Marijuana (Cannabis) Print Page

Bottom Line

Effectiveness: There are few published studies of the effects of medical cannabis in patients with rheumatic diseases; it may help to relieve pain and promote sleep. More evidence is needed to determine what dose and formulation produces the best outcomes in patients with rheumatoid arthritis or osteoarthritis.

Safety: The few studies examining cannabinoids report limited benefits with a risk of potential adverse events; long-term risks associated with medical cannabis in patients with rheumatic diseases are unknown.³

Common Names: Marijuana, Hemp
Scientific Names: Cannabis (Cannabis sativa, Cannabis indica)

What is cannabis?

Cannabis is a substance obtained from the dried leaves and buds of hemp plants
Cannabis is composed of many components. The two main components are:
- Cannabidiol (CBD): likely the main component involved in pain reduction
- Δ⁹-tetrahydrocannabinol (THC): the component causing an intense “high”; some research suggests it may assist CBD to reduce pain
- THC and CBD are found in the flowering buds of the female cannabis plant
- Synthetic cannabinoids have also been produced, available as the prescription products nabilone (Cesamet^®) and nabiximols (Sativex^®)
Cannabis is now legal in Canada and is used recreationally as well as medically to treat a variety of conditions despite unclear evidence that it works.

What is it used for in people with rheumatic conditions?

Cannabis has been used for pain relief, improvement in mood, and/or sleep.

How is it thought to work?

The human body has natural cannabinoids (neurotransmitters), called anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), which act on cannabinoid receptors in the brain and nervous system, as well as in the immune system.
These systems play an important role in regulating pain sensation, inflammation, appetite, mood, and sleep, amongst others.
THC and CBD also act on cannabinoid receptors in the body. When these receptors are activated, inflammatory and pain responses may be reduced.

What dose of cannabis is recommended?

Dosing is dependent on many factors, including reason for use, genetics, route of administration, other medical conditions and medications, and prior use (as the body can become tolerant to it).
Different types of cannabis products have different strengths. Start low and go slow with a product that preferably has low THC and higher CBD content. It may take months to find the most effective and best tolerated dose.
- Although the reported average daily dose is 1-3 grams of dried cannabis (total weight/day), inhaled doses of THC as low as 2.5-3 mg have demonstrated benefit.

What dose of cannabis is recommended?

Dosage Form	Expected Onset	Expected Duration
Oral (e.g. capsules, tablets, oils, edibles (dried plant))	1-3 hours More THC prolongs time of onset because it slows down gut movement	6-8 hours (up to ~24 hours)
Inhaled (e.g. smoking or vaping oils, dried plant, hashish)	5-10 minutes	2-4 hours (up to ~24 hours)
Topical (e.g. lotion, oil)	Variable	Variable
Oromucosal or Buccal (e.g. spray)	15-45 minutes	6-8 hours

Oral consumption is preferred to inhalation by vaping. Cannabis should not be smoked due to the toxic products of combustion.
It is not known how long patients need to consume medical cannabis before clinical effects may be expected. Cannabis should be discontinued if there is a lack of important clinical effects or if side effects are bothersome.

Does it work? What the Science says:

There are no published clinical studies of cannabis for osteoarthritis or rheumatoid
arthritis.

Blake DR et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis.	Nabiximols (Sativex®), synthetic cannabinoids, were administered by oromucosal spray to 58 patients with rheumatoid arthritis over 5 weeks; patients remained on their stable DMARDs and NSAIDs A mean of 5-6 sprays were used daily (each spray delivering 2.7 mg THC and 2.5 mg CBD) for approximately 5 weeks; patients reported a modest but statistically significant decrease in pain at rest and with movement and improved sleep. A statistically significant reduction in DAS28 was also observed, which did not meet criteria for ‘response’ (-0.9), though treatment duration was short. More patients in the nabiximols group experienced dizziness, light-headedness, dry mouth, and falls.
Allan GM et al. Systematic review of systematic reviews for medical cannabinoids.	Combining the results from 15 low quality trials, more patients taking cannabinoids instead of placebo (39 vs 30%) had at least a 30% reduction in chronic pain, with 11 patients needing to be treated in order for 1 patient to achieve a meaningful reduction in pain. However, larger and longer studies did not show this benefit and the patients in these studies had either nerve pain or cancer-related pain. Overall, more patients taking cannabinoids stopped treatment due to adverse effects (1 in 8-22 patients) or experienced dizziness (1 in 5), sedation (1 in 5), or confusion (1 in 15) compared to those taking placebo. In addition, 25-70% of patients reported a feeling of being “high”.
Vela et al., Randomized controlled trial for synthetic CBD	A double-blind, placebo-controlled, randomized controlled trial in 129 patients diagnosed with hand osteoarthritis (OA) or psoriatic arthritis (PsA) used cannabidiol (CBD) titrated up to 10 mg three times daily for 12 weeks compared to placebo. Although there was a statistically significant reduction from baseline to week 12 in both the CBD (52 to 40 mm) and placebo groups (61 to 50 mm), this change is not considered clinically important. Further, there was no difference in pain intensity seen between the CBD and placebo groups at the end of the study (0.23/100 mm on a VAS scale). While 40% of patients in the CBD group experienced a reduction in pain intensity by more than 30%, a similar number of patients in the placebo group did as well. There were no subgroup differences in the OA and PsA populations.
Heineman et al., Randomized controlled trial for topical CBD	A double-blinded, randomized controlled trial in 18 patients diagnosed with symptomatic thumb basal joint arthritis used topical CBD (6.2 mg/mL applied twice daily) or placebo for 2 weeks. Results demonstrated a 30% reduction in VAS score from baseline to week 2 in the CBD group (5 mm to 2 mm on a 10-point VAS scale), which is considered a clinically important change. No changes in the VAS scale were observed in the control group from baseline to week 2. There were no adverse events thought to be related to the CBD product.

