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Cannabis sativa (hemp, marijuana, pot, grass)

The dried flowering tops of Cannabis sativa (marijuana) contain cannabionoids, the most potent of which is delta-9-tetra-hydrocannabinol (THC). DEA: Schedule 1 [38] * 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) [31] - very limited evidence that marijuana improves appetite except in patients with advanced AIDS [79]; this is contrary to common belief of 'pot heads' that smoking 'pot' is associated with the 'munchies' - used for reducing the pain of glaucoma [9] - treatment of some symptoms of multiple sclerosis - cannabis extract, tetrahydrocannabinol, or cannabinoid spray may ease patient-reported spasticity & pain (excluding central neuropathic pain) [24] - likely not effective in improving objective measures of spasticity [24] - may help reduce urinary frequency [24] - treatment of chronic pain [68] - moderate quality evidence at best [31] - subjective improvement in pain in 82% of patients with fibromyalgia [106] - low-strength evidence for treatment of neuropathic pain [49] - also see cannabinoid - insufficient evidence for clinical use [79] - 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 [96] - placebo has a significant association with pain reduction in cannabinoid clinical trials [99] - often associated with reduction in use of other analgesics [101] - 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 [54] - may improve a variety of cancer-related symptoms, including nausea/vomiting, sleep disorders, pain, anxiety, & depression [60] - effective in chemotherapy-induced nausea & vomiting especially in patients receiving ondansetron (GRS11) [79] - cannabis is used more frequently by cancer patients than by other adults [104] - little evidence to assess benefit vs harm in PTSD [49] - elderly use to treat pain, sleep disturbance, anxiety, &/or depression [88] - prescription drug use for anxiety, pain, & sleep disorders diminished in states that legalized marijuana use [36] - Medicare spending fell by $165 million in 2013 as the result of marijuana substitution [36] - elderly, average age of 81 years, experience improvement in chronic pain, sleep, neuropathy, & anxiety with medical cannabis [74] - may improve anorexia & insomnia in elderly cancer patients [79] - medical marijuana may improve seizure control & quality of life in refractory epilepsy [55] - 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 [39] - pregnant teenagers more likely to use marijuana that non- pregnant teenagers [43] - medical marijuana may have use in children & adolescents [52] - may be recommended cannabis dispensaries to prevent morning sickness during 1st trimester of pregnancy, despite warnings against its use in pregnancy [62] - depression, anxiety, & trauma associated with cannabis use during pregnancy [81] - medical cannabis may be associated with an improvement in health-related quality of life [103] Contraindications: - ACOG recommends against use of marijuana during pregnancy or lactation [30] - tetrahydrocannabinol persists in breast milk at least 6 days [65], estimated half-life of 17 days [91] Epidemiology: - on April 20 each year, thousands of Americans celebrate marijuana as a holiday known as '4/20' [58] - cannabis use is increasing among adults with children in the home [63] - 15% reported using marijuana in the prior year [66] - 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 [66] - 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 [72] - legalization of nonmedical cannabis has been associated with increased cannabis-related emergencies in older adults [105] - 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 [77] - 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 [97] - medical marijuana legalization has been associated with less opioid dispensing & pain-related hospital events among some adults treated for newly diagnosed cancer [100] - cannabis is used more frequently by cancer patients than by other adults [104] 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 [83] - 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 [5] - one month of abstinence associated with improved memory in adolescents & young adults [69] - 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 [20] - heavy use in early adolescence associated with later problems in executive function [82] - underestimation of the time taken to complete a task after 10 years of regular use [6] - may lower IQ after 9 years of use > 4X/week (106 vs 111) [27] - 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 [94] - more-persistent cannabis use over time is associated with worse performance on learning, processing speed, & verbal memory [94] - early marijuana use may be associated with risk of later ilicit drug use [7] - 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 [15] - > once weekly for at least 1 year - increased risks for cough, sputum production, & wheezing [64] - no consistent association with chronic bronchitis or pulmonary function testing (FEV1) [64] - marijuana smoke contains many of the same constituents as tobacco smoke [15] - cardiovascular risk uncertain - not associated with cardiovascular benefits & might confer CV harms [85] - may be associated with increased risks for myocardial infarction, cardiac arrhythmias [95], heart failure, & stroke [85] - associated