Cannabis sativa (hemp, marijuana, pot, grass)

Introduction

The dried flowering tops of Cannabis sativa (marijuana) contain cannabionoids, the most potent of which is delta-9-tetra-hydrocannabinol (THC).

DEA: Schedule 1

* for cannabis use disorder, also see substance abuse

Uses

• the tough fiber derived from stems of the plant (hemp) had been used for centuries in the manufacture of rope (see Herman Melville's "Moby Dick")
• various preparations are smoked or ingested by members of various cultures or subcultures to induced psychotomimetic effects such as euphoria, hallucinations, drowsiness & other mental changes
• formerly used as a sedative & analgesic
• now used for management of iatrogenic anorexia, especially that associated with oncologic chemotherapy & anorexia secondary to AIDS (only low-quality evidence)
  • very limited evidence that marijuana improves appetite except in patients with advanced AIDS; this is contrary to common belief of 'pot heads' that smoking 'pot' is associated with the 'munchies'
• used for reducing the pain of glaucoma
• treatment of some symptoms of multiple sclerosis
  • cannabis extract, tetrahydrocannabinol, or cannabinoid spray may ease patient-reported spasticity & pain (excluding central neuropathic pain)
  • likely not effective in improving objective measures of spasticity
  • may help reduce urinary frequency
• treatment of chronic pain
  • moderate quality evidence at best
  • low-strength evidence for treatment of neuropathic pain
    • also see cannabinoid
    • insufficient evidence for clinical use
  • bone pain is unlikely to improve
  • some medical cannabis patients decreased opioid use without harming quality of life or health functioning, soon after the legalization of medical cannabis
  • placebo has a significant association with pain reduction in cannabinoid clinical trials
  • often associated with reduction in use of other analgesics
• may have benefits for cancer patients
  • in a state with legalized marijuana, 24% of cancer patients used marijuana, primarily for pain, nausea, stress, anxiety, & depression
  • may improve a variety of cancer-related symptoms, including nausea/vomiting, sleep disorders, pain, anxiety, & depression
  • effective in chemotherapy-induced nausea & vomiting especially in patients receiving ondansetron (GRS11)
  • cannabis is used more frequently by cancer patients than by other adults
• little evidence to assess benefit vs harm in PTSD
• elderly use to treat pain, sleep disturbance, anxiety, &/or depression
• prescription drug use for anxiety, pain, & sleep disorders diminished in states that legalized marijuana use
  • Medicare spending fell by $165 million in 2013 as the result of marijuana substitution
  • elderly, average age of 81 years, experience improvement in chronic pain, sleep, neuropathy, & anxiety with medical cannabis
  • may improve anorexia & insomnia in elderly cancer patients
• medical marijuana may improve seizure control & quality of life in refractory epilepsy
  • high out-of-pocket costs & inconvenient access cited as reasons for discontinuation
• marijuana may be linked to lower fasting serum insulin & greater insulin receptor sensitivity
• pregnant teenagers more likely to use marijuana that non- pregnant teenagers
• medical marijuana may have use in children & adolescents
• may be recommended cannabis dispensaries to prevent morning sickness during 1st trimester of pregnancy, despite warnings against its use in pregnancy
• depression, anxiety, & trauma associated with cannabis use during pregnancy
• medical cannabis may be associated with an improvement in health-related quality of life

Epidemiology

• on April 20 each year, thousands of Americans celebrate marijuana as a holiday known as '4/20'
• cannabis use is increasing among adults with children in the home
• 15% reported using marijuana in the prior year
  • 20% of in states where recreational marijuana is legal, 14% in states where medical use is legal, & 12% in states with no legal use
  • smoking most common method of use
• legalization of recreational marijuana for adults in Washington state has not been associated with an increase in use among high-school or middle-school students
• from 2009-2017, cannabis use in the year before pregnancy in Northern California increased from 7% to 13%, with an increase of 2.0% to 3.4% use during pregnancy
• women with heavy cannabis use are (>= 4 times in the previous month) are much less likely to have diabetes mellitus type 2 than light users or non-users
• medical marijuana legalization has been associated with less opioid dispensing & pain-related hospital events among some adults treated for newly diagnosed cancer
• cannabis is used more frequently by cancer patients than by other adults

