Medical use of cannabis and cannabinoids in adults

INTRODUCTION — Medical cannabis is legal in much of the United States as well as other parts of the world and is used in many clinical scenarios. This topic will discuss the medical use of cannabis and provide guidance on its use. The clinical manifestations and management of toxicity from cannabis (marijuana), cannabis withdrawal, epidemiology of cannabis use, and cannabis use disorder are discussed separately. (See "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects" and "Cannabis (marijuana): Acute intoxication" and "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment" and "Cannabis withdrawal: Epidemiology, clinical features, diagnosis, and treatment".)

DEFINITIONS AND TERMINOLOGY

●Cannabis – A broad term describing products and chemical compounds derived from Cannabis sativa or Cannabis indica plant species [1].

●Cannabinoids – Biologically active chemicals naturally occurring in cannabis plants. Most common are THC and CBD.

●Delta-9-tetrahydrocannabinol (THC) – The main intoxicating component of cannabis, shown to have analgesic and antiemetic properties as well [1].

●Cannabidiol (CBD) – Constituent of cannabis that is traditionally considered to be nonintoxicating and nonpsychoactive, but may have anxiolytic properties [1].

●Hemp – Cannabis plant with very low (<0.3 percent) levels of THC and more predominant CBD; often used in textiles [2].

●Hashish – An Arabic term used to describe the resin of the cannabis plant in some regions and, in other regions, used to describe the plant in general [3].

●Terpenes – Compounds that produce the cannabis plant's smell, taste, and appearance [1].

●Regulated cannabis – Cannabis that is monitored by a governmental agency to confirm cannabinoid content and/or identify contaminants that make it unsafe for use.

●Unregulated cannabis – Cannabis that does not undergo testing for contaminants or to confirm cannabinoid content; often sold from unsanctioned sources.

●Certification for medical cannabis – The mechanism by which health care providers communicate that a patient qualifies for medical cannabis in their state. The process for this is individualized by state.

●Cannabis versus marijuana – "Cannabis" and "marijuana" are terms that are often used interchangeably to refer to the same plant and the chemical compounds derived from it. Though many patients know the term "marijuana" colloquially, cannabis is preferred in a medical setting [4].

MEDICAL CANNABIS POLICY IN THE UNITED STATES

State medical cannabis laws — California was the first state in the United States to legalize cannabis for therapeutic purposes in 1996 [5]. This occurred in the context of advocacy from people living with human immunodeficiency virus (HIV) and people with cancer who were experiencing intractable symptoms such as pain, cachexia, and nausea. Despite discouragement from the federal government, and cannabis's continued categorization as a Schedule I substance by the United States Controlled Substances Act, other states have progressively followed California's lead. As of November 2022, medical cannabis is legal in 37 states, the District of Columbia, and three United States territories (Puerto Rico, Guam, and the United States Virgin Islands).

Medical cannabis is operationalized differently depending on the state in which it is legalized [6]. In general, medical cannabis products are labeled with a specific ratio of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content and many states legislate these ratios. States differ in how much and what type of training health care practitioners must have to recommend medical cannabis, the relationship health care providers must have with patients to recommend it, as well as the degree to which medical cannabis products are regulated by the state (including limits on THC content and legality of products with different ratios of THC and CBD). For this reason, health care providers are encouraged to review state laws on medical cannabis in the state(s) in which they practice [7].

Legalized adult-use (recreational) cannabis — Laws legalizing adult-use, or recreational, cannabis exist in many states, the District of Columbia, and two territories (Guam and the Northern Mariana Islands) [7]. Current information on cannabis laws can be found on the website of the National Conference of State Legislatures. These laws create an infrastructure for the legal sale of adult-use cannabis from state-regulated programs. Laws on legalization of adult-use cannabis are rapidly evolving; 10 of the 21 state laws legalizing adult-use cannabis were passed in or after 2020. Twenty-seven states have decriminalized adult-use cannabis, reducing penalties for possession of small amounts of cannabis from state crimes that could lead to jail time to minor offenses [8].

