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Marijuana DrugFacts

Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. The plant contains the mind-altering chemical THC and other similar compounds. Extracts can also be made from the cannabis plant (see “Marijuana Extracts”).

Marijuana is the most commonly used addictive drug after tobacco and alcohol. 1 Its use is widespread among young people. In 2018, more than 11.8 million young adults used marijuana in the past year. 1 According to the Monitoring the Future survey, rates of past year marijuana use among middle and high school students have remained steady, but the number of teens in 8th and 10th grades who say they use it daily has increased. With the growing popularity of vaping devices, teens have started vaping THC (the ingredient in marijuana that produces the high), with nearly 4% of 12th graders saying they vape THC daily. In addition, the number of young people who believe regular marijuana use is risky is decreasing. 2

Legalization of marijuana for medical use or adult recreational use in a growing number of states may affect these views. Read more about marijuana as medicine in our DrugFacts: Marijuana as Medicine.

How do people use marijuana?

People smoke marijuana in hand-rolled cigarettes (joints) or in pipes or water pipes (bongs). They also smoke it in blunts—emptied cigars that have been partly or completely refilled with marijuana. To avoid inhaling smoke, some people are using vaporizers. These devices pull the active ingredients (including THC) from the marijuana and collect their vapor in a storage unit. A person then inhales the vapor, not the smoke. Some vaporizers use a liquid marijuana extract.

People can mix marijuana in food (edibles), such as brownies, cookies, or candy, or brew it as a tea. A newly popular method of use is smoking or eating different forms of THC-rich resins (see “Marijuana Extracts”).

Marijuana Extracts

  • hash oil or honey oil—a gooey liquid
  • wax or budder—a soft solid with a texture like lip balm
  • shatter—a hard, amber-colored solid

These extracts can deliver extremely large amounts of THC to the body, and their use has sent some people to the emergency room. Another danger is in preparing these extracts, which usually involves butane (lighter fluid). A number of people have caused fires and explosions and have been seriously burned from using butane to make extracts at home. 3,4

How does marijuana affect the brain?

Marijuana has both short-and long-term effects on the brain.

Short-Term Effects

When a person smokes marijuana, THC quickly passes from the lungs into the bloodstream. The blood carries the chemical to the brain and other organs throughout the body. The body absorbs THC more slowly when the person eats or drinks it. In that case, they generally feel the effects after 30 minutes to 1 hour.

THC acts on specific brain cell receptors that ordinarily react to natural THC-like chemicals. These natural chemicals play a role in normal brain development and function.

Marijuana over activates parts of the brain that contain the highest number of these receptors. This causes the “high” that people feel. Other effects include:

  • altered senses (for example, seeing brighter colors)
  • altered sense of time
  • changes in mood
  • impaired body movement
  • difficulty with thinking and problem-solving
  • impaired memory
  • hallucinations (when taken in high doses)
  • delusions (when taken in high doses)
  • psychosis (risk is highest with regular use of high potency marijuana)

Long-Term Effects

Marijuana also affects brain development. When people begin using marijuana as teenagers, the drug may impair thinking, memory, and learning functions and affect how the brain builds connections between the areas necessary for these functions. Researchers are still studying how long marijuana’s effects last and whether some changes may be permanent.

For example, a study from New Zealand conducted in part by researchers at Duke University showed that people who started smoking marijuana heavily in their teens and had an ongoing marijuana use disorder lost an average of 8 IQ points between ages 13 and 38. The lost mental abilities didn’t fully return in those who quit marijuana as adults. Those who started smoking marijuana as adults didn’t show notable IQ declines. 5

In another recent study on twins, those who used marijuana showed a significant decline in general knowledge and in verbal ability (equivalent to 4 IQ points) between the preteen years and early adulthood, but no predictable difference was found between twins when one used marijuana and the other didn’t. This suggests that the IQ decline in marijuana users may be caused by something other than marijuana, such as shared familial factors (e.g., genetics, family environment). 6 NIDA’s Adolescent Brain Cognitive Development (ABCD) study, a major longitudinal study, is tracking a large sample of young Americans from late childhood to early adulthood to help clarify how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development. Read more about the ABCD study on our Longitudinal Study of Adolescent Brain and Cognitive Development (ABCD Study) webpage.

