cbd oil for ms spasticity

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment’s potential effectiveness, safety and limitations.

Methods

We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.

Results

Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.

Conclusion

We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.

Background

Spasticity, an involuntary increase in muscle tone or rapid muscle contractions, is one of the more common and distressing symptoms of multiple sclerosis (MS). Medicinal treatment may reduce spasticity, but may also be ineffective, difficult to obtain, or associated with intolerable side effects [1, 2]. Cannabis, a psychotropic drug known for its analgesic properties, also has a long history as an effective and tolerable treatment for spasticity [3, 4]. Demographic evidence has shown that many people with MS use cannabis for symptom management [5].

Clinical studies, animal models, and anecdotal reports [6–8] have suggested that cannabis may be an effective treatment of MS spasticity. The antispastic effect of cannabis has been supported through a demonstration of the inhibitory properties in exogenous agonists for cannabis receptors found in the CNS [7]. Early clinical trials reporting the efficacy and safety of cannabis use in MS have focused on the effects of Δ 9 -tetrahydrocannabinol (THC). Although these clinical studies reported a therapeutic benefit for MS symptoms, there were concerns of potential intoxication and other side effects of cannabis-based treatment [9]. Another clinical study using a cannabidiol (CBD) extract documented a reduction in spasticity-related pain but not in spasticity [10].

More recent combination therapies using whole plant extracts of both THC and CBD have been introduced and there is evidence that CBD, which is not psychotropic, may reduce THC levels in the brain and attenuate its psychotropic side effects [11–14]. Such therapies may potentially provide a tolerable yet effective treatment for MS symptoms [3]. A number of recent studies [15–22] have investigated the potential efficacy and safety of whole plant extracts of THC and CBD. One of the first large-scale studies of cannabis treatment for MS-related spasticity compared whole plant cannabis extracts with THC and a placebo, and found mixed evidence for the therapeutic benefit of spasticity in MS. A recent review [23] that included a number of these recent studies provided additional support for the benefit of cannabinoids in MS-related spasticity but called for further study into long-term treatment and side effects. A systematic evaluation of recent research had not previously been conducted, and was needed in order to provide organized evidence of cannabinoid treatments and direction for future clinical studies. We therefore systematically reviewed studies that used a combination extract of THC and CBD for the treatment of spasticity.

Methods

Searching

We conducted a comprehensive search using MEDLINE/PubMed, Ovid, and CENTRAL (Cochrane Central Register of Controlled Trials) for English-language only literature published from 1999 to April 2009 using different combinations of the following MeSH and free text terms: cannabis, cannabinoid, THC, CBD, multiple sclerosis, spasticity, spasms. Reference lists from retrieved reports were reviewed for additional studies. Unpublished data were not sought and abstracts, letters, case reports, and review articles were excluded. (See Additional file 1 for a Quality of Reporting of Meta-analyses (QUOROM) statement checklist.)

Selection and quality assessment

Only randomized, placebo-controlled, human studies of shorter treatment periods (under 6 months) were included. Studies were evaluated for methodological quality using Jadad scores [24] and only studies with Jadad scores of 4 or higher were considered for inclusion. Relevant trials included those that had administered a combination THC and CBD extract, those in which clinically stable spasticity had been established prior to trial and those that reported objective measures of pre- and post-treatment spasticity. Studies that used active control groups were not excluded. Abstracts were reviewed for relevancy and full text versions of potentially relevant randomized controlled studies were reviewed. Reports not considered relevant were excluded and all included reports were read in entirety.

Data abstraction

Data were extracted independently by the authors and any disagreements were resolved by consensus. The following information was extracted from each report: study type, study objective, sample size, controls, type and amount of cannabinoid used, treatment duration, objective and subjective outcome measures, and reported adverse events.

Analysis

A qualitative summary of the data was completed to compare the various outcome measures used across the included studies. In addition, a quantitative analysis of the one common outcome measure (Ashworth scale) used by the included studies was performed in order to assess statistical heterogeneity.

Results

Flow of included studies

Electronic searches found 38 studies that were potentially relevant to the present review. Of these, 33 did not meet the inclusion/exclusion criteria, including 27 reports that were not randomized, controlled trials. One study was excluded for focusing on spasticity-related pain and two were excluded for not assessing the effects of a combined extract of THC and CBD. Two studies were excluded for reporting long-term follow-up data (see Figure 1).

Flow diagram of included studies.

