Herbal Evidence

4 Evidence-based uses of cannabinoids

Which conditions have cannabis and cannabinoids been scientifically shown to improve?

Last updated: 21 June 2020

What are cannabinoids?

Cannabis is a plant comprising hundreds of compounds including the psychoactive tetrahydrocannabinol (THC), the non-psychotropic cannabidiol (CBD) and other cannabinoids. Cannabis can be consumed in many ways including via smoking, vapour and oil extracts. There are also pharmaceutically derived cannabinoids that can also be administered in multiple ways, such as in the form of sprays (Nabiximols; tradename Sativex), as capsules of synthetic THC (e.g. nabilone) or intravenously in hospital settings. Cannabis has been used medicinally and recreationally for millennia and continues to be used today by millions of people globally. The medicinal uses of cannabinoids have been formally investigated using clinical trials for a range of conditions. While many types of illnesses have been studied, most trials have only recruited small numbers of patients and, as a result, have provided little evidence that cannabinoids are beneficial for those conditions. However, there are at least four conditions for which multiple, large clinical trials have been conducted demonstrating that cannabinoids can be an effective treatment.

1. Multiple sclerosis

What is multiple sclerosis?

Multiple sclerosis, which affects more than 2 million people globally, is a disease of the nervous system where it is believed that the immune system attacks myelin sheaths (insulators of nerve fibres). This damage affects the signalling between the brain and the rest of the body and can lead to symptoms such as muscle weakness, partial blindness and fatigue. Many people with multiple sclerosis also experience spasticity, where the muscles feel stiff and movement becomes difficult, or spams, from sudden involuntary muscle stiffness resulting in jerking, especially in the legs. While some treatments are available, further research is needed to better understand its causes and possible treatments. Randomised controlled trials investigating cannabinoids as a potential treatment have focussed on reducing the symptom of spasticity.

Cannabinoids clinical trials for multiple sclerosis

After a systematic review of the literature, Herbal Evidence extracted the results from ten placebo-controlled trials investigating the effectiveness of various cannabinoids for treating multiple sclerosis symptoms. Overall, the current evidence is that cannabinoids performs better than placebo in treating multiple sclerosis.

One 2012 study (1) randomly assigned over 270 multiple sclerosis patients aged between 18 and 64 years to either 12 weeks of daily capsules of a cannabis extract containing THC or daily capsules of a placebo. At the end of the treatment, 31% of patients in the cannabis arm experienced a reduction in spasticity compared with 13% in the placebo arm. Success has also been observed in clinical trials investigating cannabinoids in the form of sprays. For example, in another study, multiple sclerosis patients aged between 23 and 76 years were randomly assigned to either Sativex or placebo in addition to their current antispasticity therapy (2). At 12 weeks, 74% of patients in the Sativex arm achieved at least a 30% improvement in the severity of spasticity compared with 51% in the placebo arm.

These clinical trials, together with the findings from many others, provide evidence that cannabinoids work better than placebo for treating spasticity caused by multiple sclerosis. However, some patients did report side effects including dizziness, dry mouth and fatigue. For information on all the studies included in the meta-analysis, go to the cannabinoids page, select “Multiple sclerosis” as the condition and download the related PDF fact sheet.

2. Nausea and vomiting due to chemotherapy

Nausea causes and treatments

People may experience nausea and vomiting due to a wide range of reasons. For example, it could be due to food poisoning, gastrointestinal disorders, early pregnancy or after an operation as a side effect of general anaesthesia. In addition, many people experience nausea and vomiting as a result of chemotherapy. Treatment includes rehydration as well as prescription or over-the-counter medications such as prochlorperazine. The efficacy of cannabinoids in treating and preventing chemotherapy-induced nausea and vomiting has been investigated in randomised trials using both placebo and antiemetic medication as control treatments.

Cannabinoids clinical trials for chemotherapy-induced nausea and vomiting

Herbal Evidence extracted the results of six placebo-controlled trials and 11 trials using active controls. Overall, the current evidence suggests that cannabinoids perform better than placebo in suppressing nausea and vomiting, as well as better than prochlorperazine.

In one clinical trial where adult cancer patients were assigned to either oral THC or a placebo, it was observed that 73% of the patients given THC no longer had nausea compared with 9% of those given the placebo (3). Cannabinoids have also been shown to be more effective than a standard antiemetic. One study of cancer patients found that when treated with nabilone, a synthetic THC, 80% of patients experienced some relief in their severe chemotherapy-induced nausea and vomiting compared with 32% when treated with prochlorperazine (4).

While there is evidence that cannabinoids work better than placebo and even prochlorperazine in suppressing nausea and vomiting due to cancer treatment, there have been many reported side effects including vertigo, drowsiness, dizziness, a “high” and depersonalisation syndrome. For more information on cannabinoids as a treatment for nausea and vomiting see Do cannabinoids help to relieve nausea due to chemotherapy? or go to the cannabinoids page, select “Nausea/ vomiting” as the condition and download the related PDF fact sheet.

3. Pain

Pain is an unpleasant sensation that may be experienced in many parts of the body. It may be short-lived and resolve quickly (acute) or the pain may be chronic, lasting at least 3 or 6 months. Pain may be due to injury as well as conditions such as cancer and multiple sclerosis. Pain is notoriously hard to measure and as it is subjective it is hard to compare one person’s level of pain to another’s or to an objective threshold. Therefore, studies investigating pain typically look at changes in pain levels within patients, by asking participants to rate their pain on a scale from 0 to 10, where 10 is the worst imaginable pain, before and after treatment.

