Cannabis, also known as marijuana among other names, is a
psychoactive drug from the Cannabis plant used for medical or recreational
purposes. The main psychoactive part of cannabis is tetrahydrocannabinol (THC),
one of the 483 known compounds in the plant, including at least 65 other
cannabinoids. Cannabis can be used by
smoking, vaporizing, within food, or as an extract.
Cannabis has mental and physical effects, such as creating a
"high" or "stoned" feeling, a general change in perception,
heightened mood, and an increase in appetite. Onset of effects is felt within minutes when
smoked, and about 30 to 60 minutes when cooked and eaten. The effects last for two to six hours. Short-term side effects may include a decrease
in short-term memory, dry mouth, impaired motor skills, red eyes, and feelings
of paranoia or anxiety. Long-term side
effects may include addiction, decreased mental ability in those who started
regular use as teenagers, and behavioral problems in children whose mothers used
cannabis during pregnancy. There is a strong
relation between cannabis use and the risk of psychosis, though the cause-and-effect
is debated.
Cannabis is mostly used for recreation or as a medicinal
drug, although it may also be used for spiritual purposes. In 2013, between 128
and 232 million people used cannabis (2.7% to 4.9% of the global population between
the ages of 15 and 65). It is the most commonly used illegal drug both
in the world and the United States, though it is also legal in some
jurisdictions. The countries with the highest use among adults as of 2018 are
Zambia, the United States, Canada, and Nigeria.
In 2016, 51% of people in the United States had used cannabis in their
lifetimes. About 12% had used it in the
past year, and 7.3% had used it in the past month.
While cannabis plants have been grown since at least the 3rd
millennium BCE, evidence suggests it was being smoked for psychoactive effects
at least 2,500 years ago in the Pamir Mountains. Since the early 20th century, cannabis has
been subject to legal restrictions. The possession, use, and cultivation of
cannabis is illegal in most countries of the world. In 2013, Uruguay became the first country to
legalize recreational use of cannabis. Other countries to do so are Canada, Georgia,
and South Africa, plus 11 states and the District of Columbia in the United
States (though the drug remains federally illegal). Medical use of cannabis, requiring the
approval of a physician, has been legalized in a greater number of countries.
Uses
Medical
Medical cannabis, or medical marijuana, can refer to the use
of cannabis and its cannabinoids to treat disease or improve symptoms; however,
there is no single agreed-upon definition. The rigorous scientific study of cannabis as a
medicine has been hampered by production restrictions and by the fact that it
is classified as an illegal drug by the many governments. There is limited evidence suggesting cannabis
can be used to reduce nausea and vomiting during chemotherapy, to improve
appetite in people with HIV/AIDS, or to treat chronic pain and muscle spasms. Its use for other medical applications is
insufficient for drawing conclusions about safety or efficacy.
Short-term use increases the risk of both minor and major
adverse effects. Common side effects
include dizziness, feeling tired and vomiting. The long-term effects of cannabis are not
clear. There are concerns surrounding
memory and cognition problems, risk of addiction, schizophrenia in young
people, and the risk of children taking it by accident.
Recreational
Cannabis has psychoactive and physiological effects when
consumed. The immediate desired effects
from consuming cannabis include relaxation and euphoria (the "high"
or "stoned" feeling), a general alteration of conscious perception,
increased awareness of sensation, increased libido and distortions in the
perception of time and space. At higher doses, effects can include altered body
image, auditory and/or visual illusions, pseudohallucinations and ataxia from
selective impairment of polysynaptic reflexes. In some cases, cannabis can lead
to dissociative states such as depersonalization and derealization.
Some immediate undesired side effects include a decrease in
short-term memory, dry mouth, impaired motor skills and reddening of the eyes. Aside from a subjective change in perception
and mood, the most common short-term physical and neurological effects include
increased heart rate, increased appetite and consumption of food, lowered blood
pressure, impairment of short-term and working memory, psychomotor
coordination, and concentration. Some users may experience an episode of acute
psychosis, which usually abates after six hours, but in rare instances, heavy
users may find the symptoms continuing for many days.
A reduced quality of life is associated with heavy cannabis
use, although the relationship is inconsistent and weaker than for tobacco and
other substances. The direction of cause
and effect relationship, however, is unclear.
