MS Spasticity and CBD Oil: Research, Dosage and Warnings

Q: Does CBD oil work for MS spasticity?

So far, no results show this. Pure CBD was tested in two small studies, and in neither did it reduce muscle stiffness more than an inactive treatment (placebo); one showed improvement in a short walking test and in pain. The positive results come mostly from a prescription mouth spray that contains THC and CBD in roughly equal amounts; these results cannot be applied to CBD oil.

Q: What is the THC:CBD mouth spray?

It is a prescription medicine called nabiximols that contains THC and CBD in roughly equal amounts. In studies, it increased the likelihood that people with MS reported less muscle stiffness in the short term; its effect on quality of life was small or absent. In some countries, including the United Kingdom, it is approved as an add-on to existing treatment for moderate to severe MS spasticity that has not improved enough with other spasticity medicines; according to the product information, it is tried for 4 weeks and stopped if there is no clear improvement. Because it contains THC, it can cause intoxication or mental fogginess.

Q: What are the side effects of the spray?

The most common side effects in studies were dizziness and fatigue; these mostly appeared in the first weeks and were mild to moderate. Side effects related to the nervous system and mental health, and stopping treatment because of side effects, were more common than with placebo. The product information also warns that the risk of falls may increase in people whose muscle strength is insufficient once spasticity decreases. THC can affect driving and thinking.

Q: Can CBD be used together with my MS medicines?

MS studies did not look at drug interactions separately. Because CBD can slow the breakdown of some medicines in the body, if you take medicines regularly, it is important to make this decision together with your neurologist.

Q: Can CBD oil be obtained with a prescription for MS spasticity in Turkey?

In Turkey, products derived from hemp 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 classified 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 no more than 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, which is approved for MS spasticity in some countries, is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency) (September 28, 2026), and importing it from abroad requires the agency's written approval. If you are considering using it, talk to your doctor first.

Q: Do CBD or cannabis products help with bladder problems caused by MS?

The evidence on this is weak and comes only from THC-containing products. In the bladder part of a large 630-person MS study, oral cannabis extract and THC reduced urinary incontinence slightly more than an inactive treatment (placebo). In a 135-person study done specifically for the bladder, however, the mouth spray containing THC and CBD was no different from placebo in the main measure, the number of incontinence episodes; some measures, such as nighttime urination and overall bladder complaints, improved. Two large studies that assessed the bladder as an additional measure found no difference, and in an analysis pooling the controlled studies, the effect remained very small. The American Academy of Neurology also states that the spray is probably ineffective for urinary incontinence. Pure CBD has never been tested for bladder problems in MS. This spray is approved for spasticity, not for bladder problems. The best course is to talk about your bladder complaints with your neurologist or urologist.

Q: Do CBD or cannabis products help with MS-related tremor?

The evidence on this is limited and weak. In a controlled study of 14 MS patients with tremor in their arms, oral cannabis extract did not bring improvement different from an inactive medicine (placebo) on tests measuring tremor. In a study with a mouth spray containing THC and CBD, the patient-reported tremor score also improved similarly to placebo. In an older 8-person study without a comparison group, two patients' coordination improved, but this design does not show the cause of the improvement. Pure CBD has never been tested in MS-related tremor. If tremor makes your daily life harder, you can talk with your neurologist about treatment options.

What does the research say?

According to a comprehensive review that pooled 25 studies (3,763 people) of cannabis-based products in MS, the THC:CBD mouth spray called nabiximols increases the number of people who report a marked reduction in spasticity in the short term. The certainty of this finding is moderate. The spray has little or no effect on quality of life. The difference in muscle stiffness measured by a doctor during an examination was very small or absent (low certainty). A 2026 review of 27 studies through the end of 2025 also found that the spray reduced patient-reported muscle stiffness by an average of 0.8 points on a 0–10 scale, but rated the certainty of this result as low.

In one of the large studies of the spray, all participants first tried the spray for 4 weeks; only those who responded were then randomly assigned to the spray or to an inactive treatment (placebo). Spasticity was clearly lower in the spray group. However, because people who did not respond at the start were not included, this design makes the effect look larger than it would be across all people with MS. In a 2019 study using the same design (106 people), marked improvement after 12 weeks was seen in 77% of the spray group and 32% of the placebo group. When 36 people who had used the spray for years were randomly switched from the spray to placebo, treatment was counted as failed within 4 weeks in 94% of those switched to placebo and in 44% of those who stayed on the spray (at least a 20% worsening of spasticity, or leaving the study).

In a study of the spray published in 2024 with 68 patients, muscle stiffness was measured this time not by the patients' own reports but by a doctor's examination; on this measure, there was no difference between the spray and placebo. In a companion study of 31 patients that used the same measure, muscle stiffness decreased slightly more in the spray group; in another study of 137 patients in the same program, there was no difference between the spray and placebo in the number of muscle contractions (spasms) that patients recorded in a diary. These two studies were stopped early because of a business decision by the sponsor, and their results were published only in the ClinicalTrials.gov registry (no peer-reviewed article). Looking at the reviews, the spray's benefit is seen mostly in the muscle stiffness that patients report themselves.

This spray contains THC and CBD in roughly equal amounts, so the results cannot be applied to pure CBD oil. Pure CBD, meanwhile, was randomly compared with placebo in two small studies. In a study of 49 people with MS in Iran, the CBD dose was increased to 80 mg a day over 4 weeks; there was no difference in muscle stiffness, but a short walking test and the most severe pain improved more in the CBD group. In a study in Denmark of 134 people with MS or spinal cord injury, muscle stiffness and pain in the group taking up to 45 mg of CBD a day were also no different from placebo. In a small 2003 crossover study of 24 people (18 with MS), a CBD-rich plant extract was also tested, but no separate spasticity result for this product was published. A study in Canada comparing pure CBD (up to 200 mg a day), THC, and the two together with placebo, planned to enroll 250 people, is registered; it has no results yet.

Many studies have also been done with oral cannabis extract and synthetic THC. In the largest study, with 630 participants in the United Kingdom (15 weeks), there was no difference from placebo in muscle stiffness measured by a doctor; patient-reported spasticity and pain did improve, but some participants in the treatment groups had figured out which group they were in. In another UK study of 279 people, the number of people reporting relief of muscle stiffness with cannabis extract was about twice that with placebo (29% vs. 16%). Results were mixed in smaller studies; in a 3-day study of smoked marijuana (30 people), doctor-measured muscle stiffness decreased but thinking speed slowed; most participants were used to cannabis and largely guessed correctly which cigarette they had smoked. In reviews, results with these products are less consistent than those with the spray, and the certainty of the evidence is low.

There are also data from everyday practice. In Italy's national system, which recorded 1,615 patients starting the spray, spasticity decreased by at least 20% in 70% of patients by the end of the first month; however, about 40% of patients stopped treatment within 6 months, mainly because they did not see enough effect or because of side effects. In an observational study of 276 patients in Germany, just over half of patients were still using the spray at month 3. Studies like these have no comparison group, so there is no way to know how much of the improvement is due to the medicine.

Most people with MS develop bladder problems over time (frequent urination, a sudden urge to urinate, urinary incontinence). Cannabinoids have been tested for this only with THC-containing products. There are two controlled studies that looked specifically at the bladder. In the bladder part of the large 630-person UK study, among participants who kept a bladder diary, urinary incontinence decreased by 38% with oral cannabis extract, by 33% with THC, and by 18% with placebo; both products were significantly better than placebo, but the difference from placebo was about 0.2 incontinence episodes a day. In an 8-week study of 135 people done specifically for the bladder, the mouth spray containing THC and CBD was no different from placebo in the main measure, the daily number of incontinence episodes; nighttime urination, the daily number of urinations, and patients' overall rating of their bladder improved more in the spray group. In two large studies that assessed the bladder as an additional measure, there was no difference from placebo in bladder complaints: a 160-person spray study that looked at many MS symptoms together, and a 3-year, 498-person study of oral THC that examined disease progression. A 2018 meta-analysis that pooled placebo-controlled studies found a very small benefit on bladder function; when studies supported by the manufacturer were removed, this benefit was not statistically significant. The American Academy of Neurology's MS guideline (2014; reaffirmed in 2026) states that the spray may be helpful for urinary frequency but is probably ineffective for urinary incontinence. A 2017 meta-analysis found the evidence on this weak; a 2026 review also noted that the data are limited and come mostly from studies without a comparison group. Pure CBD has never been tested for this; a small study in Canada comparing THC and CBD for thinking skills and bladder symptoms is ongoing.

Some people with MS have a tremor that becomes more noticeable with movement, especially in the arms, and problems with balance and coordination (ataxia); these symptoms can make everyday tasks such as eating and writing harder. The idea that cannabis might help tremor came from animal experiments and occasional patient accounts. In a small 1983 study without a comparison group (open-label), in which THC by mouth was given to 8 MS patients severely disabled by tremor and ataxia, two patients' coordination improved on examination and five said they felt better; but because there was no comparison group, it cannot be known whether this was due to THC. In a crossover study of 14 MS patients with tremor in their arms (each patient took both the medicine and placebo in turn), oral cannabis extract did not bring improvement different from placebo on any of the objective tests measuring tremor; patients tended to feel that their tremor eased a little more with the extract, but this difference was not significant. In the 160-person study with the mouth spray containing THC and CBD, among the 50 patients whose tremor was assessed, the patient-reported tremor score improved similarly in the spray and placebo groups. The American Academy of Neurology's MS guideline considers oral cannabis extract and THC probably ineffective for tremor and states that the mouth spray may not be recommended for tremor either; a 2022 systematic review also did not recommend cannabis-based medicines for MS tremor because the results were inconclusive and because of side effects. Pure CBD has never been tested in MS-related tremor. The evidence rests on a few small studies and is weak.

Strength of evidence: ●●○○ Weak evidence. Finding: No effect found. What does this mean?

Ongoing research on this topic

Trials testing CBD for this topic on ClinicalTrials.gov: 3 under way (3 recruiting); results are awaited from 1 that ended in the last two years. A trial being under way does not show that CBD works.

NCT05092191: Phase 2, recruiting, target 250 participants
NCT05269628: Phase 2, recruiting, target 166 participants
NCT06261489: Phase 2, recruiting, target 30 participants

Registries in other countries also list 1 recruiting trial on this topic: other registries.

All trials on this topic and their history

Possible side effects and drug interactions

The most common side effects of the THC:CBD spray are dizziness and fatigue; side effects related to the nervous system and mental health may also be more common, and more people stop treatment because of side effects. THC can affect driving, attention, and thinking. In healthy volunteers, pure CBD increased the risk of diarrhea.

These studies did not look at drug interactions separately. CBD can slow the breakdown of some medicines in the body; this matters if you take more than one medicine. The product information for the THC:CBD spray lists interactions with some antifungal, HIV, and antibiotic medicines (e.g., ketoconazole, itraconazole, fluconazole, ritonavir, clarithromycin, rifampin), some epilepsy medicines (carbamazepine, phenytoin, phenobarbital), and St. John's wort; it also lists an increased sedative effect with sleep medicines, muscle relaxants, and alcohol.

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.

MS Spasticity: medicines used and their interactions with CBD
Medicine	Importance	Warning	Source
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
Gabapentin (Gabateva, Neruda), Pregabalin (Lyrica)	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

To check interactions with the medicines you take: CBD drug interaction checker.

How was CBD used in studies?

In the pure CBD studies, the dose was between 45 and 80 mg a day (study dose; not a personal recommendation); in one study, it was started at 5 mg a day and raised to 70 mg over two weeks, then to 80 mg. These studies lasted 4–6 weeks. In the THC:CBD spray studies, the dose was adjusted for each person; on average, 6 to 12 sprays a day were taken (about 17–33 mg THC and 16–31 mg CBD; study dose, not a personal recommendation); the spray was used in addition to existing treatments, and the studies lasted between 3 and 48 weeks. In the studies of oral cannabis extract and THC capsules, the dose was increased gradually up to a maximum of 10 to 30 mg THC a day (study dose; not a personal recommendation).

