9 Cannabis Dependence Key Chapter Points • Cannabis is a genus of flowering plant that includes three species—C. sativa, C. indica, and C. ruderalis. • To produce a mood-altering effect, cannabis is used in three main forms: (1) marijuana, (2) hashish, and (3) hash oil. • Long-term health risks of marijuana use include immune system effects, cardiovascular effects, respiratory effects, reproductive effects, behavioral effects, and cancer. • Three medicinal products are derived from marijuana: dronabinol, nabilone, and nabiximols. • Depending on the state, patients may qualify for treatment with medical marijuana if they meet certain requirements. • Cannabis indica, or “ganja,” is smoked as a form of marijuana. • The synthetic cannabinoids, known as Spice or K2, are lab-synthesized liquid chemicals that mimic the effect of THC. • Hashish, or hash, is an extracted product from the cannabis plant that is composed of compressed or purified preparations of glandular resin hairs called trichomes. • Hash oil is a resinous matrix produced by a solvent extraction of cannabis. • Repeated use over days to weeks induces considerable tolerance to the behavioral and psychological effects of cannabis. • Thirty percent of those who use marijuana may develop some degree of marijuana use disorder. • Acute marijuana toxicity (bad trip) results in anxiety, agitation, difficulty with coordination, decreased muscle strength, postural hypotension, headache, sweating, and lethargy. Cannabis is a genus of flowering plant that includes three species—C. sativa, C. indica, and C. ruderalis. Cannabis sativa and Cannabis indica products are used recreationally and as a source of fiber. Cannabis ruderalis is a species of Cannabis originating in Central Russia. It is less common than the other species of Cannabis. It has a lower tetrahydrocannabinol (THC) content than the other two, so it is rarely grown for recreational use. Its much shorter stature (about 2 ft) limits its application for hemp production. It is used traditionally in Russian and Mongolian folk medicine, especially for the treatment of depression . Cannabinoids are organic substances present in the cannabis plant. More than 60 have been identified. The cannabis plant grows wild in many of the tropical and temperate areas of the world. It can be grown in almost any climate and is increasingly cultivated indoors. It consists of a male plant and a female plant. The male plant produces pollen, which pollinates the flowers of the female plant (Fig. 9.1). Once pollinated, the © Springer International Publishing AG 2018 H.T. Milhorn, Substance Use Disorders, DOI 10.1007/978-3-319-63040-3_9 131 9 Cannabis Dependence 132 Table 9.1 Prevalence of marijuana plus hashish use in 2015 for various age ranges (%) (From ) Lifetime Past year Past month Ages 12–17 15.70 12.60 7.00 Ages 18–25 52.70 32.20 19.80 Age 26 and older 46.00 10.40 6.50 resemble well-known foods. Some of the names of these products are Rastateers, KeefKat, Munchy Way, and Rasta Reese’s . Prevalence of Use Fig. 9.1 Female Cannabis sativa plant female plant produces seeds. If the female plant is not pollinated, the buds and flowers continue to develop and produce tetrahydrocannabinol (THC), which is the major psychoactive substance in the cannabis plant . There were at least 2000 medicinal cannabis products produced by over 280 manufacturers at the turn of the century. Cannabis products were on the shelf of every pharmacy and were widely prescribed until medical use was prohibited in 1937 by the Marijuana Tax Act . The Controlled Substances Act of 1970 classified marijuana, along with heroin and LSD, as a Schedule I drug. Medical marijuana was legalized in California in 1996, and several other states have followed suit. In addition, several states, including California, have made recreational marijuana legal. Such laws are in direct disagreement with federal law prohibiting the possession of marijuana . In states where marijuana has become legalized, more and more marijuana “edibles” are seen in retail establishments. Marijuana products include baked goods and candy that closely Table 9.1 gives the prevalence of marijuana plus hashish for various age ranges . To produce a mood-altering effect, cannabis is used in three main forms: (1) marijuana, (2) hashish, and (3) hash oil. Marijuana Marijuana is the most commonly used illicit drug in the United States. It is made from the dried flowers and leaves of the unpollinated female Cannabis sativa plant. It is the least potent of the three cannabis mood-altering products. Marijuana is usually smoked in hand-rolled cigarettes (joints) or in special water pipes (bongs). Marijuana can also be mixed into food or