Medical cannabis from the federal perspective — In states where medical cannabis is legalized, health care providers may recommend cannabis for medical conditions as specified by the state (see 'State medical cannabis laws' above). However, cannabis is classified as a Schedule I substance by the federal government, which prohibits its "prescription" [5]. Instead, patients are given recommendations that include dose and route of administration, and are provided with guidance on safe cannabis use, as well as risks and benefits of its use.

EPIDEMIOLOGY OF ADULT-USE CANNABIS AND MEDICAL CANNABIS IN THE UNITED STATES

Incidence and prevalence — With rapidly changing laws and increasing access to cannabis, incidence and prevalence of cannabis use has also changed. Among 12- to 20-year-old respondents to the National Survey on Drug Use and Health from 2008 to 2019, incidence of cannabis use was 6.2 percent in states without legalized cannabis and 7.8 percent in states with legalized medical or adult-use cannabis. The epidemiology of cannabis use in general is discussed in detail elsewhere (see "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects", section on 'Cannabis use'). Specific to medical cannabis, an analysis of state registry data from 26 states and the District of Columbia from 2016 to 2020 estimated that nearly three million patients were certified for medical cannabis in 2020, which was a 4.5-fold increase from 2016 [9].

Access to medical cannabis — People who use medical cannabis are most often White, male, and employed and have health insurance [10,11]. This may be due to disparities in availability of medical cannabis. In analyses of medical cannabis programs in the United States, medical cannabis is more available with increased proximity to urban centers [12,13], increasing proportion of people with bachelor's degrees, and decreased proportion of Black residents [12].

CANNABIS AND CANNABINOIDS IN THERAPEUTIC SETTINGS

Regulated versus unregulated cannabis — In addition to limiting interactions with the unregulated market and with the criminal justice system, regulated cannabis is safer and more predictable. Unregulated cannabis has been found in many studies to be contaminated with harmful pesticides, heavy metals, molds, microbes, or mycotoxins [14-19]. Most states with legalized cannabis test regulated cannabis for these contaminants, in addition to confirming cannabinoid dosing and labeling [6,18]. However, the ways in which regulation and testing are implemented differ by state. (See 'Medical cannabis policy in the United States' above.)

Cannabis formulations and routes of administration

Cannabinoid content — Medical cannabis has varying concentrations and ratios of cannabinoids, and formulations are usually characterized by the ratio of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In most states, it is mandated that cannabinoid content is reported on medical cannabis product labels [6]. The National Institutes of Health determined that a "standard unit" of THC is 5 mg, particularly for purposes of reporting research results [20]. Pharmacology of cannabinoids and the endocannabinoid system are discussed separately. (See "Cannabis (marijuana): Acute intoxication", section on 'Pharmacology and toxicity'.)

US Food and Drug Administration-approved cannabinoids — Four cannabinoid-based medications are approved for use by the US Food and Drug Administration (FDA):

●Epidiolex (cannabidiol) is the only plant-derived cannabinoid approved for medical use by the FDA. It is approved for the management of several childhood seizure disorders and is administered as an oral solution that is swallowed and processed as an ingested product [21].

●Marinol (dronabinol) is a synthetic cannabinoid similar to THC and administered as a capsule. It is FDA-approved for anorexia associated with acquired immunodeficiency syndrome (AIDS) and chemotherapy-induced nausea and vomiting [22].

●Syndros (dronabinol) contains the same active ingredient as Marinol but is an oral solution and processed as an ingested product [23]. It is FDA-approved for anorexia associated with AIDS and chemotherapy-induced nausea and vomiting.

●Cesamet (nabilone) is a synthetic cannabinoid similar to THC administered orally as a capsule. It is approved by the FDA for the management of chemotherapy-induced nausea and vomiting, but it is not currently available in the United States [24].

Cannabinoid products available at state-licensed dispensaries (not FDA approved) — There are varied routes of administration of medical cannabis available to patients depending on the state in which they live. Medical cannabis products are different from the FDA-approved products listed above in that they are not synthetic but rather are derived directly from the cannabis plant. They are not regulated by the federal government but rather by state medical cannabis programs. Not all products are available in all states.

