What does the research say?
Muscle stiffness happens when damaged nerve pathways can no longer hold the muscles back well enough. That is why it is common not only in MS but also in spinal cord injury, stroke, cerebral palsy and ALS. Because cannabinoids can reduce excitatory signaling between nerve cells, they are thought to possibly help muscle stiffness, and pain and muscle stiffness are among the main reasons people with spinal cord injury use cannabis. However, most research has been done in MS: the 2019 evidence review by NICE, England's national health body, found only 3 controlled studies for causes other than MS and did not recommend cannabinoid products for these causes. We have a separate page on results in MS spasticity; this page covers the other causes and looks at each condition separately.
Spinal cord injury: Studies in this area are small. In a crossover study of 12 men in Canada (each participant took both the medicine and an inactive medicine, or placebo, in turn), nabilone, a synthetic THC-like medicine (0.5–1 mg a day, 4 weeks), reduced the stiffness the doctor measured in the most affected muscle more than placebo did; there was no difference in the spasm frequency and stiffness reported by patients. In a study of 25 patients in Switzerland, most of which was open-label (everyone knew what they were taking), THC by mouth cut the muscle stiffness score roughly in half; but the part in which people were randomly assigned to groups included only 13 people, the comparison for that part was not given in the abstract, and some people stopped because of increased pain and psychological side effects. In a crossover study of 16 patients in Thailand, an oil containing equal amounts of THC and CBD (about 12 mg THC a day, 4 weeks) did not change the muscle stiffness measured by the doctor; the stiffness patients rated themselves went down slightly. In a study of 116 patients with nerve pain due to spinal cord injury, run by the maker of a mouth spray containing THC and CBD and with results available only in the ClinicalTrials.gov record, there was no difference from placebo in muscle stiffness and spasms, which were measured as additional outcomes. In a study in Denmark of 134 people (most with MS), 15 of whom had spinal cord injury, pure CBD, THC and the two combined also did not reduce muscle stiffness more than placebo; no separate result was given for those with spinal cord injury.
Muscle stiffness after stroke: There is only one controlled study on this. In a crossover study in Italy of 41 patients who had had a stroke (34 completed it), a mouth spray containing roughly equal amounts of THC and CBD (median 9 sprays a day, 4 weeks) did not change the muscle stiffness patients felt, the stiffness measured by the doctor, or an electrical measurement of the muscle reflex differently from placebo; there was also no difference in pain, sleep or number of spasms. Most patients were taking blood pressure medicine; during the study there was no meaningful change in blood pressure or pulse, and no new stroke or cardiovascular event. However, the study was small, and people at very high cardiovascular risk and smokers were not included.
Cerebral palsy and brain injury in children: In two well-designed, placebo-controlled studies, muscle stiffness did not drop clearly compared with an inactive medicine. In a 12-week study of 72 children and teenagers aged 8–18, a mouth spray containing THC and CBD did not reduce muscle stiffness, as rated by caregivers, more than placebo; there was also no difference in sleep, pain or quality of life. Three cases of hallucination (seeing or hearing things that are not really there) were reported in the spray group, and one of them involved a suicide attempt. In a 6-week study in Slovenia of 53 people aged 5–25 with severe cerebral palsy, a full-spectrum cannabis oil containing 10 times more CBD than THC did not change muscle stiffness, motor skills or quality of life differently from placebo; those taking the oil were clearly sleepier. In Israel, two different CBD-rich oils (CBD:THC 20:1 and 6:1) were compared for 5 months in 25 children with complex movement disorders; improvement in muscle stiffness, sleep and pain was reported in both groups, but because there was no placebo group, it is not known how much of this came from the oil; seizures increased in 2 children. All of these products contained THC; there is no controlled study of pure CBD oil for muscle stiffness in children.
ALS and motor neuron diseases: In ALS, there are only two controlled treatment studies of cannabinoids with published results; both used THC-containing products. The only placebo-controlled study for muscle stiffness comes from Italy. In a 6-week study of 60 patients with ALS or primary lateral sclerosis, a mouth spray containing THC and CBD (an average of 8 sprays a day) reduced muscle stiffness as measured by the doctor by a small but significant margin compared with placebo; there were no serious side effects, but side effects were more common in the spray group. This was an early (phase 2) study; the result has not yet been confirmed in a larger study. For the painful muscle cramps common in ALS, THC by mouth (5 mg 2 times a day) did not change cramp severity or number differently from placebo in a study of 27 patients; in the same study, there was also no difference in measures of quality of life, sleep, appetite and depression; Cochrane reviews also concluded that THC is probably ineffective for cramps (moderate certainty of evidence). In a 2022 meta-analysis combining these two controlled studies, no improvement with cannabinoids was seen on ALS-specific overall scales (daily functioning and quality of life); the pooled result was not significant and, according to the authors, leaned slightly toward placebo. Because the evidence rests on two small, short studies, it is weak. In Australia, the result of a 17-person study of a CBD-rich oil (50 mg CBD per mL, less than 2 mg THC) looking at its effect on ALS progression had not been published as of October 2026 (the study's registry entry has not been updated since April 2023). So there is no controlled study with published results that has examined the effect of cannabinoids on the course of ALS. In a study reviewing the records of 344 ALS patients, those using medical marijuana had less pain, loss of appetite and anxiety in the short term, but there was no difference in muscle stiffness or insomnia; the disease progressed faster in users, but these patients' symptoms were already more severe before they started marijuana (this is an association; cause and effect was not shown).
Other studies and reviews: In 13 patients with lasting muscle stiffness due to brain or spinal cord damage (upper motor neuron syndrome; mixed causes, at least one with MS), nabilone (1 mg a day, 4 weeks) reduced pain related to muscle stiffness but did not change muscle stiffness, motor skills or activities of daily living. There are also two real-world studies without a comparison group. In Spain, in people with spinal cord injury and treatment-resistant muscle stiffness, muscle stiffness decreased from baseline in the first two months with the mouth spray; spasm frequency, nerve pain and sleep did not change (the number of people is not in the abstract; the study was supported by a drug company). In the records of 63 severely ill children in hospital in Germany, the share in whom doctors, nurses or families subjectively saw at least moderate improvement in muscle stiffness with synthetic THC was 47.6%, according to the authors; but in the standard 24-hour records of children started on it in the unit, restlessness, seizures and need for extra medicine did not decrease, and 3 children had serious side effects such as suppressed breathing. These designs cannot separate out the effect of expectation and of natural improvement. A 2019 review focused on children wrote that evidence for causes other than MS is limited and that studies in children are of low quality; a 2021 review in spinal cord injury wrote that the size and clinical importance of the effect are uncertain; and a 2023 review in children with cerebral palsy wrote that it found only three studies and that muscle stiffness results were inconsistent.
Strength of evidence: ○○○○ Insufficient evidence. Finding: Not studied enough. What does this mean?
Ongoing research on this topic
No ongoing CBD trial on this topic appears on ClinicalTrials.gov right now. All ongoing trials
Possible side effects and drug interactions
Because almost all studies on this page involved THC, most of the side effects seen were also due to THC. In adults, the most common were dizziness, sleepiness, weakness and nausea; in the ALS study, the chance of side effects in the spray group was about three times higher than with placebo, but there were no serious side effects. Among stroke patients, complaints that led to stopping the medicine included a feeling that movements were getting worse, palpitations, sleepiness and confusion. In children, three cases of hallucination (one with a suicide attempt) were reported with the spray containing THC and CBD, marked sleepiness with the oil containing 10 times more CBD than THC, and increased seizures in two children with CBD-rich oils. Among hospitalized children with severe neurological disease, three children had serious side effects such as suppressed breathing with synthetic THC.
Muscle stiffness sometimes helps with standing and moving from place to place; according to the product information for the spray containing THC and CBD, the risk of falls may increase in people without enough muscle strength once stiffness goes down. People with these conditions often also take muscle relaxants, seizure medicines and sleep medicines; THC-containing products can add to sleepiness and fall risk when used with them. CBD can slow the breakdown of some medicines in the body; this matters if more than one medicine is being used.