Spiritual
Cannabis has held sacred status in several religions and has
served as an entheogen – a chemical substance used in religious, shamanic, or
spiritual contexts – in the Indian subcontinent since the Vedic period dating
back to approximately 1500 BCE, but perhaps as far back as 2000 BCE. There are
several references in Greek mythology to a powerful drug that eliminated
anguish and sorrow. Herodotus wrote about early ceremonial practices by the
Scythians, thought to have occurred from the 5th to 2nd century BCE. In modern
culture, the spiritual use of cannabis has been spread by the disciples of the
Rastafari movement who use cannabis as a sacrament and as an aid to meditation.
The earliest known reports regarding the sacred status of cannabis in the
Indian subcontinent come from the Atharva Veda, estimated to have been written
sometime around 2000–1400 BCE.
Available forms
Cannabis is consumed in many different ways:
·
Smoking, which typically involves burning and
inhaling vaporized cannabinoids ("smoke") from small pipes, bongs
(portable versions of hookahs with a water chamber), paper-wrapped joints or
tobacco-leaf-wrapped blunts, and other items.
·
Vaporizer, which heats any form of cannabis to
165–190 °C (329–374 °F), causing the active ingredients to evaporate into vapor
without burning the plant material (the boiling point of THC is 157 °C (315 °F)
at atmospheric pressure).
·
Cannabis tea, which contains relatively small
concentrations of THC because THC is an oil (lipophilic) and is only slightly
water-soluble (with a solubility of 2.8 mg per liter). Cannabis tea is made by first adding a
saturated fat to hot water (e.g. cream or any milk except skim) with a small
amount of cannabis.
·
Edibles,
where cannabis is added as an ingredient to one of a variety of foods,
including butter and baked goods. In India it is commonly made into a beverage,
bhang.
·
Capsules, typically containing cannabis oil, and
other dietary supplement products, for which some 220 were approved in Canada
in 2018.
Adverse effects
Addiction experts in psychiatry, chemistry, pharmacology,
forensic science, epidemiology, and the police and legal services engaged in
delphic analysis regarding 20 popular recreational drugs. Cannabis was ranked
11th in dependence, 17th in physical harm, and 10th in social harm.
Short term
Acute effects may include anxiety and panic, impaired
attention and memory, an increased risk of psychotic symptoms, the inability to
think clearly, and an increased risk of accidents. Cannabis impairs a person's driving ability,
and THC was the illicit drug most frequently found in the blood of drivers who
have been involved in vehicle crashes. Those with THC in their system were from
three to seven times more likely to be the cause of the accident than those who
had not used either cannabis or alcohol, although its role is not necessarily
causal because THC stays in the bloodstream for days to weeks after
intoxication.
According to the United States Department of Health and
Human Services, there were 455,000 emergency room visits associated with
cannabis use in 2011. These statistics include visits in which the patient was
treated for a condition induced by or related to recent cannabis use. The drug
use must be "implicated" in the emergency department visit, but does
not need to be the direct cause of the visit. Most of the illicit drug
emergency room visits involved multiple drugs. In 129,000 cases, cannabis was the only
implicated drug.
The short term effects of cannabis can be altered if it has
been laced with opioid drugs such as heroin or fentanyl. The added drugs are meant to enhance the
psychoactive properties, add to its weight, and increase profitability, despite
the increased danger of overdose.
Long term
Heavy, long-term exposure to marijuana may have biologically
based physical, mental, behavioral and social health consequences and may be
"associated with diseases of the liver (particularly with co-existing
hepatitis C), lungs, heart, and vasculature". Mothers who used marijuana during pregnancy
have children with more depression, hyperactivity, and inattention. It is recommended that cannabis use be stopped
before and during pregnancy as it can result in negative outcomes for both the
mother and baby. However, maternal use
of marijuana during pregnancy does not appear to be associated with low birth
weight or early delivery after controlling for tobacco use and other
confounding factors. A 2014 review found
that while cannabis use may be less harmful than alcohol use, the recommendation
to substitute it for problematic drinking was premature without further study. Various surveys conducted between 2015 and
2019 found that many users of cannabis substitute it for prescription drugs
(including opioids), alcohol, and tobacco; most of those who used it in place
of alcohol or tobacco either reduced or stopped their intake of the latter
substances.