Contraindications

• ACOG recommends against use of marijuana during pregnancy or lactation
  • tetrahydrocannabinol persists in breast milk at least 6 days, estimated half-life of 17 days

Pharmacokinetics

• peak plasma levels of THC are achieved 10 minutes after smoking or 3 hours after ingestion
• about 70% of a dose is excreted within 72 hours, equally divided between urine & feces.
• use of cannabis concentrates associated with higher THC levels than use of cannabis flower, but differences in short-term subjective & neurobehavioral impairments do not track specifically with strength of the cannabis
• elderly do not need escalting doses to achieve same effect
• withdrawal symptoms subtle & prolonged

Adverse effects

• for cannnabis use disorder, also see substance abuse
• literature may be conflicting
• word recall deficits persist for 1 week after use, but disappear after 28 days
• one month of abstinence associated with improved memory in adolescents & young adults
• cognitive deficits in learning, retention & retrieval persist after 17 hours of abstinence with 24 years of regular use (but not 10 years)
• persistent cannabis use begun during adolescence, leads to measurable neuropsychological decline by midlife
• heavy use in early adolescence associated with later problems in executive function
• underestimation of the time taken to complete a task after 10 years of regular use
• may lower IQ after 9 years of use > 4X/week (106 vs 111)
• at age 45 years, long-term cannabis users perform worse on most cognitive tests than never user, worse on learning & memory tests than long-term alcohol or tobacco users or recreational cannabis users
  • more-persistent cannabis use over time is associated with worse performance on learning, processing speed, & verbal memory
• early marijuana use may be associated with risk of later ilicit drug use
• pulmonary function
  • associated with occupational lung disease byssinosis
  • occasional use (< 20 times/month)
    • may not be associated with impaired lung function (FEV1)
    • may actually improve FEV1
  • > once weekly for at least 1 year
    • increased risks for cough, sputum production, & wheezing
    • no consistent association with chronic bronchitis or pulmonary function testing (FEV1)
  • marijuana smoke contains many of the same constituents as tobacco smoke
• cardiovascular risk uncertain
  • not associated with cardiovascular benefits & might confer CV harms
  • may be associated with increased risks for myocardial infarction, cardiac arrhythmias, heart failure, & stroke
  • associated with increased mortality after myocardial infarction
  • increased mortality from hypertension (RR=3.4) but no increase in cardiovascular mortality?
  • insufficient evidence to assess risk of cardiovascular mortality
  • increased risk of recurrent myocardial infarction or stroke after PCI
• psychosis
  • predisposes to psychosis, including schizophrenia
  • use of cannabis after a first episode of psychosis appears to increase risk of additional episodes & psychiatric hospitalization
  • use of cannabis during adolescence associated with increased risk of subsequent psychotic experiences (RR=3 to 3.7)
  • daily use of cannabis associated with increased risk of psychosis
  • edible cannabis may be associated with psychosis
  • no association between state legalization of cannabis & psychosis-related health care utilization
• depression & suicidal ideation
  • causal relationship suggested between frequent cannabis use & major depression & suicide ideation
  • use of cannabis by adolescents associated with increased risk of depression & suicidal ideation in young adulthood
• women report more CNS, GI, musculoskeletal & psychological adverse events than men (73 vs 53%)
• adolescent use associated with misuse other drugs & alcohol in early adulthood
• hyperemesis with chronic use
  • cannabinoid hyperemesis syndrome
  • editorialist notes that this seems counterintuitive since Cannabis is used to treat nausea & vomiting
• risk of unintentional ingestion by children is low even in states where marijuana has been decriminalized
• daily use in adolescence associated with
  • 60% reduced likelihood of graduating from high school
  • 8-fold increased risk of other drug use
  • 7-fold increased risk of suicide attempt
• motor vehicle accidents
  • 12% increase in relative risk of fatal traffic accidents after 4:20 pm on April 20 (see Epidemiology:)
  • active use is associated with fatal motor vehicle accidents
  • cannabis legalization may be associated with an increase in statewide fatal fatal motor vehicle accidents
• heavy use prior to age 19 associated with increased risk of mortality before age 60 in Swedish men (RR=1.4)
• no increase in risk of mortality but increased risk of emergency department visits
• increased emergency department visits in Colorado after ingested marijuana
  • visits associated with GI symptoms & psycosis
• use during pregnancy
  • increased risk of maternal anemia (RR=1.36)
  • increased risk of low birth weight infant (RR=1.77)
  • increased risk of infant needing NICU (RR ~2)
  • not associated with preterm birth, neonatal length, or head circumference
• tetrahydrocannabinol in breast milk up to 6 days since last maternal marijuana use; 1/2 life is 17 days
• increased exposure of children after legalization in Colorado; no death or long-term complications reported
• heavy marijuana smoking may be associated with diminshed GFR in young adults
• smoking marijuana may be associated with increased risk of testicular germ cell tumor
• increased risk of diabetic ketoacidosis in type 1 diabetes (RR=2)
• migraine patients who used cannabis were more likely to develop rebound headaches than those who did not
• cannabis dependence (8%)
  • manifestations described as craving & withdrawal
  • consequences of abstinence not defined