brewed as tea and ingested. It also has been used as cigars called “blunts.” It also may come in a “wax” form that resembles lip balm. It can be eaten or smoked . revalence of Use P Marijuana use by 8th, 10th, and 12th graders have held steady in the past few years following several years of increase in the previous decade. In 2015, 11.8% of 8th graders reported marijuana use in the past year, and 6.5% were current users. Among 10th graders, 25.4% had used marijuana in the past year and 14.8% were current users. Among 12th graders, 34.9% had used marijuana during the prior year and 21.3% were current Prevalence of Use 133 users. Six percent said they used marijuana daily or nearly daily. However, teens’ perceptions of the risks of marijuana use have steadily declined over the past decade, possibly related to increasing public debate about legalizing or loosening restrictions on marijuana for medicinal and recreational use . Street Names Because marijuana is such a popular drug, it has a large number of street names. Some of the more popular ones are: Bud Blunt Chronic Dope Ganja Sinsemilla Grass Green Hash Herb Joint Loud Mary Jane MJ Pot Reefer Skunk Smoke Trees Weed Marijuana is commonly laced with other psychoactive substances. Some of these street names are: With tobacco With PCP With formaldehyde (embalming fluid) With cocaine HCl With crack cocaine With heroin Kiff Chips, donk, illies, illing, lovelies, love leaf, killer supergrass, wack, woolies, zoom, fry, frios, yerba mala Boat, loveboat, amp, drank, clickem, ill, illy, wet, water-water Chronic, banano, caviar, champagne, cocoa puff, gremmies, lace Chronic, bazooka, cocktail, crack back, daddy, dirty, geek, gimmie, juice joint, liprimo, oolies, p-dogs, torpedo, turbo, woolies A-bomb Pharmacology Pharmacodynamics Cannabinoids exert their effect by interaction with specific endogenous neuronal cannabinoid receptors that are termed CB1 receptors. These receptors have been found in the brain and peripheral nerves. A second cannabinoid receptor, the CB2 receptor, is present in macrophages in the spleen and in other immune cells. The distribution of CB1 receptors includes the cerebral cortex, limbic areas (including hip- pocampus and amygdala), basal ganglia, cerebellum, thalamus, and brain stem. The endogenous substance, named anandamide after the Sanskrit word for bliss (ananda), has a high affinity for CB1 receptors and has most of the same actions of THC. THC has been shown to increase the release of dopamine from the nucleus accumbens and prefrontal cortex. This effect may be the basis of cannabis’s reinforcing properties and the cause of its recreational use. It appears that there may be a whole system of multiple cannabinoid receptors and anandamiderelated substances. The sensations of slight euphoria, relaxation, and amplified auditory and visual perceptions produced by marijuana are due almost entirely to its effect on the cannabinoid receptors in the brain . Pharmacokinetics In the United States, the content of marijuana was originally 1–2%. Selective breeding now yields marijuana with much higher THC concentrations. The average THC concentration in 2008 was 10.1%. The most potent marijuana is known as sinsemilla, with a THC concentration that may be 14% or higher. To obtain maximal effect from marijuana, users must master a smoking technique that is different from that used to smoke regular cigarettes. Users inhale smoke as deeply into their lungs as possible and then hold their breath for 20–30 s to extract as much of the THC from the smoke as possible. Various methods of smoking marijuana include rolling it into “joints” (marijuana cigarettes) or “blunts” (marijuana rolled into the leaf wrap of a hollowed-out cigar). Smoking it through a pipe, through a water pipe (“bong”), or a vaporizer are also common methods. While marijuana is most often smoked, it can also be ingested. The effects of smoking are typically felt within a few minutes and can peak in 10–30 min. Short-term effects from smoking generally wear off within 2–3 h. About 50% of the THC in a joint of herbal cannabis is inhaled; nearly all of this is absorbed through the lungs, rapidly enters the bloodstream, and reaches the brain within 134 seconds. Effects are perceptible within seconds and fully apparent in a few minutes. When marijuana is ingested, its onset of action is within 30–60 min, and peak effects may not occur until the second or third hour. After oral ingestion, blood concentrations reached are 25–30% of those obtained by smoking the drug, partly because of first-pass metabolism in the liver. THC is rapidly converted into its active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol, which produces