A Rise in Marijuana’s THC Levels

The amount of THC in marijuana has been increasing steadily over the past few decades. 7 For a person who’s new to marijuana use, this may mean exposure to higher THC levels with a greater chance of a harmful reaction. Higher THC levels may explain the rise in emergency room visits involving marijuana use.

The popularity of edibles also increases the chance of harmful reactions. Edibles take longer to digest and produce a high. Therefore, people may consume more to feel the effects faster, leading to dangerous results.

Higher THC levels may also mean a greater risk for addiction if people are regularly exposing themselves to high doses.

What are the other health effects of marijuana?

Marijuana use may have a wide range of effects, both physical and mental.

Physical Effects

  • Breathing problems. Marijuana smoke irritates the lungs, and people who smoke marijuana frequently can have the same breathing problems as those who smoke tobacco. These problems include daily cough and phlegm, more frequent lung illness, and a higher risk of lung infections. Researchers so far haven’t found a higher risk for lung cancer in people who smoke marijuana. 8
  • Increased heart rate. Marijuana raises heart rate for up to 3 hours after smoking. This effect may increase the chance of heart attack. Older people and those with heart problems may be at higher risk.
  • Problems with child development during and after pregnancy. One study found that about 20% of pregnant women 24-years-old and younger screened positive for marijuana. However, this study also found that women were about twice as likely to screen positive for marijuana use via a drug test than they state in self-reported measures. 9 This suggests that self-reported rates of marijuana use in pregnant females is not an accurate measure of marijuana use and may be underreporting their use. Additionally, in one study of dispensaries, nonmedical personnel at marijuana dispensaries were recommending marijuana to pregnant women for nausea, but medical experts warn against it. This concerns medical experts because marijuana use during pregnancy is linked to lower birth weight 10 and increased risk of both brain and behavioral problems in babies. If a pregnant woman uses marijuana, the drug may affect certain developing parts of the fetus’s brain. Children exposed to marijuana in the womb have an increased risk of problems with attention, 11 memory, and problem-solving compared to unexposed children. 12 Some research also suggests that moderate amounts of THC are excreted into the breast milk of nursing mothers. 13 With regular use, THC can reach amounts in breast milk that could affect the baby’s developing brain. Other recent research suggests an increased risk of preterm births. 27 More research is needed. Read our Marijuana Research Report for more information about marijuana and pregnancy.
  • Intense nausea and vomiting. Regular, long-term marijuana use can lead to some people to develop Cannabinoid Hyperemesis Syndrome. This causes users to experience regular cycles of severe nausea, vomiting, and dehydration, sometimes requiring emergency medical attention. 14

Reports of Deaths Related to Vaping

The Food and Drug Administration has alerted the public to hundreds of reports of serious lung illnesses associated with vaping, including several deaths. They are working with the Centers for Disease Control and Prevention (CDC) to investigate the cause of these illnesses. Many of the suspect products tested by the states or federal health officials have been identified as vaping products containing THC, the main psychotropic ingredient in marijuana. Some of the patients reported a mixture of THC and nicotine; and some reported vaping nicotine alone. No one substance has been identified in all of the samples tested, and it is unclear if the illnesses are related to one single compound. Until more details are known, FDA officials have warned people not to use any vaping products bought on the street, and they warn against modifying any products purchased in stores. They are also asking people and health professionals to report any adverse effects. The CDC has posted an information page for consumers.

Mental Effects

Long-term marijuana use has been linked to mental illness in some people, such as:

  • temporary hallucinations
  • temporary paranoia
  • worsening symptoms in patients with schizophrenia—a severe mental disorder with symptoms such as hallucinations, paranoia, and disorganized thinking

Marijuana use has also been linked to other mental health problems, such as depression, anxiety, and suicidal thoughts among teens. However, study findings have been mixed.

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Are there effects of inhaling secondhand marijuana smoke?

Failing a Drug Test?

While it’s possible to fail a drug test after inhaling secondhand marijuana smoke, it’s unlikely. Studies show that very little THC is released in the air when a person exhales. Research findings suggest that, unless people are in an enclosed room, breathing in lots of smoke for hours at close range, they aren’t likely to fail a drug test. 15,16 Even if some THC was found in the blood, it wouldn’t be enough to fail a test.

