tetrahydrocannabinol (THC), a partial agonist of CB1 receptors with psychoactive effects, and cannabidiol (CBD), a non-euphoric compound that acts on 5-HT1A, TRPV1, and other targets.^6,7

In rehabilitation medicine, medical marijuana is considered for symptomatic management rather than disease modification. Key non-pain indications include: spasticity in upper motor neuron syndromes (especially multiple sclerosis [MS] and spinal cord injury [SCI]); agitation and behavioral dysregulation after traumatic brain injury (TBI); sleep disturbances in neurorehabilitation populations; appetite stimulation in catabolic states such as cancer or AIDS; and anxiety or post-traumatic stress disorder (PTSD)-related symptoms, particularly in veterans.^8-10

The therapeutic rationale is rooted in the endocannabinoid system’s role in modulating neurotransmission, muscle tone, sleep-wake cycles, and appetite regulation.^6,7 CB1 receptors are densely located in the brain and spinal cord; their activation by THC inhibits presynaptic glutamate release, potentially reducing spasticity and hyperexcitability.^6,7 In hypothalamic and limbic circuits, cannabinoids influence appetite, sleep latency, anxiety, and arousal modulation.⁷ CBD, which lacks intoxicating effects, may offer anxiolytic and sedative properties without impairing cognition.^6,9

Medical marijuana is most commonly applied in the subacute and chronic phases of disease. For example, patients with chronic MS- or SCI-related spasticity who fail conventional antispasticity agents may benefit from adjunctive cannabinoids.¹¹ In TBI, agitation and insomnia are late complications in which cannabis has been explored anecdotally.¹² Cannabis is rarely used in acute rehabilitation due to insufficient safety data and risk of cognitive blunting. In pre-terminal or palliative phases, such as advanced cancer or neurodegenerative disease, it may help relieve anorexia, anxiety, and sleep disruption.^3,9,10

Although symptom relief can improve function and quality of life, there is no current evidence that medical marijuana alters disease progression or long-term prognosis in neurorehabilitation populations.⁸ Limited preclinical work suggests possible neuroprotective effects, but human trials—such as Dexanabinol in severe TBI—have failed to demonstrate benefit.^7,13 Cannabis has therefore no proven disease-modifying effects in neurorehabilitation populations.

Relevance to Clinical Practice

Specific features of clinical application

The most established indication for medical marijuana in rehabilitation is spasticity associated with MS.^8,11 Randomized controlled trials (RCTs) and meta-analyses have shown that THC:CBD oromucosal sprays (e.g., nabiximols – not Food and Drug Administration [FDA]-approved in U.S.) and oral THC formulations improve patient-reported spasticity severity more than placebo.^8,11 The National Academies of Sciences, Engineering, and Medicine (NASEM) categorized this evidence as “substantial” for subjective improvement, though only “limited” for clinician-rated scales like the Modified Ashworth Scale.⁸ Patient outcomes often include decreased muscle stiffness, improved mobility, and better sleep continuity.

In SCI, the evidence is more limited.⁸ Small trials and survey studies suggest potential benefit in reducing spasm frequency, but high-quality RCTs are lacking.^8,11 As such, cannabinoids are used off-label in SCI spasticity, typically after standard antispasticity medications fail or are poorly tolerated.

For TBI-related agitation and behavioral dysregulation, evidence is sparse and largely anecdotal.¹² A few case reports describe marked behavioral improvements in refractory cases with THC:CBD formulations, but no controlled trials exist.¹² Caution is advised due to cannabis’ potential cognitive side effects, particularly in populations with existing impairments.

Cannabinoid-related sleep benefits have been documented in patients with MS and PTSD, with modest improvements in sleep latency and quality.^8,10 Synthetic THC analogs like nabilone have shown efficacy in reducing nightmares in veterans with PTSD.¹⁰

Cannabis is also used for appetite stimulation in catabolic states (e.g., cancer or AIDS), although data are inconsistent.³ Dronabinol improved appetite in AIDS-related cachexia, but consistent weight gain in neurorehabilitation cohorts is unproven.³

Utilization rates vary by region, access, and diagnosis, with higher uptake in states where medical marijuana is legal.¹⁴

Table 1. Cannabinoid Therapies in Rehabilitation: FDA Status and Supporting Evidence

† Reflects current U.S. labeling (July 2025). Products in “Off-label” column lack FDA approval for these indications.
* AAN 2011 evidence levels:
A = established as effective (≥ 2 Class I or convincing meta-analysis)
B = probably effective (1 Class I or ≥ 2 Class II)
C = possibly effective (≥ 1 Class II or ≥ 2 Class III)
U = inadequate or conflicting data