●Inhaled – Administered as either combusted dried cannabis flower in a rolled cigarette or pipe or in a battery-operated vaporizer device. Vaporized cannabis products may use dried whole cannabis flower or an oil-based concentrate of specific doses of THC and CBD. This is the most familiar route to most patients. In unregulated use, dried cannabis flower is sometimes mixed with tobacco or rolled in cigar papers, exposing individuals to nicotine [25].

●Ingested – Administered as capsules, chewable candies (gummies), or baked goods. Baked goods may have whole cannabis flower mixed into them, while capsules and candies usually contain cannabinoids extracted from the plant.

●Sublingual/oral mucosal – Administered as an oral solution or a spray under the tongue or sprayed on the mucosa of the mouth. These solutions contain extracted cannabinoids.

●Suppository – Oil-based cannabinoid extract administered rectally.

●Topical – Extracted cannabinoids administered topically as lotions or gels.

●Dabs and waxes – Traditionally popular with people who use cannabis heavily, these are cannabinoid concentrates with very high concentrations of THC, often >60 percent, applied to a hot platform and inhaled [26]. This translates to up to 15 mg of THC in a single inhalation.

CLINICAL APPLICATIONS

Chronic pain — Chronic pain is the most well-researched indication for the use of medical cannabis [1,27,28] and the most common condition for which patients are certified for medical cannabis [29,30]. While many studies exist examining the utility of medical cannabis for the management of chronic pain, most of them are low or moderate quality due to small sample size, short follow-up periods, and nonblinded or unrandomized study design [27,28]. Further, no studies utilize a standardized dose or route of administration, and the chronic pain populations studied vary by etiology of pain. This is discussed in detail elsewhere. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Cannabis and cannabinoids'.)

Severe or persistent muscle spasms — Studies examining the utility of cannabinoids for the management of muscle spasms are limited [31]. Most studies have been conducted in people with multiple sclerosis. This is discussed in more detail elsewhere. (See "Symptom management of multiple sclerosis in adults", section on 'Cannabinoids'.)

Posttraumatic stress disorder — Published studies evaluating cannabis or cannabinoids for treatment for posttraumatic stress disorder (PTSD) focus on different specific populations (military veterans, correctional populations, outpatients with PTSD), but all used nabilone (delta-9-tetrahydrocannabinol [THC] alone, dose of 3 to 5 mg) as an intervention. Studies have found improvements in nightmares, and some (but not all) showed improvement in global PTSD outcomes, PTSD symptoms, and hyperarousal [32-35]. This is discussed in detail elsewhere. (See "Posttraumatic stress disorder in adults: Treatment overview", section on 'Medications with limited supporting evidence'.)

Chemotherapy-induced nausea — Synthetic THC (dronabinol, nabilone) is US Food and Drug Administration (FDA) approved for the management of chemotherapy-induced nausea and vomiting and has been used for this purpose for decades. This is discussed in detail elsewhere. (See "Management of poorly controlled or breakthrough chemotherapy-induced nausea and vomiting in adults", section on 'Cannabinoids and medical marijuana'.)

Seizure disorders — Cannabidiol (CBD) was approved by the FDA to treat rare forms of childhood epilepsy such as Dravet syndrome and Lennox-Gastaut syndrome. This is discussed elsewhere (see "Seizures and epilepsy in children: Refractory seizures", section on 'Cannabinoids' and "Dravet syndrome: Management and prognosis", section on 'Cannabidiol'). The use of CBD or other cannabinoids for seizure reduction in adults or children with less rare forms of seizure disorders is not yet FDA approved.

Palliative care and end-of-life care — Cannabis may be used by individuals who are seeking palliative and end-of-life symptom relief. Often, these symptoms include pain, nausea, insomnia, agitation, or night sweats. However, available studies are limited, utilize a range of products, and report varied outcomes [36]. In one guideline, medical cannabis in palliative care settings is recommended only if other evidence-based treatment options are ineffective or unavailable [37].