Interactions with medicines used for this condition
Interactions reported for these medicines in peer-reviewed publications and official prescribing information. A medicine that is not listed can still interact with CBD; tell your doctor about every medicine you take.
| Medicine | Importance | Warning | Source |
|---|---|---|---|
| Diazepam (Diazem, Nervium), Other benzodiazepines (lorazepam, etc.) | Caution | Benzodiazepines, sleep medicines and sedatives: Drowsiness and sedation may increase together with CBD. Talk to your doctor before using them together. | DailyMed Epidiolex label 7.4, EMA Epidyolex SmPC 4.4 |
| Tizanidine | Caution | Theophylline, tizanidine: CBD can raise the blood levels of these medicines; the prescribing information for approved CBD recommends considering a dose reduction. The tizanidine prescribing information itself asks that it not be combined with weak CYP1A2 inhibitors such as CBD; low blood pressure, a slowed heart rate or excessive drowsiness may occur. Tell your doctor. | FDA Epidiolex label §7.2 (05/2026), EMA Epidyolex SmPC 4.5, PMID 33951339, Tizanidine prescribing information §7.2, dailymed.nlm.nih.gov |
| Other epilepsy medicines | Caution | Other epilepsy medicines: With epilepsy medicines, CBD can change the blood levels of some of them. Your doctor may monitor your drug levels and side effects. | PMID 28782097, PMID 33541771, PMID 37593907, PMID 31211851, PMID 30791225 |
| Diazepam (Diazem, Nervium) | Information | Diazepam: No study has measured diazepam blood levels with CBD. One of the enzymes that break down diazepam (CYP2C19) is slowed by CBD: approved CBD raised the blood level of a clobazam breakdown product, which is broken down by this enzyme, about 3-fold. In epilepsy, the safety and effect of diazepam used as a nasal spray during a seizure did not change with CBD. Drowsiness may increase when they are taken together; tell your doctor. | FDA Epidiolex label §12.3 (05/2026), PMID 37313955, PMID 37210793, Diazepam prescribing information (Clinical pharmacology), dailymed.nlm.nih.gov |
To check interactions with the medicines you take: CBD drug interaction checker.
How was CBD used in studies?
The doses used in the studies were as follows (study doses; not a personal recommendation): in the mouth spray containing THC and CBD, each spray delivered 2.7 mg THC and 2.5 mg CBD; the dose was increased gradually over about two weeks (9 weeks in the children's study), and most studies allowed at most 12 sprays a day (48 in the maker's spinal cord injury study; an average of 8 sprays was used in the ALS study and a median of 9 in the stroke study). In spinal cord injury, THC by mouth was used at an average of 31 mg a day, the oil containing equal THC and CBD at about 12 mg THC a day, and the THC-like nabilone at 0.5–1 mg a day; for ALS cramps, THC was given as 5 mg 2 times a day. In the only multi-arm study that tested pure CBD (most patients had MS), the dose was at most 45 mg a day. In children's studies, the dose was adjusted gradually by body weight; in severely ill hospitalized children, synthetic THC was calculated in milligrams per kilogram per day, and the effective dose averaged 0.21 mg per kilogram a day (those started in the unit) and 0.48 mg (those already using it) (study dose; not a personal recommendation). The controlled studies lasted between 2 weeks and 5 months.
Study details (for health professionals)
Pure CBD has not been tested on its own for muscle stiffness (spasticity) from causes other than MS: in the only controlled study that tested pure CBD as a separate group (Denmark, 134 people, at most 45 mg a day), 119 patients had MS and 15 had spinal cord injury; muscle stiffness was no different from placebo, and no separate result was given for those with spinal cord injury. Nearly all the evidence concerns THC-containing products or THC-like medicines, and it varies by cause. In ALS and primary lateral sclerosis, THC:CBD mouth spray slightly reduced muscle stiffness as measured by the doctor over 6 weeks in a 60-person phase 2 study (difference −0.32; 95% CI −0.57 to −0.07), but side effects were about three times as common in the spray group; for cramps in ALS, THC by mouth (27 people) was ineffective, and Cochrane reviews wrote that THC is probably ineffective for cramps; a 2022 meta-analysis combining these two controlled studies in ALS found no difference in favor of cannabinoids on ALS-specific overall scales (daily functioning, quality of life) (pooled standardized mean difference 0.31; 95% CI −0.02 to 0.63; p = 0.07; leaning slightly toward placebo according to the authors). The results of the only controlled study examining the effect of cannabinoids on the course of ALS (17 people, an oil rich in CBD and containing a small amount of THC) had not been published as of October 2026. After stroke, in the only controlled study (41 people, crossover), the spray did not change muscle stiffness differently from placebo, whether as felt by the patient or as shown by the doctor's and electrical measurements. In children with cerebral palsy or brain injury, two placebo-controlled studies (72 people, THC:CBD spray, 12 weeks; 53 people, oil containing 10 times more CBD than THC, 6 weeks) found no difference in muscle stiffness; 3 cases of hallucination were reported with the spray and marked sleepiness with the 10:1 oil; a 25-child study without placebo comparing two CBD-rich oils reported improvement in both groups. In spinal cord injury the results are mixed: nabilone (12 people) and a mostly open-label study of THC by mouth (25 people) reported a reduction in doctor-measured muscle stiffness; 1:1 THC:CBD oil (16 people) did not change the doctor's measurement and only slightly improved patients' own ratings; in a 116-person nerve pain study by the maker of the THC:CBD spray, with results available only in the registry, there was no difference in muscle stiffness and spasms. In upper motor neuron syndrome, nabilone (13 people) reduced related pain, not muscle stiffness itself. England's NICE evidence review (2019) found only 3 controlled studies for causes other than MS and made no recommendation for these causes; the product information for the THC:CBD spray does not recommend use under age 18. Two real-world studies without a comparison group (spray in spinal cord injury; synthetic THC in 63 severely ill hospitalized children) reported improvement in muscle stiffness from baseline or by subjective rating, but they cannot separate out the effect of expectation; in the children's series, standard 24-hour records did not show a reduction in restlessness and seizures, and 3 serious breathing problems were seen with synthetic THC; in the records of 344 ALS patients, medical marijuana was not associated with improvement in muscle stiffness. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 12 controlled studies of cannabinoids for muscle stiffness from causes other than MS and for cramps in ALS were found (10 randomized and placebo-controlled, 1 a two-product comparison without placebo, 1 with a 13-person controlled part; one available only in the ClinicalTrials.gov record; in one, most patients had MS); all of them, together with 5 topic-specific systematic reviews, a general meta-analysis that gives a separate analysis for ALS, and 3 observational studies, are in the table below. One more study in which most patients had MS and that gave no separate result for non-MS patients (24 people, 6 without MS) is in the table on the MS spasticity page; small uncontrolled series and satisfaction surveys were not included in the table. In none of these studies was pure CBD assessed separately in non-MS patients; 4 controlled studies with unreported results (two completed, two listed with status 'unknown' in the registry) are being followed; no studies from Turkey were found. In an additional October 2026 search (ALS only; PubMed, Cochrane, ClinicalTrials.gov, Europe PMC), no other controlled study or registry entry with results for cannabinoids in ALS was found; the meta-analysis combining the two ALS studies was added to the table; surveys, case reports and a 9-patient single-dose drug level study (its safety finding is in the warnings) were not included in the table.
Evidence assessment: Pure CBD: Insufficient (pure CBD has not been tested on its own for causes other than MS; in the only study with a pure CBD group, most patients had MS and muscle stiffness was no different from placebo)
CBD alone
There is no separate controlled study of pure CBD oil for muscle stiffness from causes other than MS. In the only study that tested pure CBD (at most 45 mg a day, 6 weeks) as a separate group (Denmark, 134 people), 119 patients had MS and 15 had spinal cord injury; muscle stiffness was no different from placebo, and no separate result was given for patients with spinal cord injury. All the CBD-dominant oils tested in children also contained THC (see the section on THC-containing products). In ALS, the result of a 17-person study of a CBD-rich oil that also contains a small amount of THC (50 mg CBD per mL, less than 2 mg THC) had not been published as of October 2026.
