Cannabis and cannabinoid agents are widely used to alleviate symptoms or treat disease, but their efficacy for specific indications is not well established. For chronic pain, the analgesic effect remains unclear. A systematic review of randomized controlled trials was conducted examining cannabinoids in the treatment of chronic noncancer pain, including smoked cannabis, oromucosal extracts of cannabis-based medicine, nabilone, dronabinol, and a novel THC analogue.55 Pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Fifteen of the 18 included trials demonstrated a significant analgesic effect of cannabinoids compared with placebo. Cannabinoid use was generally well tolerated; adverse effects most commonly reported were mild to moderate in severity. Overall, evidence suggests that cannabinoids are safe and moderately effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis.55
While there is not enough evidence to suggest routine use of medicinal cannabis for alleviating chemotherapy-related nausea and vomiting by national or international cancer societies, therapeutic agents based on THC (e.g., dronabinol) have been approved for use as an antiemetic in the United States for a number of years. Only recently has the efficacy and safety of cannabis-based medicines in managing nausea and vomiting due to chemotherapy been evaluated. In a review of 23 randomized, controlled trials, patients who received cannabis-based products experienced less nausea and vomiting than subjects who received placebo.56 The proportion of people experiencing nausea and vomiting who received cannabis-based products was similar to those receiving conventional antiemetics. Subjects using cannabis-based products experienced side effects such as “feeling high,” dizziness, sedation, and dysphoria and dropped out of the studies at a higher rate due to adverse effects compared with participants receiving either placebo or conventional antiemetics. In crossover trials in which patients received cannabis-based products and conventional antiemetics, patients preferred the cannabis-based medicines. Cannabis-based medications may be useful for treating chemotherapy-induced nausea and vomiting that responds poorly to conventional antiemetics. However, the trials produced low to moderate quality evidence and reflected chemotherapy agents and antiemetics that were available in the 1980s and 1990s.
With regard to the management of neurological disorders, including epilepsy and MS, a Cochrane review of four clinical trials that included 48 epileptic patients using CBD as an adjunct treatment to other antiepileptic medications concluded that there were no serious adverse effects associated with CBD use but that no reliable conclusions on the efficacy and safety of the therapy can be drawn from this limited evidence.57 The American Academy of Neurology (AAN) has issued a Summary of Systematic Reviews for Clinicians that indicates oral cannabis extract is effective for reducing patient-reported spasticity scores and central pain or painful spasms when used for MS.58 THC is probably effective for reducing patient-reported spasticity scores but is likely ineffective for reducing objective measures of spasticity at 15 weeks, the AAN found; there is limited evidence to support the use of cannabis extracts for treatment of Huntington’s disease, levodopa-induced dyskinesias in patients with Parkinson’s disease, or reducing tic severity in Tourette’s.58
In older patients, medical cannabinoids have shown no efficacy on dyskinesia, breathlessness, and chemotherapy-induced nausea and vomiting. Some evidence has shown that THC might be useful in treatment of anorexia and behavioral symptoms in patients with dementia. The most common adverse events reported during cannabinoid treatment in older adults were sedation-like symptoms.59
Despite limited clinical evidence, a number of medical conditions and associated symptoms have been approved by state legislatures as qualifying conditions for medicinal cannabis use. Table 1 contains a summary of medicinal cannabis indications by state, including select disease states and qualifying debilitating medical conditions or symptoms.10,60,61 The most common conditions accepted by states that allow medicinal cannabis relate to relief of the symptoms of cancer, glaucoma, human immunodeficiency virus/acquired immunodeficiency syndrome, and MS. A total of 28 states, the District of Columbia, Guam, and Puerto Rico now allow comprehensive public medical marijuana and cannabis programs.10 The National Conference of State Legislatures uses the following criteria to determine if a program is comprehensive:
Protection from criminal penalties for using marijuana for a medical purpose;
Access to marijuana through home cultivation, dispensaries, or some other system that is likely to be implemented;
Allows a variety of strains, including more than those labeled as “low THC;” and
Allows either smoking or vaporization of some kind of marijuana products, plant material, or extract.
Some of the most common policy questions regarding medical cannabis now include how to regulate its recommendation and indications for use; dispensing, including quality and standardization of cultivars or strains, labeling, packaging, and role of the pharmacist or health care professional in education or administration; and registration of approved patients and providers.
REGULATORY IMPLICATIONS OF MEDICINAL CANNABIS
The regulation of cannabis therapy is complex and unique; possession, cultivation, and distribution of this substance, regardless of purpose, remain illegal at the federal level, while states that permit medicinal cannabis use have established individual laws and restrictions on the sale of cannabis for medical purposes. In a 2013 U.S. Department of Justice memorandum to all U.S. attorneys, Deputy Attorney General James M. Cole noted that despite the enactment of state laws authorizing marijuana production and sale having a regulatory structure that is counter to the usual joint efforts of federal authorities working together with local jurisdictions, prosecution of individuals cultivating and distributing marijuana to seriously ill individuals for medicinal purpose has not been identified as a federal priority.62
There are, however, other regulatory implications to consider based on the federal restriction of cannabis. Physicians cannot legally “prescribe” medicinal cannabis therapy, given its Schedule I classification, but rather in accordance with state laws may certify or recommend patients for treatment. Medical cannabis expenses are not reimbursable through government medical assistance programs or private health insurers. As previously described, the Schedule I listing of cannabis according to federal law and DEA regulations has led to difficulties in access for research purposes; nonpractitioner researchers can register with the DEA more easily to study substances in Schedules II–V compared with Schedule I substances.63 Beyond issues related to procurement of the substance for research purposes, other limitations in cannabis research also exist. For example, the Center for Medicinal Cannabis Research at the University of California–San Diego had access to funding, marijuana at different THC levels, and approval for a number of clinical research trials, and yet failed to recruit an adequate number of patients to conduct five major trials, which were subsequently canceled.64 Unforeseen factors, including the prohibition of driving during the clinical trials, deterred patients from trial enrollment. The limited availability of clinical research to support or refute therapeutic claims and indications for use of cannabis for medicinal purposes has frequently left both state legislative authorities and clinicians to rely on anecdotal evidence, which has not been subjected to the same rigors of peer review and scrutiny as well-conducted, randomized trials, to validate the safety and efficacy of medicinal cannabis therapy. Furthermore, although individual single-entity pharmaceutical medications, such as dronabinol, have been isolated, evaluated, and approved for use by the FDA, a plant cannot be patented and mass produced by a corporate entity.65 Despite this limitation, some corporations, including GW Pharmaceuticals, are mass producing cannabis plants and extracting complex mixtures or single cannabinoids for clinical trials.65 The complex pharmacology related to the numerous substances and interactions among chemicals in the cannabis plant coupled with environmental variables in cultivation further complicate regulation, standardization, purity, and potency as a botanical drug product.