Getting High from Passive Exposure?

Similarly, it’s unlikely that secondhand marijuana smoke would give nonsmoking people in a confined space a high from passive exposure. Studies have shown that people who don’t use marijuana report only mild effects of the drug from a nearby smoker, under extreme conditions (breathing in lots of marijuana smoke for hours in an enclosed room). 17

Other Health Effects?

More research is needed to know if secondhand marijuana smoke has similar health risks as secondhand tobacco smoke. A recent study on rats suggests that secondhand marijuana smoke can do as much damage to the heart and blood vessels as secondhand tobacco smoke. 20 But researchers haven’t fully explored the effect of secondhand marijuana smoke on humans. What they do know is that the toxins and tar found in marijuana smoke could affect vulnerable people, such as children or people with asthma.

How Does Marijuana Affect a Person’s Life?

Compared to those who don’t use marijuana, those who frequently use large amounts report the following:

  • lower life satisfaction
  • poorer mental health
  • poorer physical health
  • more relationship problems

People also report less academic and career success. For example, marijuana use is linked to a higher likelihood of dropping out of school. 18 It’s also linked to more job absences, accidents, and injuries. 19

Is marijuana a gateway drug?

Use of alcohol, tobacco, and marijuana are likely to come before use of other drugs. 21,22 Animal studies have shown that early exposure to addictive substances, including THC, may change how the brain responds to other drugs. For example, when rodents are repeatedly exposed to THC when they’re young, they later show an enhanced response to other addictive substances—such as morphine or nicotine—in the areas of the brain that control reward, and they’re more likely to show addiction-like behaviors. 23,24

Although these findings support the idea of marijuana as a “gateway drug,” the majority of people who use marijuana don’t go on to use other “harder” drugs. It’s also important to note that other factors besides biological mechanisms, such as a person’s social environment, are also critical in a person’s risk for drug use and addiction. Read more about marijuana as a gateway drug in our Marijuana Research Report.

Can a person overdose on marijuana?

An overdose occurs when a person uses enough of the drug to produce life-threatening symptoms or death. There are no reports of teens or adults dying from marijuana alone. However, some people who use marijuana can feel some very uncomfortable side effects, especially when using marijuana products with high THC levels. People have reported symptoms such as anxiety and paranoia, and in rare cases, an extreme psychotic reaction (which can include delusions and hallucinations) that can lead them to seek treatment in an emergency room.

While a psychotic reaction can occur following any method of use, emergency room responders have seen an increasing number of cases involving marijuana edibles. Some people (especially preteens and teens) who know very little about edibles don’t realize that it takes longer for the body to feel marijuana’s effects when eaten rather than smoked. So they consume more of the edible, trying to get high faster or thinking they haven’t taken enough. In addition, some babies and toddlers have been seriously ill after ingesting marijuana or marijuana edibles left around the house.

Is marijuana addictive?

Marijuana use can lead to the development of a substance use disorder, a medical illness in which the person is unable to stop using even though it’s causing health and social problems in their life. Severe substance use disorders are also known as addiction. Research suggests that between 9 and 30 percent of those who use marijuana may develop some degree of marijuana use disorder. 25 People who begin using marijuana before age 18 are four to seven times more likely than adults to develop a marijuana use disorder. 26

Many people who use marijuana long term and are trying to quit report mild withdrawal symptoms that make quitting difficult. These include:

  • grouchiness
  • sleeplessness
  • decreased appetite
  • anxiety
  • cravings

What treatments are available for marijuana use disorder?

No medications are currently available to treat marijuana use disorder, but behavioral support has been shown to be effective. Examples include therapy and motivational incentives (providing rewards to patients who remain drug-free). Continuing research may lead to new medications that help ease withdrawal symptoms, block the effects of marijuana, and prevent relapse.

WHAT IS MARIJUANA?

Marijuana is one of the most abused drugs in the world. There is an ever-growing gap between the latest science about marijuana and the myths surrounding it. Some people think that since it is legal in some places, it must be safe. But your body doesn’t know a legal drug from an illegal drug. It only knows the effect the drug creates once you have taken it. The purpose of this publication is to clear up some of the misunderstandings about pot.