Products containing THC
A mouth spray containing roughly equal amounts of THC and CBD reduced muscle stiffness as measured by the doctor slightly more than placebo over 6 weeks in 60 patients with ALS or primary lateral sclerosis (difference on the Modified Ashworth Scale −0.32; 95% CI −0.57 to −0.07); the same spray was no different from placebo for muscle stiffness after stroke (41 people, crossover) or in children with cerebral palsy or brain injury (72 people, 12 weeks); in the study of nerve pain due to spinal cord injury (116 people, registry results only), there was also no difference in muscle stiffness and spasms. In spinal cord injury, a 25-patient study of THC by mouth, most of it open-label, reported benefit (the comparison for the 13-person controlled part is not in the publication's abstract); an oil containing equal THC and CBD did not change the doctor's measurement in a 16-person crossover study and only slightly improved patients' own ratings. An oil containing 10 times more CBD than THC did not reduce muscle stiffness in 53 people with severe cerebral palsy. For cramps in ALS, THC by mouth (10 mg a day) was no different from placebo (27 people); in a meta-analysis combining the two controlled studies in ALS, there was no difference in favor of cannabinoids on overall ALS scales (daily functioning, quality of life). The synthetic THC-like medicine nabilone reduced muscle stiffness as measured by the doctor in spinal cord injury in a 12-person crossover study; in 13 patients with upper motor neuron syndrome, however, it reduced the related pain, not the muscle stiffness itself. In children, hallucinations and marked sleepiness were reported with THC-containing products.
Evidence: THC-containing products: Weak (1–4 small controlled studies depending on the cause; in ALS, small benefit in doctor-measured muscle stiffness in a single 60-person study; no difference after stroke in 41 people or in children with cerebral palsy in studies of 72 and 53 people; mixed results in spinal cord injury); THC-like nabilone: Very weak (two studies of 12 and 13 people)
Approved drug regimen
There is no approved CBD or cannabinoid medicine for muscle stiffness from causes other than MS. The mouth spray containing THC and CBD (nabiximols; 2.7 mg THC + 2.5 mg CBD per spray) is licensed in the United Kingdom only in adults, for moderate to severe MS spasticity that has not responded well enough to other spasticity medicines and that shows clear improvement during a trial period; it is not recommended under age 18 because efficacy was not shown in a placebo-controlled study in children with cerebral palsy or brain injury (UK product information, text revision April 2, 2026, §4.1, §4.2, §5.1). According to NICE's 2019 evidence review, this spray is not licensed for motor neuron disease or spinal cord injury, and the guideline made no recommendation for cannabinoid products for causes other than MS. Turkey: the spray's active substance (tetrahydrocannabinol and cannabidiol, oromucosal spray) is on the TİTCK (Turkish Medicines and Medical Devices Agency) List of Active Substances from Abroad (September 28, 2026), among medicines that require a red prescription and can be imported with the agency's written approval.
Dose range in studies
THC:CBD mouth spray at most 12 sprays a day (at most 32.4 mg THC + 30 mg CBD; an average of 8 sprays/day in ALS and a median of 9 after stroke; the maker's spinal cord study allowed at most 48 sprays a day); THC by mouth 10 mg/day (ALS cramps) and an average of 31 mg/day (spinal cord injury); 1:1 THC:CBD oil an average of 11.6 mg THC/day; nabilone 0.5–1 mg/day; pure CBD at most 45 mg/day (multi-arm study in which most patients had MS); synthetic THC in severely ill hospitalized children an average of 0.21 mg per kilogram a day (started in the unit) and 0.48 mg (already using it)
Starting dose and titration
Gradual increase over about 14 days in the spray studies (9 weeks in the children's study); in the stroke study, 1 spray every 2 days for the first 4 days, then an increase of 1 each day; nabilone started at 0.5 mg/day and increased to 1 mg/day; 1 week of dose adjustment with the 1:1 oil; THC by mouth started with a single 10 mg dose, then individually adjusted; these are research protocols
These are doses researchers gave under medical supervision; they are not a recommended dose for you. "mg/kg/day" means milligrams per kilogram of body weight per day.
| Study | Participants | Product | Dose and titration | Duration | Result | Source |
|---|---|---|---|---|---|---|
| Stefanović 2025 Randomized, double-blind, placebo-controlled parallel study (6 weeks), followed by a 6-week open-label period; preceded by an open-label pilot (feasibility) study of 7 patients | 53 randomized (1:1); plus a 7-person pilot study Children, teenagers and young adults aged 5–25 with severe spastic cerebral palsy (GMFCS IV–V) (Slovenia) | Full-spectrum cannabis oil, CBD:THC 10:1 (HemPhar), by mouth | Dose taken not in the abstract; per the registry, THC was started at 0.08 mg per kilogram a day and increased gradually, with an upper limit of 1 mg per kilogram a day (NCT04634136) Per the registry, started with a dose divided into 2 a day and increased in steps of 0.08 mg THC per kilogram | 6 weeks double-blind + 6 weeks open-label | There was no significant difference between the oil and placebo in muscle stiffness (Modified Ashworth Scale), the primary outcome; there was also no difference in gross motor function (GMFM-88) or quality of life (the authors mentioned a possible benefit in quality of life). The oil and placebo were supplied by the manufacturer (PharmaHemp), which appears as a study partner in the registry; the authors declared no conflicts of interest. Full text could not be read Side effects: Sleepiness significantly more common in the oil group than with placebo; side effects mild to moderate, no life-threatening events (abstract) | PMID 39626543, doi:10.1016/j.ejpn.2024.11.007, NCT04634136, partner: PharmaHemp, which supplied the product, 55 people enrolled, October 2020–February 2024, no results in the registry), editorial: Grunt 2025, PMID 40057427 |
| Fairhurst 2020 Multicenter, double-blind, placebo-controlled parallel RCT (2:1), followed by a 24-week open-label extension | 72 randomized (47 spray, 25 placebo) Children and teenagers aged 8–18 (mean age 12) with spasticity due to cerebral palsy or traumatic central nervous system injury not responding well enough to current treatment; most with severe mobility limitation (GMFCS IV–V) | THC:CBD mouth spray (nabiximols, Sativex; 2.7 mg THC + 2.5 mg CBD per spray), added to current treatment | At most 12 sprays a day depending on clinical response and tolerability (at most 32.4 mg THC + 30 mg CBD); average dose taken not in the abstract Gradual increase over 9 weeks (UK product information §5.1) | 12 weeks | Caregiver-rated muscle stiffness on a 0–10 scale decreased by 1.85 points with the spray and 1.57 points with placebo; the difference was not significant (−0.17; 95% CI −1.12 to 0.79; p = 0.73). There was no difference in any secondary outcome, including sleep, pain, quality of life, comfort and depression. The manufacturer's study (2 of the 5 authors were GW Research employees) Side effects: Side effects mostly mild to moderate; 3 cases of hallucination, one with an auditory hallucination and a suicide attempt | PMID 32342496, doi:10.1111/dmcn.14548, NCT01898520, sponsor today Jazz Pharmaceuticals, no results in the registry), figures from section §5.1 of the UK product information (text revision April 2, 2026), commentary: Nielsen 2020, PMID 32562496 |
| Riva 2019 (CANALS) Multicenter, double-blind, placebo-controlled parallel phase 2 RCT | 60 randomized (30 spray, 30 placebo); 59 analyzed (29 and 30) Patients aged 18–80 with ALS or primary lateral sclerosis, spasticity for at least 3 months and stable muscle stiffness treatment (Italy, 4 centers) | THC:CBD mouth spray (nabiximols; 2.7 mg THC + 2.5 mg CBD per spray), added to current treatment | At most 12 sprays a day; an average of 8.0 sprays/day in the spray group (NICE 2019 evidence table) Increased by the patient on a preset schedule over the first 14 days, then fixed for 4 weeks | 6 weeks (14 days of dose adjustment + 4 weeks at a fixed dose) | On the Modified Ashworth Scale, the primary outcome, muscle stiffness decreased by an average of 0.11 points in the spray group and increased by 0.16 points in the placebo group (adjusted difference −0.32; 95% CI −0.57 to −0.07; p = 0.013). The authors considered this a preliminary (proof-of-concept) result and called for confirmation in larger studies. Investigator-initiated study funded by an ALS research foundation Side effects: No serious side effects; no one stopped during the double-blind period. Per NICE 2019, the risk of any side effect was higher in the spray group (RR 2.84; 95% CI 1.52 to 5.33; drug-related side effects RR 5.43); common ones were weakness, sleepiness, dizziness and nausea | PMID 30554828, doi:10.1016/S1474-4422(18)30406-X, NCT01776970, commentary: de Visser 2019, PMID 30554829 |