Laboratory

• oral fluid testing for marijuana impairment may be an effective tool for roadside sobriety tests
  • Belgium has required oral fluid tests in cases of suspected marijuana-related DUI since 2009

Radiology

• neuroimaging: magnetic resonance imaging
  • structural & functional changes in the orbitofrontal cortex (central to the reward system), probably via cannabinoid CB-1 receptors
    • increased in functional connectivity representing higher, & less efficient, energy use
    • greater myelination, possibly arising from marijuana's anti-inflammatory & antioxidant properties
    • cannabinoids also might alter synaptic pruning
  • long-term cannabis use associated with smaller hippocampal volumes, but did not mediate cannabis-related cognitive deficits

Management

• documented medical examination & clinical history required
• informed & shared decision making
• treatment plans with objectives should be established as early as possible & revisited regularly
• treatment plans should specify measurable goals & objectives for used in evaluation of treatment progress, such as relief of pain & improved physical & psychosocial function
• treatment plans should also include
  • advice about other options
  • risk of cannabis use disorder
  • potential adverse events
  • risks of using cannabis during pregnancy or breast feeding
  • need to safeguard all cannabis & cannabis-infused products from children, pets or domestic animals
  • reminder that the cannabis is for the patient only
• specific duration for the cannabis authorization for a period no longer 12 months
• gabapentin may be useful for smoking cessation
• N-acetylcysteine may be useful for smoking cessation
• cannabis dependence:
  • nabiximols in combination with motivational enhancement therapy & cognitive behavioral therapy may reduce craving but not dependence

Comparative biology

• a chronic low dose of delta-9 tetrahydrocannabinol may restore CB1 receptor signaling in old mice
  • potential effective strategy to treat age-related cognitive impairment

Notes

• legalization of medical marijuana is associated with a decline in mortality from opioid overdose
• local cannabis dispensaries associated lower mortality from synthetic opioids, prescription opioids, & heroin
• highly concentrated tetrahydrocannabinol (THC) prepared by passing butane through a tube packed with dried cannabis is known as "blasting"
  • once the butane evaporates, the remaining product (butane hash oil can reach THC concentrations up to 80%
  • the hash-oils is then vaporized by lighting/burning & inhaled ("dabbing") through a water pipe ("oil rig")
• electronic cigarettes can be used to vaporize cannabis, including marijuana, tetrahydrocannabinol, or hash oil
• ingredients of edible products often mislabeled

More general terms

• Cannabis

Additional terms

• cannabinoid (spice, K2, AMB-FUBINACA)
• cannabinoid in urine
• substance abuse
• tetrahydrocannabinol; delta-9-tetrahydrocannabinol; THC