Marijuana comes from the Indian hemp plant, and the part that contains the “drug” is found primarily in the flowers (commonly called the “buds”) and much less in the seeds, leaves, and stems of the plant.

Marijuana, when sold, is a mixture of dried out leaves, stems, flowers and seeds of the hemp plant. It is usually green, brown or gray in color.

Hashish is tan, brown or black resin that is dried and pressed into bars, sticks or balls. When smoked, both marijuana and hashish give off a distinctive, sweet odor.

There are over 400 chemicals in marijuana and hashish.1 The chemical that causes intoxication or the “high” in users is called THC (short for tetrahydrocannabinol). THC creates the mind-altering effects that classifies marijuana as a “drug.”

Plants, like animals, have traits that protect them in the wild. Plants can have colors or patterns that camouflage them from predators, or they can contain poisons or toxins that, when eaten, make animals sick or alter their mental capacity, putting them at risk in the wild. THC is the protective mechanism of the marijuana plant.

Intoxication literally means “to poison by taking a toxic substance into your body.” Any substance that intoxicates causes changes in the body and the mind. It can create addiction or dependence, causing a person to want to take that drug even if it harms him or her.

You may have heard someone say that because marijuana is a plant, it’s “natural” and so it’s harmless. But it’s not. Hemlock, a poisonous plant, is also “natural,” but it can kill.

The other thing to know is that burning dried leaves and buds and inhaling the smoke into your lungs is definitely not “natural” and like smoking cigarettes, can be harmful to your body.

As for the medical uses of marijuana, it contains another chemical called CBD (short for cannabidiol). This is the substance most often associated with creating medical benefits. Unlike THC, CBD does not cause a high.2 Its medical benefits are still being studied, as are methods to breed marijuana plants with high CBD and low THC for medical use.

Marijuana is a drug like alcohol, cocaine, or ecstasy. And like these other drugs, it has side effects that can be harmful.

Cannabinoid Poisoning

Marijuana (leaves, stems, seeds) is derived from the hemp plants Canniabis sativa or Cannabis indica. The term marijuana became popular in the 1930s; it was originally a slang word for the psychoactive part of cannabis smoked by Mexican soldiers. Hemp refers to the roots, stalk, and stems of the plant, which can be used to make rope and twine.

The most potent form of this plant’s extracts is hash oil, a liquid. The dried resins are referred to as “hashish”. The dried flowering tops and leaves can be smoked as a cigarette, known colloquially as a “joint,” in water pipes or “bongs.’ Both the plant material and the hash oil may be inhaled using a vaporizer, which volatilizes the active compounds by heating them without combustion. These forms may also be ingested. This plant has been used for several thousands of years both recreationally and medicinally. See the image below.

More than 400 active compounds have been isolated from the cannabis plant. Sixty active compounds are unique to the plant and are collectively known as cannabinoids. Delta-9-tetrahydrocannanbinol (THC) is the most psychoactive cannabinoid, producing euphoria, relaxation, intensification of ordinary sensory experiences, perceptual alterations, diminished pain, and difficulties with memory and concentration. Cannabidiol, (CBD), is another cannabinoid that acts as an antagonist of the endocannabinoid system. It has been studied as a potential therapeutic agent for severe epilepsy.

Acute cannabis toxicity results in difficulty with coordination, decreased muscle strength, decreased hand steadiness, postural hypotension, lethargy, decreased concentration, slowed reaction time, slurred speech, and conjunctival injection. Large doses of THC may produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation, but most episodes remit rapidly. Long-term users may experience paranoia, panic disorder, fear, or dysphoria.

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The relationship of cannabis to other drugs of abuse is described in two conflicting models. The “gateway” theory of the development of abuse describes the escalation of drug use from adolescence to adulthood. According to this theory, a person will progress from legal drugs, such as alcohol and cigarettes, to illicit drugs, such as marijuana. [1]

In contrast, the common liability to addiction (CLA) model posits that a set of set of factors (which may include psychological characteristics, social environment, and genetic tendencies) is associated with risk for all types of substance use disorders. In this model, which is supported by increasing evidence, a sequence of use can start with any substance, legal or illegal. [2]

Pathophysiology

The most potent cannabinoid, THC, was isolated in the 1960s. Nearly 3 decades later, in the early 1990s, the specific cannabinoid receptors were discovered, CB1 (or Cnr1) and CB2 (or Cnr2).