| Marinelli 2022 (SativexStroke) Single-center, double-blind, placebo-controlled crossover pilot RCT | 41 started; 34 completed and were analyzed Adults who had a stroke at least 3 months earlier and have spasticity in an arm or leg (median age 68); people at very high cardiovascular risk (CHA2DS2-VASc ≥ 7) and smokers were not included (Italy) | THC:CBD mouth spray (nabiximols, Sativex), added to current treatment | At most 12 sprays a day (morning and evening); during the medicine period a median of 9 (4–12) sprays/day 1 spray every 2 days for the first 4 days, then increasing by 1 each day to the highest tolerated dose within 14 days | Two 4-week periods, with a 2-week drug-free break in between (10 weeks in total) | There was no difference between the spray and placebo in the two primary outcomes (patient-reported muscle stiffness on a 0–10 scale and electrical measurement of the stretch reflex in the wrist flexor muscles) (p = 0.7 and p = 0.2); there was also no difference in pain, sleep, bladder, number of spasms or doctor-measured muscle stiffness (Modified Ashworth). Those whose stiffness decreased by at least 20%: 32.4% in the spray period, 29.4% in the placebo period. Small pilot study; medicine and placebo provided free by the manufacturer, part of the costs from Almirall Side effects: 7 people withdrew (4 because of side effects, all during the spray period: feeling that movements were getting worse, palpitations, sleepiness, confusion, fatigue, nausea); 2 serious side effects during the spray period (an overnight hospital stay for severe nausea; a first seizure judged by the investigators to be unrelated to the medicine); no meaningful change in blood pressure or pulse, no new stroke or cardiovascular event | PMID 35812088, doi:10.3389/fneur.2022.892165, EudraCT 2016-001034-10, protocol: Marinelli 2017, PMID 28882919, additional analysis of blood pressure and pulse: Rosa 2022, PMID 36386386, blood pressure and pulse did not change during the spray period) |
| Boonthanakorn 2026 Single-center, double-blind, placebo-controlled crossover pilot RCT | 16 randomized; 16 completed Adults aged 20–65 with spinal cord injury for at least 1 year whose muscle stiffness persisted despite the highest tolerated baclofen (16/16) and tizanidine (13/16); 15 men, 10 with tetraplegia; no previous cannabis use (Thailand) | 1:1 THC:CBD oil (27 mg THC + 25 mg CBD per mL; about 1 mg THC and 1 mg CBD per drop; Thai Government Pharmaceutical Organization), by mouth, added to current treatment | Protocol ceiling 12 mg THC a day; an average of 11.6 mg THC a day (and a similar amount of CBD); 15 patients reached the ceiling Gradual increase over 1 week (details in a supplementary file) | Two 4-week periods (1 week of dose adjustment + 3 weeks fixed), with a 2-week drug-free break in between | There was no difference between the oil and placebo in the primary outcome (total Ashworth score of all affected muscle groups) (adjusted difference −1.2; 95% CI −5.9 to 3.5; p = 0.31); there was also no difference in spasm frequency, doctor-rated stiffness or H-reflex measurement. Only the stiffness patients rated themselves on a 0–100 scale decreased more with the oil (−13.9; 95% CI −25.5 to −2.3; p = 0.010). Very small; funded by the state body that makes the product Side effects: No serious side effects or dropouts; mild side effects 5 during the oil period, 1 during the placebo period (p = 0.073): with the oil, 1 symptomatic drop in blood pressure (70/40 mmHg), 1 asymptomatic slowed heart rate, 3 raised liver enzymes (2 times normal) | PMID 42544174, doi:10.1177/17562864261468464, Thai Clinical Trials Registry TCTR20220329001 |
| NCT01606202 (maker's spinal cord injury study, registry results) Double-blind, placebo-controlled, parallel phase 3 RCT; primary outcome nerve pain, spasticity a secondary outcome; results only in the registry (no peer-reviewed publication) | 116 randomized (56 active, 60 placebo); spasticity severity analyzed in 35 and 43 people, Modified Ashworth in 40 and 44 Adults with central neuropathic pain due to spinal cord injury not relieved by current treatment (spasticity was not an entry criterion) | Oromucosal spray: THC 27 mg/ml + CBD 25 mg/ml (GW-1000-02, Sativex), added to current treatment | 2.7 mg THC + 2.5 mg CBD per spray; at most 8 sprays in 3 hours and 48 sprays a day | At most 51 days (about 7 weeks) | No difference in spasticity: the difference in patient-reported spasticity severity on a 0–10 scale was 0.07 (95% CI −0.61 to 0.75; p = 0.83), in doctor-measured Modified Ashworth score −0.14 (−0.33 to 0.05; p = 0.14), in spasm severity 0.05 (−0.54 to 0.65; p = 0.86); no difference either in the percentage of days with spasticity and spasms. No difference in the primary outcome of pain (−0.08; −0.51 to 0.35); those saying their overall condition had improved: 30/56 vs 12/60 (p < 0.001). The manufacturer's study; no peer-reviewed publication Side effects: Reported side effects 46/56 vs 29/60 (dizziness 14 vs 5, sleepiness 7 vs 0); stopping due to side effects 5 vs 0; serious side effects 3 vs 2 | NCT01606202, results in the registry, September 28, 2012, sponsor today Jazz Pharmaceuticals), the same study is in the neuropathic-pain table with its pain result |
| Weber 2010 Randomized, double-blind, placebo-controlled crossover RCT | 27 randomized; complete data for 22 people ALS patients with moderate to severe daily muscle cramps (at least 4 on a 0–10 scale) (20 men, 7 women; mean age 57; Switzerland) | Oral THC (dronabinol according to the registry) | 5 mg 2 times a day (10 mg/day) Fixed dose | Two 2-week treatment periods, each preceded by a 2-week drug-free period | No difference was seen between THC and placebo in cramp severity (primary outcome), daily number of cramps, severity of muscle twitching (fasciculations), or quality of life, sleep, appetite and depression scales Side effects: Well tolerated (abstract) | PMID 20498181, doi:10.1136/jnnp.2009.200642, NCT00812851, no results) |
| Libzon 2018 Pilot study comparing two products; no placebo group (tagged as a randomized controlled trial in PubMed, and its likely registry entry NCT02470325 is randomized and triple-blind; no details on randomization and blinding in the abstract; the Murni 2023 review counted it as a non-randomized study) | 25 (19 with cerebral palsy; diagnosis breakdown from Murni 2023 Table 1, secondary source) Children aged 1–17 with moderate to severe complex movement disorders in which different types of abnormal movements occur together (Israel, Wolfson Medical Center); according to one review, 19 had cerebral palsy (Murni 2023, secondary source) | Two CBD-rich cannabis oils (5% CBD): with 0.25% THC (CBD:THC 20:1) and with 0.83% THC (6:1) | Not in the abstract (full text could not be read) Not in the abstract | 5 months | Significant improvement in spasticity, dystonia, sleep difficulty, pain severity and quality of life was reported in the whole group, regardless of which oil was taken. Because there was no placebo group, it cannot be known how much of the improvement came from the oil. Very small; 3 of the 8 authors were from the research department of a cannabis company (Tikun Olam) Side effects: Rare: increased seizures in 2 children, behavior change in 2, sleepiness in 1 | PMID 29766748, doi:10.1177/0883073818773028, NCT02470325, 6:1 and 20:1 CBD:THC oils, 40 people planned, record not updated since 2015, status 'unknown'), match not confirmed |
| Pooyania 2010 Randomized, double-blind, placebo-controlled crossover pilot RCT | 12 (11 completed; all men; 6 with tetraplegia, 5 with paraplegia) Adults with spinal cord injury and spasticity (Canada) | Nabilone (synthetic THC-like cannabinoid), by mouth | 0.5 mg as 1 dose a day; if needed, 0.5 mg 2 times a day Could be increased to 2 doses a day in weeks 3–4 (NICE 2019 evidence table) | Two 4-week periods with a 2-week drug-free break in between | The Ashworth score measured by the doctor in the most affected muscle group decreased more with nabilone than with placebo (difference 0.91 ± 0.85; p = 0.003); there was also a significant difference in the total Ashworth score (p = 0.001). There was no difference in patient-reported spasm frequency and stiffness, the pendulum test or global impression measures. Very small; the registry lists a drug company (Valeant Canada) as an industry partner Side effects: Mild and tolerable (abstract); per NICE 2019, sleepiness, dry mouth, weakness, mild dizziness, mild balance problems, headache | PMID 20434606, doi:10.1016/j.apmr.2009.12.025, NCT00623376, partner: Valeant Canada, July–December 2007, no results in the registry) |