A limited number of studies have examined the effects of
cannabis smoking on the respiratory system. Chronic heavy marijuana smoking is associated
with coughing, production of sputum, wheezing, and other symptoms of chronic
bronchitis. The available evidence does
not support a causal relationship between cannabis use and chronic obstructive
pulmonary disease. Short-term use of
cannabis is associated with bronchodilation. Other side effects of cannabis use include
cannabinoid hyperemesis syndrome.
Cannabis smoke contains thousands of organic and inorganic
chemical compounds. This tar is chemically similar to that found in tobacco
smoke, and over fifty known carcinogens have been identified in cannabis smoke,
including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including
benz[a]pyrene. Cannabis smoke is also
inhaled more deeply than tobacco smoke. As of 2015, there is no consensus regarding
whether cannabis smoking is associated with an increased risk of cancer. Light and moderate use of cannabis is not
believed to increase risk of lung or upper airway cancer. Evidence for causing
these cancers is mixed concerning heavy, long-term use. In general there are
far lower risks of pulmonary complications for regular cannabis smokers when
compared with those of tobacco. A 2015
review found an association between cannabis use and the development of
testicular germ cell tumors (TGCTs), particularly non-seminoma TGCTs.[99]
Another 2015 meta-analysis found no association between lifetime cannabis use
and risk of head or neck cancer. Combustion products are not present when using
a vaporizer, consuming THC in pill form, or consuming cannabis foods.
There is concern that cannabis may contribute to
cardiovascular disease, but as of 2018, evidence of this relationship was
unclear. Research in these events is
complicated because cannabis is often used in conjunction with tobacco, and
drugs such as alcohol and cocaine. Smoking cannabis has also been shown to
increase the risk of myocardial infarction by 4.8 times for the 60 minutes
after consumption.
Neuroimaging
Although global abnormalities in white matter and grey
matter are not associated with cannabis abuse, reduced hippocampal volume is
consistently found. Amygdalar abnormalities are sometimes reported, although
findings are inconsistent. Preliminary
evidence suggests that this effect is largely mediated by THC, and that CBD may
even have a protective effect.
Cannabis use is associated with increased recruitment of
task-related areas, such as the dorsolateral prefrontal cortex, which is
thought to reflect compensatory activity due to reduced processing efficiency. Cannabis use is also associated with
downregulation of CB1 receptors. The magnitude of down regulation is associated
with cumulative cannabis exposure, and is reversed after one month of
abstinence. There is limited evidence
that chronic cannabis use can reduce levels of glutamate metabolites in the
human brain.
Cognition
A 2015 meta-analysis found that, although a longer period of
abstinence was associated with smaller magnitudes of impairment, both
retrospective and prospective memory were impaired in cannabis users. The
authors concluded that some, but not all, of the deficits associated with cannabis
use were reversible. A 2012 meta-analysis
found that deficits in most domains of cognition persisted beyond the acute
period of intoxication, but was not evident in studies where subjects were
abstinent for more than 25 days. Few
high quality studies have been performed on the long-term effects of cannabis
on cognition, and the results were generally inconsistent. Furthermore, effect
sizes of significant findings were generally small. One review concluded that, although most
cognitive faculties were unimpaired by cannabis use, residual deficits occurred
in executive functions. Impairments in
executive functioning are most consistently found in older populations, which
may reflect heavier cannabis exposure, or developmental effects associated with
adolescent cannabis use. One review
found three prospective cohort studies that examined the relationship between self-reported
cannabis use and intelligence quotient (IQ). The study following the largest
number of heavy cannabis users reported that IQ declined between ages 7–13 and
age 38. Poorer school performance and increased incidence of leaving school
early were both associated with cannabis use, although a causal relationship
was not established. Cannabis users
demonstrated increased activity in task-related brain regions, consistent with
reduced processing efficiency.
Psychiatric
At an epidemiological level, a dose–response relationship
exists between cannabis use and increased risk of psychosis and earlier onset
of psychosis. Although the
epidemiological association is robust, evidence to prove a causal relationship
is lacking. But a biological causal
pathway is plausible, especially if there is a genetic predisposition to mental
illness, in which case cannabis may be a trigger.
It is not clear whether cannabis use affects the rate of
suicide. Cannabis may also increase the
risk of depression, but insufficient research has been performed to draw a
conclusion. Cannabis use is associated
with increased risk of anxiety disorders, although causality has not been
established.
