Arthritis

Arthritis appears to be one of the earliest symptoms for which cannabis was used as a treatment (Backes, 2017). Studies have shown that the cannabinoid THC can reduce arthritis pain and, used singly or in combination, THC and CBD reduce cytokine release from inflammatory cells believed to be responsible for tissue deterioration in arthritis (Backes, 2017).

Burstein’s review articles (Burnstein et al, 2009) summarize the large amount of preclinical and animal study data that documents the anti-inflammatory effect of CBD and its analogs in preclinical trials, as well as the possibility that THC and CBD may have synergistic anti-inflammatory actions. THC alone has been cites as having twice as much anti-inflammatory activity as hydrocortisone (Sofia et al, 1973).

Cannabis can augment or replace opioid medications (Abrams et al, 2010). Preclinical laboratory studies also indicate a dynamic interaction between cannabinoids and nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs and cannabinoids, when used in combination, may work I tandem or perhaps synergistically to relieve pain (Vanegas et al, 2010).

There is one human study of rheumatoid arthritis comparing placebo to a spray (Sativex) containing a 1:1 concentration of THC to CBD (Vanegas et al, 2010). The 31 patients randomised to Sativex had statistically significant improvements in pain on movement, pain at rest, and active pain when evaluated, compared to the 27 patients who received the placebo.

Mark Feldman at Imperial College, London, tested CBD on mice that had a version of rheumatoid arthritis. At the right dosage it was found that CBD reduced the mice’s inflammation by 50% (Minchin, 2016).

Unknown or expected adverse effects, risks and safety issues & related toxicology:

A systematic review by Whiting et al. (2015) stated in their conclusions that “Cannabinoids were associated with an increased risk of short-term adverse effects”.

According to the Guidance for the Use of Medicinal Cannabis in Australia: Overview, Therapeutics Good Administration

(2017): Cannabis is not appropriate for patients who:

• Are under the age of 25 (with the exception of intractable epilepsy or severe pain syndrome)
• Have a personal history or strong family history of psychosis
• Have a current or past cannabis use disorder, or active substance use disorder
• Have unstable respiratory or cardiovascular disease (including angina, peripheral vascular disease, cerebrovascular disease, arrhythmias)
• Are pregnant, planning to become pregnant, or

Breastfeeding.

Cannabis should be authorized with caution in patients who:

• Smoke tobacco
• Have risk factors for cardiovascular disease
• Are heavy users of alcohol
• Are taking sedating medications or any other medication metabolized by the CYP450 pathway
• At risk or have liver disease

Potential drug interactions

Increasing THC concentration:

Examples of inhibitors:

– Antidepressants (e.g. Fluoxetine, Fluvoxamine)

– Proton Pump Inhibitors (e.g. Omeprazole)

– Cimetidine

– Macrolides (Clarithromycin, Erythromycin)

– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)

– Calcium Antagonists (e.g. Diltiazem, Verapamil)

– HIV protease inhibitors (e.g. Ritonavir)

– Amiodarone

– Isoniazid

– Grapefruit juice

Increasing CBD concentration:

– Metabolized by CYP 2C19 and CYP 3A4

– Bioavailability could be increased by many of the same substances as for THC

Decreasing THC and CBD concentration:

• CYP 2C9 and 3A4 Inducers accelerate THC and CBD metabolism
• Examples of inducers:

– Rifampicin

– Primidone

– Carbamazepine

– Phenobarbital

– Phenytoin

– Rifabutin

– Saint John’s Wort

Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen in the study by Gaston et al (2017) on interactions between cannabidiol (Epidiolex.) and commonly used antiepileptic

drugs. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with supraphysiological doses of CBD (e.g. 1000mg/kg).

• Caution with blood thinners like Warfarin, Heparin,

Clopidogrel (Plavix)

• Additionally, pharmacodynamic interactions should be expected between cannabis and drugs with sympathomimetic activity (tachycardia,

hypertension), central nervous system depressants (drowsiness, ataxia), and drugs with anticholinergic effects (tachycardia, drowsiness).

Many of these drug interactions can be mitigated in complex patients with polypharmacy by slowly titrating cannabis.