Cachexia or wasting — There is little to no evidence to support cannabis use for the management of cachexia or wasting. Clinically, cannabis has been used primarily in AIDS wasting syndrome or cancer-associated cachexia, but evidence has not supported that use. In a meta-analysis of efficacy of cannabis for cachexia and wasting, no change in appetite, quality of life, or weight gain was observed with cannabis treatment [38]. Cannabis is not recommended for use in cancer-related anorexia/cachexia; this is discussed elsewhere. (See "Management of cancer anorexia/cachexia", section on 'Cannabis and cannabinoids'.)

ASSESSING THE PATIENT — Patients are increasingly interested in using medical cannabis to manage their symptoms. While the evidence base remains limited, as described above, patients are seeking and using cannabis, and clinicians have a role to play in advising their patients on safe use. Below, we describe our approach to medical cannabis recommendations in a well-established clinical program at an academic medical center [39]; these principles can be extrapolated to clinical scenarios in which patients seek advice on safely using cannabis.

History — We start by understanding the patient's motivations for seeking out medical cannabis. We obtain a history of the condition for which the patient is seeking medical cannabis including onset, duration, characteristics, prior treatment attempts, and the degree of their success. If they exist, we use standardized tools to characterize the severity of patients' symptoms. For example, we use the Pain, Enjoyment of Life and General Activity (PEG) Scale [40] to characterize pain and the Diagnostic and Statistical Manual of Mental Disorders-5 posttraumatic stress disorder (PTSD) checklist [41] to characterize PTSD symptoms.

We obtain a full psychiatric history, with special attention to history of psychosis, psychiatric hospitalization, auditory or visual hallucinations and context in which that occurred, as well as family history of schizophrenia or psychosis. We ask patients about history of prior substance use disorders and treatment. Finally, we ask patients about their medical history (especially their cardiac history), planned or current pregnancy or breastfeeding, and medication reconciliation.

Then, we gather a thorough history of the patient's current and past cannabis use. We ask about:

●Current and past cannabis use (unregulated, regulated adult-use, and medical cannabis)

●Frequency of use (number of days in the past 7 or 30)

●Amount of cannabis use per week (amount in milligrams purchased per month)

●Route of administration (inhaled, ingested, sublingual, etc)

●Other substances mixed with cannabis (nicotine in the form of cigar papers or tobacco leaf mixed with whole flower cannabis, synthetic cannabinoids, hashish)

Unregulated cannabis is thought to be between 10 and 20 percent delta-9-tetrahydrocannabinol (THC) [42]. These details help us estimate the amount of average THC consumed per day. In patients who endorse cannabis use, we assess for cannabis use disorder at initial evaluation. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment".)

Co-occurring conditions that require caution

Substance use disorder — People with preexisting substance use disorders may be at increased risk for developing cannabis use disorder. In these patients, clinicians should review with patients the risk of cannabis use disorder, assess for existing cannabis use disorder, and offer treatment if it exists. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment", section on 'TREATMENT'.)

If patients plan to use cannabis regardless of a recommendation to avoid it, clinicians should take a harm reduction approach by encouraging patients to use regulated cannabis (medical or adult-use) if it is available to them, use safer modes of cannabis delivery, and reduce their THC dose over time. Patients would likely benefit from more frequent follow-up visits and monitoring for cannabis use disorder if they have a history of substance use disorder.

Chronic opioid therapy — Many patients with severe and chronic pain who seek medical cannabis are prescribed opioids and wish to have supplemental pain management or to use medical cannabis as a means to reduce opioid use [43]. In such situations, we coordinate closely with the patient's opioid-prescribing clinician to ensure that treatment agreements are not violated and that care plans are consistent with each other. We follow patients closely to monitor for oversedation and side effects.

Cognitive disorders — Acute administration of cannabis, and particularly THC, is associated with impaired episodic and working memory, processing speed, and executive function, though these effects resolve after a short period of abstinence [44]. These effects may be greater in older patients or patients with preexisting cognitive impairment, and so we use medical cannabis with caution in these patients. There is a small body of research on the use of cannabis and cannabinoids for the management of agitation, irritability, and other symptoms associated with late-stage dementia; however, review of this literature concluded that there was minimal evidence that medical cannabis may be effective in managing neuropsychiatric symptoms of dementia [45].

