Medicinal Cannabinoids explained CBD explained THC Explained Endocannabinoid System
Chronic Pain Multiple Sclerosis Epilepsy Other Uses
Medicinal Cannabis Scheme Regulations How to take Medicinal Cannabinoids Product Options Talking with your Doctor
Overview Legislation Efficacy Clinical Fact Sheets Undesirable Effects Product Options How to Prescribe Verified Medicinal Cannabis Products Presentations Zoom series
New Zealand's Medicinal Cannabinoid Information Service

Efficacy of Medicinal Cannabinoid Products

Although there have been systematic reviews published on the use of Medicinal Cannabinoids in a variety of clinical settings perhaps the most comprehensive review is that commissioned by the Australian Government’s Department of Health.

A team from the University of New South Wales, University of Sydney and University of Queensland under the coordination of the National Drug and Alcohol Research Centre (NDARC) reviewed the available evidence for the use of medicinal cannabis in 5 clinic settings. Their findings for chronic pain, multiple sclerosis and epilepsy are summarised below with particular emphasis on data related to CBD products. The full analysis is available on the Therapeutics Goods Administration (TGA) website which is the Australian Medicines Regulatory body equivalent of Medsafe.

Chronic Non-Cancer Pain (CNCP)

Given the burden chronic pain has on patients, it is hardly surprising that there is considerable interest in the potential for medical cannabis to play a role in alleviating symptoms from both patients and clinicians.

In the setting of CNCP, potential new pharmacotherapeutic agents such as medicinal cannabis need to be considered alongside established therapeutic approaches. Active self-management strategies, which generally incorporate a reduction in drug utilization (particularly high risk opioids) have a proven place in the treatment of CNCP.

A total of 102 studies examined the impact of medicinal cannabis on patients with CNCP. This included 26 parallel RCTs, 23 cross-over RCTS, and 53 observational studies.

Pain Efficacy Summary

A meta-analysis of all randomised studies in CNCP averaging across all medicinal cannabis products indicated that medicinal cannabis was more likely than placebo to produce 30% and 50% reductions in pain scores and more likely than placebo to produce a significantly greater reduction in pain intensity ratings. Nabiximols, nabilone and THC extract, when separately examined, were much less consistently superior to placebo in producing a 30% reduction in pain or reducing average pain intensity. The lack of consistency for some individual cannabinoids probably reflects the small number of trials and their small sample sizes.

CBD Specific Data

As of yet, there is little specific data examining the efficacy of Cannabidiol (CBD) alone in patients with CNCP. The Australian review highlights two small studies noted below. Click the icon to see the abstract or paper.

 
iconfinder_Medical_Report-1_1400295.png

Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies.

 
 
iconfinder_Medical_Report-1_1400295.png

Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination.

 

Multiple Sclerosis (MS)

The Australian review considered evidence supporting the use of medicinal cannabis in treating symptoms of MS, including pain, spasticity, bladder spasm, ataxia and tremor, adverse events, quality of life and disability and the recommendations of the Multiple Sclerosis Working Group.

In New Zealand increasing interest in Medicinal Cannabis for managing pain and spasticity in MS and other chronic conditions led Multiple Sclerosis NZ and Motor Neurone New Zealand to jointly commission their own report in 2017.

MS Efficacy Summary

A literature search for high quality systematic reviews was conducted on the use of cannabinoids to treat the symptoms of multiple sclerosis, with a cut-off date of November 30, 2016. Overall, there is low to moderate quality evidence which suggests pharmaceutical-grade THC (dronabinol or THC extract) is effective for treating symptoms of pain.

THC:CBD combinations may be effective for treating symptoms of pain and spasticity in MS, in certain patient populations.

Findings were mixed as to whether cannabinoids assisted in improving bladder function, sleep, patient quality of life, ataxia/tremor and disability/disease progression.

No studies included active alternatives (non-cannabinoid medicines) as comparators, which is an important limitation.

CBD Specific Data

As of yet, there is little specific data examining the efficacy of Cannabidiol (CBD) alone in patients with Multiple Sclerosis. The Australian review highlights two small studies noted below. Click on the icon to see the abstract or full text.

 
iconfinder_Medical_Report-1_1400295.png

Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies.

 
 
iconfinder_Medical_Report-1_1400295.png

A preliminary controlled study to determine whether whole-plant cannabis extracts can improve neurogenic symptoms

 

Epilepsy

The role of therapeutic substances in treating epilepsy is primarily focused on reducing seizure frequency, with the ultimate goal of achieving complete seizure freedom. It is also important to optimise the quality of life for the epilepsy patient, and to consider adverse events and likelihood of treatment withdrawal.

The Australian review considered evidence supporting the use of medicinal cannabis in treating epilepsy where the primary endpoint was achieving a 50% or greater reduction in seizures and a number of secondary endpoints such as achieving complete seizure freedom and improvements in quality of life.