The CB1 receptors are predominantly located in the brain, with a wide distribution. The highest densities are found in the frontal cerebral cortex (higher functioning), hippocampus (memory, cognition), basal ganglion and cerebellum (movement), and striatum (brain reward). Other brain regions in which the CB1 receptors are found include areas responsible for anxiety, pain, sensory perception, motor coordination, and endocrine function. This distribution is consistent with the clinical effects elicited by cannabinoids.

The CB2 receptor, on the other hand, is located peripherally. Specifically, it is involved in the immune system (splenic macrophages, T and B lymphocytes), peripheral nerves, and the vas deferens.

Both the CB1 and CB2 receptors inhibit adenylate cyclase and stimulate potassium channels. As a result, the CB1 receptors inhibit the release of several neurotransmitters, including acetylcholine, glutamate, norepinephrine, dopamine, serotonin, and gamma–aminobutyric acid (GABA). CB2 receptor signaling is involved in immune and inflammatory reactions.

Potency

In recent decades, the average THC potency of cannabis has increased due to more sophisticated plant breeding and cultivation. [3] In the 1970s, the average marijuana cigarette contained approximately 10 mg of THC. Currently, a comparable cigarette contains 60-150 mg. Because the effects of THC are dose dependent, modern cannabis users may experience greater morbidity than their predecessors.

Cannabis is available in several forms. Marijuana is a combination of the cannabis flowering tops and leaves. The THC content is 0.5-5%. Two preparations are possible:

Bhang – Dried leaves and tops

Ganja – Leaves and tops with a higher resin content, which results in greater potency

Hashish is dried resin collected from the flowering tops. The THC concentration is 2-20%. Hash oil is a liquid extract; it contains 15% THC.

Sinsemilla is unpollinated flowering tops from the female plant. THC content is as high as 20%. Dutch hemp (Netherweed) has a THC concentration as high as 20%.

Absorption

The route of administration determines the absorption of the cannabis product, as follows:

Smoking – Onset of action is rapid (within minutes); it results in 10-35% absorption of the available THC; peak plasma concentrations occur within 8 minutes.

Ingestion – Onset occurs within 1-3 hours (unpredictable); 5-20% is absorbed, due to stomach acid content and metabolism; peak plasma levels occur 2-6 hours after ingestion.

Behavioral effects

THC most commonly produces euphoria, or a “high,” including feelings of intoxication and detachment, relaxation, altered perception of time and distance, intensified sensory experiences, laughter, talkativeness, decreased anxiety, decreased alertness, and depression. These effects depend on the dose, expectations of the user, mode of administration, social environment, and personality.

THC triggers dopaminergic neurons in the ventral tegmental area of the brain, a region known to mediate the reinforcing (rewarding) effects. This dopaminergic drive is thought to underlie the reinforcing and addicting properties of this drug.

Dysphoric reactions to cannabis are not uncommon, especially in naive users. Reactions can include severe anxiety or panic, unpleasant somatic sensations, delirium, mania, or paranoia. Anxiety and/or panic are the most common reactions; they are of sudden onset during or shortly after smoking, or they can appear more gradually 1-2 hours after an oral dose. These effects often occur in those who unwittingly consume marijuana (eg. those ingesting baked goods that they did not know contained marijuana). Cannabidiol may mitigate the adverse psychiatric effects of THC. These anxiety/panic reactions usually resolve without intervention.

Although flashbacks, in which the original drug experience (usually dysphoria) is relived weeks or months after use., have been reported, they are uncommon.

Mental effects

Short-term memory is impaired even after small doses in both naive and experienced users. The deficits appear to be in acquisition of memory, which may result from an attentional deficit, combined with the inability to filter out irrelevant information and the intrusion of extraneous thoughts.

Chronic use can be associated with subtle impairment in cognitive function, which is dependent on dose and duration of use. At present, most of the available data indicate that these cognitive deficits are reversible after more than a week of abstinence.