Study details (for health professionals)

Most of the evidence in MS spasticity concerns the prescription THC:CBD medicine nabiximols (Sativex): it increases the number of people reporting a significant reduction in spasticity in the short term (moderate certainty), with little or no effect on quality of life; the difference in doctor-measured muscle tone, however, is very small or absent (Cochrane: −0.23 points on the Ashworth scale, low certainty); in a 2024 RCT (68 people) with muscle tone as the primary endpoint there was no difference from placebo, and a small difference was found only in its 31-person companion study of the same design, whose results were published only on ClinicalTrials.gov; in the same program's 137-person parallel study, there was no difference in the number of muscle spasms that patients recorded in a diary (these two studies were stopped early by a business decision of the sponsor). The largest differences come from studies that first gave the drug to everyone and then randomized those who responded (enriched designs); a 2026 review of 27 studies through the end of 2025 rated the certainty of the patient-reported benefit as low. In the largest study with oral cannabis extract or synthetic THC (CAMS, 630 people), there was no difference in doctor-measured spasticity, but patient-reported spasticity improved; in the 279-person MUSEC trial, the number of people reporting relief of muscle stiffness was about twice that with placebo (29.4% vs. 15.7%). For pure CBD, there are only two small, short RCTs (55 people in total received pure CBD): in the study that raised the dose to 80 mg/day over 4 weeks (49 people), spasticity was no different from placebo, and only the walking test and peak pain improved more; in the CBD arm that took up to 45 mg/day for 6 weeks (31 people), there was no difference in spasticity or pain. Higher doses have not been tested in controlled parallel studies. Oral synthetic THC (dronabinol) did not slow disease progression over 3 years in progressive MS (498-person RCT). Nabiximols results cannot be applied to pure CBD oil. Two RCTs looked specifically at bladder problems caused by MS, both with THC-containing products: in the CAMS bladder substudy, incontinence frequency adjusted for baseline imbalance decreased by 38% with cannabis extract, by 33% with THC, and by 18% with placebo (both active groups significantly better than placebo; absolute difference vs. placebo 0.21 and 0.16 episodes a day, as calculated by Torres-Moreno 2018); in the 135-person nabiximols RCT done specifically for the bladder (8 weeks, sponsored by the manufacturer), there was no difference in the primary outcome, the daily number of incontinence episodes (−0.11; 95% CI −0.47 to 0.26), while secondary measures such as nighttime urination, the daily number of urinations, and the patient's overall bladder assessment favored nabiximols. Two large RCTs that assessed the bladder as a secondary measure found no difference: in Wade 2004 (160 people, spray), on the bladder problem VAS (difference −6.3; 95% CI −14.9 to 2.4; p = 0.15) and on the bladder control test (p = 0.89; ClinicalTrials.gov result), and in CUPID (498 people, 3 years, oral THC), on secondary measures including the bladder (full report; Torres-Moreno 2018). In the 2018 meta-analysis pooling placebo-controlled RCTs, the effect on bladder function was very small (standardized mean difference −0.11; 95% CI −0.22 to −0.0008) and was not significant once the studies supported by the manufacturer were removed. The MS-specific 2017 meta-analysis (2 RCTs and 1 study without a comparison group, 426 patients) reported a reduction in urinary incontinence but considered the evidence base weak; from the abstract it is not clear what its pooled figure (−0.35 episodes a day) compares with what, and this figure is larger than the differences vs. placebo in the included RCTs (0.11–0.21 a day). A 2026 scoping review (12 studies, 3 of them RCTs) also found the evidence limited and largely observational. In three small studies without a comparison group (15–31 people; Brady 2004, PMID 15327041; Maniscalco 2018, PMID 29052091; Torri Clerici 2023, PMID 37062198), urinary symptoms and some urodynamic measures improved. There are no bladder studies of pure CBD in MS. In a controlled study of 40 people with MS who had smoked cannabis almost daily for a long time and had cognitive impairment (groups were assigned by registration number, not randomly), those who stopped for 28 days showed clear improvement on tests of memory, processing speed, and executive function, while those who continued did not (Feinstein 2019). The UK national guideline (NICE, 2019) recommends a 4-week trial of the THC:CBD spray for moderate to severe MS spasticity that has not improved with other medicines, and continuing it if patient-reported symptoms decrease by at least 20%; the committee judged most of the evidence to be of low quality and noted that the evidence for other cannabis products was much more limited. The American Academy of Neurology's guideline on complementary therapies in MS (2014; reaffirmed on February 21, 2026) lists oral cannabis extract (level A), THC, and the THC:CBD spray (level B) as options for patient-reported spasticity symptoms and pain (excluding central neuropathic pain); it states that these products are probably ineffective for doctor-measured spasticity, and that the spray is probably helpful for urinary frequency and probably ineffective for urinary incontinence (level B); the guideline is based on studies up to September 2013. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 25 randomized controlled trials examining spasticity or the course of the disease with cannabinoids in people with MS (three with results only in the ClinicalTrials.gov registry) and more than 20 systematic reviews asking the same question were found; all of the randomized trials, the 3 most comprehensive reviews, and 3 large real-world and safety registries from different countries are in the table below. Only two of the randomized trials tested pure CBD. In an additional October 2026 search (bladder problems in MS only; PubMed and ClinicalTrials.gov), the only separate RCT on bladder problems, two reviews on this topic, and the American Academy of Neurology's MS guideline were added to the table; the CAMS bladder substudy is in the CAMS row, the bladder results of the other RCTs in the table and of the 2018 meta-analysis are in their own rows, and the three small bladder studies without a comparison group are mentioned only in this text. The NICE guideline and the controlled study of the effect of stopping on thinking skills in long-term cannabis users were also added to the table. Trials in MS done only for pain were not included in this table; no studies from Turkey were found. In an additional October 2026 search (MS-related tremor and ataxia only; PubMed, Cochrane, ClinicalTrials.gov, Europe PMC), the only randomized study that looked specifically at tremor (Fox 2004: 14 people, crossover, oral cannabis extract; no difference from placebo on objective tremor measures, finger tapping faster with placebo), an 8-person THC study without a comparison group (open-label) (Clifford 1983; improvement in coordination on examination in 2 patients) and a systematic review on this topic (Pourmohammadi 2022; did not recommend cannabis-based medicines) were added to the table; the tremor result of Wade 2004 (no difference in the patient-reported tremor score: −6.85; 95% CI −20.31 to 6.60) was written into its own row. There are no studies of pure CBD in MS-related tremor; the evidence for tremor is weak.

Evidence assessment: Pure CBD: weak (two small, short RCTs, both negative for spasticity; low doses: 45–80 mg/day)

CBD alone

In two small RCTs, pure CBD did not reduce spasticity more than placebo (45–80 mg/day, 4–6 weeks); one study found improvement in a walking test and in peak pain. Pure CBD has never been tested for MS-related bladder problems or tremor.

Products containing THC

Nabiximols (THC:CBD about 1:1, prescription) reduces perceived spasticity in the short term (OR 2.51; pooled from four spray studies and one oral cannabis extract study; moderate certainty, a 2026 review rated certainty as low); the difference in doctor-measured muscle tone is very small or absent (low certainty; the 2024 RCT was negative, its unpublished 31-person companion study was positive); in the same program's unpublished 137-person study, there was no difference in the number of muscle spasms patients recorded in a diary; results with oral cannabis extract and THC are mixed (in the largest study, benefit only in patient reports); nervous system and psychiatric side effects may be increased. In MS-related tremor, oral cannabis extract (14-person crossover RCT) and THC:CBD spray (tremor measurement in a 160-person RCT) were no different from placebo.

Evidence: Nabiximols: moderate (benefit in patient-reported spasticity; certainty moderate in Cochrane 2022, low in a 2026 review; difference in doctor-measured muscle tone very small or absent); MS-related tremor: weak (a single 14-person RCT looking specifically at tremor and a secondary tremor measurement in one RCT; no difference in either)

Approved drug regimen

Pure CBD is not approved for MS spasticity. Nabiximols (a mouth spray containing THC and CBD; 2.7 mg THC + 2.5 mg CBD per spray) is approved in many countries, including the United Kingdom (in 29 countries, according to a 2024 publication by authors from the manufacturer), as an add-on to existing treatment for moderate to severe MS spasticity in adults who have not responded adequately to other spasticity medicines and who show clear improvement during an initial trial period. Treatment is started and supervised by a specialist doctor experienced in treating these patients. Dosing schedule in the product information: 1 spray in the evening on day 1; a morning dose is added on day 5; the daily number is increased gradually up to a maximum of 12 by day 14 (at least 15 minutes between sprays); in clinical studies, the median was 8 sprays/day; more than 12 a day is not recommended. If there is no clinically meaningful improvement in spasticity symptoms after 4 weeks (at least 20% on a 0–10 scale in studies), treatment is stopped. Not recommended under 18 years of age or in moderate or severe liver impairment. Source: UK product information (text revision April 2, 2026) §4.1, §4.2. Turkey: the active substance (tetrahydrocannabinol and cannabidiol, oromucosal spray) is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency) (September 28, 2026), among medicines that require a red prescription and can be imported with the agency's written approval.

Dose range in studies

Pure CBD 45–80 mg/day (4–6 weeks); nabiximols up to 12 sprays a day (32.4 mg THC + 30 mg CBD); mean 8.3 sprays/day in Novotna 2011; mean 6.4–12.4 sprays/day in the other spray studies; oral cannabis extract and THC capsules up to 10–30 mg THC/day (CAMS and MUSEC 25 mg, CUPID 28 mg)

Starting dose and titration

Mousavi 2025: from 5 mg/day to 70 mg/day over 2 weeks, then 80 mg/day; Hansen 2023: standard 3-week titration; Bethoux 2024: 14 days of dose adjustment in each period; nabiximols product information: start with 1 spray in the evening on day 1, increase the number gradually up to a maximum of 12 by day 14 (at least 15 minutes between sprays), stop if there is no clear improvement at 4 weeks (at least 20% on a 0–10 scale in studies); MUSEC: from 5 to 25 mg THC/day over 2 weeks

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.

