Medical marijuana or medical cannabis refers to the use of the unprocessed Cannabis sativa plant, part of the plant, or extracts from the plant as medical therapy to treat disease or alleviate symptoms.

Medical cannabis

Cannabinoids-biologically active compounds that activate the cannabinoid receptors. They may be derived from the plant or be synthetic.

CBD-cannabinol

THC-Δ⁹-tetrahydrocannabinol

• Medical use of marijuana has been restricted since classification as a Schedule I substance by the Controlled Substance Act in 1970.¹
• First medical marijuana law (MML) was enacted in California in 1996, allowing for use of medical cannabis despite lack of Food and Drug Administration (FDA) testing for safety and efficacy.¹
• As of February 2022, medical use of marijuana is permitted at the state level for 37 states, 3 territories, and the District of Columbia.¹
• Cannabis is the second most commonly used recreational drug worldwide after alcohol.²
  1. In 2019, 48.2 million Americans >12 yr old (18% of the U.S. population) reported any marijuana use at least once in the past year.³
  2. In 2018, 2% of the U.S. population reported medical marijuana use.
  3. Of 2014 marijuana smokers, 6.2% used medical marijuana only, and 3.6% used medical and recreational marijuana.⁴
  4. Residents of medical marijuana states were 1.3 times more likely to use medical marijuana in 2015 compared to 2013.^,5

• Cannabinoids elicit their effects by interacting with cannabinoid receptors in various central nervous system (CNS) locations, eliciting diverse CNS and peripheral nervous system (PNS) effects (Box 1).
• Primarily bind to CB1 G-protein-coupled receptors in the basal ganglia, hippocampus, cortex, and cerebellum, eliciting antinociception, locomotor, and psychoactive effects.
• Marijuana contains >400 plant-derived compounds, >60 classified as cannabinoids, with the major phytocannabinoids being cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC).

Research has demonstrated a wide range of THC and CBD concentrations in various formulations, with frequent inaccurate labelling.

• Cigarettes
• Tinctures
• Capsules
• Vaporization cartridges
• Purified cannabinoids butane hash oil (BHO)
• Supercritical fluid extracts (SFEs or “dabs”)
• Buccal sprays
• Edibles
• Lozenges
• Transdermal patches

• Variable evidence for treatment of:
  1. Chronic pain
  2. Chemotherapy-induced nausea/vomiting
  3. HIV-related anorexia
  4. Glaucoma
  5. Anxiety
  6. Multiple sclerosis (MS)
  7. Seizures
• Marijuana has not been FDA approved as safe and effective for any indication and remains a Schedule I drug.
• However, there are phytocannabinoids and synthetic phytocannabinoid analogs that have received FDA approval.
  1. Dronabinol and Nabilone (synthetic THC analogs) are schedule II FDA approved medications for AIDS-associated anorexia and chemotherapy-induced nausea, respectively.⁶
  2. Purified cannabidiol oral solution (Epidiolex) is FDA approved for seizures associated with Dravet or Lennox-Gastaut syndrome.
• Qualifying diagnoses for certification for prescription medical marijuana vary by state, but typically include:
  1. Cancer
  2. Glaucoma
  3. HIV/AIDS
  4. Hepatitis C
  5. Cachexia
  6. Severe, debilitating, chronic pain
  7. Severe nausea
  8. Seizures
  9. Severe muscle spasms
  10. Crohn disease
  11. Alzheimer disease
  12. PTSD
  13. Sickle cell disease

