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According to the European Pain Federation position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management, “in the absence of available literature, it is the panel expert opinion that cannabis use could worsen the cognitive impairment caused by high doses of opioids and benzodiazepines. If cannabis is prescribed, it should be prescribed at a low dose and should be discontinued if it affects patients’ memory, mood or function. Physicians should consider tapering high opioid (≥90 mg morphine equivalent/day) or benzodiazepine doses, especially in patients with chronic noncancer pain.”
A “key point” from that position paper is: “Do not prescribe cannabis‐based medicines to patients taking high doses of opioids or benzodiazepines.”
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According to the Health Canada document entitled “Information for Health Care Professionals – Cannabis (marihuana, marijuana) and the Cannabinoids,” “If intolerable adverse effects appear without significant benefit, dosing should be tapered and stopped. Tapering guidelines have not been published, but the existence of a withdrawal syndrome suggests that tapering should be done slowly (i.e. over several days or weeks).” Note: When discontinuing cannabidiol therapies used for the treatment of seizure disorders, the dose should be decreased gradually. As with all antiepileptic drugs, abrupt discontinuation should be avoided when possible, to minimize the potential risk of increased seizure frequency and status epilepticus.
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There are many reasons why the effects of cannabinoids vary among individuals. SOME of the reasons are: diet, age, health of the patient, and co-administered medications may impact metabolism and efficacy of cannabinoid-based products. Also, some patients have a genetic profile such that they are predisposed to experience side effects (for ex., exacerbation of a psychotic disorder/schizophrenia) after exposure to THC. In addition, patients that have been consuming cannabinoid-based products long-term react differently than patients who have never consumed cannabinoid-based products.
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The effects of cannabinoids may change over time due to multiple factors, including:

• tolerance to the cannabinoids may develop
• a change in the patient’s health status/ medical condition may change over time and lead to physiological changes in the endocannabinoid system (For example, inflammation impacts the ECS. Also, impaired G.I./liver function affects the absorption and metabolism of cannabinoids.)
• The patient may start or stop taking a medication that interacts with cannabinoids or affects the metabolism of the cannabinoid-based product.
• Physiologic changes in the endocannabinoid system take place as patients age.

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Yes. The adverse event profile of cannabinoid-based formulations is dependent upon the ratio of CBD:THC, the presence of other cannabinoids and terpenes, and the dose consumed. The known common adverse effects of cannabinoid-based medicines include sedation/somnolence, dizziness, anxiety, cognitive dysfunction, nausea, vomiting, diarrhea, vertigo, increased or decreased appetite and dry mouth.
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As suggested by the Australian Centre for Cannabinoid Clinical and Research Excellence, monitoring should initially involve reviewing the patient weekly in person, and via phone if required in the interim between clinical reviews.
“There are three areas of outcomes that should be considered:

1. Symptom control
   “A pre-defined measure of success should be negotiated with the patient prior to commencement of therapy. This can be measured by using a validated tool, for example by the Palliative Care Symptom Assessment Scale. “
2. Drug adverse events
   “Careful monitoring of patients for adverse events and the need for a change in dosage is important. Adverse events may become apparent after commencement or after change in dose…
   Adverse events may be related to other concurrent medications. Doses of these medicines should be adjusted as appropriate. “
3. Pathology monitoring
   “Drug concentrations of drugs where there is a potential or actual drug-drug interaction may be important. Cannabidiol may cause hepatocellular injury. Patient’s liver function biochemistry should be monitored prior to initiation and periodically as clinically indicated. “

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According to the European Pain Federation position paper on the appropriate use of cannabis-based medicines, “a testing period of maximum 3 months should be considered both by patients and prescribers [or recommenders], to assess treatment efficacy and safety. At the end of this testing period, long‐term treatment should only be considered with significant improvement and lack of safety issues….If a satisfactory outcome is achieved, the patient should remain under close medical surveillance for the duration of cannabis‐based medicine therapy… If the predefined treatment goals are not achieved and/or unacceptable burden of side effects occur and/or signs of abuse and misuse are observed, the specific cannabis‐based medicines should be safely withdrawn and alternative options actively explored.”
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According to Health Canada’s document entitled Information for Health Care Professionals: Cannabis and Cannabinoids, “consumption of … oral cannabis should proceed slowly, waiting a … minimum of 30 minutes, but preferably 3 h, between bites of cannabis-based oral products (e.g. cookies, baked goods) to gauge for strength of effects or for possible overdosing.”
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As stated by the authors of “Brief Commentary: Cannabinoid Dosing for Chronic Pain Management” in the Annals of Internal Medicine, “We advocate a “start-low, go-slow” dosing philosophy, applied to both quantity and adverse effect profiles. We recommend starting with CBD extract, 5 to 10 mg twice daily, to be increased weekly over 1 to 2 months until pain relief is achieved. If CBD extract alone provides insufficient relief, we suggest adding THC, 1.0 to 2.5 mg, and slowly titrating up as needed.” “We do not regard cannabinoids as first-line treatments but as adjuvant therapies to be used before opioids if other options fail to control chronic non-cancer pain. As with any pain medication, cannabinoids should be used as part of an integrated, patient-centric management program, with particular emphasis on appropriate non-pharmacologic treatment options (for example, exercise, cognitive behavioral therapy, and mindfulness). We recommend selecting products verified for safety and potency by third-party testing. We propose that patients use oral formulations (such as capsules) for long-term relief, with tinctures for breakthrough pain. We suggest vaping for patients who prefer to inhale cannabinoids, because this method probably has fewer adverse effects than smoking.”

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Yes. In September 2021, California Governor G. Newsom signed “Ryan’s Law” – legislation that expands end-of-life treatment options for Californians by requiring that hospitals and certain types of healthcare facilities in the state allow terminally-ill patients to use medical cannabis for treatment and/or pain relief. “Ryan’s Law,” (SB311) “requires healthcare facilities to reasonably restrict the manner in which a patient stores and uses medical cannabis to ensure the safety of other patients, guests, and employees of the healthcare facility. It does NOT apply to patients receiving emergency care, and smoking and vaping cannabis is expressly PROHIBITED. The legislation does NOT require the health facility to provide the medicinal cannabis, nor does it require the facility to dispense the cannabis from the pharmacy.” “Currently, the US DOJ is prohibited to use any federal funds to interfere with state medical cannabis laws… SB 311 includes a strong safe harbor clause that would allow facilities to suspend compliance should any federal agency initiate an enforcement action or indicate its interest in once again enforcing federal cannabis laws.”
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