Clinical trials of cannabinoids for pain

Effective pain management treatments include physical therapy, psychotherapies and prescribed or over-the-counter medication. Clinical trials have also investigated the efficacy of herbal medication, including cannabinoids. After a systematic review of the literature, Herbal Evidence extracted the results from two dozen randomised controlled studies of cannabinoids treating pain. Overall, there is strong evidence that cannabinoids work better than placebo in improving pain outcomes for a range of patient groups and forms of treatment.

One group of researchers have investigated vaporised cannabis as a potential treatment for neuropathic pain (such as due to spinal cord injury or diseases) and found that when given cannabis most patients experienced at least a 30% reduction in pain scores (61% (5) and 88% (6)) compared with under 50% when given placebo (26% and 45%, respectively). Cannabinoids have also been shown to be an effective treatment for other causes of pain. For instance, in one study of multiple sclerosis patients (7), 71% of patients given Sativex experienced an improvement compared with 31% who were given placebo.

While there is evidence that cannabinoids work better than placebo for pain relief, some patients have reported side effects including dizziness, disorientation and nausea. For more information on cannabinoids as a treatment for pain see Do cannabinoids help to reduce pain? or go to the cannabinoids page, select “Pain” as the condition and download the related PDF fact sheet.

4. Seizures

Seizures are periods of abnormal electrical activity in the brain. These can lead to changes in feelings, uncontrolled movements and reduced levels of consciousness. Seizures can have many causes including head injury, alcohol withdrawal and infections. Recurrent seizures are indicative of epilepsy, a group of neurological disorders affecting millions of people worldwide, with onset often occurring in childhood. While anti-seizure medication is effective for many patients, some people live with drug-resistant seizures which can be life-limiting or even lead to an increased risk of death.

CBD for reducing seizure frequency

Randomised clinical trials have investigated the efficacy of cannabinoids in patients with drug-resistant seizures. Herbal Evidence extracted the results from four randomised controlled studies of cannabinoids treating children and adults with epileptic seizures. Overall, there is strong evidence that cannabinoids work better than placebo in reducing the number of seizures.

For instance, in a study of 120 children with Dravet Syndrome, a childhood epilepsy disorder, who were receiving standard antiepileptic treatment, after 14 weeks of CBD treatment 43% of children experienced at least a 50% reduction in the frequency of their drug-resistant seizures. Among the children who were instead randomly assigned to receive placebo, this was 27% (8). Lennox-Gastaut syndrome is another type of epilepsy for which CBD has been demonstrated to be effective. A study of 171 patients with Lennox–Gastaut syndrome aged between 2 and 45 years were randomly assigned to either a pharmaceutical formulation of purified cannabidiol or placebo. After 14 weeks, 44% of patients in the CBD arm experienced at least a 50% reduction in the frequency of drop seizures compared with 24% in the placebo arm (9).

Currently, there is strong evidence that cannabinoids are effective in reducing the number of epileptic seizures, however, some patients have reported adverse events such as diarrhoea, fatigue and decreased appetite. For more information on cannabinoids as a treatment for seizures go to the cannabinoids page, select “Seizures” as the condition and download the related PDF fact sheet.

Should I take cannabinoids for these and other conditions?

As the current evidence highlighted above shows, people receiving some form of cannabinoid in clinical trials were more likely to experience improvements in multiple sclerosis spasticity, relief from chemotherapy-induced nausea and vomiting, reductions in pain severity and less frequent seizures compared with people receiving placebos. Randomised clinical trials have also been conducted to assess the effects of cannabinoids on many more conditions including ulcerative colitis, alcohol dependence and Alzheimer’s disease and dementia. However, as yet the evidence on whether cannabis or cannabinoids can improve those conditions is currently lacking. Though it is hoped that with the gradual moves towards legalisation and decriminalisation of recreational and medicinal cannabis in many countries and states around the world, the research into its efficacy will increase.

Even though positive outcomes are more common among patients with particular conditions who were given cannabinoids compared to those who were given placebos, not every patient experienced improvement in their conditions. In addition, no drug is completely safe for everyone who takes it and that includes medication derived from cannabis. Reported side effects of cannabinoids include dizziness, disorientation, nausea and dry mouth. Therefore, as with every treatment, one needs to consider the potential risks versus the potential benefits, and this should always be done with the supervision of a physician.

References

1. Zajicek, J. P. et al. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J. Neurol. Neurosurg. Psychiatry 83, 1125–1132 (2012).
2. Novotna, A. et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur. J. Neurol. 18, 1122–1131 (2011).
3. Orr, L. E. & McKernan, J. F. Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine. J Clin Pharmacol 21, 76S-80S (1981).
4. Herman, T. S. et al. Superiority of Nabilone over Prochlorperazine as an Antiemetic in Patients Receiving Cancer Chemotherapy. New England Journal of Medicine 300, 1295–1297 (1979).
5. Wilsey, B. et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain 14, 136–148 (2013).
6. Wilsey, B. et al. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease. J Pain 17, 982–1000 (2016).
7. Rog, D. J., Nurmikko, T. J., Friede, T. & Young, C. A. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 65, 812–819 (2005).
8. Devinsky, O., Cross, J. H. & Wright, S. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N. Engl. J. Med. 377, 699–700 (2017).
9. Thiele, E. A. et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 391, 1085–1096 (2018).