____________________________________________________ Medical Marijuana and Other Cannabinoids
As with any drug therapy, important considerations include the dose-response relationship and margin of safety that sepa- rates beneficial dose from dosage producing adverse effects [2]. Safety concerns can be addressed, as with any drug, by appropriate patient screening and monitoring, adherence to known contraindications, and administration with alternative delivery systems (as in patients with lung disease). In many (non-cannabis) contexts, clinical medicine involves balancing risk and benefit even when limited evidence is available to base a decision, and the needs and wishes of patients should be considered while the merits of medical cannabis use are debated [15]. Cannabinoid-drug interactions should be considered in all patients. CBD and possibly THC are known to increase the levels of direct-acting oral anticoagulants and clopidogrel. In patients using cannabis or products containing CBD or THC, other agents should be considered [129]. THC and CBD also inhibit metabolism of warfarin, which can lead to elevated INRs. There is also some evidence that cannabis or canna- binoid use can effect postoperative outcomes. As such, the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommends universal screening for cannabinoids prior to surgery, including type of cannabis or cannabinoid product, time of last consumption, route of administration, amount, and frequency of use [129]. Further, the ASRA recom- mends delaying or postponing elective surgery in patients who are acutely intoxicated or who have recently smoked cannabis. DATA FROM PHARMACEUTICAL CANNABINOID TRIALS Cannabinoid safety and side effect data from 23 RCTs and 8 observational studies involving 1,932 participants with medical conditions such as cancer and multiple sclerosis were reviewed [124]. The cannabinoids included dronabinol and nabiximols spray. In the RCTs, median cannabinoid exposure was two weeks (range: 8 hours to 12 months). Serious adverse events occurred in 164 cannabinoid subjects and 60 control subjects; the most frequent by category were respiratory (16.5%), gas- trointestinal (16.5%), and nervous system disorders (15.2%) with cannabinoids, and nervous system disorders (30%) with placebo. The difference in incidence between cannabinoid and placebo subjects was not statistically significant. Non-serious adverse events were significantly more prevalent with can- nabinoids, with the most common being blurred vision, dry mouth, weakness, dizziness, somnolence, sedation, confusion, hypotension, and altered mood [124]. Data from two recent high-quality systematic reviews found sufficient evidence that cannabinoids (e.g., nabiximols, nabilone, dronabinol) may be effective for reducing the symptoms of patient-reported pain and spasticity in multiple sclerosis [130; 131]. A systematic review conducted by the American Academy of Neurology found that oral cannabis extract is effective for symptoms of spasticity in patients with multiple sclerosis and that nabixi- mols and THC are probably effective for reducing patient- centered measures [132].
SIDE EFFECTS AND SAFETY Information on medical cannabis safety and side effects should ideally come from RCTs that control for confound- ing factors that may otherwise account for the results. Such studies are increasingly being published, but similar to other drug efficacy trials, safety information is available with short- term (less than three months) use while long-term safety data remains sparse. In contrast to studies with medicinal users, many studies of long-term heavy recreational users have been published. Generalizing safety outcomes from chronic recre- ational users to medicinal users is cautioned against because of numerous confounding factors, including differences in age of first regular use; duration, quantity, and THC content of cannabis use; concurrent alcohol or other drug use; drug delivery approaches; and past or current psychiatric, neuro- logic, and comorbid medical histories [124; 125; 126]. Raphael Mechoulam, who in 1964 co-discovered THC, concluded that most cannabis safety data from “street users” are “useless” (his words) for extrapolation to medicinal cannabis safety, based on the before-mentioned factors and the widely variable THC and unknown CBD content of illicitly obtained cannabis in contrast to cannabis now cultivated under tightly controlled environmental conditions to ensure reliability [127; 128]. In the following sections, the available evidence on medical can- nabis and pharmaceutical cannabinoids is presented. RISK/BENEFIT CONSIDERATIONS Importantly, the potential acute and long-term adverse effects with medical cannabis should be weighed against the known side effect profiles of standard therapeutic agents for the same indication [88]. For example, in standard therapies for chronic pain or spasticity, opioids often produce sedation, nausea, constipation, physiologic dependence, and with abrupt cessation of long-term use, a more severe withdrawal syndrome than cannabis withdrawal. Tricyclic antidepressants and antiepileptic drugs are frequently prescribed for chronic neuropathic pain and may produce sedation, constipation, dizziness, palpitations, visual disturbance, urinary retention, and neuromuscular effects. Antispasmodic drugs may pro- duce sedation (e.g., baclofen), hypotension (e.g., tizanidine), and potentially serious interactions with antibiotics (as with tizanidine and ciprofloxacin). Benzodiazepines prescribed for spasticity may produce sedation, psychomotor incoordination, memory impairment, paradoxical reactions, dependence, and with daily long-term use, a severe protracted withdrawal syndrome. Opioids and benzodiazepines are also drugs with potential for abuse, addiction, diversion, and fatal overdose exceeding cannabis. This comparison helps put consideration of the relative benefits and risks of medical cannabis in the proper context [88].
131
EliteLearning.com/Dental
Powered by FlippingBook