Epilepsy Efficacy Summary

In two randomised controlled trials (RCTs) comprising 291 patients (mean age: 25.9 years, range: 10-45 years), CBD was more likely to produce a greater than 50 percent reduction in seizures than placebo (Relative Risk [RR] 1.74, 95 percent CI: 1.24-2.43). The NNT for one person to achieve a 50 percent reduction in seizures was eight (95 percent CI: 6-17). Estimates did not differ by epilepsy type, sample age or study risk of bias.

An estimated 48.5 percent of the 970 patients in 17 observational studies achieved a 50 percent or greater reduction in seizures (95 percent CI: 39.0-58.1). This estimate is marginally larger than the proportion of responders in the two larger, high-quality RCTs (42.6 percent and 44.2 percent). Estimates did not differ by epilepsy type, sample age or study risk of bias.

Quality of life in the two RCTs was measured by parents'/caregivers' global impression of change. The pooled RR of parents/caregivers reporting that patients' overall condition had improved (using the patient global impression of change measure) in those receiving CBD versus placebo was 1.73 (95 percent CI: 1.33-2.26), and this did not differ on the basis of epilepsy type, sample age or study risk of bias. The NNT for one person receiving CBD to experience an improvement in parental-reported quality of life was five (95 percent CI: 4-9).

Epilepsy treatment with medicinal cannabis or cannabinoids is only recommended as an adjunctive treatment - that is, in addition to existing anti-epileptic drugs.

CBD Specific Data

Most published clinical and pre-clinical data on efficacy in epilepsy is with CBD. Its role in treatment is as an add-on treatment to current treatment in drug resistant epilepsy where four or five other anti-epileptic drugs (AEDS) have not controlled the epilepsy. Current advice is that CBD should be commenced orally at 5mg/kg/day in two divided doses. This can then be titrated up on a weekly basis by 5mg/kg/day to 20mg/kg/day with a maximum dose of 1gm/day. The more recent studies that describe data based on participant weight reported CBD dose ranges of 2.5-20mg/kg/day across a mean treatment length of 14 weeks. Earlier RCTs reported using 100mg of CBD administered two to three times per day for a treatment period between eight to twenty six weeks. The Australian review highlights several studies, the largest of which are noted below. Click the icon to see the abstract or paper.

 
iconfinder_Medical_Report-1_1400295.png

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

 
iconfinder_Medical_Report-1_1400295.png

Cannabidiol in patients with seizures associated with Lennox Gastaut Syndrome (GWPCARE4): a randomized, double-blind, placebo-controlled phase 3 trial

 
iconfinder_Medical_Report-1_1400295.png

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.

 

New Zealand Experience

A paper published in 2020, Cannabidiol prescription in clinical practice, reported on an audit of the first 400 patients prescribed CBD in New Zealand by Dr Graham Gulbransen. Although this data is not a controlled trial, it nevertheless provides interesting information on the characteristics of patients who seek or are referred for medical cannabis treatment and for which medical conditions. The paper provides patient reported impacts of CBD therapy via a standardized instrument for measuring generic health status called the EQ-5D-5L. The paper is summarised below along with a link to the full text.

Patients Overview and Outcome measures

The audit included all 400 patients presenting to Dr Gulbransen’s Cannabis Care clinic between December 7th, 2017 and December 7th, 2018. The mean patient age was 51.5 (SD 19.1) with slightly more women (53.9%) than men (46.1%). Each patient was grouped into a primary indication based on their presenting symptoms. If a patient fit multiple categories they were assigned to a primary group by the clinician. The primary indications are noted in the pie chart. Patients were prescribed CBD oil 100mg/ml.

Patients completed the EQ-5D-5L questionnaire both at baseline and after at least 3 weeks of CBD treatment. The EQ-5D-5L contains two parts: a descriptive measure of 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems) over 5 domains (mobility, self-care, usual activities, pain or discomfort, anxiety or depression). In additional patients are asked to use a vertical visual analogue scale (EQ-VAS) to indicate their level of health today on a 0-100 scale, where 100 is the best health you can imagine and 0 is the worst.

Primary Indication for CBD prescription (n=397)

 

CBD Treatment Outcomes

A large number of patients were lost to follow-up. Of the 397 patients initially prescribed CBD oil, 253 were followed up with by visit or phone. 250 patients reported their satisfaction with CBD use and of those, a subset of 110 completed before and after questionnaires. Median follow-up duration for these patients was 36 days (interquartile range 28-65). Their results are summarised in the table below where a p value of 0.05 or less is deemed as statistically significant.

Treatment with CBD in all populations showed an increase in overall health as determined by the EQ-VAS score which overall had a mean increase of 13.6 points (P<0.001, 95% CI = 9.72 - 16.76). This increase appeared to be independent of primary indication for CBD prescription. The majority (70%) of patients for whom data was available reported some level of satisfaction with their treatment (good, very good or excellent). There was no statistically significant relationship between patient reported satisfaction and age or gender.