A February 2019 review found that cannabis use during
adolescence was associated with an increased risk of developing depression and
suicidal behavior later in life, while finding no effect on anxiety.
Reinforcement
disorders
About 9% of those who experiment with marijuana eventually
become dependent according to DSM-IV (1994) criteria. A 2013 review estimates daily use is
associated with a 10-20% rate of dependence.
The highest risk of cannabis dependence is found in those with a history
of poor academic achievement, deviant behavior in childhood and adolescence,
rebelliousness, poor parental relationships, or a parental history of drug and
alcohol problems. Of daily users, about
50% experience withdrawal upon cessation of use (i.e. are dependent),
characterized by sleep problems, irritability, dysphoria, and craving. Cannabis withdrawal is less severe than
withdrawal from alcohol.
According to DSM-V criteria, 9% of those who are exposed to
cannabis develop cannabis use disorder, compared to 20% for cocaine, 23% for
alcohol and 68% for nicotine. Cannabis abuse disorder in the DSM-V involves a
combination of DSM-IV criteria for cannabis abuse and dependence, plus the
addition of craving, minus the criterion related to legal troubles.
Overdose
THC, the principal psychoactive constituent of the cannabis
plant, has low toxicity. The dose of THC needed to kill 50% of tested rodents
is extremely high. Cannabis has not been reported to cause fatal overdose in
humans.
Pharmacology
Mechanism of action
The high lipid-solubility of cannabinoids results in their
persisting in the body for long periods of time. Even after a single administration of THC,
detectable levels of THC can be found in the body for weeks or longer
(depending on the amount administered and the sensitivity of the assessment
method). A number of investigators have
suggested that this is an important factor in marijuana's effects, perhaps
because cannabinoids may accumulate in the body, particularly in the lipid membranes
of neurons.
Not until the end of the 20th century was the specific
mechanism of action of THC at the neuronal level studied. Researchers have subsequently confirmed that
THC exerts its most prominent effects via its actions on two types of
cannabinoid receptors, the CB1 receptor and the CB2 receptor, both of which are
G protein-coupled receptors. The CB1
receptor is found primarily in the brain as well as in some peripheral tissues,
and the CB2 receptor is found primarily in peripheral tissues, but is also expressed
in neuroglial cells. THC appears to
alter mood and cognition through its agonist actions on the CB1 receptors,
which inhibit a secondary messenger system (adenylate cyclase) in a
dose-dependent manner. These actions can be blocked by the selective CB1
receptor antagonist rimonabant (SR141716), which has been shown in clinical
trials to be an effective treatment for smoking cessation, weight loss, and as
a means of controlling or reducing metabolic syndrome risk factors. However, due to the dysphoric effect of CB1
receptor antagonists, this drug is often discontinued due to these side effects.
Via CB1 receptor activation, THC indirectly increases
dopamine release and produces psychotropic effects. Cannabidiol (CBD) also acts as an allosteric
modulator of the μ- and δ-opioid receptors. THC also potentiates the effects of the glycine
receptors. It is unknown if or how these
actions contribute to the effects of cannabis.
Chemistry
Detection in body
fluids
THC and its major (inactive) metabolite, THC-COOH, can be
measured in blood, urine, hair, oral fluid or sweat using chromatographic
techniques as part of a drug use testing program or a forensic investigation of
a traffic or other criminal offense. The
concentrations obtained from such analyses can often be helpful in
distinguishing active use from passive exposure, elapsed time since use, and
extent or duration of use. These tests cannot, however, distinguish authorized
cannabis smoking for medical purposes from unauthorized recreational smoking. Commercial cannabinoid immunoassays, often
employed as the initial screening method when testing physiological specimens
for marijuana presence, have different degrees of cross-reactivity with THC and
its metabolites. Urine contains
predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC.
Blood may contain both substances, with
the relative amounts dependent on the recency and extent of usage.
The Duquenois–Levine test is commonly used as a screening
test in the field, but it cannot definitively confirm the presence of cannabis,
as a large range of substances have been shown to give false positives. Researchers at John Jay College of Criminal
Justice reported that dietary zinc supplements can mask the presence of THC and
other drugs in urine. However, a 2013
study conducted by researchers at the University Of Utah School Of Medicine refutes
the possibility of self-administered zinc producing false-negative urine drug
tests.
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