Psychiatric symptoms — High doses of THC are associated with developing or worsening psychosis [46,47]. In patients naïve to cannabis with current psychotic symptoms, medical cannabis should not be recommended. In those who are currently using cannabis, the THC dose should be minimized as much as possible.

Arrhythmia and coronary artery disease — Acute THC exposure, particularly at high doses, is associated with tachycardia (see "Cannabis (marijuana): Acute intoxication") and, in very rare situations, angina, myocardial infarction, and cardiac dysrhythmia [48-50]. For this reason, initiation of medical cannabis in patients with arrhythmia or coronary artery disease should be delayed until their cardiac symptoms are stable. If patients are already using cannabis, the THC dose should be minimized.

Drug-drug interactions — THC and cannabidiol (CBD) are metabolized by the cytochrome P450 (CYP450) system, which could interact with other CYP450-active medications [51,52]. Examples of some medications that could be impacted include warfarin, phenobarbital, digoxin, and certain antibiotics (eg, fluconazole) (table 1). In situations in which patients are using other CYP450-active medications, they may need closer monitoring if they initiate cannabis or if they stop using cannabis.

When combined with other sedating medications, cannabis can worsen sedation [53]. Particularly, when cannabis is combined with alcohol, impairment of complex task performance is worsened more with both cannabis and alcohol together than with either alone [54]. This has implications on driving and operating heavy machinery.

Pregnancy or breastfeeding — Chronic THC exposure in people who are pregnant is associated with preterm labor and intrauterine growth retardation [55]. There is very little evidence to guide recommendations on cannabis use in people who are breastfeeding. Despite this, there is evidence that cannabinoids including THC can be transmitted in breast milk and concern that this can lead to downstream negative effects on the infant [56]. It is important for clinicians to ask patients who use cannabis about current pregnancy and plans to become pregnant and advise against its use during pregnancy and lactation.

INITIATING MEDICAL CANNABIS — The decision to recommend medical cannabis to a patient should be based on a thorough review of the risks and benefits of cannabis use and shared decision-making with the patient.

Using the principles of harm reduction — In patients initiating or continuing cannabis use, clinicians can promote harm reduction (see "Primary care management of adults with opioid use disorder", section on 'Harm reduction interventions'). We stress that regulated cannabis is safer than unregulated cannabis. Additional cannabis harm reduction points include:

●Discuss risks of benefits of different routes of administration

●Limit unintentionally high doses of delta-9-tetrahydrocannabinol (THC; ie, from dose-stacking ingested cannabis or using dabs or waxes)

●Start at a low dose, and increase slowly (every two to three days)

●Limit or eliminate nicotine additives (cigar papers or tobacco leaf mixed with cannabis flower)

●Avoid mixing cannabis with other sedating agents (eg, alcohol, benzodiazepines)

●Do not operate heavy machinery or drive under the influence

●Store cannabis products in a safe, locked location

Choosing a cannabis product — Choosing a starting product and route of administration requires an in-depth discussion with the patient about the risks and benefits of each of the available products. In patients who are naïve to cannabis, our practice is to advise initiating sublingual tinctures to address acute symptoms because of its relatively quick onset of action and lack of respiratory side effects. For chronic, daily symptoms, we advise use of ingested cannabis products because of their long duration and lack of respiratory side effects. In patients who are experienced with using cannabis, the choice of starting cannabis products is driven by a harm reduction approach. We explain to patients that there is a spectrum of risks and benefits with each cannabis product and that sublingual tinctures or ingested cannabis products are the ideal. If patients are not willing to try these alternatives to smoked cannabis, or if they try them and find them to be ineffective, we encourage patients to use vaporized forms of cannabis if they are going to use inhaled cannabis.

Choice of cannabis product may also depend on the condition that is being treated. For example, patients using medical cannabis to manage severe nausea may find a sublingual tincture or edible product to be intolerable. In this case, vaporized cannabis may be preferred.