MS Spasticity and CBD: studies reviewed
Study	Participants	Product	Dose and titration	Duration	Result	Source
Mousavi 2025 Randomized, placebo-controlled study (blinding not stated in the abstract)	49 (24 CBD / 25 placebo) People with MS who have walking difficulty due to spasticity (Iran)	Purified CBD, oral drops	From 5 mg/day to 70 mg/day over 2 weeks, 80 mg/day in weeks 3–4 Gradual increase over 2 weeks (details not in the abstract)	1 month (spasticity measured at weeks 4 and 8)	Spasticity severity did not differ between groups; the time on the 7.6-meter (25-foot) timed walk test (p=0.031) and peak pain (p=0.033) decreased more with CBD Side effects: Not reported (in the abstract)	PMID 40498097, doi:10.1007/s00210-025-04347-w
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; the two together	CBD up to 45 mg/day, THC up to 22.5 mg/day (divided into 3 doses a day, up to 9 capsules) Standard titration over 3 weeks; patients stayed at a lower dose if they had sufficient effect or side effects	6 weeks + 1 week of tapering	In the pure CBD group, improvement in spasticity did not differ 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; no group differed from placebo in neuropathic pain either. Spasticity was assessed in the 100 patients who met the criterion; only 134 of the targeted 448 people could be enrolled Side effects: Side effects most common in the THC-containing 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
Wade 2003 Double-blind, placebo-controlled, randomized series of single-patient crossover trials	24 (18 MS, 4 spinal cord injury, 2 other) Patients with neurological symptoms (pain, spasticity, muscle spasms, bladder problems) not responding to standard treatment; most with MS (United Kingdom)	Sublingual spray: THC-rich, CBD-rich, and 1:1 THC:CBD plant extracts, and placebo	2.5–120 mg per 24 hours (based on symptoms and unwanted effects) Self-titrated by the patient	2-week periods for each product (four periods)	Pain decreased significantly more than with placebo with both the THC-rich and the CBD-rich extract. Bladder control, muscle spasms, and spasticity improved with the extracts in some patients; a separate spasticity result by product and the THC content of the CBD extract are not in the abstract. Cochrane 2022 did not include it in the review because no separate data were given for patients with MS; in the 2026 network meta-analysis, the CBD-rich extract was not significantly different from placebo. Very small Side effects: With the THC-containing extract, transient drops in blood pressure and intoxication in 3 patients during rapid initiation; unwanted effects were generally well tolerated (abstract)	PMID 12617376, doi:10.1191/0269215503cr581oa
Novotna 2011 Phase 3, enriched design, double-blind RCT	572 enrolled; 241 randomized (124 nabiximols / 117 placebo) Resistant MS spasticity	Nabiximols mouth spray, add-on treatment	2.7 mg THC + 2.5 mg CBD per spray; up to 12 sprays a day (32.4 mg THC + 30 mg CBD). Mean: 6.9 sprays/day in the single-blind phase, 8.3 sprays/day in the randomized phase (~22.4 mg THC + 20.8 mg CBD)	4-week single-blind trial + 12 weeks randomized	Significant difference in favor of nabiximols in spasticity NRS (0.84 points on a 0–10 scale; 95% CI 0.40–1.29; p=0.0002). Only those who responded in the first 4 weeks were randomized; this design makes the effect look larger than it would be across all people with MS. No significant difference on objective measures (Ashworth, 10 m walk) (ClinicalTrials.gov) Side effects: In the randomized phase, serious side effects 6/124 vs. 1/117; vertigo 7 vs. 1, fatigue 6 vs. 1 (ClinicalTrials.gov)	PMID 21362108, doi:10.1111/j.1468-1331.2010.03328.x, NCT00681538, Sativex product information, mean number of sprays from review tables (PMC6324456, PMC8214588)
Bethoux 2024 (RELEASE MSS1) Phase 3, multicenter, double-blind, placebo-controlled crossover RCT	68 People with MS whose lower limb spasticity persisted despite an oral antispastic medicine	Nabiximols (THC:CBD mouth spray, prescription)	Up to 12 sprays a day; 14 days of dose adjustment in each period, then 7 days at a stable dose (ClinicalTrials.gov); mean dose taken not reported 14 days of dose adjustment + 7 days at a stable dose in each period	2 × 3 weeks	No difference from placebo in doctor-measured muscle tone (MAS LLMT-6) (difference 0.04; p=0.72); a different result from earlier studies using patient-reported measures; in the 31-person companion study using the same measure (RELEASE MSS5; stopped early, results only in the registry), there was a small but significant difference (−0.29; 95% CI −0.48 to −0.10) Side effects: Any side effect 27/66 vs. 15/65; dizziness 10 vs. 1, fatigue 5 vs. 1; serious side effects 1 vs. 1 (ClinicalTrials.gov); according to the authors, consistent with the known safety profile	PMID 39106541, doi:10.1016/j.msard.2024.105740, NCT04657666
Zajicek 2013 (CUPID) Multicenter, parallel, double-blind, placebo-controlled RCT (2:1)	498 randomized (dronabinol 329, placebo 164 received at least one dose) Primary or secondary progressive MS, aged 18–65 years (United Kingdom)	Oral synthetic THC (dronabinol)	Up to 28 mg/day; adjusted based on body weight and side effects Based on weight and side effects	36 months	No difference from placebo in EDSS progression (HR 0.92; 95% CI 0.68–1.23; p = 0.57); no difference on the MSIS-29 physical subscale (−0.9; −2.0 to 0.2). No significant effect on secondary clinical measures or MRI measures either (full report: Ball 2015); according to a meta-analysis, patient-reported spasticity, pain, and bladder dysfunction results numerically favored placebo (Torres-Moreno 2018). Because progression was slower than expected, the power to detect change may have been limited Side effects: At least one serious side effect 35% (dronabinol) and 28% (placebo); according to the authors, no serious safety concerns	PMID 23856559, doi:10.1016/S1474-4422(13)70159-5, ISRCTN 62942668, full report: Ball 2015, PMID 25676540
Markovà 2019 (SAVANT) Two-phase, enriched design: 4-week open-label trial, washout, then double-blind, placebo-controlled parallel RCT (15 centers)	191 entered the open-label trial; 106 randomized (53 nabiximols / 53 placebo) People with MS whose moderate to severe spasticity persisted despite an optimized oral spasticity medicine (baclofen, tizanidine) (Czechia, Austria)	Nabiximols (THC:CBD mouth spray; 2.7 mg THC + 2.5 mg CBD per spray) and placebo; in both groups, the doses of current spasticity medicines could be adjusted	Up to 12 sprays a day; mean 7.3 sprays/day (~20 mg THC + 18 mg CBD) Dose readjustment after washout	4-week open-label trial + 12 weeks randomized	Only those whose spasticity improved by at least 20% in the first 4 weeks were randomized. At week 12, at least 30% improvement 77.4% vs. 32.1% (p < 0.0001); spasticity NRS (p < 0.0001), pain (p = 0.0013), and modified Ashworth (p = 0.0007) also favored the spray. This design makes the effect look larger than it would be across all patients: in Cochrane 2022, this study had the largest effect (OR 7.24) and was the main source of heterogeneity. Funded by the manufacturer Side effects: Side effects mild to moderate, no new safety concerns (abstract)	PMID 29792372, doi:10.1080/00207454.2018.1481066, EudraCT 2015-004451-40, PMID 32065006, PMID 37209500
Notcutt 2012 Multicenter (5), placebo-controlled, randomized withdrawal study (parallel)	36 randomized (18 nabiximols / 18 placebo) People with MS spasticity who had been using the spray with benefit for at least 12 weeks (mean 3.6 years) (United Kingdom)	Nabiximols (THC:CBD mouth spray) or placebo (abrupt discontinuation of the spray)	The patient's current effective dose; mean 8.25 sprays/day	4 weeks	Treatment failure (at least 20% worsening of spasticity or leaving the study) was 44% (8/18) among those continuing the spray and 94% (17/18) among those switched to placebo (p = 0.013). The between-group difference in change in spasticity NRS and modified Ashworth score was not significant (registry); patient and caregiver global impressions favored the spray. Very small; most of the placebo group left the study early. Funded by the manufacturer Side effects: Serious side effects 1 vs. 0 (registry); the effect of abrupt discontinuation is not detailed in the abstract	PMID 21878454, doi:10.1177/1352458511419700, NCT00702468
Collin 2007 Multicenter (8 in the United Kingdom, 4 in Romania), double-blind, placebo-controlled parallel RCT (2:1)	189 randomized (124 nabiximols / 65 placebo); 184 ITT People with MS with marked spasticity (Ashworth ≥2) in at least two muscle groups who were not getting adequate benefit from current treatment	Nabiximols (THC:CBD mouth spray; 2.7 mg THC + 2.5 mg CBD per spray) and placebo	Up to 48 sprays a day; mean 9.4 sprays/day (~25 mg THC + 23.5 mg CBD) Self-titrated by the patient	6 weeks	Primary outcome, spasticity NRS (0–10): difference −0.52 points (95% CI −1.03 to −0.004; p = 0.048); at least 30% improvement 40% vs. 22% (p = 0.014). The product information considers the clinical importance of this difference debatable. No difference in Ashworth score (difference −0.11; −0.29 to 0.07) or spasm frequency. Funded by the manufacturer Side effects: Discontinuation due to side effects 6 vs. 2; dizziness 40/124 vs. 7/65 (registry). In the open-label extension (146 patients, mean 334 days, mean 7.3 sprays a day), 36% stopped in the first year (14% due to side effects, 9% due to lack of effect); most common dizziness (24.7%) and fatigue (12.3%); no tolerance developed	PMID 17355549, doi:10.1111/j.1468-1331.2006.01639.x, NCT00711646, PMID 22878432, NCT01606137
Collin 2010 Multicenter (15 in the United Kingdom, 8 in Czechia), double-blind, placebo-controlled parallel RCT	337 randomized (167 nabiximols / 170 placebo) People with advanced MS and moderate to severe spasticity (NRS ≥4) not adequately improved by current treatment	Nabiximols (THC:CBD mouth spray) and placebo, added to current treatment	Up to 24 sprays a day; mean 8.5 sprays/day (1–22) Self-titrated by the patient	15 weeks (14 weeks of treatment)	In the primary analysis (ITT), the difference in spasticity NRS was not significant (−0.23; 95% CI −0.59 to 0.14; p = 0.22); at least 30% improvement in 51 vs. 42 people (OR 1.34; 0.83–2.17). Only in the 79% per-protocol group was the difference significant (−1.3 vs. −0.8; p = 0.035). No difference in modified Ashworth score. The product information summarizes this study as 'failed to show a significant treatment effect'. Funded by the manufacturer Side effects: Serious side effects 15/167 vs. 7/170; dizziness 53 vs. 17 (registry); mostly mild to moderate	PMID 20307378, doi:10.1179/016164109X12590518685660, NCT01599234
Wade 2004 Multicenter (3), double-blind, placebo-controlled parallel RCT	160 randomized (80 nabiximols / 80 placebo) People with MS with at least one prominent symptom among spasticity, spasms, bladder problems, tremor, or pain (United Kingdom)	Nabiximols (THC:CBD mouth spray; 27 mg THC + 25 mg CBD per mL) and placebo	2.5–120 mg THC and CBD a day (up to 48 sprays); mean 12.4 sprays/day (~33 mg THC + 31 mg CBD) Self-titrated by the patient (up to 8 sprays in 3 hours)	6 weeks	The primary outcome (patient's most troublesome symptom, 0–100 VAS) did not differ from placebo (difference −5.9; 95% CI −13.5 to 1.7). The spasticity VAS improved significantly vs. placebo in the publication's abstract (p = 0.001); in the ClinicalTrials.gov result, the difference for the same measure was −7.1 points (95% CI −14.6 to 0.4; p = 0.062): the two sources may have used different analyses. No difference from placebo on the bladder problem VAS (−28.1 vs. −21.6; median difference in final values −6.3, 95% CI −14.9 to 2.4; p = 0.15) or on the bladder control test (difference −0.12; 95% CI −1.77 to 1.54; p = 0.89) (ClinicalTrials.gov result, secondary measures). No difference from placebo on the tremor VAS (25 vs. 25 people whose tremor was assessed) (−21.4 vs. −15.7 points; difference −6.85; 95% CI −20.31 to 6.60; p = 0.31; ClinicalTrials.gov result, secondary measure). No clear negative effect on cognitive function or mood. Funded by the manufacturer Side effects: Dizziness 25/80 vs. 10/80, fatigue 12 vs. 3 (registry); intoxication generally mild. In the open-label extension (137 patients, mean 434 days), 42% stopped (24 for lack of effect, 17 for side effects); a first-ever seizure in 4 patients; no consistent withdrawal syndrome during a planned 2-week interruption	PMID 15327042, doi:10.1191/1352458504ms1082oa, NCT01610700, PMID 17086911, NCT01610687
NCT04203498 (RELEASE MSS3, registry results) Multicenter (37), double-blind, placebo-controlled parallel phase 3 RCT; terminated early by a business decision of the sponsor	139 randomized (69 / 70); 137 received the drug; 121 completed People with MS whose spasticity persisted despite at least one optimized oral spasticity medicine (baclofen or tizanidine) (US, United Kingdom, Czechia, Poland, Romania)	Nabiximols (THC:CBD mouth spray) and placebo, added to current treatment	Morning and evening; up to 12 sprays a day	12 weeks	The primary outcome (change in daily number of muscle spasms, weeks 9–12) did not differ from placebo: −3.84 vs. −3.11; difference −0.73 (95% CI −2.54 to 1.08; p = 0.43). No clear difference on the MS spasticity scale (MSSS-88) either (no statistics given). Stopped before reaching the planned number of participants; results only on ClinicalTrials.gov, no peer-reviewed publication. Sponsor: the manufacturer Side effects: Any side effect 47/67 vs. 32/70; discontinuation due to side effects 4 vs. 1; dizziness 14 vs. 5, drowsiness 7 vs. 2; serious side effects 3 vs. 5	NCT04203498, EudraCT 2019-002623-14, results in the registry, May 8, 2024, no publication found in PubMed as of October 2026)
NCT04984278 (RELEASE MSS5, registry results) Multicenter (7), triple-blind, placebo-controlled, randomized crossover phase 3 study; terminated early by a business decision of the sponsor	31 randomized (16 / 15); 30 people analyzed on both treatments People with MS and lower limb spasticity (MAS ≥2 in at least 2 muscle groups) (Poland, Czechia, Spain, United Kingdom)	Nabiximols (THC:CBD mouth spray) and placebo	Up to 12 sprays a day (split between morning and evening); mean dose taken not in the registry In each period, starting at 1 spray/day and reaching the optimal dose or a maximum of 12 within the first 14 days	2 × 21 days (about 14 days of dose adjustment + 7 days at a stable dose in each period; at least 7 days of washout in between)	Primary outcome, doctor-measured lower limb muscle tone (MAS LLMT-6): −0.32 vs. −0.04; difference −0.29 (95% CI −0.48 to −0.10; p = 0.005), in favor of the spray. Positive, unlike the 68-person companion study using the same measure (Bethoux 2024, RELEASE MSS1); very small and stopped early; results only on ClinicalTrials.gov, no peer-reviewed publication. Sponsor: the manufacturer Side effects: Any side effect 19/30 vs. 6/30; fatigue 4 vs. 0, vertigo 2 vs. 0; no serious side effects; 1 person withdrew because of side effects	NCT04984278, EudraCT 2020-003271-18, results in the registry, February 5, 2024, no publication found in PubMed as of October 2026)
Vachová 2013 Multicenter, double-blind, placebo-controlled parallel RCT (phase 4)	121 randomized (62 nabiximols / 59 placebo); 98 completed People with MS and moderate spasticity not adequately improved by current treatment (Czechia)	Nabiximols (THC:CBD mouth spray) and placebo	Up to 12 sprays a day; mean 7.6 sprays/day in the first month and 6.4 in the last period	48 weeks	Primary outcome, cognitive function (PASAT): no decline with the spray over 48 weeks, not worse than placebo (difference −1.47). No difference in depression score. Patient global impression of spasticity favored the spray (OR 4.02; 95% CI 1.96–8.22); caregiver and doctor impressions also favored the spray. No difference in modified Ashworth score (difference −2.36; −6.09 to 1.37; p = 0.21) or in the 10-meter walk. Results from the ClinicalTrials.gov registry; the article is in a journal not indexed in PubMed. Funded by the manufacturer; according to the registry, all publications had to be submitted to the company for review before publication Side effects: Any side effect 39/62 vs. 19/59; discontinuation due to side effects 8 vs. 2; serious side effects 5 vs. 0; vertigo 6 vs. 0, fatigue 5 vs. 1	doi:10.4172/jmso.1000122, NCT01964547, results in the registry, May 2, 2014), article: J Mult Scler (Foster City) 2013, 1(2)