Specific diagnostic criteria that justify use

There are no formal diagnostic tests that mandate medical marijuana use; rather, it is typically justified by the presence of a well-characterized condition, refractory symptoms, and failure or intolerance of standard therapies. The strongest clinical justification exists in MS-associated spasticity. Patients often present with sustained muscle stiffness, spasms, or clonus, corroborated by elevated scores on the Modified Ashworth Scale or Spasm Frequency Scale.^8,11 When conventional antispasticity medications such as baclofen or tizanidine prove insufficient, cannabinoids may be considered as second- or third-line adjuncts.^8,11

In spinal cord injury, similar criteria apply. Though evidence is less robust, cannabinoids may be trialed in patients with chronic spasticity that limits functional independence (e.g., transfers, hygiene) and persists despite physical therapy and pharmacologic agents.^8,11 In practice, patient-reported severity and interference with daily activities guide decision-making more than quantitative thresholds.

For TBI-related agitation, justification typically stems from persistent behavioral dysregulation—such as impulsivity, aggression, or sleep-wake cycle inversion—that has failed to respond to standard psychotropic agents (e.g., antipsychotics, mood stabilizers).¹² Clinicians should document attempts with conventional therapies, neuropsychiatric consults, and behavioral interventions before considering cannabinoids as off-label adjuncts. In such cases, target symptoms—not TBI itself—are the clinical rationale.

In PTSD, especially in veteran populations, symptoms such as nightmares, hyperarousal, and severe insomnia may persist despite SSRIs, prazosin, or trauma-focused psychotherapy.¹⁰ In states where PTSD is a qualifying condition, use of THC analogs like nabilone has been justified when these symptoms substantially impair function and resist guideline-based care.¹⁰

Appetite loss and cachexia due to conditions like advanced cancer or AIDS are also recognized indications.^3,8 Documented weight loss >10%, BMI <18, or sarcopenia despite use of standard appetite stimulants (e.g., megestrol, mirtazapine) can justify a trial of dronabinol or dispensary-based THC products.^3,8

Other factors that may influence clinical decision-making

Clinicians may support medical marijuana use when the underlying diagnosis is clearly established, the symptom is severe and functionally impairing, and conventional management has proven inadequate or contraindicated.

The decision to initiate medical marijuana in rehabilitation often extends beyond clinical severity. Legal status is a major determinant: although medical marijuana is legalized in most U.S. states, it remains federally classified as a Schedule I substance, restricting use in federal institutions (e.g., Veterans Affairs hospitals) and complicating access in skilled nursing facilities or inpatient rehabilitation units.¹⁴ Physician certification requirements also vary, and not all rehabilitation physicians are registered providers.

Cost and insurance coverage pose additional barriers. Dispensary-based cannabis products are rarely reimbursed, and patients often face out-of-pocket expenses ranging from hundreds to thousands of dollars annually.¹⁴ In contrast, synthetic cannabinoids like dronabinol or nabilone may be partially covered when prescribed for FDA-approved indications.

Patient factors—including health literacy, substance use history, and cognitive status—strongly influence appropriateness. For example, patients with cognitive impairment (TBI, stroke) may be at higher risk for adverse psychoactive effects.¹¹ Similarly, those with active psychosis, a history of schizophrenia, or substance use disorders require cautious risk-benefit analysis and close monitoring.¹¹

Social and occupational considerations are also relevant. Patients in safety-sensitive professions (e.g., transportation, construction) may face employment consequences if drug testing reveals THC, even when use is legal and medically indicated.¹⁴ Family or caregiver attitudes toward cannabis, particularly in older or dependent populations, may influence adherence and acceptance.¹⁴

Finally, formulation and delivery route are environmental considerations. In smoke-free housing or assisted living settings, inhaled cannabis may not be feasible, requiring adaptation to tinctures or capsules.

A comprehensive, individualized assessment—including medical, legal, and psychosocial context—is critical before recommending medical marijuana.

Formal guidelines for using the assessment/treatment procedure(s); Translation into practice

Formal clinical guidelines for medical marijuana use in rehabilitation are limited, though several organizations offer position statements. The American Academy of Neurology acknowledges moderate evidence for cannabinoids in MS-related spasticity but stops short of endorsing widespread use, citing safety concerns and the need for further research.¹¹ The NASEM similarly concluded that substantial evidence supports cannabinoids for patient-reported MS spasticity, while other rehab-relevant uses—such as SCI spasticity, PTSD symptoms, or cachexia—have insufficient or limited evidence.⁸

The American Academy of PM&R has not issued formal treatment guidelines but promotes clinician awareness, individualized risk-benefit assessment, and patient-centered care in jurisdictions where cannabis is legal.