Choosing a starting dose — In patients who are naïve to cannabis, we advise that patients start with formulations that have equal parts THC and cannabidiol (CBD). We instruct patients to start at the lowest possible dose (usually 2.5 mg THC:2.5 mg CBD) and increase their dose in 2.5 mg THC increments every two to five days.

Patients who are experienced with cannabis often need cannabinoid formulations that are THC predominant (usually 2:1, 10:1, or 20:1 THC:CBD). To select a starting dose, we use one-half of the patient's estimated daily unregulated THC consumption. This is administered either at night before bed or as a split dose (afternoon and evening). Patients are advised to cease unregulated cannabis use for 24 to 48 hours prior to initiating medical cannabis. Patients then titrate their total dose by 2 to 5 mg every two to three days until they experience symptom relief.

We instruct patients to initiate their medical cannabis in a safe and familiar setting and to refrain from mixing it with other sedating medications or alcohol. We counsel patients to keep their medical cannabis and all other controlled substances in a locked medication safe where youth, other adults, and pets cannot access it. We advise patients not to drive for six to eight hours after using cannabis.

Writing the recommendation — When we write our recommendations, we do so directly in a state-specific medical cannabis certification form that is printed and provided to the patient and the medical cannabis dispensary. For example, in New York State, the form specifies the recommended THC:CBD ratio; directions to the pharmacist at the dispensary; and additional recommendations such as route of administration, when to initiate, and whether and how to titrate the dose. We also specify when the certification is valid and when the patient should return for follow-up evaluation.

Treatment agreements — We review and sign a cannabis patient-provider agreement that outlines appropriate use of cannabis, risks of cannabis use, limitations of medical cannabis, and expectations for ongoing care (form 1) [39].

MONITORING

Routine follow-up — We ask patients to return for follow-up appointments every three to six months depending on their comorbidities. We make ourselves available to patients when they first initiate cannabis use through televisits or electronic medical record messaging to answer any questions that arise or address side effects that occur. Patients in some, but not all, states have access to a clinical pharmacist at medical cannabis dispensaries to speak to about these concerns. At follow-ups, we review medical cannabis consumption (cannabinoid content, route of administration, frequency of use), review response to treatment, and assess for adverse events and side effects. We adjust recommendations on dosing or route of administration based on this data.

Patients should be screened for cannabis use disorder at follow-up visits. Patients with co-occurring substance use disorders may require more frequent follow-up to monitor for improvement of symptoms and for behavior or symptoms concerning for cannabis use disorder. If patients screen positive for cannabis use disorder, they should be informed of this diagnosis and offered evidence-based treatment. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment", section on 'TREATMENT'.)

Assessing side effects — Side effects or adverse effects of medical cannabis are primarily attributed to the effects of delta-9-tetrahydrocannabinol (THC). THC can cause dizziness, falls, paranoia, or panic attacks, among other symptoms (table 2). To mitigate the adverse effects of cannabis, patients should be advised to start at a low dose of THC and slowly increase their dose until they experience symptom improvement. In studies examining the effect of cannabis dosed two different ways (low and slow versus full dose at initiation), starting at a low dose of THC and slowly increasing it was associated with fewer adverse effects such as dry mouth, vertigo, dizziness, and somnolence [57,58]. Another strategy to limit adverse effects is to combine THC with cannabidiol (CBD), which is associated with fewer adverse events and can dampen THC effects. Inhaled products may also have respiratory side effects, the etiologies of which are not clearly THC related.

The table outlines adverse effects of cannabis, how common they are, as well as practical considerations for prevention and management of symptoms if they occur (table 2). Recommendations to patients should be as patient centric as possible to promote patient buy-in and adherence to the plan.

In patients who are acutely intoxicated with THC, cognition may be impaired [59]. These effects are particularly pronounced in young adults and older adult patients. Medical cannabis should be used with caution in these groups. Other adverse effects we monitor for include cannabis use disorder and cannabis hyperemesis syndrome. Cannabis intoxication is discussed elsewhere. (See "Cannabis (marijuana): Acute intoxication".)