Leocani 2015 Double-blind, placebo-controlled, randomized crossover study (single center)	44 randomized; 34 analyzed People with progressive MS and lower limb spasticity (Italy)	Nabiximols (THC:CBD mouth spray) and placebo	Up to 12 sprays a day; mean 7 sprays/day (~19 mg THC + 17.5 mg CBD) 2 weeks, according to the product information	2 × 4 weeks (including 2 weeks of dose adjustment; 2-week break in between)	The primary outcome (reflex ratio measured by nerve conduction, H/M) did not differ from placebo. At least 20% improvement in modified Ashworth score: 50% with the spray, 23.5% with placebo (p = 0.041). 6 people withdrew and 4 were excluded from the analysis; the study's power was reduced. Sponsored by a drug company (Almirall) Side effects: Side effects did not differ between groups (abstract)	PMID 26289497, doi:10.1007/s00415-015-7878-1, NCT01538225
Aragona 2009 Double-blind, placebo-controlled, randomized crossover study (single center)	17 People with secondary progressive MS and spasticity who had never used cannabis (Italy)	Nabiximols (THC:CBD mouth spray) and placebo	Flexible dose; mean 8.2 sprays/day (~22 mg THC + 20.5 mg CBD) Self-titrated by the patient	2 × 3 weeks (2-week break in between)	The primary aim was safety: no difference from placebo in psychiatric symptoms, cognitive function (PASAT), quality of life, fatigue, or motor function; spasticity was not measured in this publication. Blood THC levels were associated with some psychiatric symptom scores (interpersonal sensitivity, hostility, paranoid ideation). Very small; public funding Side effects: No serious side effects, abuse, or withdrawal; 1 person had increasing craving for the drug followed by depression	PMID 18978501, doi:10.1097/WNF.0B013E3181633497, PMID 18603457, pain reflex) and Tomassini 2014 (J Neurosci Rehabil, neurophysiology, not in PubMed)
De Blasiis 2021 Randomized controlled study without placebo (the control group received no treatment, no blinding); randomization method unclear	32 (22 nabiximols / 10 control) People with MS and spasticity (Italy)	Nabiximols (THC:CBD mouth spray); the control group received no spray	Not reported (in the abstract)	4 weeks	45 minutes after the first dose, improvement vs. control in several clinical measures and in 3D gait analysis in the spray group; the improvement was still present at week 4. Because there was no placebo or blinding, the effect cannot be separated from the medicine; Cochrane 2022 placed the study's classification on hold because the randomization and the definition of the control were unclear Side effects: Not reported (in the abstract)	PMID 33862313, doi:10.1016/j.msard.2021.102805
Zajicek 2003 (CAMS) Multicenter (33), double-blind, placebo-controlled, three-arm parallel RCT	667 enrolled; 630 treated (211 cannabis extract, 206 THC, 213 placebo); 611 in the primary outcome Patients with stable MS and muscle spasticity (Ashworth ≥2 in at least two muscle groups) (United Kingdom)	Oral capsules: cannabis extract (2.5 mg THC + 1.25 mg CBD per capsule), synthetic THC (dronabinol), and placebo	Based on body weight, up to 25 mg THC a day; mean ~13.6 mg THC (+ 6.8 mg CBD in the extract group) Gradual increase based on body weight and side effects	15 weeks; those who wished continued double-blind for up to 12 months	No difference in the primary outcome, the Ashworth spasticity score (p = 0.40; difference vs. placebo 0.32 for extract, 95% CI −1.04 to 1.67; 0.94 for THC, −0.44 to 2.31). Improvement in patient-reported spasticity 61%, 60%, and 46% (p = 0.003); some participants in the active groups figured out their group; the authors also reported an objective improvement in mobility. At 12-month follow-up, the Ashworth score decreased by 1.82 points in the THC group and by 0.10 with the extract, and increased by 0.23 with placebo (unadjusted p = 0.04). In the bladder substudy (CAMS-LUTS; among those keeping an incontinence diary, number of participants not in the abstract), incontinence frequency adjusted for baseline imbalance decreased by 38% with cannabis extract, 33% with THC, and 18% with placebo; both active groups were significantly better than placebo (p = 0.005 and p = 0.039); absolute difference vs. placebo 0.21 (extract) and 0.16 (THC) incontinence episodes a day (as calculated by Torres-Moreno 2018). Public funding Side effects: No details in the abstract; no important safety concerns reported at 12-month follow-up	PMID 14615106, doi:10.1016/S0140-6736(03)14738-1, PMID 16291891, PMID 16552618
Zajicek 2012 (MUSEC) Multicenter (22), double-blind, placebo-controlled parallel phase 3 RCT	279 randomized (144 cannabis extract / 135 placebo); 277 analyzed People with stable MS and muscle stiffness lasting at least 3 months (United Kingdom)	Oral standardized cannabis extract capsule (2.5 mg THC + 0.8–1.8 mg CBD per capsule) and placebo	From 5 mg up to a maximum of 25 mg THC a day; at the end of the study, mean ~17 mg THC + 8.5 mg CBD; 47% of the extract group reached the highest dose From 5 to 25 mg THC/day over 2 weeks	12 weeks (2 weeks of dose adjustment + 10 weeks at a stable dose)	Primary outcome: patient-reported relief from muscle stiffness at week 12, 29.4% vs. 15.7% (OR 2.26; 95% CI 1.24–4.13; one-sided p = 0.004); also in favor of the extract at weeks 4 and 8 and on the pain, spasm, and sleep scales. Doctor-measured spasticity was not the primary outcome. In the ClinicalTrials.gov registry, the study is listed as 'terminated due to recruitment problems and on the recommendation of an independent committee'. Joint public and manufacturer funding Side effects: Consistent with the known side effects of cannabinoids; no new safety concerns (abstract)	PMID 22791906, doi:10.1136/jnnp-2012-302468, NCT00552604, Germany)
Vaney 2004 Double-blind, placebo-controlled, randomized crossover study (single center, during inpatient rehabilitation)	57 enrolled; 50 ITT; 37 per protocol People with MS and spasticity not controlled by other medicines (Switzerland)	Oral cannabis extract capsule (2.5 mg THC + 0.9 mg CBD per capsule) and placebo	Starting at 15 mg THC a day and, if tolerated, increasing by 5 mg a day up to a maximum of 30 mg THC (mean ~18 mg THC + 6.5 mg CBD) Increase of 5 mg a day	14 days of extract + 7 days of placebo (3-day breaks in between)	In the ITT analysis, no significant difference from placebo on any measure; trends in favor of the extract in spasm frequency, mobility, and falling asleep. In the 37 patients who took at least 90% of the dose, spasm frequency (p = 0.013) and mobility (p = 0.01) improved (subgroup analysis). Public funding Side effects: Mild side effects and signs of intoxication were somewhat more frequent and pronounced in the active period; generally mild	PMID 15327040, doi:10.1191/1352458504ms1048oa
Killestein 2002 Double-blind, placebo-controlled, randomized three-period crossover study (single center)	16 People with progressive MS and severe spasticity (Netherlands)	Oral capsules: dronabinol (synthetic THC), cannabis plant extract containing the same amount of THC (20–30% CBD), and placebo	2.5 mg THC twice a day; if well tolerated, 5 mg twice a day (5–10 mg THC a day) Dose increase after 2 weeks	3 × 4 weeks (4-week breaks in between)	Neither THC nor the plant extract reduced spasticity more than placebo; the patients' global assessment worsened with both treatments. Very small; public funding Side effects: Side effects were more common with the plant extract; both treatments were found to be safe (abstract)	PMID 12011290, doi:10.1212/wnl.58.9.1404, Immune system publication from the same study: Killestein 2003, J Neuroimmunol
van Amerongen 2018 Two phases: double-blind crossover dose finding + 4-week double-blind, placebo-controlled parallel RCT (single center)	24 (12 THC / 12 placebo) People with progressive MS and moderate spasticity (Netherlands)	Oral THC tablet (ECP002A) and placebo	Based on the dose-finding phase; about 24 mg a day according to the Cochrane 2022 table, with a 4.5 mg increase after week 2 Increase after week 2; reduced in 2 patients because of side effects	4 weeks (parallel phase)	Pain and patient-perceived spasticity decreased when measured in the clinic right after the medicine, but not when measured in the daily diary; no difference from placebo in other clinical outcomes; no cognitive decline at weeks 2 and 4. Very small; funded by the manufacturer Side effects: Well tolerated (abstract); the dose was lowered in 2 patients because of side effects (Cochrane table)	PMID 28189366, doi:10.1016/j.clinthera.2017.01.016, EudraCT 2010-022033-28
Ungerleider 1987 Double-blind, placebo-controlled, randomized crossover study (repeated paired periods with increasing doses)	13 randomized; 12 completed at least two paired periods People with MS and spasticity not responding to treatment (US)	Oral THC (Δ9-THC) and placebo	2.5–15 mg (increasing doses) The dose was increased with each new paired period	5 days of THC and 5 days of placebo, with a 2-day break in between (paired periods)	At doses above 7.5 mg, patients' self-rated spasticity improved significantly compared with placebo; the result of the neurological examination is not in the abstract. Very small and short Side effects: No details in the abstract	PMID 2831701, doi:10.1300/j251v07n01_04
Corey-Bloom 2012 Placebo-controlled, randomized crossover study (single center)	37 randomized; 30 completed People with MS and treatment-resistant spasticity (modified Ashworth ≥3) (US); 80% had used cannabis before	Smoked marijuana cigarette (about 4% THC) and THC-extracted placebo cigarette	1 cigarette a day (on average 4 puffs)	2 × 3 days (11-day break in between)	The modified Ashworth score decreased 2.74 points more with marijuana than with placebo (p < 0.0001); pain (0–100 VAS) decreased 5.28 points more (p = 0.008); no difference in walking time. The thinking speed test (PASAT) score was 8.67 points worse (p = 0.003). Very short; 80% of participants were used to cannabis and most guessed correctly which cigarette they had smoked (17 of 30 people at all six visits), so blinding was largely broken. Public funding Side effects: No serious side effects; 5 people withdrew because of side effects (2 for uncomfortable intoxication, 2 for dizziness, 1 for fatigue); feeling high markedly more common than with placebo	PMID 22586334, doi:10.1503/cmaj.110837
NCT00682929 (UC Davis, registry results) Double-blind, placebo-controlled, three-arm parallel randomized study (double-dummy); terminated early because enrollment could not be completed	41 randomized (13 inhaled cannabis, 14 oral THC, 14 placebo); 28 completed People with MS and moderate to severe spasticity (US)	Smoked cannabis cigarette (THC content not in the registry), oral dronabinol (synthetic THC), and placebo	1 cigarette a day or 10 mg dronabinol a day	7 weeks	The data were not statistically analyzed (registry: insufficient patients and funding, departure of the investigator). Primary outcome, the resistance to movement applied to the knee joint by a motorized device (weeks 3 and 7): no clear pattern between groups in the descriptive values in the registry (25 people at week 3). Secondary outcome, change in modified Ashworth score (a positive value means worsening): at week 3, −0.33 with cannabis (6 people), 0 with THC (11), −0.45 with placebo (11); at week 7, +1.14 with cannabis (7), −0.38 with THC (8), −0.25 with placebo (12). Very small; results only on ClinicalTrials.gov, no peer-reviewed publication. Public funding Side effects: Discontinuation due to side effects 4/13 with cannabis, 1/14 with THC, 1/14 with placebo; serious side effects 3/13, 1/14, 0/14; euphoria 10/13, 6/14, 2/14	NCT00682929, May 18, 2018, no publication found in PubMed as of October 2026)
Kavia 2010 Multicenter (United Kingdom, Belgium, Romania; countries per the table of a meta-analysis), double-blind, placebo-controlled, parallel-group phase 3 RCT	135 randomized (67 nabiximols / 68 placebo); 118 completed (56 / 62); 60 / 64 in the primary analysis People with MS and overactive bladder (detrusor overactivity) not fully controlled by current treatment; at least 3 incontinence episodes in 5 days at baseline, anticholinergic dose stable for at least 14 days; people using intermittent self-catheterization were excluded (registry)	Nabiximols (THC:CBD mouth spray; 2.7 mg THC + 2.5 mg CBD per spray) and placebo spray	Up to 48 sprays a day (about 130 mg THC + 120 mg CBD) were allowed (registry); mean use 8.9 sprays a day (median 7.2; about 24 mg THC + 22 mg CBD; per the table of a meta-analysis) Self-titrated by the patient (details not in the abstract)	8 weeks of treatment (preceded by a 2-week baseline period; 10 weeks in total)	The primary outcome (reduction in the daily number of incontinence episodes) did not differ from placebo: −1.08 vs. −0.99; difference −0.11 (95% CI −0.47 to 0.26; p = 0.57). Among secondary measures, nighttime urination (difference −0.28; −0.50 to −0.07; p = 0.010), daily number of urinations (−0.85; −1.47 to −0.23), the patient's overall bladder condition on a 0–10 scale (−1.16; −1.82 to −0.51; p = 0.001), and the global impression of change (improvement 51/63 vs. 39/67) favored nabiximols; there was no difference in urgency (p = 0.071), pad use (p = 0.74), or incontinence-related quality of life (p = 0.17). Figures from the ClinicalTrials.gov results; the p values for daily urinations and the global impression of change differ between the publication's abstract (0.001 and 0.005) and the registry (0.007 and 0.002). Sponsored by the manufacturer; according to the registry, all publications from the study had to be submitted to the company for review before publication Side effects: Serious side effects in 2 people in each group; dizziness 12/67 vs. 5/68, disorientation 4/67 vs. 0, feeling detached from oneself or one's surroundings (dissociation) 4/67 vs. 0; discontinuation due to side effects 7/67 vs. 3/68; urinary tract infection 4/67 vs. 7/68 (registry)	PMID 20829244, doi:10.1177/1352458510378020, NCT00678795, the sponsor today is Jazz Pharmaceuticals)
Feinstein 2019 Controlled, non-randomized study (groups assigned by whether the registration number was odd or even; single center, Toronto): continuing cannabis or stopping for 28 days; abstinence monitored with urine tests	40 (1 person in the abstinence group was excluded for being unable to stay off cannabis; 19 people in the abstinence group) People with MS (Canada) who had started using cannabis after MS onset, had used it at least 4 days a week for years, and had impairment in at least two cognitive domains at baseline	Their own cannabis (mostly smoked; mainly THC according to urine tests)	Not reported (in the abstract); in the abstinence group, the THC breakdown product in urine fell to zero by day 28 (Feinstein 2021)	28 days	On day 28, the abstinence group was markedly better than the continuation group on all cognitive measures (verbal and visual memory, processing speed, executive function) (p < 0.0001 for all); improvement over time occurred only in those who stopped, so it cannot be explained by practice effects. On functional MRI, those who stopped gave more correct answers on the symbol-digit test and were faster, with increased activity in the relevant brain regions; no difference on structural MRI. Self-reported cognitive complaints did not differ between the groups, and all 19 people who stopped went back to cannabis after the study ended (Feinstein 2021, PMID 34087949). Among those who used cannabis for mood, the depression score fell after stopping (p = 0.006; subgroup size not in the abstract; Feinstein 2021, PMID 32589554). Spasticity and pain results are not in the abstracts; groups were not randomized. Funding source not in the abstract; the lead author's disclosure lists speaker fees from MS drug manufacturers, and no cannabis company is mentioned (Feinstein 2021, PMID 34087949) Side effects: Not reported (in the abstract); those who stopped reported more difficulty carrying on their activities away from home (Feinstein 2021, PMID 34087949)	PMID 31363742, doi:10.1093/brain/awz213, Other publications from the same study: Feinstein 2021 (depression, PMID 32589554, Feinstein 2021 (cognitive awareness, PMID 34087949, PMC8413765), Meza 2024 (resting-state brain network, 33 people, PMID 38815510, and Meza 2024 (sex differences, 19 who stopped, PMID 39024968