What are possible side effects and what can be done to lessen them?

Body System	Side Effect	Comment
Cardiovascular	Increased heart rate (dose related), decreased blood pressure upon standing	After 8-10 days in a row of use, your body develops a tolerance to cannabis and your heart rate may normalize
Central Nervous System	Drowsiness, dizziness, confusion; mood elevation or “high”; headache; short term reduction in coordination, attention, problem solving, and judgement; decreased reactivity and reduced inhibition	Avoid driving any vehicle or heavy machinery when using cannabis (minimum 4h for inhalation and 6h for oral routes of administration or while experiencing a “high”)
Gastrointestinal	Dry mouth, constipation, increased hunger, recurrent vomiting (Cannabis Hyperemesis Syndrome)	Hot showers or capsaicin cream may help control recurrent vomiting
Ophthalmologic	Dry and/or red eyes
Psychiatric	Abnormal thinking, memory loss, nervousness, anxiety, distrust, fear, panic, paranoia; acute psychosis; cannabis use disorder (addiction) May worsen pre-existing anxiety, depression, or bipolar disorder.
Respiratory	Cough, wheeze	Using oral rather than inhaled route of administration
Reproductive	Decreased sex drive and hormone (testosterone) levels

Cannabis can also cause more serious side effects such as high blood pressure, heart attack, stroke, and/or peripheral vascular disease in susceptible users and altered brain development in children and young adults.

Cannabis smoke contains many of the same toxic chemicals as tobacco smoke and may be linked with certain types of cancer (in particular testicular cancer).

The long-term risks associated with medical cannabis in patients with rheumatic diseases are not known.

Interactions

With drugs:

Cannabis may interact with other medications that you may be currently taking. Speak to your physician or pharmacist to determine if you are at risk.

Effect	Interacting Medications
Increased heart rate and blood pressure	anticholinergics (e.g. amitriptyline, diphenhydramine, dimenhydrinate, oxybutinin); cocaine; nicotine; salbutamol; methylphenidate
Increased drowsiness; decreased coordination, attention, and inhibition	alcohol, benzodiazepines (e.g. lorazepam, diazepam), phenobarbital
Increased metabolism of other medications (when smoking cannabis)	acetaminophen, amitriptyline, caffeine, clozapine, duloxetine, estrogens, fluvoxamine, imipramine, melatonin, mirtazapine, olanzapine, theophylline
Decreased metabolism of other medications	clobazam, phenytoin, valproic acid
Increased metabolism of cannabis	azole antifungals (e.g. fluconazole), grapefruit juice, macrolides (e.g. clarithromycin) mifepristone, protease inhibitors (e.g. darunavir, ritonavir), amiodarone, fluoxetine
Decreased metabolism of cannabis	carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s wort
Increased effect of other medications	opioid analgesics (e.g. morphine, oxycodone, hydromorphone) (opioid sparing and/or synergistic response)
Increased heart rate, prolongation of increased body temperature, impairment of cognitive function (long term use)	ecstasy, MDMA, amphetamines

Guidance for Special Populations:

Medical cannabis is not recommended for patients who:

- Have a personal or family history of schizophrenia or psychosis
- Have cardiovascular and/or respiratory disease
- Are under the age of 25 years old
  - use in this age group when the brain is still developing has been linked to long-term effects on memory, thought, and learning as well as the ability of the brain to function, suicidal thought, and increased risk of addiction and street drug use
- Are pregnant and/or breastfeeding
  - exposure during pregnancy may result in altered brain development in the baby, low birth weight, premature birth, and/or miscarriage
- Have an allergy to cannabis products: some people have developed allergic responses to medical cannabis
Patients who are elderly or with risk factors for heart disease, ongoing mood or anxiety disorder(s), who smoke tobacco, or are heavy users of alcohol or other sedating medications should use cannabis with caution

If you are using any type of cannabis product, make your health care team aware. Follow up with a member of your health care team 4-8 weeks after initiating cannabis for a bone and joint disorder and continue to follow up with a member of your team every 3 months.