| Hagenbach 2007 Three-phase study: two open-label dose-finding phases (oral THC; rectal THC-hemisuccinate), followed by a small, randomized, double-blind, placebo-controlled parallel phase | 25 (open oral THC phase 22, 15 completed; rectal phase 8, 7 completed; randomized phase 6 THC, 7 placebo) Adults with spinal cord injury and spasticity; spasticity medicines were stopped before the study (Switzerland) | Oral THC and rectal THC-hemisuccinate | An average of 31 mg a day (oral THC) and 43 mg (rectal THC-hemisuccinate); started with a single 10 mg dose Individual dose adjustment | 6 weeks per phase | In the open-label oral THC phase, the total spasticity score (Modified Ashworth) fell from 16.7 to 8.9 on day 43; similar improvement with rectal use. The p = 0.001 in the abstract is not a comparison between randomized groups but between two periods in the same 7 people, who first took THC in the open phase and then placebo in the randomized phase; the comparison for the randomized phase itself (6 THC, 7 placebo) is not in the abstract. The supplementary table of Nabata 2021 gives, for this phase, an effect size on the Modified Ashworth of −0.66 (95% CI −1.73 to 0.50; not significant) and a difference in favor of THC in the patient's own rating only on day 1 (p = 0.033) (secondary source; could not be confirmed from the publication). According to the authors, at least 15–20 mg a day was needed for an effect. Most of the study was open-label Side effects: The main reasons for stopping were increased pain and psychological side effects | PMID 17043680, doi:10.1038/sj.sc.3101982, Commentary: Villan 2008, PMID 18332890 |
| Wissel 2006 Randomized, double-blind, placebo-controlled crossover RCT | 13 (11 completed) Adults with chronic upper motor neuron syndrome and spasticity-related pain not relieved by standard treatment (due to brain or spinal cord damage; at least 1 patient with MS; per NICE, Austria, Germany, Switzerland) | Nabilone (synthetic THC-like cannabinoid), by mouth | 1 mg a day Started at 0.5 mg a day and increased to 1 mg | Two 4-week periods with a 1-week break in between (NICE 2019 evidence table) | Pain related to muscle stiffness (11-point box test) decreased significantly more with nabilone than with placebo (p < 0.05); spasticity, motor function and activities of daily living did not change. Very small; NICE 2019 rated the risk of bias as high because of missing information on randomization and blinding Side effects: Side effects in 5 patients: with nabilone, 1 case of moderate temporary leg weakness (withdrew) and 2 of mild sleepiness; with placebo, 1 of sleepiness and 1 of mild difficulty swallowing; 1 patient was withdrawn during the nabilone period because of an MS relapse | PMID 16988792, doi:10.1007/s00415-006-0218-8 |
| Hansen 2023 Multicenter, double-blind, placebo-controlled, 4-arm parallel RCT (THC / CBD / THC+CBD / placebo) | 134 (MS 119, spinal cord injury 15; CBD 31, THC 32, THC+CBD 31, placebo 40) Neuropathic pain and/or spasticity due to MS or spinal cord injury (Denmark) | Oral capsules: synthetic pure CBD; THC; both combined | CBD at most 45 mg/day, THC at most 22.5 mg/day (divided into 3 doses a day, at most 9 capsules) Standard increase over 3 weeks; a lower dose was kept if there was enough effect or side effects | 6 weeks + 1 week tapering | 119 patients had MS and 15 had spinal cord injury (73% of those with spinal cord injury had both pain and spasticity); no separate result was given for patients with spinal cord injury. Spasticity was assessed in the 100 patients who met the criterion (both conditions together): improvement in the pure CBD group was no different from placebo (difference 0.46 points; 95% CI −0.74 to 1.65); there was also no difference in the THC (0.24; −0.67 to 1.45) and THC+CBD (0.10; −1.18 to 1.39) groups. Only 134 of the targeted 448 people could be enrolled Side effects: Side effects most common in the THC arms; dry mouth 29% with CBD, 27.5% with placebo; 1 hospitalization in the CBD arm (gallstone attack) | PMID 37630995, doi:10.3390/ph16081079, EudraCT 2018-002315-98, protocol: Hansen 2021, PMID 34573231, pharmacokinetic substudy in 23 MS patients: Hansen 2024, PMID 38054364, the same study is in the ms-spasticity and neuropathic-pain tables |
| NICE 2019 (evidence review C: spasticity) Systematic review and meta-analysis (GRADE) for a national guideline, England (NICE NG144) | 15 RCTs (12 parallel, 3 crossover); non-MS: 2 motor neuron disease or upper motor neuron syndrome, 1 spinal cord injury; no studies in children Adults and children with spasticity from any cause | THC:CBD mouth spray, synthetic THC capsule, cannabis extract capsule, nabilone | Varied by study | Varied by study | Evidence for causes other than MS was found to be very limited: in motor neuron disease, a small reduction in doctor-measured muscle stiffness with THC:CBD spray (1 study, 59 people; difference −0.27; 95% CI −0.51 to −0.03; high quality) but a higher risk of side effects (RR 2.84); in spinal cord injury, a reduction in Ashworth score with nabilone (1 small crossover study; moderate quality). The committee found sufficient evidence only for MS; it made no recommendation for cannabinoid products for other causes, recommended research, and specifically mentioned people with cerebral palsy as a group that might benefit Side effects: Common in motor neuron disease: weakness, sleepiness, dizziness, nausea | PMID 35107908, NCBI Bookshelf NBK577084, PMID 31909928, PDF: nice.org.uk/guidance/ng144/evidence (final version November 2019) |
| Nielsen 2019 Systematic review (narrative synthesis) | 32 studies (adults and children) Spasticity from any cause; focused on applicability to children | Various cannabinoids | Varied by study | Varied by study | In adults with MS, cannabinoids are slightly more effective than placebo for spasticity, with benefit mostly on patient-reported measures and small; for causes other than MS there are few studies and none are large; studies in children are of low quality and not at a level to guide practice Side effects: Cannabinoids have a narrow therapeutic window in spasticity; benefit should be weighed together with side effects (abstract) | PMID 30680713, doi:10.1111/dmcn.14165, Commentary: O'Callaghan 2019, PMID 30993669 |
| Nabata 2021 Systematic review (no meta-analysis; effect sizes calculated for RCTs) | 34 studies (26 on patterns of use, 8 on treatment effect; 7 RCTs) People with spinal cord injury | Dronabinol, oral THC, inhaled cannabis, oromucosal spray extracts, nabilone | Varied by study | Varied by study | Pain, muscle stiffness and recreation stand out among reasons for use. All experimental studies reported a reduction in spasticity, but looking at RCTs only, effect sizes for spasticity ranged from −0.95 to 0.09; the size and clinical importance of the effect are uncertain; long-term, double-blind studies are needed Side effects: Cannabinoid use was associated with fatigue and cognitive impairment | PMID 32310048, doi:10.2174/1570159X18666200420085712 |
| Murni 2023 Systematic review (PRISMA 2020; no meta-analysis; PROSPERO CRD42022358383) | 3 studies, 133 participants (2 experimental: 1 RCT and 1 counted as non-randomized; 1 observational) Children with cerebral palsy | THC:CBD mouth spray, CBD-rich oils with THC, prescription cannabinoids | Varied by study | Varied by study | Muscle stiffness results were inconsistent: no difference in the only placebo-controlled study (Fairhurst 2020), improvement in the study without placebo (Libzon 2018). Although the authors summarized overall efficacy and safety as 'good', they wrote that efficacy has not been studied enough and that larger studies are needed. Conducted before Stefanović 2025 Side effects: Side effects mostly mild to moderate; serious events reported included changes in seizure characteristics and disorientation | PMID 37991091, doi:10.31744/einstein_journal/2023RW0387 |
| Baldinger 2012 (Cochrane) Cochrane systematic review and meta-analysis | 20 studies, 4,789 participants (the only study looking at cramps as the primary outcome was a THC study) Muscle cramps in ALS / motor neuron disease | Medicines tested for cramps; THC as the only cannabinoid | Varied by study | Varied by study | No intervention was shown to benefit cramps in ALS; most studies were too small for firm conclusions. Cochrane's 2017 overview of symptomatic treatments in ALS (Ng 2017) wrote that THC is probably ineffective for cramps (moderate-quality evidence) Side effects: Not reported (in the abstract) | PMID 22513921, doi:10.1002/14651858.CD004157.pub2, Cochrane overview: Ng 2017, PMID 28072907 |
| Austin 2024 Retrospective cohort (comparison group: people with the same symptoms who did not receive a medical marijuana prescription) | 344 ALS patients Patients followed at a single ALS clinic (Texas, USA) | Medical marijuana (product type and THC/CBD content not in the abstract) | Not reported (in the abstract) | 2-year chart review | Medical marijuana use was associated with short-term reductions in pain, loss of appetite and anxiety; there was no association with muscle stiffness, insomnia or weight maintenance. ALS progressed faster in users, but these patients' symptoms were already more severe and their disease was progressing faster before the marijuana prescription (association; cause and effect not shown). The authors recommended a randomized study Side effects: Not reported (in the abstract) | PMID 39307005, doi:10.1016/j.jns.2024.123243 |