Study characteristics

Six double-blind, randomized, placebo-controlled trials published between 2002 and 2007 were analyzed [15–20]. These studies included a total of 481 patients with MS who were administered a combined extract of both THC and CBD. Three trials used a crossover design. Three trials used a parallel design in which 339 patients were administered a placebo only. Trial periods ranged from 2 to 15 weeks. Objective spasticity measures were extracted when included in the assessment data from at least two studies. All six trials reported an adjusted mean change score in the Ashworth scale assessment. Other measures of spasticity included mean changes from a baseline score in the following assessments: Visual Analogue Scale (VAS), a rating scale to measure the severity of spasticity; walk time; Rivermead Mobility Index (RMI), a measure of disability related to mobility; and self-reported ratings of spasm frequency or severity. (See Table 1 for the specific characteristics of each reviewed study.)

Qualitative analysis

Overall reduction of spasticity

Five studies [16–20] concluded that cannabis extract may decrease spasticity and improve mobility in patients with MS. One study [15] reported no reduction in spasticity. Adverse effects were reported in each study; however side effects from combined extracts of THC and CBD were generally well-tolerated. Two blinded studies comparing combined extracts of THC and CBD to extracts of THC alone found a lower incidence of adverse events in the combined THC and CBD trials [16, 17], and one study found a higher incidence of adverse events [15]. In all three comparison studies, there was no distinction in efficacy between THC extracts and combined THC and CBD extracts.

Ashworth score

In one study [18], 50 patients were assessed with the Ashworth scale for muscle tone and showed significant improvement during the active treatment trial. The other five studies reported little to no improvement in their versions of the Ashworth scale. It should be noted that the Ashworth scale is subject to individual assessor evaluation and there may have been variation between studies in the modification of scale measures.

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Visual Analogue Scale

Three studies reported data from VAS scores [15, 17, 19]. Two studies reported that patients on active treatment showed a significant improvement in VAS scores [17, 19], and one reported no significant difference [15]. In one study [17], daily recorded assessment data from 14 MS patients were mixed with data from six patients with other neurological disorders. The other studies recorded daily [15] or weekly [19] assessments.

Walk time

Although five studies included walk time in their proposed assessments, only two studies [16, 19] reported data from 160 patients with MS. Although both showed a trend for improvement in walk time, P-value did not reach statistical significance in one study [19] and was not reported in the other [16].

Rivermead Mobility Index

Three studies [16–18] reported RMI scores for 275 MS patients. Although there was a trend for improvement from baseline to study completion, mean changes in assessment were significant in one study [18] and insignificant in the other two studies.

Other subjective rating scales

All six studies reported an additional measure of subjective assessment. Rating scales were completed by a total of 379 patients in order to record various changes in spasticity throughout the trials. Five studies [16–20] reported significant improvements in spasticity as subjectively rated by patients with MS and one reported deterioration [15].

Meta-analysis

Three of the studies [15, 19, 20] did not report adequate (mean and standard deviation) Ashworth scale data for inclusion in the quantitative meta-analysis. This left three studies for the calculation of the pooled mean difference in Ashworth scores. The chi-square test for heterogeneity showed evidence of significant variation between the three studies (χ 2 = 5.25, P = .07, l 2 = 62%). Given that only three of the six studies reported adequate Ashworth scale data [16–18], of these three only one demonstrated statistically significant findings [18], and the high level of heterogeneity, a quantitative analysis of the data was deemed inappropriate.

Discussion

Limitations

There were some limitations to the systematic review. First, this review did not include unpublished data. There may be ongoing clinical trials of combination THC and CBD therapy as it is a relatively recent therapy. There is also the possibility that other clinical reports using whole plant cannabis extracts may have been appropriate for review, but were not included without report of specific methodology. A meta-analytical review of the effects of cannabis on spasticity would be useful, but was not deemed appropriate for the present review because of the variation in assessment data.

Subjective vs. objective measures

The validity of the Ashworth scale as an outcome measure has been previously questioned [16]. However, we have shown that other objective measures of spasticity (i.e. RMI, walk time) may also fail to adequately support the improvements found in scores from more subjective measures (i.e. rating scales, diary entries). A long-term follow-up study [21] showed a significant improvement in the Ashworth scale, however, the change was still small and was found in the THC group only. Another concern is that participants of both active and placebo trials may not be entirely blind to their treatment status [16], and this may affect subjective assessments. It remains that, without a validated, objective measure of spasticity, it will be difficult to accurately measure the effects of cannabis therapy on MS spasticity.