Fox 2004 Randomized, double-blind, placebo-controlled crossover RCT (for tremor)	14 (8 women, 6 men) People with MS with tremor in the arms (mean age 45, mean EDSS 6.25; Plymouth, UK)	Oral cannabis extract (Cannador; contains THC and CBD; amounts not in the abstract)	Not in the abstract (gradually increased over 2 weeks in each period) Gradual increase over 2 weeks before each assessment	2 weeks of dose increase before each assessment; period length and washout interval not in the abstract	On the primary outcome, the tremor index of a validated tremor scale, and on secondary objective measures (accelerometer, ataxia scale, spiral drawing, finger tapping, nine-hole peg test), there was no significant difference between the cannabis extract and placebo; finger tapping was faster with placebo (p < 0.02). There was a non-significant trend in favor of the extract in patients’ subjective tremor relief. The study was planned to be powered to detect a 50% improvement in the tremor index; it may have missed smaller effects. Very small; the full text could not be read Side effects: Not in the abstract. According to two reviews, 10 patients reported side effects during the extract period and 2 during the placebo period (mild cognitive changes, sleepiness, light-headedness, dry mouth); 9 of 13 patients correctly guessed the period in which they received the drug, suggesting that blinding was partly broken (Koch 2007, Kluger 2015; the full text could not be read)	PMID 15079008, doi:10.1212/01.wnl.0000118203.67138.3e
Filippini 2022 (Cochrane) Cochrane systematic review and meta-analysis (25 RCTs; search up to December 2021)	3,763 Multiple sclerosis	Nabiximols (13 studies); oral synthetic THC or related compounds (dronabinol 3, nabilone 1, oral THC tablet 1); oral THC-rich cannabis extract (3); inhaled cannabis (1); dronabinol together with extract or inhaled cannabis in 3 studies	Variable	3–48 weeks	Nabiximols and oral cannabis extract increase the number of people reporting an important (at least 30%) reduction in spasticity (OR 2.51; 95% CI 1.56–4.04; 4 spray studies and 1 oral extract study, 1,143 people; moderate certainty); mean difference on a 0–10 scale −0.55 points (7 studies, two of them with oral THC or cannabis extract; moderate certainty). The difference on the doctor-measured Ashworth scale is very small or absent (−0.23; −0.44 to −0.03; 11 studies; low certainty). Little or no effect on quality of life. Of the 25 studies in the review, 15 were funded by the manufacturer and 2 by joint public and company sources Side effects: Discontinuation due to side effects (OR 2.41), nervous system (OR 2.61), and psychiatric (OR 1.94) side effects may be increased	PMID 35510826, doi:10.1002/14651858.CD013444.pub2
Hamm-Buiar 2026 Systematic review, meta-analysis, and network meta-analysis (RCTs only; RoB 2, GRADE)	27 RCT publications, more than 3,000 people Spasticity due to MS (a small number with other neurological diseases in 2 studies)	THC:CBD mouth spray, oral cannabis extracts, synthetic THC and related compounds (dronabinol, nabilone), pure CBD, smoked marijuana	Variable	2 weeks – 36 months	The THC:CBD spray reduced patient-reported spasticity by an average of 0.82 points on a 0–10 scale (95% CI 0.40–1.24; 7 studies; low certainty). In the network analysis, the THC:CBD spray was the only product significantly better than placebo; no significant difference for pure CBD, dronabinol, or other extracts. Limited benefit in doctor-measured muscle tone; side effects common but mostly mild to moderate, serious events rare. No funding Side effects: Most common: dizziness, fatigue, drowsiness, dry mouth, nausea; a feeling of intoxication especially with THC alone	PMID 42543771, doi:10.1002/bcp.70719, PROSPERO CRD42024557313, search December 2, 2025
Torres-Moreno 2018 Systematic review and meta-analysis (double-blind, placebo-controlled RCTs)	17 RCTs, 3,161 people MS (spasticity, pain, or bladder problems)	Nabiximols, oral cannabis extract, dronabinol, nabilone	Variable	A few weeks – 3 years	Small benefit in patient-reported spasticity (standardized mean difference −0.25; 95% CI −0.38 to −0.13); no effect on the Ashworth scale; small benefit in pain (−0.17) and bladder function (−0.11; 95% CI −0.22 to −0.0008); when company-supported studies were removed, the bladder result was no longer significant (according to the authors, company-supported studies appear to have favored the active treatment), and in the largest and longest study independent of the company (CUPID), the spasticity, pain, and bladder results leaned toward placebo. According to the authors, efficacy is limited. Public funding; no conflicts of interest reported Side effects: Any side effect RR 1.72 (1.46–2.02); discontinuation due to side effects RR 2.95 (2.14–4.07); no significant difference in serious side effects	PMID 30646241, doi:10.1001/jamanetworkopen.2018.3485, PROSPERO CRD42014015391, search up to July 2016
Abo Youssef 2017 Systematic review and meta-analysis (PRISMA; Cochrane register, Embase, Medline, Scopus; last search November 11, 2016)	3 studies (2 RCTs, 1 open-label), 426 patients Neurogenic lower urinary tract dysfunction due to MS (bladder problems)	THC-containing cannabis products: nabiximols, oral cannabis extract and synthetic THC (CAMS-LUTS), plant extracts containing THC and CBD (open-label study)	Variable		According to the authors, the number of incontinence episodes decreased markedly in all three studies; when the data from the three studies were pooled, the mean difference in incontinence episodes per 24 hours was −0.35 (95% CI −0.46 to −0.24). A study without a comparison group was also included in the pooling, and it is not clear from the abstract what was compared with what; in the two included RCTs, the difference vs. placebo was only 0.11–0.21 incontinence episodes a day (as calculated by Torres-Moreno 2018), so the pooled figure should not be read as a difference vs. placebo; the main measure of the only separate bladder RCT was no different from placebo (Kavia 2010). According to the authors, the evidence base is weak; better-designed, adequately powered studies are needed (from the abstract; full text could not be read) Side effects: Mild side effects common (38–100%); serious side effects in 2 patients (0.7%)	PMID 28058780, doi:10.1111/bju.13759
Cheng 2026 Scoping review (following Cochrane and PRISMA methods; MEDLINE, EMBASE, CENTRAL; English-language publications only)	12 studies (9 in MS; 3 RCTs) Adults with overactive bladder and lower urinary tract symptoms due to neurological disease, benign prostate enlargement, or cystitis	Cannabis products containing THC, CBD, or both	Variable		Some improvements in urinary incontinence, urinary frequency, and quality of life were reported with cannabis products, especially in patients with MS; however, only 3 studies were randomized controlled trials, and according to the authors the evidence is limited and largely observational; randomized studies focusing on outcomes that matter to patients are needed. No pooled effect size (scoping review; from the abstract, full text could not be read) Side effects: Mild side effects such as dizziness and dry mouth were common (2–18%); they sometimes led to stopping treatment	PMID 42678682, doi:10.5489/cuaj.9478
NICE 2019 (guideline NG144) National clinical guideline (United Kingdom; systematic evidence review and cost-effectiveness model)	Adults with moderate to severe MS spasticity (the guideline also covers nausea, chronic pain, and epilepsy)	Cannabis-based medicinal products; the spasticity recommendation is for the THC:CBD mouth spray			Recommends a 4-week trial of the THC:CBD spray in adults with moderate to severe MS spasticity that has not improved with other medicines (on the condition of a 'pay for responders' scheme in which the manufacturer covers the first 3 bottles); treatment continues if, at the end of 4 weeks, patient-reported spasticity symptoms on a 0–10 scale have decreased by at least 20%; treatment is started and supervised by a doctor who specializes in MS spasticity. The committee's rationale: there was a reduction in some measures of patient-reported spasticity, and in the committee's assessment side effects did not differ from placebo, but most of the evidence was of low quality and the effect on quality of life was unclear; the cost-effectiveness model built for the guideline predicted a gain equivalent to about 30 days in full health for the average patient and supported the recommendation only if the reduction in spasticity halved care costs and the price of the medicine came down. It states that the evidence for other cannabis products is much more limited and recommends research on them (including in children)	PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021, last reviewed May 20, 2025, recommendations 1.3.1–1.3.2, rationale section, research recommendation 5), PMID 35107908, NBK577084, could not be opened in this search)
Yadav 2014 (American Academy of Neurology) Evidence-based clinical guideline (American Academy of Neurology guideline subcommittee; complementary and alternative therapies in MS; literature 1970–September 2013; recommendations at levels A–C)	Adults with MS (spasticity, pain, bladder complaints, and tremor; the guideline also covers other complementary approaches)	Oral cannabis extract, THC, and THC:CBD mouth spray (nabiximols)			Doctors may offer oral cannabis extract (level A) and THC (level B) for patient-reported spasticity symptoms and pain (excluding central neuropathic pain); patients should be told that these products are probably ineffective for doctor-measured spasticity (in the short term) and for tremor (level B), and possibly helpful for spasticity and pain in the long term (level C). The THC:CBD mouth spray may be offered for patient-reported spasticity, pain, and urinary frequency (level B); it is probably ineffective for doctor-measured spasticity and urinary incontinence (level B); it may not be offered for tremor (level C). Cannabinoids can cause side effects; caution is needed with non-standardized cannabis extracts. The abstract contains no recommendation for pure CBD. The guideline is based on studies up to September 2013; later RCTs (e.g., the pure CBD studies, RELEASE MSS) were not assessed. The Academy reaffirmed the guideline on February 21, 2026	PMID 24663230, doi:10.1212/WNL.0000000000000250, Status: 'Reaffirmed on February 21, 2026' in the American Academy of Neurology guideline list (aan.com, October 28, 2026), the same academy's 2014 systematic review of medical marijuana (Koppel 2014, PMID 24778283, 2023 and is not in the table. PMC3962995 (abstract and author disclosures)
Pourmohammadi 2022 Systematic review (PRISMA; no meta-analysis; risk of bias with the CASP checklist)	26 clinical studies (13 judged at low risk of bias and examined in detail); the names and number of the cannabinoid studies are not in the abstract Adults with MS-related tremor (drug treatments only)	Medicines tried for MS tremor, including cannabis-based medicines	Varied by study		The effect of cannabis-based medicines on MS-related tremor was not found to be conclusive, and they were not recommended because of their many side effects. The only medicine with a clear effect in the review was botulinum toxin (side effects and difficult injections limit its use); results for the other medicines were inconsistent or small. The full text could not be read Side effects: Many side effects were reported with cannabis-based medicines (no details in the abstract)	PMID 35339007, doi:10.1016/j.msard.2022.103722
Patti 2016 (Italian AIFA registry) Prospective observational study based on a mandatory national drug registry (30 centers; no comparison group)	1,615 patients Patients starting the spray for moderate to severe MS spasticity (NRS ≥4) that had not responded to other spasticity medicines (Italy, January 2014 – February 2015)	Nabiximols (THC:CBD mouth spray), according to the approved conditions of use	Mean 6.3–6.8 sprays/day According to the product information; 1-month trial	6 months	At month 1, at least 20% improvement in spasticity NRS in 70.5% of patients and at least 30% in 28.2%; mean NRS from 7.5 to 5.8. 39.5% stopped within 6 months (main reasons insufficient effect and side effects). In an 18-month analysis of the same registry (1,845 patients), 48% of those who responded in the first month had stopped by month 18. No comparison group; 27 of the 33 authors declared fees or support from drug companies, 21 of them from Almirall Side effects: Among discontinuations due to side effects, mainly cognitive and psychiatric complaints (55 people, 3.9%; mostly confusion), fatigue (2.5%), drowsiness (2.2%), and dizziness (2%)	PMID 27160523, doi:10.1136/jnnp-2015-312591, PMID 28763462, discontinuation), PMID 32335779, PMID 32661083, 18 months, 1, 845 patients), PMID 35590453
Flachenecker 2014 (MOVE 2) Prospective, multicenter, non-interventional observational study (no comparison group)	335 patients; 276 in the efficacy analysis Patients starting the spray for moderate to severe MS spasticity resistant to other medicines (Germany)	Nabiximols (THC:CBD mouth spray), in routine care	Not reported (in the abstract)	3–4 months (12-month extension in 52 patients)	At month 1, relief in 74.6% of patients according to specialist assessment; mean NRS from 6.1 to 5.2. At month 3, 55.3% of patients were continuing treatment, and NRS was 25% lower than baseline. In the 12-month extension (52 patients), NRS from 6.0 to 4.5. No comparison group; funding and conflict of interest statements could not be read Side effects: 17% of patients reported side effects; in the 12-month extension, 84% reported no side effects	PMID 24525548, doi:10.1159/000357427, 12-month extension: Flachenecker 2014, PMID 24943098
Etges 2016 (manufacturer safety registry) Postmarketing observational safety registry (voluntary reporting by doctors; no comparison group)	941 patients (2,214 patient-years); 78% for MS, 59% with a confirmed diagnosis of MS spasticity Patients using the spray on prescription in the United Kingdom, Germany, and Switzerland	Nabiximols (THC:CBD mouth spray)	Not reported (in the abstract)	About 5 years of registry data	60% of patients were continuing treatment, and according to their doctors 83% benefited; 32% stopped (about one third because of lack of effect, one quarter because of side effects). No signal of abuse, diversion, or dependence. Based on voluntary reporting by doctors; all authors were employees and shareholders of the manufacturer (GW Pharmaceuticals), and the registry was funded by the company Side effects: Clinically significant psychiatric side effects 6%, falls requiring medical care 6%, suicidal thoughts or attempts 2%; driving ability worsened in 2% and improved in 7%; the most common treatment-related side effects were dizziness (2.3%) and fatigue (1.7%); side effects were more common in the first month	PMID 27956834, doi:10.2147/TCRM.S115014
Clifford 1983 Small open-label study (case series); no comparison group and no blinding (as reported by two reviews; tagged in PubMed as ‘clinical trial’ and ‘case report’; the full text could not be read)	8 People with MS severely disabled by tremor and ataxia (a disorder of balance and coordination) (USA)	Oral THC (tetrahydrocannabinol)	Oral THC, 5–15 mg per dose (4 times a day according to one review; as reported by Koch 2007 and Kluger 2015)	Not reported (in the abstract)	In this study, started after one patient spontaneously described benefiting from THC, motor coordination improved on examination in 2 of 8 patients; according to two reviews, 5 patients reported feeling better. There is no comparison group, and no numerical measurements were given in the abstract; this design cannot separate the effect of expectation and spontaneous change, and no cause and effect can be inferred Side effects: Not reported (in the abstract); according to one review, no side effects were reported (Koch 2007)	PMID 6309074, doi:10.1002/ana.410130616, Ann Neurol 1983, 13(6):669–671, funding: US National Institutes of Health (NINDS, NCRR) grants (PubMed record)