| Hauch 2024 Retrospective chart review (single center, inpatient pediatric palliative care unit) | 63 children and young people (out of 1,219 patients admitted to the unit); 26 were started in the unit, 37 were already using it; in 42, one of the reasons for giving the medicine was muscle stiffness Children with life-limiting illness, 96.8% with severe neurological disease (mean age 10.4; Germany) | Dronabinol (semi-synthetic THC), oral drops | Effective dose averaged 0.21 mg per kilogram a day (started in the unit) and 0.48 mg (already using it) | Admissions 2011–2021 | The rate of at least moderate response in muscle stiffness, by subjective assessment of doctors, nurses or families, was 47.6% in total as given by the authors in the discussion (given in the Results as '9.5%/38.1% for groups A/B, n = 42'; response was reported by doctors and nurses for those started in the unit and by families for those already using it). In the standard 24-hour records of those started in the unit, seizures, restlessness and need for extra medicine did not decrease (muscle stiffness was not in these records); the authors wrote that the subjective positive impression was not confirmed by objective data. No comparison group Side effects: 3 serious side effects (respiratory failure, one needing non-invasive breathing support; reduced breathing rate), all resolved when the medicine was stopped; fatigue 22.2%, behavior problems 14.3% | PMID 39334587, doi:10.3390/children11091054 |
| Martins Braga 2025 Prospective, single-arm (uncontrolled) observational study | Not reported (in the abstract); full text could not be read Adults with spinal cord injury for at least 6 months and moderate to severe spasticity resistant to conventional treatment (Guttmann Institute, Spain) | THC:CBD mouth spray (nabiximols, Sativex) | Weekly individual dose adjustment (no details in the abstract) Weekly individual adjustment | 2 months (assessments at months 1 and 2) | Spasticity decreased significantly from baseline at month 1 (30% reduction on the patient scale, 60% on the Modified Ashworth) and at month 2 (30% and 52%); 67% of patients reported overall improvement. Spasm frequency, functional independence, nerve pain and sleep quality did not change. No comparison group; supported by Almirall Side effects: Not reported (in the abstract) | PMID 40675989, doi:10.1038/s41394-025-00712-2, EudraCT 2022-001777-31 |
| Bilbao 2022 Systematic review and meta-analysis of RCTs split by drug type (8 databases, up to May 2021, updated in October 2021; PROSPERO CRD42021229932; GRADE); separate analysis for ALS | 152 RCTs, 12,123 participants (all indications); in the ALS analysis, 2 RCTs: Weber 2010 (dronabinol, 22 people) and Riva 2019 (nabiximols, 59 people) All medical indications; the ALS analysis covers adults with ALS or motor neuron disease | In the ALS analysis: dronabinol (synthetic THC) and a THC:CBD mouth spray (nabiximols); across the whole review, dronabinol, nabilone, pure CBD and nabiximols (smoked cannabis excluded) | In the ALS studies, dronabinol 10 mg/day (2 weeks) and nabiximols up to 32.4 mg THC + 30 mg CBD a day (6 weeks) (Table 2 of the review) | Only two RCTs were found in ALS. The review pooled general ALS-specific scales (according to the supplementary tables, the ALS quality of life questionnaire in Weber 2010 and the ALS functional rating scale in Riva 2019): neither study showed improvement; according to the authors, the pooled effect pointed toward placebo but was not significant (SMD 0.31; 95% CI −0.02 to 0.63; p = 0.07; the publication does not say how the direction of the two scales was aligned). Separately: dronabinol SMD 0.26 (95% CI −0.17 to 0.68), nabiximols SMD 0.38 (−0.13 to 0.90). Comparisons with a single RCT were not graded with GRADE. This analysis uses the general ALS scales, not the doctor-measured muscle stiffness that was the primary outcome of Riva 2019. The authors reported no conflicts of interest. The search ended in October 2021; from then until October 2026, no new controlled study with published results has appeared in ALS Side effects: No side effect analysis specific to ALS was given | PMID 35982439, doi:10.1186/s12916-022-02459-1, PROSPERO CRD42021229932, PMC9389720 (ALS forest plot: Appendix 4, Figure S10, measures: Appendix 2 tables), the same review is also a row in the glaucoma, irritable bowel, appetite loss, generalized anxiety and Parkinson’s tables |
Reported side effects
- THC:CBD spray in ALS: any side effect RR 2.84 (1.52–5.33), drug-related side effect RR 5.43 (2.12–13.90); no serious side effects (Riva 2019; NICE 2019)
- THC:CBD spray in spinal cord injury: side effects 46/56 vs 29/60; dizziness 14 vs 5, sleepiness 7 vs 0; stopping due to side effects 5 vs 0 (NCT01606202)
- 1:1 THC:CBD oil (spinal cord injury): mild side effects 5 vs 1; symptomatic drop in blood pressure, slowed heart rate and raised liver enzymes (Boonthanakorn 2026)
- THC:CBD spray after stroke: 4 patients stopped because of side effects (all during the spray period); 2 serious side effects (severe nausea; a seizure judged unrelated to the medicine); no meaningful change in blood pressure or pulse (Marinelli 2022; Rosa 2022)
- In children: 3 hallucinations with THC:CBD spray, one an auditory hallucination with a suicide attempt (Fairhurst 2020); sleepiness significantly more common than with placebo with CBD:THC 10:1 oil (Stefanović 2025); with CBD:THC 20:1 and 6:1 oils, 2 cases of increased seizures, 2 behavior changes, 1 sleepiness (Libzon 2018)
- In 63 children receiving synthetic THC in palliative care, 3 serious side effects (respiratory failure or reduced breathing rate), fatigue 22%, behavior problems 14% (Hauch 2024)
Monitoring done in studies
- EMERALD (NCT03690791, Australia): effect of a CBD-rich oil (50 mg CBD per mL, less than 2 mg THC) on disease progression in ALS; 17 people, double-blind, placebo-controlled; estimated completion January 2024; the registry entry has not been updated since April 2023 and its status is 'unknown'; no results in the registry and no publication found in PubMed in October 2026 (protocol: Urbi 2019, PMID 31719072); its 7-person open-label extension (NCT04997954) also has no results
- NCT01222468 (Canada): nabilone (at most 3 mg a day) in spinal cord injury, muscle stiffness and nerve pain; 12 people, crossover; completed in February 2015; no results in the registry and no publication in PubMed
- NCT04057456 (Canada): nabilone and an anti-inflammatory diet in spinal cord injury; primary outcome nerve pain, muscle stiffness secondary; 14 people; completed in December 2024; no results in October 2026
- NCT06190470 (Thailand): THC-containing cannabis extract in spinal cord injury; nerve pain and muscle stiffness; 20 people planned, crossover; estimated completion June 2024; the record has not been updated since March 2024, no results
Who should be careful
- Product information for the mouth spray containing THC and CBD: licensed only for MS spasticity in adults; not recommended under age 18 (efficacy was not shown in a placebo-controlled study in children with cerebral palsy or brain injury); not used if the person or their family has a history of schizophrenia or other psychosis, or during breastfeeding; not recommended in serious cardiovascular disease; once spasticity goes down, the risk of falls may increase in people without enough muscle strength (UK product information, April 2, 2026, §4.1–4.4)
- Children: hallucinations (with a suicide attempt in one case), marked sleepiness and increased seizures were reported with THC-containing products; suppressed breathing was seen with synthetic THC in severely ill children taking several seizure and sedative medicines (Fairhurst 2020, Stefanović 2025, Libzon 2018, Hauch 2024)
- After stroke: in the only controlled study, blood pressure and pulse did not change, but people at very high cardiovascular risk and smokers were not included; according to the product information, changes in pulse and blood pressure during initial dose adjustment and fainting during use have been seen with the spray (Marinelli 2022; UK product information §4.4)
- ALS: in a 9-patient single-dose study, 10 mg THC clearly increased sleepiness, euphoria, dizziness, drop in blood pressure on standing, and weakness compared with 5 mg (Joerger 2012, PMID 22594565)
Drug interactions
- The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
- Product information for the THC:CBD spray (§4.5): with muscle relaxants (baclofen, benzodiazepines), muscle tone and strength may decrease and the risk of falls may increase; with sleep-inducing and sedative medicines and alcohol, the sedative effect may increase; strong CYP3A4 inhibitors such as ketoconazole raise THC and CBD levels (the dose may need readjusting if itraconazole, ritonavir or clarithromycin is started or stopped); fluconazole increases THC exposure; strong inducers such as rifampin, carbamazepine, phenytoin, phenobarbital and St. John's wort are avoided where possible
- Children with cerebral palsy and people with severe neurological disease often take several seizure medicines; CBD can interact with some seizure medicines (details on the epilepsy pages and in the drug interactions section)
Abbreviations: RCT, randomized controlled trial (a study in which participants are assigned to groups by chance); placebo, an inactive substance; SMD, OR and RR, effect measures used in analyses that pool studies; CYP, liver enzymes that break down medicines.