Immune system effects

Based on extrapolation from in vitro data, cannabis use may impair the immune system’s ability to fight off microbial and viral infection. In a dose-dependent fashion, lung macrophage functions, including phagocytosis, migration, and cytokine production, appear to be compromised by cannabis use in vitro. Although cannabinoid receptors are found on human T and B lymphocytes, to date, no conclusive effects have been found on the use of cannabis and the clinical effects related to the presence of these receptors.

Cardiovascular effects

These include the following:

Naive users may experience a sudden 20-100% rise in heart rate, lasting up to 2-3 hours

Peripheral vasodilatation causes postural hypotension, which may lead to dizziness or syncope

Cardiac output increases by as much as 30%, and cardiac oxygen demand is also increased; tolerance to these effects can develop within a few days of use

Naive users can experience angina; in addition, users with preexisting coronary artery disease or cerebrovascular disease may experience myocardial infarctions, congestive heart failure, and strokes

Respiratory effects

Transient bronchodilatation may occur after an acute exposure. With chronic heavy smoking, users experience increased cough, sputum production, and wheezing. These complaints are augmented by concurrent tobacco use. One study cites that the rate of decline of respiratory function in an 8-year period was greater among marijuana smokers than among tobacco smokers.

Aside from nicotine, marijuana cigarettes contain some of the same components as tobacco smoke, including bronchial irritants, tumor initiators (mutagens), and tumor promoters. The amount of tar in a marijuana cigarette is 3 times the amount in a tobacco cigarette when smoked, with one-third greater deposition in the respiratory tract.

Chronic cannabis use is associated with bronchitis, squamous metaplasia of the tracheobronchial epithelium, and emphysema. These problems have been reported more frequently in cannabis-only users than in tobacco-only users.

Several case reports strongly suggest a link between cannabis smoking and cancer of the aerodigestive system, including the oropharynx and tongue, nasal and sinus epithelium, and larynx.

Most illegally obtained marijuana is contaminated with Aspergillus species, which can cause invasive pulmonary aspergillosis in immunocompromised users.

Reproductive effects

These include the following:

High-dose THC in animals causes a reversible drop in testosterone levels, decreased sperm production, and compromised sperm motility and viability.

THC alters the normal ovulatory cycle by decreasing follicle stimulating hormone, luteinizing hormone, and prolactin and impairing sex hormone secretion. [4]

THC crosses the placenta and accumulates in breast milk.

THC impairs placental development and homeostasis, fetal nourishment and gas exchange. For this reason, it is implicated in low birth weight, growth restriction, pre-eclampsia, spontaneous miscarriage, and stillbirth. Human studies show mixed results, largely from limitations of self-reporting and testing marijuana use. [4, 5]

A growing body of evidence suggests permanent, though subtle, effects on memory, informational processing, and executive functions in the offspring of women who use cannabis during pregnancy.

Children younger than 1 week of age born to mothers who used cannabis during pregnancy had increased incidence of tremors and staring. Children of chronic users (>5 joints per wk) were found to have lower verbal and memory scores at age 2 years.

Three studies have demonstrated a possible increased risk of nonlymphoblastic leukemia, rhabdomyosarcoma, and astrocytoma in children whose mothers reported using cannabis during their pregnancies.

Psychosis association

Large doses of THC may produce confusion, amnesia, delusions, hallucinations, anxiety, and agitation. Most episodes remit rapidly.

A clear relationship exists between long-term cannabis use and mental health problems, however, it is unclear whether the relationship is causative. [6] Substance-abusing adolescents commonly suffer one or more comorbid health or behavioral problems. Several studies have demonstrated marijuana abuse to coexist with attention deficit hyperactivity disorder, other learning disabilities, depression, and anxiety. Cohort and well-designed cross-sectional studies suggest a modest association between early, regular, or heavy cannabis use and depression. [7]

An association exists between cannabis use and schizophrenia. A prospective study of 50,000 Swedish conscripts found a dose-response relationship between the frequency of cannabis use by age 18 and the risk of a diagnosis of schizophrenia over the subsequent 15 years. [8] Five prospective studies with well-defined samples looked at cannabis use and psychosis and concluded an overall 2-fold increase in the relative risk for developing schizophrenia. Yet, cannabis use appears to be neither necessary nor sufficient to cause schizophrenia. Among people who already have schizophrenia, cannabis use is predicted to worsen psychotic symptoms. Strains of cannabis that are high in CBD may be less likely to trigger psychotic symptoms.