Reported side effects

In healthy volunteers, CBD increased the risk of diarrhea (RR 5.85); a non-significant trend toward more abdominal pain and headache (Sawaira 2026, PMID 41789242)
Psychiatric and nervous system side effects are more common with THC-containing products (Filippini 2022); the likelihood of side effects increased with any cannabinoid (OR 1.75; Wilson 2026, PMID 41856154)
Long-term use of the THC:CBD spray (open-label follow-up and registries): in a 137-patient extension study (mean 434 days), 4 patients had a first-ever seizure (Wade 2006); in the 1,615-patient Italian registry, the main reasons for stopping because of side effects within 6 months were cognitive and psychiatric complaints such as confusion, fatigue, drowsiness, and dizziness (Patti 2016); in the manufacturer's 941-patient safety registry, 6% clinically significant psychiatric side effects and 6% falls requiring medical care were reported, with no signal of dependence or abuse (Etges 2016; all authors were employees of the manufacturer)
In people with MS and cognitive impairment who had smoked cannabis almost daily for a long time (mainly THC according to urine tests) (40 people, controlled but not randomized), those who stopped for 28 days showed clear improvement on tests of memory, processing speed, and executive function, while those who continued did not; those who stopped did not notice this improvement in their own assessments, and all of them went back to cannabis after the study ended (Feinstein 2019; Feinstein 2021, PMID 34087949)

Monitoring done in studies

CANSEP in Canada (NCT05092191): pure CBD (up to 200 mg a day), THC, and the two together vs. placebo; 250 people planned, participant-blinded only; primary outcome patient-reported spasticity. The registry was last updated in December 2024; no results as of October 2026
DroSpas-1 (NCT03756974): a 397-person phase 3 placebo-controlled study of oral dronabinol was completed in March 2021; as of October 2026, there are no results in the registry and no publication was found in PubMed
A double-blind study in Canada (University of Calgary) comparing oral THC with CBD for 15 weeks in 30 people with MS, with thinking skills and bladder symptoms as the main outcomes (NCT06261489; no placebo group): started in December 2025, estimated completion September 2027; as of October 2026, the registry shows 'recruiting'

Who should be careful

High doses and market doses cannot be compared: in low-dose (≤175 mg/day) studies, plasma levels were 5–100 times lower than with the 20 mg/kg Epidiolex dose (Warren 2026, PMID 42473010)
Anyone taking long-term medicines should consult a doctor before starting; the studies on this page did not systematically assess interactions
Nabiximols is a prescription THC:CBD medicine; THC carries driving, cognitive, and psychiatric risks
Product information for the THC:CBD spray: not to be used if the person or their family has a history of schizophrenia or other psychosis, or during breastfeeding; not recommended in serious cardiovascular disease; use with caution in people with a history of epilepsy or recurrent seizures; an additional contraceptive method is needed because it may reduce the effectiveness of hormonal contraceptives; the risk of falls may increase in people whose muscle strength is insufficient once spasticity decreases; do not drive while dizzy or drowsy (UK product information, April 2, 2026, §4.3–4.7)

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): strong CYP3A4 inhibitors such as ketoconazole raise THC and CBD levels (the dose may need to be readjusted 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 should be avoided if possible; sedative effects and fall risk may increase with sleep medicines, muscle relaxants, and alcohol; hormonal contraceptives may become less effective

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 the treatments you use for spasticity and MS on your own.
Remember that the THC:CBD spray is a prescription medicine and is not the same thing as CBD oils.
If you take MS medicines or other regular medicines, review CBD together with your neurologist or pharmacist.
THC-containing products can affect driving and thinking; use the label and the certificate of analysis to check whether a product contains THC.

Choose your age group, medicines and situation to prepare a short summary you can take to your doctor. Nothing you enter is sent anywhere.

Open the personal warnings tool Convert drops ↔ mg

Bottom line

For MS spasticity, there is moderate evidence that the prescription spray containing both THC and CBD reduces the muscle stiffness patients feel in the short term; its effect on muscle stiffness measured by a doctor's examination is very small or unclear. Pure CBD did not reduce muscle stiffness in the two small studies in which it was tested; higher doses have not yet been tested in controlled parallel studies. Talking through the options with your neurologist is the best way forward.

Frequently asked questions

Does CBD oil work for MS spasticity?

So far, no results show this. Pure CBD was tested in two small studies, and in neither did it reduce muscle stiffness more than an inactive treatment (placebo); one showed improvement in a short walking test and in pain. The positive results come mostly from a prescription mouth spray that contains THC and CBD in roughly equal amounts; these results cannot be applied to CBD oil.

What is the THC:CBD mouth spray?

It is a prescription medicine called nabiximols that contains THC and CBD in roughly equal amounts. In studies, it increased the likelihood that people with MS reported less muscle stiffness in the short term; its effect on quality of life was small or absent. In some countries, including the United Kingdom, it is approved as an add-on to existing treatment for moderate to severe MS spasticity that has not improved enough with other spasticity medicines; according to the product information, it is tried for 4 weeks and stopped if there is no clear improvement. Because it contains THC, it can cause intoxication or mental fogginess.

What are the side effects of the spray?

The most common side effects in studies were dizziness and fatigue; these mostly appeared in the first weeks and were mild to moderate. Side effects related to the nervous system and mental health, and stopping treatment because of side effects, were more common than with placebo. The product information also warns that the risk of falls may increase in people whose muscle strength is insufficient once spasticity decreases. THC can affect driving and thinking.

Can CBD be used together with my MS medicines?

MS studies did not look at drug interactions separately. Because CBD can slow the breakdown of some medicines in the body, if you take medicines regularly, it is important to make this decision together with your neurologist.

Can CBD oil be obtained with a prescription for MS spasticity in Turkey?

In Turkey, products derived from hemp 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 classified 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 no more than 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, which is approved for MS spasticity in some countries, is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency) (September 28, 2026), and importing it from abroad requires the agency's written approval. If you are considering using it, talk to your doctor first.