CESSATION OF CANNABIS USE — In patients who experience adverse effects of cannabis use or who wish to cease cannabis use after a period of chronic use, abrupt cessation may lead to cannabis withdrawal. Patients may have fewer withdrawal symptoms if they reduce their use over time. Other strategies for management of cannabis withdrawal are discussed elsewhere. (See "Cannabis withdrawal: Epidemiology, clinical features, diagnosis, and treatment".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Medical cannabis and cannabinoids".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Medical cannabis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Context – Medical cannabis is legal in much of the United States as well as other parts of the world and is increasingly utilized in clinical encounters. (See 'Medical cannabis policy in the United States' above and 'Epidemiology of adult-use cannabis and medical cannabis in the United States' above.)

●Formulations – There are several formulations of medical cannabis, with different routes of administration. Medical cannabis has varying concentrations and ratios of cannabinoids, and formulations are usually characterized by the ratio of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In the United States, some formulations of medical cannabis are US Food and Drug Administration (FDA) approved and some are not. (See 'Cannabis formulations and routes of administration' above.)

●Clinical applications – Chronic pain is one of the most common applications for medical cannabis. Other conditions include, but are not limited to, multiple sclerosis, posttraumatic stress disorder (PTSD), chemotherapy-induced nausea, and seizure disorders. (See 'Clinical applications' above.)

●Assessing the patient

•History – We obtain a history of the condition for which patients are seeking medical cannabis including onset, duration, characteristics, and prior treatment attempts. We also obtain a personal and family psychiatric history, as well as a history of the patient's current and prior cannabis use. (See 'Assessing the patient' above.)

•Co-occurring conditions – Certain co-occurring conditions require caution including substance use disorder, chronic opioid therapy, cognitive or psychiatric disorders, arrhythmias or coronary artery disease, pregnancy, and breastfeeding. (See 'Co-occurring conditions that require caution' above.)

•Medications – Certain medications have important interactions with cannabis (table 1). (See 'Drug-drug interactions' above.)

●Initiating medical cannabis

•Harm reduction – In patients initiating or continuing cannabis use, we promote harm reduction by stressing that regulated cannabis is safer than unregulated cannabis. We also advise patients of cannabis harm reduction points. (See 'Using the principles of harm reduction' above.)

•Choosing a cannabis product – Choosing a starting product and route of administration is based on the risks and benefits of each of the available products. Our general approach is as follows (see 'Choosing a cannabis product' above):

-For cannabis-naïve patients who are using cannabis to treat acute symptoms, we suggest a sublingual tincture rather than other products (Grade 2C) because sublingual tinctures have relatively quick onset and lack respiratory side effects.

-For patients using cannabis to treat chronic daily symptoms, we suggest an ingested product rather than other products (Grade 2C) because ingested products have longer duration and lack respiratory side effects.

-For patients who cannot tolerate edible or sublingual products (eg, those using cannabis to treat severe nausea), vaporized cannabis is a reasonable alternative.

•Starting dose – In patients who are naïve to cannabis, we advise that patients start with formulations that have equal parts THC and CBD, at the lowest possible dose (usually 2.5 mg THC:2.5 mg CBD), and increase their dose in 2.5 mg THC increments every two to five days. Patients who are experienced with cannabis often need cannabinoid formulations that are THC predominant (usually 2:1, 10:1, or 20:1 THC:CBD). (See 'Choosing a starting dose' above.)

•Recommendations and treatment agreements – There are state-specific medical cannabis certification forms that must be provided to the patient and the medical cannabis dispensary. We review and sign a cannabis patient-provider agreement that outlines appropriate use of cannabis, risks of cannabis use, limitations of medical cannabis, and expectations for ongoing care (form 1). (See 'Writing the recommendation' above and 'Treatment agreements' above.)

●Monitoring and assessing for side effects – We ask patients to return for follow-up appointments every three to six months depending on their comorbidities to review consumption (cannabinoid content, route of administration, frequency of use) and response to treatment and to assess for adverse events or side effects (table 2). (See 'Monitoring' above.)