Medical Cannabis

 

Original Editors -Mark Wojda from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Ryan Scinta, Lucinda hampton, Elaine Lonnemann, Kim Jackson, Ryan Barry, WikiSysop, Mark Wojda and Joseph Ayotunde Aderonmu   

Introduction

C. sativa is a flowering, fast growing shrub, commonly known as hemp, cannabis, or marijuana. It originates from Central Asia, and is widely distributed in temperate and tropical areas. For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is THC. The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body.

• Many people around the world believe that the drug should be readily available for both medical and recreational use; however governments around the world still have strict laws about its usage.
• Each country has its own laws and regulations surrounding the drug; some places are more relaxed, whist others still believe the drug should be an illegal substance.

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for certain conditions See below).

Types of medicinal cannabis products

Cannabis is a complex plant comprising more than 500 constituents, including approximately 100 cannabinoids. The main active ingredients used for medical purposes are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive part of cannabis that produces a ‘high’, and has been used to treat symptoms such as nausea, pain and muscle spasticity. CBD has no psychoactive properties, and has been used to treat several inflammatory disorders and epilepsy.

Medicinal cannabis products can come in three main forms:

1. Pharmaceutical: Natural and synthetic medical-grade products with standardised content. The three main products are:
   • Dronabinol: Synthetic form of THC
   • Nabilone: Synthetic form of THC
   • Nabiximols: Chemically pure 50:50 mixture of TCH and CBD.
2. Medicinal-grade herbal cannabis: Produced and processed in controlled standard conditions to a medical grade, free of adulterants, higher levels of CBD and other cannabinoids, and contains lower levels of THC. This is provided in herbal form, or processed as an oil, balm, capsule or pill.
3. Herbal cannabis on the illegal market: Potentially unstable THC and CBD, and may contain adulterants.

The Evidence

At present, the evidence base for the use of medicinal cannabis products is limited. The current evidence base for the use of medicinal cannabis products is heterogeneous, comprising a small number of randomised clinical trials when stratified by condition, symptom or intervention type. These studies are of variable quality, including those with high risk of bias (eg incomplete outcome data), low statistical power, and short follow-up time.

• Recent reviews and analyses indicate there may be some therapeutic benefits of medicinal cannabis products in certain conditions but further research on the treatment efficacy and longer term side effects are warranted.
• Currently, most research and evidence on medicinal cannabis products have come from five clinical conditions: multiple sclerosis; palliative care; epilepsy; nausea and vomiting; and chronic non-cancer pain.
• As there is limited scientific evidence to support the use of medicinal cannabis in most conditions, and in many cases the evidence is for its use together with other medicines, it should be used only when approved treatments have been tried and have failed to manage conditions and symptoms.

Chronic Pain

The International Association for the Study of Pain taskforce looked at all the available research published in peer-reviewed journals on the use of medicinal cannabis for pain management, from preclinical studies to human trials.

They concluded overall the studies’ “quality, rigour, and transparency of reporting” of benefits and harms needs to be improved across the board. We would require higher quality data, for example through randomised controlled trials, to determine the safety and efficacy of using medicinal cannabis for pain

Multiple sclerosis

Around half the studies in a recent systematic reviews found that medicinal cannabis products may be effective for pain, spasticity, sleep and bladder function; the others were inconclusive.

Epilepsy

A number of studies have found low evidence for the use of medicinal cannabis products for the treatment of paediatric epilepsy, and for patients up to aged 25 years, especially when first-line treatments (ie anti-epileptic drugs) have been found to be ineffective. The numbers needed to treat are as follows:

• 50% or greater reduction in seizure frequency: 8
• Complete seizure freedom: 17
• Improvement in parental-reported quality of life: 5
• The numbers needed to harm for any adverse event was 3, and serious adverse event was 23.

Palliative care

The use of medicinal cannabis products in palliative care is currently unclear.

Nausea and vomiting

A small number of studies have found relief of nausea and vomiting in patients with cancer who are undergoing chemotherapy; however, the evidence is lacking and some were compared with now out-of-date practices.

Chronic non-cancer pain

There is some evidence available for the treatment of neuropathic pain using medicinal cannabis products; however, the magnitude of effect is small. One systematic review found that the numbers needed to treat was 22 for a 30% reduction and 26 for a 50% reduction in self-reported pain intensity

Side Effects

Like all prescription medicines, medicinal cannabis products can have side effects. The extent of effects of these can vary with the type of medicinal cannabis product and between individuals.

• In general, the side effects of CBD-rich products are less than those for high-THC products, but because the required doses for CBD can be quite high in conditions such as paediatric epilepsies, a proportion of patients encounter side-effects with these CBD doses.
• The known side-effects from medicinal cannabis treatment (both CBD and THC) include fatigue and sedation, vertigo, nausea and vomiting, fever, decreased or increased appetite, dry mouth, and diarrhoea.
• THC (and products high in THC) have been associated with convulsions, feeling high or feeling dissatisfied, depression, confusion, hallucinations, paranoid delusions, psychosis, and cognitive distortion (having thoughts that are not true).

Relevance to Physical Therapy

Physiotherapists should be able to educate patients on the reported benefits of cannabis (eg chronic pain,MS, spasticity, and chemotherapy-induced nausea and vomiting) as well as potential adverse effects.

More detail of evidence for those interested: Summary of evidence by condition

Condition	Products	Current evidence quality
Multiple sclerosis
Pain	Dronabinol, THC extracts	Low to high and inconsistent
Disability and its progression		None
Spasticity	Nabiximols and THC:CBD	Low and inconsistent
Bladder function		None
Ataxia and tremor		None
Sleep		None
Quality of life	Nabiximols and THC:CBD	Low and inconsistent
Epilepsy
To reduce and/or eliminate the number of seizures	CBD when used in conjunction with anti-epileptic drugs	Low to very low
	Oral cannabis extracts (OCEs)	Very low
	CBD:THC	Very low
	Cannabis sativa	Very low
Quality of life	CBD	Low
	Oral cannabis extracts (OCEs)	Very low
	CBD:THC	Very low
	Cannabis sativa	Very low
	THC	Very low
Palliative care
Alzheimer's disease	Dronabinol	Unclear
Advanced cancer symptom control	Dronabinol, THC:CBD, THC	Unclear but some evidence against use
	Cannabis sativa	Unclear
	Nabilone	Unclear
Nausea and vomiting
	Dronabinol	Low to moderate
	Nabilone	Very low to moderate
	THC	Low, insufficient evidence
	Levonantradol	Low to moderate
	THC:CBD	Insufficient evidence
	Cannabis sativa extract	Unclear
	Naximols	Insufficient evidence
Chronic non-cancer pain
	Nabiximols	Moderate to high
	Dronabinol	Low to moderate
	Nabilone	Very low
	Cannabis sativa	Very low
	THC extract	Moderate
	THC:CBD extract	Low to moderate
	Ajulemic acid	Very low

Nabiximols is a TGA-registered medicine, under the tradename Sativex. It is a standardised extract of cannabis, containing roughly equal amounts of THC and CBD.

Dronabinol is a synthetic form of THC.

Nabilone is a cannabinoid synthesised in the laboratory, and has actions similar to THC although its chemical structure is different.

Ajulemic acid is a cannabinoid synthesised in the laboratory. It is similar to a breakdown product (metabolite) of THC but does not have psychoactive properties.