Across the EQ-5D-5L domains patients with non-cancer pain had a significant improvement in self-reported mobility, usual activities, pain and anxiety or depression. Patients with mental health symptoms experienced improvements in usual activities, pain and anxiety or depression. Patients with neurological symptoms experienced no significant differences. Patients with cancer experienced improvements in pain. The full results are reported below in the table.

Score of 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = extreme problems. IQR = interquartile range

Adverse events were experienced by 9.9% of the patient group with sedation, vivid dreams and emotional disturbances being the most frequently reported. Positive side effects were also reported with 12.3% of patients experiencing improved sleep and 2.8% improved appetite. For the 110 patients for whom complete dosing data was available, the daily dose ranged from 40mg to 300mg per day. The prescriptions issued recommended dosing to at least 100mg/day.

iconfinder_Medical_Report-1_1400295.png

Cannabidiol prescription in clinical practice: an audit on the first 400 patients in New Zealand

Discussion

This study reported on a large range of chronic medical conditions in a clinical context. Of the 250 patients with follow-up, the majority (70%) reported good to excellent benefit with 30% reporting no benefit. Statistically significant improvements in quality of life measures were self-reported for patients with non-cancer pain and mental health related symptoms. For patients with a primary diagnosis of cancer or neurological symptoms there was no statistically significant improvement.

The study has a number of limitations that are fully elucidated in the original paper linked on the left. These include the number of patients lost to follow-up, the potential for the patient base to not accurately reflect the wider patient population and the lack of a control group.

You can find plenty of information on medicinal cannabinoids online but little of it is accurate and balanced. We provide links to all our sources in the body of each section. Below you will find a summary for our Efficacy section.

Chronic non-cancer Pain

  1. Guidance for the use of medicinal cannabis in the treatment of chronic non-cancer pain in Australia (https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-treatment-chronic-non-cancer-pain-australia)

  2. Print version: Guidance for the use of medicinal cannabis in the treatment of chronic non-cancer pain in Australia (https://www.tga.gov.au/sites/default/files/guidance-use-medicinal-cannabis-treatment-chronic-non-cancer-pain-australia.pdf)

  3. Notcutt, W., et al., Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies. Anaesthesia, 2004. 59: 440-452. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2044.2004.03674.x)

  4. Palmieri, B., C. Laurino, and M. Vadalà, Short-Term Efficacy of CBD-Enriched Hemp Oil
    in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination.     The Israel Medical Association journal: IMAJ, 2017. 19: 79. (https://www.ima.org.il/FilesUpload/IMAJ/0/228/114214.pdf)

Multiple Sclerosis

  1. Medicinal Cannabis Research Report December 2017 MSNZ and MND (https://www.msnz.org.nz/wp-content/uploads/2018/02/Medicinal-Cannabis-Research-Report-December-2017-MSNZ-and-MND.pdf)

  2. Guidance for the use of medicinal cannabis in the treatment of multiple sclerosis in Australia (https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-treatment-multiple-sclerosis-australia)

  3. Print version: Guidance for the use of medicinal cannabis in the treatment of multiple sclerosis in Australia (https://www.tga.gov.au/sites/default/files/guidance-use-medicinal-cannabis-treatment-multiple-sclerosis-australia.pdf)

  4. Notcutt, W., et al., Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies. Anaesthesia, 2004. 59: 440-452. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2044.2004.03674.x)

  5. Wade, D., et al., A preliminary controlled study to determine whether whole-plant cannabis extracts can improve neurogenic symptoms. Clinical Rehabilitation, 2003. 17(1): 21-9 (https://www.researchgate.net/publication/10874091_A_preliminary_controlled_study_to_determine_whether_whole-plant_cannabis_extracts_can_improve_neurogenic_symptoms)

Epilepsy

  1. Guidance for the use of medicinal cannabis in the treatment of epilepsy in paediatric and young adult patients in Australia (https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-treatment-epilepsy-paediatric-and-young-adult-patients-australia)

  2. Print version: Guidance for the use of medicinal cannabis in the treatment of epilepsy in paediatric and young adult patients in Australia (https://www.tga.gov.au/sites/default/files/guidance-use-medicinal-cannabis-treatment-epilepsy-paediatric-and-young-adult-patients-australia.pdf)

  3. Devinsky, O., et al., Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal of Medicine, 2017. 376: 2011-2020. (https://www.nejm.org/doi/full/10.1056/nejmoa1611618)

  4. Thiele, E., et al., Cannabidiol in patients with seizures associated with Lennox Gastaut Syndrome (GWPCARE4): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2018 Mar 17;391(10125): 1085-96. (https://www.ncbi.nlm.nih.gov/pubmed/29395273)

  5. Devinsky, O., et al., Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet Neurology, 2016. 15: 270-278. (https://www.ncbi.nlm.nih.gov/pubmed/26724101)

  1. Gulbransen, G., Xu, W, Arroll, B, Cannabidiol prescription in clinical practice: an audit on the first 400 patients in New Zealand. BJGP Open 2020 DOI: 10.3399/bjgopen20X101010. (https://bjgpopen.org/content/early/2020/02/03/bjgpopen20X101010)

NZ Experience