Adverse events

Adverse effects were reported in each trial in which patients received active treatment (including THC-only treatment). There is some evidence that combined extracts of THC and CBD may attenuate side effects of THC alone, and future studies are needed to compare the safety of combined cannabis extracts with traditional treatment. Dosage is another concern that should be considered in the context of side effects. Incidence of side effects varies greatly depending on the amount of cannabis needed to effectively limit spasticity. In one study [17], it was noted that the initially permitted dosage level sometimes resulted in marked side effects, and the dosage was thereafter reduced. The careful monitoring of symptom relief and side effects is critical in reaching an individual’s optimal dose. Finally, it should be noted that several adverse events were also reported in each trial in which patients received a placebo. In a long-term follow-up [22] of one of the reviewed studies [19], it was determined that most of the reported adverse events were unrelated to cannabis treatment. Considering the distress and limitations spasticity brings to individuals with MS, it would be important to carefully weigh the potential for side effects with the potential for symptom relief, especially in view of the relief reported in subjective assessment.

Conclusion

We found evidence that combined extracts of THC and CBD may reduce symptoms of spasticity in patients with MS. Although the subjective experience of symptom reduction was generally found to be significant, objective measures of spasticity failed to provide significant changes. In a previous study of spasticity-related pain, MS patients also reported a subjective perception of symptom reduction with cannabinoids [10]. However, since at least one past animal study has provided objective, physiological evidence for the antispastic properties of cannabinoids [7], the distinction between perceived symptom relief and objective physiological changes in humans should therefore be primary in future research efforts.

Given that adverse events occurred in each reviewed trial, we also encourage future comparison studies of cannabis treatments at a wide range of dosage in order to balance potential side effects with maximum therapeutic benefit.

Finally, there is evidence that cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS. Neuroinflammation, found in autoimmune diseases such as MS, has been shown to be reduced by cannabinoids through the regulation of cytokine levels in microglial cells [25]. The therapeutic potential of cannabinoids in MS is therefore comprehensive and should be given considerable attention.

Medicinal Cannabis and MS

Medicinal cannabis is a drug made from any of the parts of the plants from the Cannabis group that is used to treat a medical condition or symptoms of a disease.

Medicinal cannabis does not include recreational use of the drug. It is a medical product that is regulated by the government and produced by a pharmaceutical company. This ensures that the quality of the cannabis product is maintained, and the amounts of the active ingredients are known.

On the 1st of November 2016, medicinal cannabis became a controlled drug that could be prescribed in Australia. However, each state or territory has its own laws for prescribing medicinal cannabis. More detail about access and supply can be found here.

Tetrahydrocannabinol (THC) and cannabidiol (CBD)

Cannabinoids are compounds found within cannabis, the two most commonly used in medicinal cannabis products are tetrahydrocannabinol and cannabidiol. Tetrahydrocannabinol (THC) is the main compound responsible for the psychoactive properties of cannabis (the “high” associated with cannabis use). THC is able to affect cells in the brain and spinal cord and cells of the immune system. Cannabidiol (CBD) is sometimes called cannabis oil. CBD appears to be non-psychoactive and is also able to affect cells in the brain and spinal cord and immune system. Medicinal cannabis products (see more below) may contain specific quantities of these components in a synthetic preparation (for example Sativex), or they may be preparations made from the original plant (such as oils or tinctures) that have been carefully prepared and analysed so that the quantity of each ingredient, or dose, is consistent.

How does medicinal cannabis work?

The active components of medicinal cannabis, THC and CBD (see above), act on cells via a specific set of receptors known as the cannabinoid receptors. Receptors are found on the surface of cells and are like ‘docking stations’ which allow cells to respond to molecules in their environment and communicate with each other. Different cannabinoid receptors are found in the brain and spinal cord of humans, while other cannabinoid receptors are found in other areas of the body, including the immune system. Researchers are determining if other synthetically made drugs can also activate these receptors.

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Research into medicinal cannabis and MS

Research has shown that medicinal cannabis can be useful to treat some of the symptoms of MS in some people. There is limited evidence that medicinal cannabis can have an effect on the disease course itself, by reducing the number of relapses, or slowing the progression of the disease and accumulation of disability. More information on the evidence for particular aspects of MS are outlined below.