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Metabolism and elimination

THC is metabolized via the hepatic cytochrome P450 (CYP) system. THC is metabolized into an active compound, 11-hydroxy-THC (11-OH-THC), which is further metabolized into inactive forms.

The elimination half-life of THC can range from 2-57 hours following intravenous use and inhalation. The half-life of 11-OH-THC, the active metabolite of THC, is 12-36 hours. Intravenous use or inhalation results in 15% excretion in the urine and 25-35% in the feces. Within 5 days, nearly 90% of THC is eliminated from the body.

The duration of acute clinical effects is mediated by drug redistribution into body fat stores rather than metabolism or elimination.

Tolerance

Repeated use over days to weeks induces considerable tolerance to the behavioral and psychological effects of cannabis. Several studies have noted partial tolerance to its effect on mood, memory, motor coordination, sleep, brain wave activity, blood pressure, temperature, and nausea. The rate of tolerance depends on the dose and frequency of administration. The casual cannabis user experiences more impairment in cognitive and psychomotor function to a particular acute dose than heavier, chronic users. The desired recreational high from cannabis also diminishes with use, prompting many users to escalate the dose.

Pharmacologically, chronic use results in the downregulation of the CB1 receptor in several regions of the rat brain. No correlations have been made in human physiology.

Toxicity

Acute cannabis toxicity results in the following:

Although acute toxicity is benign in the average adult, the same cannot always be said for children. In a systematic review of unintentional cannabis ingestion in children under 12 years of age, the most common presenting signs and findings were lethargy, hypotonia, hypoventilation, tachycardia, ataxia, and mydriasis. Vomiting and seizures have also been reported, as well as paradoxical hyperactivity and irritability. Treatment is largely supportive, including intubation in some instances. Having a clinical suspicion for cannabis toxicity is important as these patients may otherwise undergo lengthy and invasive evaluations for their symptoms. [9]

Unintentional ingestion in children has been on the rise with the increase in availability afforded by state de-criminalization. A majority of these cases are from unintentional ingestion of edibles, many of which have colorful packaging and are made to look like cookies and candies. Nationwide, children’s exposure to cannabis products rose 148% from 2006 to 2013, and in states allowing medical cannabis, that figure increased by 610%

Adverse reactions

Chronic users may experience paranoia, panic disorder, fear, or dysphoria. Transient psychotic episodes may also occur with cannabis use. These psychiatric effects may be less likely to occur with strains that contain higher concentrations of CBD.

Ventricular tachycardia is also reported in association with use of this drug, but is unclear whether the association is causative.

Dependence and withdrawal

Nearly 7-10% of regular users become behaviorally and physically dependent on cannabis. Furthermore, early onset of use and daily/weekly use correlates with future dependence. According to the National Institute on Drug Abuse (NIDA), 100,000 people are treated annually for primary (may be self-perceived) marijuana abuse. [10]

Animal studies demonstrate withdrawal symptoms with use of CB1 receptor antagonists. However, in humans, the withdrawal syndrome is not well characterized. Classic manifestations—which may develop upon withdrawal after as little as 1 week of daily use—include the following [11] :

Epidemiology

Frequency

United States

Marijuana became the major drug of abuse in the 1960s. Its use peaked in the late 1970s. According to the NIDA-funded Monitoring the Future survey, the peak year of use occurred in 1979, with 60.4% of 12th-grade students having used cannabis in their lifetimes, 50.8% in the preceding year, and more than 10.3% on a daily basis. Cannabis use began a continuous decline, with the lowest use occurring in 1992. At that time, 32.6% of 12th-grade students reported ever using cannabis, 21.9% reported use in the preceding year, and 1.9% reported using on a daily basis. The decline in use was attributed to perceived risk and to personal disapproval of drugs.