If you are considering CBD
- Do not stop or change your muscle stiffness medicines (such as baclofen or tizanidine) or your physical therapy program on your own.
- If you are considering it for your child, talk with your child's pediatric neurologist; all the products tested in children contained THC, and side effects such as hallucinations and marked sleepiness were reported.
- If seizure, sleep or muscle relaxant medicines are being used, go over possible interactions with your doctor or pharmacist.
- If you have had a stroke or have cardiovascular disease, talk with your doctor about how THC-containing products affect pulse and blood pressure.
- Check the product label and certificate of analysis; find out whether it contains THC. Remember that the mouth spray containing THC and CBD is a prescription medicine, is licensed in the United Kingdom only for MS spasticity in adults, and is not the same thing as CBD oils.
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Bottom line
The effect of CBD oil on muscle stiffness from causes other than MS has not yet been studied on its own. The results of small studies with THC-containing products vary by condition: in ALS there is a sign of small benefit in a single early study, while no clear difference was seen after stroke or in children with cerebral palsy; in spinal cord injury the results are mixed, and side effects in children are significant; for THC-containing products, the strength of evidence is weak. Planning muscle stiffness treatment together with your neurologist and your physical medicine and rehabilitation team is the soundest approach.
Frequently asked questions
Does CBD oil work for muscle stiffness due to spinal cord injury, stroke or cerebral palsy?
There is not yet enough research to say. In these conditions, pure CBD oil has not been tested on its own for muscle stiffness. Almost all products used in the studies also contained THC, and results varied by condition: in ALS a sign of small benefit was seen, while after stroke and in children with cerebral palsy there was no clear difference compared with an inactive medicine (placebo). In spinal cord injury the results are mixed: a few very small studies reported a reduction, while a 116-person study with results available only in the ClinicalTrials.gov record found no difference. For THC-containing products, the strength of evidence is weak.
I am considering cannabis oil for my child with cerebral palsy; what should I watch out for?
In two well-designed studies in children, cannabis products did not reduce muscle stiffness more than placebo. All of these products contained THC, and the side effects were significant: with the mouth spray containing THC and CBD, three children had hallucinations (one made a suicide attempt); with the oil containing 10 times more CBD than THC, children were clearly sleepier; and in another study, seizures increased in two children. Cases of suppressed breathing with synthetic THC have also been reported in the palliative care of severely ill children. If your child takes seizure, sleep or muscle relaxant medicines, it is important to make this decision together with your child's pediatric neurologist. The strength of evidence is weak.
Do cannabis products help muscle stiffness, cramps or the course of the disease in ALS?
In a study of 60 patients with ALS and similar motor neuron diseases, a mouth spray containing roughly equal amounts of THC and CBD reduced muscle stiffness, as measured by the doctor, slightly more than placebo over 6 weeks; no serious side effects were seen, but side effects were more common. This was an early study, and the result has not yet been confirmed in a larger study. For painful muscle cramps, THC by mouth did not change cramp severity or number differently from an inactive medicine (placebo) in a 27-patient study. In the same study, there was also no difference in quality of life, sleep and appetite; in a meta-analysis combining the two studies, there was also no improvement on overall ALS scales (daily functioning, quality of life). The result of a 17-person controlled study looking at the course of ALS with an oil rich in CBD that also contains a small amount of THC had not been published as of October 2026. In a study that looked at the records of 344 patients at one clinic, the disease progressed faster in those using medical marijuana; but these patients' symptoms were already more severe before they started marijuana, and their disease was already progressing faster at that time; in other words, this is an association and does not show cause and effect. The strength of evidence is weak.
Have cannabis products been tested for muscle stiffness after a stroke?
There is only one controlled study on this: in a study in Italy of 41 people who had had a stroke, a mouth spray containing THC and CBD did not reduce muscle stiffness over 4 weeks any differently from an inactive medicine. The evidence rests on a single small study. No meaningful change in blood pressure or pulse was seen in the study; however, people at very high cardiovascular risk and smokers were not included. If you have had a stroke, it is important to talk this over with your doctor, because THC-containing products can change pulse and blood pressure.
Can it be used together with my muscle stiffness medicines?
These studies did not look at drug interactions separately. The product information for the spray containing THC and CBD states that, together with muscle relaxants such as baclofen or benzodiazepines, muscle strength may decrease and the risk of falls may increase, and that sleep-inducing medicines and alcohol may add to the sedative effect. CBD can also slow the breakdown of some medicines in the body. If you take medicines regularly, it is important to make this decision together with your doctor and pharmacist.
In Turkey, can CBD oil or a cannabis medicine be obtained with a prescription for muscle stiffness?
In Turkey, cannabis-derived products are regulated by the Kenevirden Elde Edilen Ürünlere Dair Yönetmelik (Regulation on Products Derived from Hemp) dated January 31, 2026. These products, including CBD, can be sold only in pharmacies. Those classed as medicines and health products are dispensed with a prescription; the regulation does not state a prescription requirement for supplement products and cosmetics with a THC content of at most 0.3%. As of October 2026, there is no approved CBD medicine in Turkey. The active substance of the mouth spray containing THC and CBD is on the TİTCK (Turkish Medicines and Medical Devices Agency) List of Active Substances from Abroad (September 28, 2026), and importing it requires the agency's written approval; this medicine is licensed in the United Kingdom only for MS spasticity in adults. If you are thinking of using it, talk with your doctor first.