Nabiximols (a THC:CBD oromucosal spray) is approved in the UK and Canada as an add-on therapy for moderate-to-severe MS spasticity unresponsive to first-line medications; it remains unapproved by FDA in the U.S.^18,19 Translation into practice includes defining treatment goals, selecting appropriate formulations (e.g., THC:CBD ratios), and documenting objective and subjective outcomes. Short-term therapeutic trials (e.g., 4 weeks) with reassessment are recommended.¹⁸ “Start low, go slow” titration, non-inhalational delivery methods, and shared decision-making improve both safety and adherence.²⁰

Cutting Edge/Unique Concepts/Emerging Issues

Research into non-intoxicating and precision-targeted cannabinoids is a growing frontier in rehabilitation. High-CBD, low-THC formulations are being developed to maximize symptom relief (e.g., spasticity, anxiety) while minimizing psychoactive effects.⁶ Early studies suggest that minor cannabinoids (e.g., cannabigerol, cannabinol) and terpenes may contribute therapeutic effects via the “entourage effect,” though clinical data remain sparse.⁷

Neuroprotective applications are also under investigation. Preclinical models suggest cannabinoids may reduce neuroinflammation and oxidative stress after TBI or stroke, but human trials (e.g., dexanabinol in severe TBI) have thus far failed to demonstrate efficacy.^8,13

In pediatric neurorehabilitation, interest in cannabinoids for conditions such as refractory spasticity or autism-related agitation is rising, yet ethical concerns and limited data restrict clinical use.²¹ Meanwhile, federal rescheduling efforts—such as moving cannabis from Schedule I to Schedule III—could dramatically expand research access, standardization, and insurance coverage, thereby reshaping clinical use patterns in rehabilitation medicine.

Gaps in Knowledge/Evidence Base

Despite growing clinical interest, medical marijuana remains under-researched in most rehabilitation contexts. High-quality RCTs are lacking for SCI spasticity, TBI-related behavioral symptoms, stroke-related spasticity, and PTSD in neurologically impaired populations.⁸ Most available data rely on observational studies, case reports, or off-label use, limiting generalizability and guideline development.⁸

The optimal dosing, cannabinoid ratio, and route of administration for specific symptoms (e.g., nocturnal spasticity vs. daytime agitation) remain undefined.⁷ While some early studies suggest anxiolytic effects of CBD in non-neurorehabilitation contexts, its role in neurobehavioral symptom management without THC remains unclear.

Long term safety, especially in populations with baseline cognitive impairment (e.g., TBI, dementia), has not been adequately studied.¹¹ Questions also remain about potential drug interactions, functional impact during active rehabilitation, and effects on neuroplasticity or recovery trajectories.

Federally restricted access, variability in cannabis product composition, and stigma continue to hamper large-scale research.⁸

References

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3. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management. 1995;10:89-97. doi:10.1016/0885-3924(94)00117-4
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9. Hurd YL, Spriggs S, Alishayev J, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial. American Journal of Psychiatry. 2019;176:911-922. doi:10.1176/appi.ajp.2019.18101191
10. Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015/1// 2015;51:585-588. doi:10.1016/j.psyneuen.2014.11.002
11. Koppel BS, Brust JCM, Fife T, et al. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology: Lippincott Williams and Wilkins; 2014. p. 1556-1563.
12. Hergert DC, Mayer AR, Hutchinson K, Sadek JR, Quinn DK. Medical Cannabis Reduced Agitation in Acquired Brain Injury: A Case Study. Psychosomatics. 2020/11// 2020;61:819-824. doi:10.1016/j.psym.2020.01.006
13. Maas AIR, Murray G, Henney H, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: Results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurology. 2006/1// 2006;5:38-45. doi:10.1016/S1474-4422(05)70253-2
14. Monte AA, Zane RD, Heard KJ. The implications of marijuana legalization in Colorado. JAMA – Journal of the American Medical Association: American Medical Association; 2015. p. 241-242.
15. Frytak S, Moertel CG, O’Fallon JR, et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo. Ann Intern Med. Dec 1979;91(6):825-30. doi:10.7326/0003-4819-91-6-825
16. Tramèr MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. Jul 07 2001;323(7303):16-21. doi:10.1136/bmj.323.7303.16
17. Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. Mar 17 2018;391(10125):1085-1096. doi:10.1016/S0140-6736(18)30136-3
18. (NICE) NIfHaCE. Cannabis-based medicinal products: NICE Guideline NG144. 2019. Accessed April 24, 2025. https://www.nice.org.uk/guidance/ng144/chapter/Recommendations#spasticity
19. Pharmaceuticals G. Sativex® Product Monograph. 2012. Accessed April 24, 2025. https://pdf.hres.ca/dpd_pm/00016162.PDF
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21. Aran A, Cassuto H, Lubotzky A, Wattad N, Hazan E. Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study. J Autism Dev Disord. Mar 2019;49(3):1284-1288. doi:10.1007/s10803-018-3808-2

Author Disclosure

Shawn McGargill, MD
Nothing to Disclose

Zachary Gulergun, MD
Nothing to Disclose

Nikhil Gopal, MBBS
Nothing to Disclose