Muscle spasticity

Spasticity is commonly experienced as stiffness of a muscle or muscles. Studies have reported that up to 90% of people with MS will experience some form of muscle spasticity. In people with MS, common treatments can be ineffective or have unwanted side effects.

Human trials using medicinal cannabis to treat spasticity have produced mixed results, although on balance the evidence suggests that medicinal cannabis can be effective for the treatment of spasticity.

One review looked at the average result of objective measures of spasticity in seven trials and found that overall spasticity improved on treatment with medicinal cannabis. This review also showed that medicinal cannabis reduced the frequency of spasms and the pain associated with muscle spasms. Another recent review that included evidence from 34 different clinical trials found that both patients’ perceptions of spasticity and the objective measures of spasticity improved on treatment with medicinal cannabis. A further review of six clinical trials of medicinal cannabis for MS found that it might be effective in the short term, but the benefits did not last after treatment had ended.

In the CAMS study over 600 people with MS took medicinal cannabis to treat their spasticity as part of a clinical trial. Most of these people (95%) had a progressive form of MS. In this study, people taking medicinal cannabis felt their spasticity had improved and felt their symptoms of pain related to spasticity and sleep disturbance were also improved. The study participants were able to complete a walking task faster, but not all objective measurements of spasticity were improved. At the one year follow up of the CAMS study, there was a small improvement in objective measurements of spasticity over the 12 months and participants felt that their spasticity had improved.

Neuropathic pain

Neuropathic pain can be experienced as a spontaneous burning or severe tingling sensation, and it can change with temperature or touch. It may be a direct consequence of a MS lesion and affects up to half of all people with MS. Often this type of pain does not respond well to the currently available pain medications.

The scientific evidence that medicinal cannabis reduces pain in people with MS is varied and there is currently less certainty about its benefits than there is for spasticity in MS.

Several human trials have shown that medicinal cannabis can reduce this neuropathic pain in people with MS and reviews of the research in this area have found there is some evidence for the use of medicinal cannabis to treat neuropathic pain in MS. One clinical trial showed that people with relapsing remitting MS who did not respond to standard pain medications had lower pain scores after 10 weeks of treatment with Sativex (a pharmaceutical preparation of cannabis-based compounds – see below). However, the benefits were not sustained to the 14 week mark or after the participants stopped taking the medication. Another study looking at the effect of sativex on neuropathic pain in a small group of people with MS showed an improvement in pain intensity and sleep disturbance related to pain. A longer 96 week study in a large group of people with MS found that while it was safe to use over a longer period it did not have an effect on neuropathic pain.

A study looking at whether a synthetic cannabinoid might be effective in people with MS already taking gabapentin for their neuropathic pain found that pain intensity and the impact of pain on their ability to perform daily activities was improved.

In a short four week study of people with progressive MS and higher levels of disability, people reported an immediate improvement after taking medicinal cannabis but this was not borne out in a daily record of pain levels.

Urinary or bladder issues

Urinary or bladder issues can affect people with MS and these symptoms are often under-reported to health professionals, but can have serious long term consequences. Only a few studies have investigated if medicinal cannabis can affect urinary issues in people with MS. In an analysis of the CAMS participants and other studies (see here and here), medicinal cannabis was found to improve a range of urinary issues, including the volume and number of urinary incontinence episodes during the day and night and the number of voids per day. Participants also felt that their bladder symptoms improved.

Sleep

Improvements in sleep disturbances due to a reduction in spasticity or neuropathic pain have been seen in some studies. Participants in studies investigating medicinal cannabis for other symptoms of MS have also noted improvements in sleep quality when taking medicinal cannabis. Very few scientific studies have specifically investigated how medicinal cannabis affects sleep disturbances and fatigue in people with MS. Trials have noted an improvement in sleep quality and reduced sleep disturbance in people taking medicinal cannabis, but these changes were only small. However, the authors note that this treatment may improve short term sleep outcomes in people with MS.

Medicinal cannabis as a disease modifying therapy for MS

At the moment there is no strong evidence that medicinal cannabis can be used as a disease modifying therapy to treat MS itself rather than the symptoms of MS. In laboratory models of MS, research has shown that medicinal cannabis is able to dampen down the attack by the immune system, however most human clinicals trials show that it has no effect on the progression of the disease.

In the CAMS clinical trial, no changes to the number of relapses were seen in people taking medicinal cannabis. In the CUPID trial, almost 500 people with primary progressive or secondary progressive MS were studied for three years. Overall, the researchers found that taking medicinal cannabis did not slow the progression of the disease and accumulation of disability as measured by the EDSS (standard measure of disability in MS), other rating scales or on magnetic resonance imaging. There was some evidence that it may have slowed the progression of the disease in people with mild disability (EDSS 4-5.5).