Do CBD or cannabis products help with bladder problems caused by MS?

The evidence on this is weak and comes only from THC-containing products. In the bladder part of a large 630-person MS study, oral cannabis extract and THC reduced urinary incontinence slightly more than an inactive treatment (placebo). In a 135-person study done specifically for the bladder, however, the mouth spray containing THC and CBD was no different from placebo in the main measure, the number of incontinence episodes; some measures, such as nighttime urination and overall bladder complaints, improved. Two large studies that assessed the bladder as an additional measure found no difference, and in an analysis pooling the controlled studies, the effect remained very small. The American Academy of Neurology also states that the spray is probably ineffective for urinary incontinence. Pure CBD has never been tested for bladder problems in MS. This spray is approved for spasticity, not for bladder problems. The best course is to talk about your bladder complaints with your neurologist or urologist.

Do CBD or cannabis products help with MS-related tremor?

The evidence on this is limited and weak. In a controlled study of 14 MS patients with tremor in their arms, oral cannabis extract did not bring improvement different from an inactive medicine (placebo) on tests measuring tremor. In a study with a mouth spray containing THC and CBD, the patient-reported tremor score also improved similarly to placebo. In an older 8-person study without a comparison group, two patients' coordination improved, but this design does not show the cause of the improvement. Pure CBD has never been tested in MS-related tremor. If tremor makes your daily life harder, you can talk with your neurologist about treatment options.

References

Show 40 references

Mousavi 2025. Randomized, placebo-controlled study (blinding not stated in the abstract). PMID 40498097, doi:10.1007/s00210-025-04347-w
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
Wade 2003. Double-blind, placebo-controlled, randomized series of single-patient crossover trials. PMID 12617376, doi:10.1191/0269215503cr581oa
Novotna 2011. Phase 3, enriched design, double-blind RCT. PMID 21362108, doi:10.1111/j.1468-1331.2010.03328.x, NCT00681538, Sativex product information, mean number of sprays from review tables (PMC6324456, PMC8214588)
Bethoux 2024 (RELEASE MSS1). Phase 3, multicenter, double-blind, placebo-controlled crossover RCT. PMID 39106541, doi:10.1016/j.msard.2024.105740, NCT04657666
Zajicek 2013 (CUPID). Multicenter, parallel, double-blind, placebo-controlled RCT (2:1). PMID 23856559, doi:10.1016/S1474-4422(13)70159-5, ISRCTN 62942668, full report: Ball 2015, PMID 25676540
Markovà 2019 (SAVANT). Two-phase, enriched design: 4-week open-label trial, washout, then double-blind, placebo-controlled parallel RCT (15 centers). PMID 29792372, doi:10.1080/00207454.2018.1481066, EudraCT 2015-004451-40, PMID 32065006, PMID 37209500
Notcutt 2012. Multicenter (5), placebo-controlled, randomized withdrawal study (parallel). PMID 21878454, doi:10.1177/1352458511419700, NCT00702468
Collin 2007. Multicenter (8 in the United Kingdom, 4 in Romania), double-blind, placebo-controlled parallel RCT (2:1). PMID 17355549, doi:10.1111/j.1468-1331.2006.01639.x, NCT00711646, PMID 22878432, NCT01606137
Collin 2010. Multicenter (15 in the United Kingdom, 8 in Czechia), double-blind, placebo-controlled parallel RCT. PMID 20307378, doi:10.1179/016164109X12590518685660, NCT01599234
Wade 2004. Multicenter (3), double-blind, placebo-controlled parallel RCT. PMID 15327042, doi:10.1191/1352458504ms1082oa, NCT01610700, PMID 17086911, NCT01610687
NCT04203498 (RELEASE MSS3, registry results). Multicenter (37), double-blind, placebo-controlled parallel phase 3 RCT; terminated early by a business decision of the sponsor. NCT04203498, EudraCT 2019-002623-14, results in the registry, May 8, 2024, no publication found in PubMed as of October 2026)
NCT04984278 (RELEASE MSS5, registry results). Multicenter (7), triple-blind, placebo-controlled, randomized crossover phase 3 study; terminated early by a business decision of the sponsor. NCT04984278, EudraCT 2020-003271-18, results in the registry, February 5, 2024, no publication found in PubMed as of October 2026)
Vachová 2013. Multicenter, double-blind, placebo-controlled parallel RCT (phase 4). doi:10.4172/jmso.1000122, NCT01964547, results in the registry, May 2, 2014), article: J Mult Scler (Foster City) 2013, 1(2)
Leocani 2015. Double-blind, placebo-controlled, randomized crossover study (single center). PMID 26289497, doi:10.1007/s00415-015-7878-1, NCT01538225
Aragona 2009. Double-blind, placebo-controlled, randomized crossover study (single center). PMID 18978501, doi:10.1097/WNF.0B013E3181633497, PMID 18603457, pain reflex) and Tomassini 2014 (J Neurosci Rehabil, neurophysiology, not in PubMed)
De Blasiis 2021. Randomized controlled study without placebo (the control group received no treatment, no blinding); randomization method unclear. PMID 33862313, doi:10.1016/j.msard.2021.102805
Zajicek 2003 (CAMS). Multicenter (33), double-blind, placebo-controlled, three-arm parallel RCT. PMID 14615106, doi:10.1016/S0140-6736(03)14738-1, PMID 16291891, PMID 16552618
Zajicek 2012 (MUSEC). Multicenter (22), double-blind, placebo-controlled parallel phase 3 RCT. PMID 22791906, doi:10.1136/jnnp-2012-302468, NCT00552604, Germany)
Vaney 2004. Double-blind, placebo-controlled, randomized crossover study (single center, during inpatient rehabilitation). PMID 15327040, doi:10.1191/1352458504ms1048oa
Killestein 2002. Double-blind, placebo-controlled, randomized three-period crossover study (single center). PMID 12011290, doi:10.1212/wnl.58.9.1404, Immune system publication from the same study: Killestein 2003, J Neuroimmunol
van Amerongen 2018. Two phases: double-blind crossover dose finding + 4-week double-blind, placebo-controlled parallel RCT (single center). PMID 28189366, doi:10.1016/j.clinthera.2017.01.016, EudraCT 2010-022033-28
Ungerleider 1987. Double-blind, placebo-controlled, randomized crossover study (repeated paired periods with increasing doses). PMID 2831701, doi:10.1300/j251v07n01_04
Corey-Bloom 2012. Placebo-controlled, randomized crossover study (single center). PMID 22586334, doi:10.1503/cmaj.110837
NCT00682929 (UC Davis, registry results). Double-blind, placebo-controlled, three-arm parallel randomized study (double-dummy); terminated early because enrollment could not be completed. NCT00682929, May 18, 2018, no publication found in PubMed as of October 2026)
Kavia 2010. Multicenter (United Kingdom, Belgium, Romania; countries per the table of a meta-analysis), double-blind, placebo-controlled, parallel-group phase 3 RCT. PMID 20829244, doi:10.1177/1352458510378020, NCT00678795, the sponsor today is Jazz Pharmaceuticals)
Feinstein 2019. Controlled, non-randomized study (groups assigned by whether the registration number was odd or even; single center, Toronto): continuing cannabis or stopping for 28 days; abstinence monitored with urine tests. PMID 31363742, doi:10.1093/brain/awz213, Other publications from the same study: Feinstein 2021 (depression, PMID 32589554, Feinstein 2021 (cognitive awareness, PMID 34087949, PMC8413765), Meza 2024 (resting-state brain network, 33 people, PMID 38815510, and Meza 2024 (sex differences, 19 who stopped, PMID 39024968
Fox 2004. Randomized, double-blind, placebo-controlled crossover RCT (for tremor). PMID 15079008, doi:10.1212/01.wnl.0000118203.67138.3e
Filippini 2022 (Cochrane). Cochrane systematic review and meta-analysis (25 RCTs; search up to December 2021). PMID 35510826, doi:10.1002/14651858.CD013444.pub2
Hamm-Buiar 2026. Systematic review, meta-analysis, and network meta-analysis (RCTs only; RoB 2, GRADE). PMID 42543771, doi:10.1002/bcp.70719, PROSPERO CRD42024557313, search December 2, 2025
Torres-Moreno 2018. Systematic review and meta-analysis (double-blind, placebo-controlled RCTs). PMID 30646241, doi:10.1001/jamanetworkopen.2018.3485, PROSPERO CRD42014015391, search up to July 2016
Abo Youssef 2017. Systematic review and meta-analysis (PRISMA; Cochrane register, Embase, Medline, Scopus; last search November 11, 2016). PMID 28058780, doi:10.1111/bju.13759
Cheng 2026. Scoping review (following Cochrane and PRISMA methods; MEDLINE, EMBASE, CENTRAL; English-language publications only). PMID 42678682, doi:10.5489/cuaj.9478
NICE 2019 (guideline NG144). National clinical guideline (United Kingdom; systematic evidence review and cost-effectiveness model). PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021, last reviewed May 20, 2025, recommendations 1.3.1–1.3.2, rationale section, research recommendation 5), PMID 35107908, NBK577084, could not be opened in this search)
Yadav 2014 (American Academy of Neurology). Evidence-based clinical guideline (American Academy of Neurology guideline subcommittee; complementary and alternative therapies in MS; literature 1970–September 2013; recommendations at levels A–C). PMID 24663230, doi:10.1212/WNL.0000000000000250, Status: 'Reaffirmed on February 21, 2026' in the American Academy of Neurology guideline list (aan.com, October 28, 2026), the same academy's 2014 systematic review of medical marijuana (Koppel 2014, PMID 24778283, 2023 and is not in the table. PMC3962995 (abstract and author disclosures)
Pourmohammadi 2022. Systematic review (PRISMA; no meta-analysis; risk of bias with the CASP checklist). PMID 35339007, doi:10.1016/j.msard.2022.103722
Patti 2016 (Italian AIFA registry). Prospective observational study based on a mandatory national drug registry (30 centers; no comparison group). PMID 27160523, doi:10.1136/jnnp-2015-312591, PMID 28763462, discontinuation), PMID 32335779, PMID 32661083, 18 months, 1, 845 patients), PMID 35590453
Flachenecker 2014 (MOVE 2). Prospective, multicenter, non-interventional observational study (no comparison group). PMID 24525548, doi:10.1159/000357427, 12-month extension: Flachenecker 2014, PMID 24943098
Etges 2016 (manufacturer safety registry). Postmarketing observational safety registry (voluntary reporting by doctors; no comparison group). PMID 27956834, doi:10.2147/TCRM.S115014
Clifford 1983. Small open-label study (case series); no comparison group and no blinding (as reported by two reviews; tagged in PubMed as ‘clinical trial’ and ‘case report’; the full text could not be read). PMID 6309074, doi:10.1002/ana.410130616, Ann Neurol 1983, 13(6):669–671, funding: US National Institutes of Health (NINDS, NCRR) grants (PubMed record)

Points that could not be verified from the full text

The full text of Novotna 2011 was not read (paywalled); dose from the ClinicalTrials.gov registry and product information, mean number of sprays from review tables
The full text of Mousavi 2025 could not be read (no publisher access); blinding, side effects, and the product's THC content are not in the abstract
The full text of Bethoux 2024 could not be read; the mean number of sprays taken is not in the abstract or the registry (the registry gives only a maximum of 12 sprays a day and 14 days of dose adjustment); side effect counts from the ClinicalTrials.gov registry (NCT04657666)
RELEASE MSS3 (NCT04203498) and RELEASE MSS5 (NCT04984278) were stopped early by a business decision of the sponsor; their results are only in the ClinicalTrials.gov registry, with no peer-reviewed publication as of October 2026; for MSS5, the registry gives only the dosing schedule (up to 12 sprays within 14 days), not the mean dose taken. The data from the UC Davis study (NCT00682929) were never statistically analyzed
The full texts of Wade 2003, Wade 2004, Collin 2007, Collin 2010, Notcutt 2012, Markovà 2019, CAMS, MUSEC, Vaney 2004, Killestein 2002, Leocani 2015, and Flachenecker 2014 could not be read (paywalled); figures from abstracts, ClinicalTrials.gov results, product information, and the tables of Cochrane 2022 and Torres-Moreno 2018. In Wade 2004, the difference on the spasticity scale was significant in the publication's abstract (p = 0.001) and borderline in the registry analysis (p = 0.062)
Vachová 2013 was published in a journal not indexed in PubMed and could not be read; the row is based on ClinicalTrials.gov results (NCT01964547). The first THC study in 1981 (Petro 1981, 9 patients, single dose) was not included in the table: it could not be confirmed from the abstract whether it was randomized or whether the patients had MS (Cochrane 2022 counted it as a non-randomized study)
The full texts of the bladder studies added in the additional October 2026 search (Kavia 2010, the CAMS bladder substudy Freeman 2006, Abo Youssef 2017, Cheng 2026) and of Feinstein 2019 could not be read (paywalled); figures from abstracts, ClinicalTrials.gov results (NCT00678795; NCT01610700 for Wade 2004), and the open-access full text of the 2018 meta-analysis (Torres-Moreno 2018). In Kavia 2010, the p values for the daily number of urinations and the patient's global impression of change differ between the publication's abstract (0.001 and 0.005) and the registry (0.007 and 0.002); the number of people in the CAMS bladder substudy is not in the abstract. From the abstract, it is not clear what the pooled figure in Abo Youssef 2017 (−0.35 a day) compares with what; which studies entered the bladder analysis of the 2018 meta-analysis is shown only in a figure, and the figure could not be opened. NICE's spasticity evidence review could not be opened because it required human verification; the guideline's recommendation, rationale, and research recommendation pages were read. Only the abstract of the American Academy of Neurology guideline was read.
The full texts of Fox 2004, Clifford 1983 and Pourmohammadi 2022, added for MS-related tremor, could not be read (paywalled; Clifford 1983's publisher page blocked access); the numbers are from the abstracts. Fox 2004's dose, period lengths and side effects are not in the abstract; the information on side effects and blinding in the row is as reported by two reviews (Koch 2007, Kluger 2015). That Clifford 1983 was open-label (no comparison group), the amount of THC and the number of subjective improvements also come from the same two reviews; the length of the study is not known. Which cannabinoid studies Pourmohammadi 2022 included is not clear from the abstract. The tremor results of the CAMS study are reported only in a secondary review and were not included because they could not be verified from the primary source; whether the 2007 Cochrane review on ataxia included any cannabinoid studies is not clear from the abstract.