with increased mortality after myocardial infarction [13] - increased mortality from hypertension (RR=3.4) [48] but no increase in cardiovascular mortality? - insufficient evidence to assess risk of cardiovascular mortality [57] - increased risk of recurrent myocardial infarction or stroke after PCI [86] - psychosis - predisposes to psychosis [8], including schizophrenia [12] - use of cannabis after a first episode of psychosis appears to increase risk of additional episodes & psychiatric hospitalization [40] - use of cannabis during adolescence associated with increased risk of subsequent psychotic experiences (RR=3 to 3.7) [56] - daily use of cannabis associated with increased risk of psychosis [75] - edible cannabis may be associated with psychosis [76] - no association between state legalization of cannabis & psychosis-related health care utilization [102] - depression & suicidal ideation - causal relationship suggested between frequent cannabis use & major depression & suicide ideation [51] - use of cannabis by adolescents associated with increased risk of depression & suicidal ideation in young adulthood [73] - women report more CNS, GI, musculoskeletal & psychological adverse events than men (73 vs 53%) [97,98] - adolescent use associated with misuse other drugs & alcohol in early adulthood [47] - hyperemesis with chronic use [17] - cannabinoid hyperemesis syndrome [22] - editorialist notes that this seems counterintuitive since Cannabis is used to treat nausea & vomiting [17] - risk of unintentional ingestion by children is low even in states where marijuana has been decriminalized [23] - 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 [27] - motor vehicle accidents - 12% increase in relative risk of fatal traffic accidents after 4:20 pm on April 20 [58] (see Epidemiology:) - active use is associated with fatal motor vehicle accidents [10,16] - cannabis legalization may be associated with an increase in statewide fatal fatal motor vehicle accidents [84] - heavy use prior to age 19 associated with increased risk of mortality before age 60 in Swedish men [35] (RR=1.4) - no increase in risk of mortality but increased risk of emergency department visits [97] - increased emergency department visits in Colorado after ingested marijuana [33] - visits associated with GI symptoms & psycosis [76] - use during pregnancy - increased risk of maternal anemia (RR=1.36) [34] - increased risk of low birth weight infant (RR=1.77) [34] - increased risk of infant needing NICU (RR ~2) [34] - not associated with preterm birth, neonatal length, or head circumference [34] - tetrahydrocannabinol in breast milk up to 6 days since last maternal marijuana use [65]; 1/2 life is 17 days [91] - increased exposure of children after legalization in Colorado [37]; no death or long-term complications reported - heavy marijuana smoking may be associated with diminshed GFR in young adults [50] - smoking marijuana may be associated with increased risk of testicular germ cell tumor [80] - increased risk of diabetic ketoacidosis in type 1 diabetes (RR=2) [70] - migraine patients who used cannabis were more likely to develop rebound headaches than those who did not [90] - cannabis dependence (8%) [59] - manifestations described as craving & withdrawal [59] - consequences of abstinence not defined Laboratory: - oral fluid testing for marijuana impairment may be an effective tool for roadside sobriety tests [46] - Belgium has required oral fluid tests in cases of suspected marijuana-related DUI since 2009 [46] Radiology: - neuroimaging: magnetic resonance imaging [27] - 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 [27] - long-term cannabis use associated with smaller hippocampal volumes, but did not mediate cannabis-related cognitive deficits [94,97] Management: - documented medical examination & clinical history required [53] - informed & shared decision making [53] - treatment plans with objectives should be established as early as possible & revisited regularly [53] - treatment plans should specify measurable goals & objectives for used in evaluation of treatment progress, such as relief of pain & improved physical & psychosocial function [53] - 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 [53] - gabapentin may be useful for smoking cessation [18] - N-acetylcysteine may be useful for smoking cessation [19] - cannabis dependence: - nabiximols in combination with motivational enhancement therapy & cognitive behavioral therapy may reduce craving but not dependence [59] Comparative biology: - a chronic low dose of delta-9 tetrahydrocannabinol may restore CB1 receptor signaling in old mice [45] - potential effective strategy to treat age-related cognitive impairment [45] Notes: - legalization of medical marijuana is associated with a decline in mortality from opioid overdose [26,61] - local cannabis dispensaries associated lower mortality from synthetic opioids, prescription opioids, & heroin [89] - 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") [29] - electronic cigarettes can be used to vaporize cannabis, including marijuana, tetrahydrocannabinol, or hash oil [67] - ingredients of edible products often mislabeled [31]

Related

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

General

Cannabis

Properties

KINGDOM: plant

References

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