Side effects

Human trials have shown that medicinal cannabis is generally well tolerated, but there are some side effects. Often side effects present within the first week of treatment.

The most common side effects are dizziness, drowsiness and disorientation. Other side effects can include, nausea, vomiting, fatigue, headache, sleepiness, diarrhoea, constipation, memory deficits, dry mouth, aggression, agitation, irritability, insomnia, and other cognitive effects. Serious side effects can occur more rarely and include seizures, pneumonia, altered liver function, psychiatric symptoms and falls.

It is advised that people with MS with a family or personal history of psychiatric disorders avoid using medicinal cannabis until more research can be performed. This is especially important as people with MS are at a higher risk of developing some of these disorders, when compared to the general public. As some of the side effects of cannabis-based medications include effects on memory and thinking, it is also possible that medicinal cannabis could further exacerbate these symptoms in people with MS who have cognitive symptoms. This should be taken into careful consideration by the individual in consultation with their health care providers.

It is important, as with all medications related to a person’s MS that treatment decisions are made in conjunction with your medical team so that the risks for each individual and potential treatment interactions can be assessed.

How to access medicinal cannabis in Australia

Currently in Australia the only Therapeutic Goods Administration (TGA) approved medicinal cannabis product specifically for people with MS, is Sativex. This can be prescribed for the treatment of moderate to severe muscle spasticity in MS, in those who have not responded adequately to other anti-spasticity medications, and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy. For other products and for other symptoms the prescribing of medicinal cannabis is at the discretion of the treating doctor and needs to follow the specific processes established within each State.

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The Federal Government changed the Narcotic Drugs Act so that individual states could legislate the use of medicinal cannabis. There are several steps to accessing medicinal cannabis in Australia and the TGA has provided a good overview here.

Firstly, a person with MS needs to have a discussion with their doctor. Together they will determine if medicinal cannabis may be an appropriate treatment option for their circumstances. The position of the Australian Medical Association (AMA) is that medicinal cannabis is unlikely to be a first-line treatment option for symptoms of MS. This is mainly based on their assessment of the current level of evidence for most uses of medicinal cannabis. You can read their position statement see here.

In light of this, it is likely that most medical practioners will consider medicinal cannabis on a case-by-case basis. To be able to prescribe medicinal cannabis a medical practitioner can take one of two possible approaches. They can apply to be an Authorised Prescriber so that they can prescribe medicinal cannabis to a specific group of patients for a specific condition (e.g. spasticity associated with MS). More information about this can be found here. They can also apply through the Special Access Scheme for approval to prescribe medicinal cannabis for a single patient.They may also need to meet the requirements from the Office of Drug Control to import the medication. Medical practitioners will also need to comply with local state and territory laws outlined below. Please note that these laws are subject to change.

State Details
New South Wales Medical practitioners in NSW can apply to NSW Health to prescribe medicinal cannabis to an individual patient, or group of patients. Those importing the drug must hold an appropriate licence from the NSW Ministry of Health. More details can be found here. In March 2018, NSW Health announced that they will be changing the laws to rely on a single clinical assessment by the Therapeutic Goods Administration (TGA). This is yet to come into effect. If successful, this model may be replicated across other states and territories.
Victoria In Victoria, medicinal cannabis needs to be prescribed by a medical practitioner. To use medicinal cannabis to treat MS symptoms the medical practitioner will need a Schedule 8 Treatment Permit from the Victorian Department of Health and Human Services. Further details can be found here and here.
Queensland Queensland Health can grant approval to general practitioners and specialists to prescribe medicinal cannabis to individual patients, and specialists can prescribe it to a group of patients (i.e. people with MS that suffer from spasticity). More information can be found here, here, and here.
Northern Territory People with MS living in the Northern Territory can access medicinal cannabis through a Northern Territory doctor who is authorised under the Special Access or Authorised Prescriber Scheme administered by the Therapeutic Goods Administration. More information can be found here.
South Australia Medicinal cannabis is available in South Australia through a patient access pathway. An approved specialist will have to provide the prescription. More details can be found here.
Western Australia In Western Australia medicinal cannabis is a Schedule 8 item. Neurologists are able to apply to be an authorised prescriber for people with MS. More details can be found here.
Tasmania If your Tasmanian GP considers that medicinal cannabis may be a potential treatment they will refer you to a specialist. Specialists may apply for legal authorisation to prescribe medicinal cannabis through a controlled access scheme. More details can be found here and here. If prescribed, it will be dispensed through a Tasmania Service hospital pharmacy.
Australian Capital Territory Medical practitioners in the ACT can apply to the ACT Chief Health Officer for a Category Approval for Medicinal Cannabis. More details can be found here.