Research history

Here we record what changed on this page, when and why, with dates. The newest change is at the top.

October 31, 2026
A separate section on MS-related tremor was added to the page. In the only randomized study that looked specifically at tremor (Fox 2004; 14 people, oral cannabis extract), there was no difference from placebo on objective tests measuring tremor; in the 160-person study with the mouth spray containing THC and CBD (Wade 2004), there was also no difference in the tremor measurement. An old 8-person THC study without a comparison group (Clifford 1983) and a 2022 systematic review that did not recommend cannabis-based medicines for MS tremor (Pourmohammadi 2022) were also added to the table. Pure CBD has never been tested in MS-related tremor; the evidence for tremor is weak. For spasticity, the conclusion and the strength of evidence did not change.
Related studies: Fox 2004, published April 13, 2004 (PMID 15079008, doi:10.1212/01.wnl.0000118203.67138.3e); Pourmohammadi 2022, published April 2022 (PMID 35339007, doi:10.1016/j.msard.2022.103722); Clifford 1983, published June 1983 (PMID 6309074, doi:10.1002/ana.410130616, Ann Neurol 1983, 13(6):669–671, funding: US National Institutes of Health (NINDS, NCRR) grants (PubMed record))
October 30, 2026
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.
October 28, 2026
October 2026 additional review: sources found for this page during the searches for other topics were read and incorporated into the page. A separate section on bladder problems caused by MS was added: the only randomized study done specifically for the bladder (Kavia 2010; the mouth spray containing THC and CBD was no different from placebo in the main measure, urinary incontinence, and helpful on some secondary measures), the figures from the bladder part of the 630-person CAMS study (urinary incontinence decreased slightly more with cannabis extract and with THC than with placebo), the absence of a difference in bladder complaints in two large studies in the table, the loss of significance of the 2018 meta-analysis's very small bladder effect once manufacturer-supported studies were removed, two reviews on this topic (Abo Youssef 2017, Cheng 2026; both found the evidence weak), and the American Academy of Neurology's MS guideline reaffirmed in 2026 (the spray is probably ineffective for urinary incontinence); pure CBD has never been tested for this. Also added to the table: the UK NICE guideline's (2019) recommendation of a 4-week trial of the THC:CBD spray, and a controlled study showing that stopping improved thinking skills in people with MS who had smoked cannabis for a long time (Feinstein 2019). Assessed but not added: the Brazilian Academy of Neurology's 2021 position paper (adds no new information; its statement that the spray is approved in the US is incorrect) and a 19-person uncontrolled sleep study. For spasticity, the conclusion and the strength of evidence did not change.
Related studies: Kavia 2010, published November 2010 (online September 9, 2010) (PMID 20829244, doi:10.1177/1352458510378020, NCT00678795, the sponsor today is Jazz Pharmaceuticals)); Feinstein 2019, published September 1, 2019 (PMID 31363742, doi:10.1093/brain/awz213, Other publications from the same study: Feinstein 2021 (depression, PMID 32589554, Feinstein 2021 (cognitive awareness, PMID 34087949, PMC8413765), Meza 2024 (resting-state brain network, 33 people, PMID 38815510, and Meza 2024 (sex differences, 19 who stopped, PMID 39024968); Abo Youssef 2017, published April 2017 (online February 23, 2017) (PMID 28058780, doi:10.1111/bju.13759); Cheng 2026, published August 20, 2026 (PMID 42678682, doi:10.5489/cuaj.9478); NICE 2019 (guideline NG144), published November 11, 2019 (updated March 22, 2021) (PMID 31909928, www.nice.org.uk, 2019, last updated March 22, 2021, last reviewed May 20, 2025, recommendations 1.3.1–1.3.2, rationale section, research recommendation 5), PMID 35107908, NBK577084, could not be opened in this search)); Yadav 2014 (American Academy of Neurology), published March 25, 2014 (PMID 24663230, doi:10.1212/WNL.0000000000000250, Status: 'Reaffirmed on February 21, 2026' in the American Academy of Neurology guideline list (aan.com, October 28, 2026), the same academy's 2014 systematic review of medical marijuana (Koppel 2014, PMID 24778283, 2023 and is not in the table. PMC3962995 (abstract and author disclosures))

Older changes (8)

October 28, 2026
Display fix: internal working notes left over from the previous cleanup were removed; content and evidence did not change.
October 28, 2026
Display fix: internal working file names left in the text were removed; content and evidence did not change.
October 27, 2026
In October 2026, PubMed, Cochrane, and ClinicalTrials.gov were systematically searched; 25 studies were added: 19 randomized studies with THC-containing products (mouth spray containing THC and CBD, oral cannabis extract, synthetic THC, smoked marijuana) (three with results only in the ClinicalTrials.gov registry), 1 small crossover study in which a CBD-rich extract was also tested, 2 systematic reviews, and 3 real-world or safety registries. The product type of the Cochrane 2022 review was corrected to 'Multiple product types' (it also includes a nabilone study), and its conclusion was completed with the very small difference in doctor-measured muscle stiffness; in the row for the Danish study, the result for the pure CBD group is now given first. The dosing schedule, warnings, and drug interactions of the approved THC:CBD spray were added from the product information. There are still only two small randomized studies with pure CBD. The conclusion and the strength of evidence did not change.
Related studies: Wade 2003, published February 2003 (PMID 12617376, doi:10.1191/0269215503cr581oa); Markovà 2019 (SAVANT), published February 2019 (PMID 29792372, doi:10.1080/00207454.2018.1481066, EudraCT 2015-004451-40, PMID 32065006, PMID 37209500); Notcutt 2012, published February 2012 (PMID 21878454, doi:10.1177/1352458511419700, NCT00702468); Collin 2007, published March 2007 (PMID 17355549, doi:10.1111/j.1468-1331.2006.01639.x, NCT00711646, PMID 22878432, NCT01606137); Collin 2010, published June 2010 (PMID 20307378, doi:10.1179/016164109X12590518685660, NCT01599234); Wade 2004, published August 2004 (PMID 15327042, doi:10.1191/1352458504ms1082oa, NCT01610700, PMID 17086911, NCT01610687); NCT04203498 (RELEASE MSS3, registry results), published May 8, 2024 (registry results) (NCT04203498, EudraCT 2019-002623-14, results in the registry, May 8, 2024, no publication found in PubMed as of October 2026)); NCT04984278 (RELEASE MSS5, registry results), published February 5, 2024 (registry results) (NCT04984278, EudraCT 2020-003271-18, results in the registry, February 5, 2024, no publication found in PubMed as of October 2026)); Vachová 2013, published 2013 (doi:10.4172/jmso.1000122, NCT01964547, results in the registry, May 2, 2014), article: J Mult Scler (Foster City) 2013, 1(2)); Leocani 2015, published November 2015 (PMID 26289497, doi:10.1007/s00415-015-7878-1, NCT01538225); Aragona 2009, published 2009 (PMID 18978501, doi:10.1097/WNF.0B013E3181633497, PMID 18603457, pain reflex) and Tomassini 2014 (J Neurosci Rehabil, neurophysiology, not in PubMed)); De Blasiis 2021, published June 2021 (PMID 33862313, doi:10.1016/j.msard.2021.102805); Zajicek 2003 (CAMS), published November 8, 2003 (PMID 14615106, doi:10.1016/S0140-6736(03)14738-1, PMID 16291891, PMID 16552618); Zajicek 2012 (MUSEC), published November 2012 (PMID 22791906, doi:10.1136/jnnp-2012-302468, NCT00552604, Germany)); Vaney 2004, published August 2004 (PMID 15327040, doi:10.1191/1352458504ms1048oa); Killestein 2002, published May 14, 2002 (PMID 12011290, doi:10.1212/wnl.58.9.1404, Immune system publication from the same study: Killestein 2003, J Neuroimmunol); van Amerongen 2018, published September 2018 (PMID 28189366, doi:10.1016/j.clinthera.2017.01.016, EudraCT 2010-022033-28); Ungerleider 1987, published 1987 (PMID 2831701, doi:10.1300/j251v07n01_04); Corey-Bloom 2012, published July 10, 2012 (PMID 22586334, doi:10.1503/cmaj.110837); NCT00682929 (UC Davis, registry results), published May 18, 2018 (registry results) (NCT00682929, May 18, 2018, no publication found in PubMed as of October 2026)); Hamm-Buiar 2026, published October 2026 (PMID 42543771, doi:10.1002/bcp.70719, PROSPERO CRD42024557313, search December 2, 2025); Torres-Moreno 2018, published October 5, 2018 (PMID 30646241, doi:10.1001/jamanetworkopen.2018.3485, PROSPERO CRD42014015391, search up to July 2016); Patti 2016 (Italian AIFA registry), published September 2016 (PMID 27160523, doi:10.1136/jnnp-2015-312591, PMID 28763462, discontinuation), PMID 32335779, PMID 32661083, 18 months, 1, 845 patients), PMID 35590453); Flachenecker 2014 (MOVE 2), published 2014 (PMID 24525548, doi:10.1159/000357427, 12-month extension: Flachenecker 2014, PMID 24943098); Etges 2016 (manufacturer safety registry), published November 2016 (PMID 27956834, doi:10.2147/TCRM.S115014)
October 27, 2026
A 3-year controlled study (CUPID) showing that synthetic THC did not slow disease progression in progressive MS was added; the statement 'higher doses have not been tested' was limited to controlled parallel studies. The conclusion and the strength of evidence did not change. The Turkey question now notes that the active substance of the mouth spray containing THC and CBD is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency).
October 22, 2026
The names of the conclusion labels were simplified: the "No benefit seen" label on this page became "No effect found". The assessment did not change.
October 21, 2026
Newly published and previously missed clinical studies were searched for in PubMed and ClinicalTrials.gov. 3 studies added: Mousavi 2025, Hansen 2023, and Bethoux 2024 (RELEASE MSS1). In the first two randomized studies with pure CBD, spasticity was no different from placebo (Mousavi 2025, Hansen 2023). With the new studies, the strength of evidence changed from "Insufficient" to "Weak", and the conclusion from "Not studied enough" to "No effect found".
Studies that led to the change: Mousavi 2025, published December 2025 (PMID 40498097, doi:10.1007/s00210-025-04347-w); Hansen 2023, published July 28, 2023 (PMID 37630995, doi:10.3390/ph16081079, EudraCT 2018-002315-98); Bethoux 2024 (RELEASE MSS1), published September 2024 (PMID 39106541, doi:10.1016/j.msard.2024.105740, NCT04657666)
October 21, 2026
The full texts of the studies were reread and the information on the page was checked against its sources. Corrected: the registration number, number of participants, side effect, and dose information in the study table; the dose range in the studies. The conclusion and the strength of evidence did not change.
October 19, 2026
Page published. This first assessment reviewed 2 studies.

Evidence changes across all topics