From 1992-1997, marijuana use increased dramatically and then plateaued in the last 2 years. In 1999, 22% of 8th-grade students and 49.7% of 12th-grade students reported ever using cannabis. Daily use was 1.4% and 6%, respectively. [12]

Since the turn of the 21st century, marijuana use by middle and high school students has fluctuated. In 2014, 15.6% of 8th-grade students and 44.4% of 12th-grade students reported ever using cannabis, and daily use was 1.0% and 5.8%, respectively. [12]

In 2019, there was a significant increase in daily use in the younger grades. In addition, teens’ perceptions of the risks of marijuana use have steadily declined over the past decade. In 2019, 11.8% of 8th graders reported marijuana use in the past year and 6.6% in the past month. Among 10th graders, 28.8% had used marijuana in the past year and 18.4% in the past month. Rates of use among 12th graders were highest with 35.7% having used marijuana during the year prior to the survey and 22.3% in the past month; 6.4% said they used marijuana daily or near-daily. [13]

The Drug Abuse Warning Network (DAWN) reported 21% increase from 2009 to 2011 in medical emergencies possibly related to marijuana use. DAWN estimated that in 2011, nearly 456,000 drug-related emergency department (ED) visits in which marijuana use was mentioned in the medical record occurred in the United States; however, mentions of marijuana in medical records do not necessarily indicate that these emergencies were directly related to marijuana intoxication. Marijuana accounted for 146.2 visits per 100,000 population. [13, 14] The increase in ED visits may be due to an increase in the use of marijuana, an increase in the potency of marijuana (ie, amount of THC it contains), or to some other factors

International

According to the United Nations, an estimated 192 million people used cannabis in 2018, making it the most used drug globally. In comparison, 58 million people used opioids in 2018. [15] European monitoring noted in a 2020 report that lifetime use among 15-64 year olds was 27.2%. Among 15-34 year olds, use in the past year was 15%. [16]

Mortality/Morbidity

In March of 2014, ingested marijuana was thought to be a chief contributing factor in the death of a 19-year-old man in Colorado. According to the investigation, the marijuana-naive patient bought a cookie containing 65 mg of THC in 6.5 servings. He reportedly ate one serving and, upon not feeling any effects 30-60 minutes later, ate the remainder of the cookie. Over the next 2.5 hours, the patient became erratic, hostile, and jumped from a 4th floor balcony, later dying from his injuries. At autopsy, only cannabinoids were found in his system. [17]

This case report highlights the delay and variability in absorption rates and intoxication with ingesting THC products, taking 1-2 hours to peak vs 5-10 minutes when smoked.

Race-, Sex-, and Age-related Demographics

No differences are reported in patterns of cannabis use according to racial or ethnic background. Little information is available regarding gender differences in cannabis use. Of drug-related emergency department visits in 2011 in which the medical record mentioned marijuana use, about two-thirds of patients were male and 13% were 12-17 years old.

Most cannabis users begin use when younger than 20 years of age, with the peak incidence of onset between 16 and 18 years. Most stop using marijuana by their mid to late 20s. Only about 10% become daily users.

Prognosis

THC has a long half-life and widespread neurocognitive effects. However, Hooper et al found that adolescents with cannabis use disorder who were in full remission after successful first treatment (n=33) showed no difference in intellectual, neurocognitive, and academic achievement compared with healthy adolescents (n=43) or controls who had psychiatric disorders without a history of substance use disorder (n=37). These researchers concluded that adolescents with cannabis use disorder may not be vulnerable to THC-related neuropsychological deficits once they achieve remission from all drugs for at least 30 days. [18]

Some evidence suggests that heavy marijuana use during adolescence may lead to increased health problems in later adulthood. These may include both physical disorders (eg, respiratory illness) and mental disorders. For example, Meier et al reported that people who started smoking marijuana heavily in their teens and had an ongoing cannabis use disorder lost an average of 8 IQ points between ages 13 and 38, and that those who quit marijuana as adults did not fully recover those losses. [19]

On the other hand, the Pittsburgh Youth Study, which tracked 408 boys (54% black, 42% white) from adolescence into their mid-30s found no differences in any of the mental or physical health outcomes measured, regardless of the amount or frequency of marijuana used during adolescence. The mental health outcomes included anxiety and mood and psychotic disorders. The physical health outcomes included asthma, allergies, headaches, high blood pressure, limitations in physical activities, physical injuries, and concussions. [20, 21]

These researchers hypothesized that the overall pattern of use between adolescence and adulthood, which their study focused on, may be a less important than other factors (eg, cumulative tetrahydrocannabinol exposure, age of initiation of use, or use at a particular age) for predicting negative health outcomes. [20, 21]