References
Show 21 references
- Stefanović 2025. Randomized, double-blind, placebo-controlled parallel study (6 weeks), followed by a 6-week open-label period; preceded by an open-label pilot (feasibility) study of 7 patients. PMID 39626543, doi:10.1016/j.ejpn.2024.11.007, NCT04634136, partner: PharmaHemp, which supplied the product, 55 people enrolled, October 2020–February 2024, no results in the registry), editorial: Grunt 2025, PMID 40057427
- Fairhurst 2020. Multicenter, double-blind, placebo-controlled parallel RCT (2:1), followed by a 24-week open-label extension. PMID 32342496, doi:10.1111/dmcn.14548, NCT01898520, sponsor today Jazz Pharmaceuticals, no results in the registry), figures from section §5.1 of the UK product information (text revision April 2, 2026), commentary: Nielsen 2020, PMID 32562496
- Riva 2019 (CANALS). Multicenter, double-blind, placebo-controlled parallel phase 2 RCT. PMID 30554828, doi:10.1016/S1474-4422(18)30406-X, NCT01776970, commentary: de Visser 2019, PMID 30554829
- Marinelli 2022 (SativexStroke). Single-center, double-blind, placebo-controlled crossover pilot RCT. PMID 35812088, doi:10.3389/fneur.2022.892165, EudraCT 2016-001034-10, protocol: Marinelli 2017, PMID 28882919, additional analysis of blood pressure and pulse: Rosa 2022, PMID 36386386, blood pressure and pulse did not change during the spray period)
- Boonthanakorn 2026. Single-center, double-blind, placebo-controlled crossover pilot RCT. PMID 42544174, doi:10.1177/17562864261468464, Thai Clinical Trials Registry TCTR20220329001
- NCT01606202 (maker's spinal cord injury study, registry results). Double-blind, placebo-controlled, parallel phase 3 RCT; primary outcome nerve pain, spasticity a secondary outcome; results only in the registry (no peer-reviewed publication). NCT01606202, results in the registry, September 28, 2012, sponsor today Jazz Pharmaceuticals), the same study is in the neuropathic-pain table with its pain result
- Weber 2010. Randomized, double-blind, placebo-controlled crossover RCT. PMID 20498181, doi:10.1136/jnnp.2009.200642, NCT00812851, no results)
- Libzon 2018. Pilot study comparing two products; no placebo group (tagged as a randomized controlled trial in PubMed, and its likely registry entry NCT02470325 is randomized and triple-blind; no details on randomization and blinding in the abstract; the Murni 2023 review counted it as a non-randomized study). PMID 29766748, doi:10.1177/0883073818773028, NCT02470325, 6:1 and 20:1 CBD:THC oils, 40 people planned, record not updated since 2015, status 'unknown'), match not confirmed
- Pooyania 2010. Randomized, double-blind, placebo-controlled crossover pilot RCT. PMID 20434606, doi:10.1016/j.apmr.2009.12.025, NCT00623376, partner: Valeant Canada, July–December 2007, no results in the registry)
- Hagenbach 2007. Three-phase study: two open-label dose-finding phases (oral THC; rectal THC-hemisuccinate), followed by a small, randomized, double-blind, placebo-controlled parallel phase. PMID 17043680, doi:10.1038/sj.sc.3101982, Commentary: Villan 2008, PMID 18332890
- Wissel 2006. Randomized, double-blind, placebo-controlled crossover RCT. PMID 16988792, doi:10.1007/s00415-006-0218-8
- Hansen 2023. Multicenter, double-blind, placebo-controlled, 4-arm parallel RCT (THC / CBD / THC+CBD / placebo). PMID 37630995, doi:10.3390/ph16081079, EudraCT 2018-002315-98, protocol: Hansen 2021, PMID 34573231, pharmacokinetic substudy in 23 MS patients: Hansen 2024, PMID 38054364, the same study is in the ms-spasticity and neuropathic-pain tables
- NICE 2019 (evidence review C: spasticity). Systematic review and meta-analysis (GRADE) for a national guideline, England (NICE NG144). PMID 35107908, NCBI Bookshelf NBK577084, PMID 31909928, PDF: nice.org.uk/guidance/ng144/evidence (final version November 2019)
- Nielsen 2019. Systematic review (narrative synthesis). PMID 30680713, doi:10.1111/dmcn.14165, Commentary: O'Callaghan 2019, PMID 30993669
- Nabata 2021. Systematic review (no meta-analysis; effect sizes calculated for RCTs). PMID 32310048, doi:10.2174/1570159X18666200420085712
- Murni 2023. Systematic review (PRISMA 2020; no meta-analysis; PROSPERO CRD42022358383). PMID 37991091, doi:10.31744/einstein_journal/2023RW0387
- Baldinger 2012 (Cochrane). Cochrane systematic review and meta-analysis. PMID 22513921, doi:10.1002/14651858.CD004157.pub2, Cochrane overview: Ng 2017, PMID 28072907
- Austin 2024. Retrospective cohort (comparison group: people with the same symptoms who did not receive a medical marijuana prescription). PMID 39307005, doi:10.1016/j.jns.2024.123243
- Hauch 2024. Retrospective chart review (single center, inpatient pediatric palliative care unit). PMID 39334587, doi:10.3390/children11091054
- Martins Braga 2025. Prospective, single-arm (uncontrolled) observational study. PMID 40675989, doi:10.1038/s41394-025-00712-2, EudraCT 2022-001777-31
- Bilbao 2022. Systematic review and meta-analysis of RCTs split by drug type (8 databases, up to May 2021, updated in October 2021; PROSPERO CRD42021229932; GRADE); separate analysis for ALS. PMID 35982439, doi:10.1186/s12916-022-02459-1, PROSPERO CRD42021229932, PMC9389720 (ALS forest plot: Appendix 4, Figure S10, measures: Appendix 2 tables), the same review is also a row in the glaucoma, irritable bowel, appetite loss, generalized anxiety and Parkinson’s tables
Points that could not be verified from the full text
- The full texts of Riva 2019, Fairhurst 2020, Stefanović 2025, Libzon 2018, Weber 2010, Hagenbach 2007, Pooyania 2010, Wissel 2006, Nielsen 2019 and Austin 2024 could not be read (paywalled, or the publisher's page required bot verification); the figures come from the abstracts, the UK product information (Fairhurst 2020), the NICE 2019 evidence tables (Riva 2019, Pooyania 2010, Wissel 2006) and ClinicalTrials.gov records
- The dose actually taken in Stefanović 2025 is not in the abstract; the dosing schedule comes from the study's registry entry (NCT04634136). In Libzon 2018, the doses and the patients' diagnoses are not in the abstract (according to one review, 19 of the 25 children had cerebral palsy: Murni 2023); the study's registry entry may be NCT02470325 (same center and same two products), but that record has not been updated since 2015 and the match could not be confirmed
- In Hagenbach 2007, the comparison for the randomized phase itself (6 THC, 7 placebo) is not given separately in the abstract; the p = 0.001 in the abstract is a comparison between the open THC period and the placebo period in the same 7 people
- The number of people and side effects in Martins Braga 2025 are not in the abstract; the full text is not open access. Hansen 2023 has no separate results for patients with spinal cord injury
- The maker's THC:CBD spray study in spinal cord injury (NCT01606202) was not published in a peer-reviewed journal; its results are only in the ClinicalTrials.gov record
- In Hauch 2024, the denominator for the muscle stiffness percentages (9.5% for those started in the unit, 38.1% for those already using it) is not clear in the publication; the text uses the total rate the authors gave in the discussion (47.6%). The comparison for the randomized phase of Hagenbach 2007 appears only in the table of one review (Nabata 2021)
Research history
Here we record what changed on this page, when and why, with dates. The newest change is at the top.
The ALS section was expanded: all controlled studies with cannabinoids in ALS, registry records with results and large observational data sets were searched again. No new controlled study or registry record with published results was found; a 2022 meta-analysis pooling the two controlled studies in ALS (Bilbao 2022; no difference in favor of cannabinoids on ALS scales of daily function and quality of life) was added to the table. The quality of life, sleep and appetite results of the cramp study and the status of a 17-person study looking at the course of the disease (results not published as of October 2026) were added to the ALS section. The conclusion and the strength of evidence did not change.
Related studies: Bilbao 2022, published August 19, 2022 (PMID 35982439, doi:10.1186/s12916-022-02459-1, PROSPERO CRD42021229932, PMC9389720 (ALS forest plot: Appendix 4, Figure S10, measures: Appendix 2 tables), the same review is also a row in the glaucoma, irritable bowel, appetite loss, generalized anxiety and Parkinson’s tables)
The last sentence of the page's short summary was rewritten in a calmer, more guiding tone: instead of "Talk to your doctor before you start.", it now says whom you can talk with, and about what, if you are considering CBD. The conclusion and the strength of evidence did not change.
Page published. This first assessment reviewed 20 studies.