RELEVANCE TO HOSPITAL PRACTITIONERS
Although the public has largely accepted medicinal cannabis therapy as having a benefit when used under a provider’s supervision, the implications of the use of this substance when patients transition into the acute care setting are additionally complex and multifaceted. The Schedule I designation of cannabis causes hospitals and other care settings that receive federal funding, either through Medicare reimbursement or other federal grants or programs, to pause to consider the potential for loss of these funds should the federal government intercede and take action if patients are permitted to use this therapy on campus. Similarly, licensed practitioners registered to certify patients for state medicinal cannabis programs may have comparable concerns regarding jeopardizing their federal DEA registrations and ability to prescribe other controlled substances as well as jeopardizing Medicare reimbursements. In 2009, U.S. Attorney General Eric Holder recommended that enforcement of federal marijuana laws not be a priority in states that have enacted medicinal cannabis programs and are enforcing the rules and regulations of such a program; despite this, concerns persist.
The argument for or against the use of medicinal cannabis in the acute care setting encompasses both legal and ethical considerations, with the argument against use perhaps seeming obvious on its surface. States adopting medical cannabis laws may advise patients to utilize the therapy only in their own residence and not to transport the substances unless absolutely necessary.66 Further, many acute care institutions have policies prohibiting smoking on facility grounds, thus restricting the smoking of cannabis, regardless of purpose or indication. Of note, several Canadian hospitals, including Montreal’s Jewish General Hospital and Quebec’s Centre Hospitalier Universitaire de Sherbrooke, have permitted inpatient cannabis use via vaporization; the pharmacy departments of the respective institutions control and dispense cannabis much like opioids for pain. Canada has adopted national regulations to control and standardize dried cannabis for medical use.67,68 There are complicated logistics for self-administration of medicinal cannabis by the patient or caregiver; in particular, many hospitals have policies on self-administration of medicines that permit patients to use their own medications only after identification and labeling by pharmacy personnel. The argument can be made that an herb- or plant-based entity cannot be identified by pharmacy personnel as is commonly done for traditional medicines, although medicinal cannabis dispensed through state programs must be labeled in accordance with state laws. Dispensing and storage concerns, including an evaluation of where and how this product should be stored (e.g., within the pharmacy department and treated as a controlled substance, by security personnel, or with the patient); who should administer it, and implications or violations of federal law by those administering treatment; what pharmaceutical preparations should be permitted (e.g., smoked, vaporized, edible); and how it should be charted in the medical record represent other logistical concerns. Inpatient use of medicinal cannabis also carries implications for nursing and medical staff members. The therapy cannot be prescribed, and states may require physicians authorizing patient use to be registered with local programs. In a transition into the acute care setting from the community setting, a different clinician who is not registered could be responsible for the patient’s care; that clinician would be restricted in ordering continuation of therapy.
Despite the complexities in the logistics of continuing medicinal cannabis in the acute care setting, proponents of palliative care and continuity of care argue that prohibiting medicinal cannabis use disrupts treatment of chronic and debilitating medical conditions. Patients have been denied this therapy during acute care hospitalizations for reasons stated above.69 Permission to use medicinal cannabis in the acute care setting may be dependent on state legislation and restrictions imposed by such laws. Legislation in Minnesota, as one example, has been amended to permit hospitals as facilities that can dispense and control cannabis use; similar legislative actions protecting nurses from criminal, civil, or disciplinary action when administering medical cannabis to qualified patients have been enacted in Connecticut and Maine.70–73Proposed legislation to remove restrictions on the certification of patients to receive medicinal cannabis by doctors at the Department of Veterans Affairs was struck down in June; prohibitions continue on the use of this therapy even in facilities located in states permitting medicinal cannabis use.74
Despite lingering controversy, use of botanical cannabis for medicinal purposes represents the revival of a plant with historical significance reemerging in present day health care. Legislation governing use of medicinal cannabis continues to evolve rapidly, necessitating that pharmacists and other clinicians keep abreast of new or changing state regulations and institutional implications. Ultimately, as the medicinal cannabis landscape continues to evolve, hospitals, acute care facilities, clinics, hospices, and long-term care centers need to consider the implications, address logistical concerns, and explore the feasibility of permitting patient access to this treatment. Whether national policy—particularly with a new presidential administration—will offer some clarity or further complicate regulation of this treatment remains to be seen.