• There is published evidence demonstrating that marijuana improves noncancer-related pain, chemotherapy-induced nausea and vomiting, and spasticity in multiple sclerosis.^6,7
  1. A 2011 systematic review of randomized controlled trials (RCTs) demonstrated statistically significant improvement in pain scores for noncancer-related chronic pain in 15 of 18 trials with no serious adverse effects.⁷
  2. A 2015 systematic review and meta-analysis showed improved response in nausea and vomiting compared to placebo (OR 3.82).⁸
  3. A 2018 systematic review demonstrated a decrease in nausea and vomiting following chemotherapy (RR 3.60 compared to placebo), improved spasticity with MS (RR 1.45 compared to placebo), and a modest benefit with primarily neuropathic pain (RR 1.37 compared to placebo) with frequent adverse effects including psychosis, “feeling high,” and somnolence (number needed to harm = 5 to 8).⁹
     1. No statistically significant improvement was noted in acute pain.
  4. A Cochrane review in 2013 found no statistically significant weight gain with dronabinol in HIV/AIDS patients, and multiple RCTs have identified megestrol acetate as superior to dronabinol for weight gain in cancer patients.¹⁰
  5. A 2020 systematic review and meta-analysis showed extremely limited evidence for benefits for Crohn disease and ulcerative colitis, with only three RCTs all showing no improvement of marijuana over placebo.¹¹
  6. In 2019, a systematic review determined that there was sufficient evidence from five reviews that cannabinoids may be effective for multiple sclerosis symptoms of pain and/or spasticity.^8,12
  7. In a study of 54,000 adults in 37 states with medical cannabis access, more than half reported that cannabis use led to less use of other analgesics both opioid and nonopioid and one quarter to one third reported that cannabis use led to less use of physical therapy or cognitive-behavioral therapy.^12a

• Marijuana use has been demonstrated to impair short-term memory consolidation, reaction time, and concept formation, and to increase incidence of road traffic accidents, ataxia, euphoria, disorientation, dry mouth, somnolence, and, at high doses, psychosis, panic, and paranoia.
• Marijuana has been shown to worsen preexisting anxiety, depression, and schizophrenia. It should be used with caution, particularly in combination with other drugs with similar effects.¹³
• Meta-analyses demonstrate increased respiratory symptoms of cough, sputum production, and wheeze with smoking marijuana; however, there was no statistical difference in pulmonary function.
• Medical marijuana does have drug-drug interactions, and adverse effects can be potentiated by other medications. In particular, concomitant use of other medications such as opiates and benzodiazepines should be avoided as it could lead to somnolence and respiratory suppression.¹³
• Acute marijuana intoxication is associated with reversible changes in P and T waves and ST segments (pseudo-Wellens syndrome).
• Medical marijuana should be stored away from children given the risk of toxic ingestion.

• Marijuana remains classified as a schedule I drug under the Controlled Substance Act of 1970.
• However, the Justice Department declared it would not prosecute any physician who recommends medical marijuana for a legitimate medical indication in a state where it has been legalized.¹
• Medical marijuana card (MMC)
  1. MMC allows a patient to possess a certain amount of marijuana for medical use and not be prosecuted for possession of marijuana.
  2. To obtain an MMC, a patient must obtain physician certification confirming a clinical indication for medical marijuana.
  3. With an MMC, the patient can go to a licensed medical marijuana compassion center (dispensary), which will dispense a dose and formulation of medical marijuana appropriate for the patient’s medical condition.
  4. Physicians do not prescribe the dose or formulation of medical marijuana.
• To certify a patient for a medical marijuana card, physicians must
  1. Complete a Department of Health certification form.
  2. Forms vary by state, but typically consist of a single-page form indicating a qualifying diagnosis that is to be signed by the physician. Complete and document a full medical history and physical exam.
  3. Explain the risks, benefits, and side effects of medical marijuana.
  4. Continue an ongoing role on the patient’s health care team.
  5. Maintain accurate medical records and documentation of the patient’s clinical indication for medical marijuana.
• Some states require additional physician training and registration with the state medical marijuana program prior to being able to certify patients.
• Physicians are under no obligation to issue medical marijuana certifications.

• Patients must possess a valid state-issued ID and apply for a state medical marijuana card.
• Patients can obtain medical marijuana from compassion centers without a medical marijuana card but could then be prosecuted for possession of marijuana.
• Patients should be aware that concomitant use of other medications such as opiates and benzodiazepines should be avoided as it could lead to somnolence and respiratory suppression.
• Patients should store medical marijuana away from children given the risk of toxic ingestions.

Pain Management in Chronic Pain (Related Key Topic)

Chemotherapy-Induced Nausea and Vomiting (Related Key Topic)