Supply of medicinal cannabis products in Australia

In early 2016 legislation was passed to allow suppliers to apply for licences to grow and manufacture medicinal cannabis in Australia. This law allows for the raw materials for medicinal cannabis to be sourced in Australia and Australian quality control measures to be enforced. The government has also worked with other suppliers to approve the import of some products into Australia.

More information about manufacturers and suppliers of medicinal cannabis in Australia can be found here.

Sativex (a drug based on the cannabis derived ingredient nabiximols containing both THC and CBD compounds) was the first medicinal cannabis product approved in Australia by the Therapeutic Goods Administration (TGA) in 2012 for the treatment of spasticity in people with MS. However, it was not possible to access Sativex in Australia until the recent changes to the regulations. Since 6 November 2017, Sativex became accessible through specific access schemes depending on the state or territory (see above). It can be prescribed for the treatment of moderate to severe muscle spasticity in people with MS who have not responded adequately to other anti-spasticity medications. It is an oromucosal spray (mouth spray). It is not reimbursed under the Pharmaceutical Benefits Scheme.

Useful links

The Therapeutic Goods Administration (TGA) has produced a number of documents and guides on medicinal cannabis in Australia and the processes for accessing it via prescription. Links below:

THC, CBD Combo Eases MS Symptoms, Extends Cutaneous Silent Period

Oral spray containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) offers several benefits for neurophysiological symptoms affecting patients with secondary progressive multiple sclerosis (MS), according to new study results.

The small pilot study of 15 patients analyzed how the THC-CBD spray affected spasticity and pain scores, concluding that the spray not only improved measures of spasticity and pain—one of the most disabling and undertreated symptoms of MS—but also extended the duration of patients’ cutaneous silent period (CSP), the brief interruption in voluntary contraction that follows strong electrical stimulation of a cutaneous nerve.

The results of these patients with secondary progressive MS were compared against those of 14 healthy controls of similar age and sex. Four weeks following the optimum individual THC-CBD dose, 4 different measurements confirmed that the spray significantly improved spasticity and pain:

  • The Modified Ashworth Scale (MAS) scores, which measure various muscle tones on a 5-point scale with a maximum score of 48, dropped by a median of 10 points, from 14 to 4
  • The 9-Hole Peg Test (9HPT) times, which assesses how long it takes patients to place and remove 9 pegs from 9 holes, dropped by a median of 3.7, from 46.0 to 42.3
  • The numeric rating scale (NRS) ratings, which measures spasticity on an 11-point scale, dropped by a median of 3 points, from 7 to 4
  • The 10-cm visual analogue scale (VAS) measures, which patients used to indicate their pain levels, dropped in 10 (67%) patients by a median of 3 cm, from 5 to 2

However, there was an additional test in which researchers measured how long it took patients to walk 25 feet that saw no changes from baseline to the time of analysis.

“THC relieves spasticity by modulating muscle tone, but it also possesses psychotropic effects, being a partial agonist of the cannabinoid-1 receptor (CB1R),” explained the researchers. “At forebrain sites, CBD antagonises both CB1Rs and cannabinoid-2 receptors (CB2Rs) in the presence of THC. Thus, the THC-CBD combination can prevent underisable psychoactive effects and abuse phenomena.”

The researchers added that cannabinoids also interact with neural pathways mediating pain and inflammation at central and peripheral sites, thus creating an analgesic effect in several conditions, such as MS.

In addition to improving spasticity and pain scores, the spray simultaneously prolonged CSP duration, which according to the authors could prove a promising tool for assessing the analgesic effects of THC-CBD in MS. At baseline, the CSP duration was 39, which increased to 47.9 at the time of analysis.

Reference

Vecchio D, Varrasi C, Virgilio E, Spagarino A, Naldi P, Cantello R. Cannabinoids in multiple sclerosis: a neurophysiological analysis. Acta Neurol Scand. Published online July 6, 2020. doi: 10.1111/ane.13313.