effects identical to the parent compound. The active metabolite is then converted to inactive metabolites and excreted in the feces (65%) and urine (25%). Very little unmetabolized THC is found in the urine. Once absorbed, THC and other cannabinoids are rapidly distributed to all other tissues at rates dependent on the blood flow. Because they are extremely lipid soluble, cannabinoids accumulate in fatty tissues, reaching peak concentrations in 4–5 days. They are then slowly released back into other body compartments, including the brain. Because of the sequestration in fat, the tissue elimination half-life of THC is about 7 days, and complete elimination of a single dose may take up to 30 days. With repeated dosage, high levels of cannabinoids can accumulate in the body [9, 10]. Cannabis short-term effects include a burning sensation in the mouth, a dry throat, and bloodshot eyes. It produces euphoria and altered senses, such as seeing brighter colors. It produces muscle relaxation, slowed reflexes, an altered sense of time, and altered cognitive function. It decreases muscle coordination, causes a loss of short-term and working memory, increases heart rate, and increases appetite causing the “munchies.” It negatively affects perception and judgment; increases chances of risky behavior, such as unprotected sex and trying more dangerous drugs; and creates difficulty problem solving. Short-term pharmacological effects of marijuana are given in Table 9.2 . Cardiovascular effects of marijuana include increased heart rate, increased systolic pressure, decreased blood pressure while erect, and a marked red- 9 Cannabis Dependence Table 9.2 Short-term pharmacological effects of marijuana (From Milhorn . Approved with permission, Springer) Central nervous system Altered perception of time (time seems to pass more slowly) Antiemetic effect Anxiety Balance difficulty Coordination problems Decreased reaction time Depersonalization Difficulty carrying out tasks requiring multiple mental steps to reach a goal Euphoria Feelings of relaxation and sleepiness Impaired perception, attention, and information processing Impaired psychomotor sensation Increased hunger Increased risk of contracting sexually transmitted diseases Increased sense of well-being Keener sense of hearing Paranoia Psychosis Sense of detachment Senses of touch, taste, and smell seem to be enhanced Short-term memory impairment Subtle visual and auditory stimuli may take on novel characteristics Vivid visual imagery Peripheral effects Increased heart rate Increased systolic pressure in the supine position Decreased blood pressure in the erect position Marked reddening of conjunctiva Plasma volume expansion Increased body temperature due to impaired sweating Decreased intraocular pressure Dry mouth and throat Muscle weakness Tremors Unsteadiness Increased deep tendon reflexes dening of the conjunctiva due to blood vessel dilation. Sodium retention and expanded plasma volume occur. Muscle weakness, tremors, unsteadiness, and increased deep tendon reflexes occur. Intraocular pressure is decreased and an antiemetic effect occurs. Marijuana is known to produce flashbacks in previous users of lysergic acid diethylamide (LSD). Prevalence of Use Drugs that sometimes are mixed with marijuana to increase its effects include phencyclidine (PCP), opium, formaldehyde, and Raid insect spray . 135 believed to increase the risk of bleeding (Ginkgo biloba, garlic, saw palmetto) [13, 14]. Health Risks Interactions with Other Drugs Marijuana may increase the risk of bleeding when taken with drugs such as aspirin, warfarin (Coumadin), and heparin, antiplatelet drugs such as clopidogrel (Plavix), and nonsteroidal antiinflammatory drugs such as ibuprofen (Motrin, Advil) or naproxen (Naprosyn, Aleve). Marijuana may increase blood sugar levels by interacting with medications that are used for blood sugar control. Medication adjustments may be necessary. Marijuana may cause low blood pressure, so caution is advised in people taking medications that lower blood pressure. Marijuana may interfere with the way the body processes certain drugs using the liver’s cytochrome P450 enzyme system. As a result, the levels of these drugs may increase in the blood and may cause increased effects or potentially serious adverse reactions. Marijuana may increase the amount of drowsiness caused by benzodiazepines such as lorazepam (Ativan) or diazepam (Valium), barbiturates such as phenobarbital, narcotics such as hydrocodone, some antidepressants, and alcohol. In addition, marijuana may adversely affect the immune system. Marijuana may interfere with agents that treat lung disorders, heart disorders, nausea or vomiting, nervous system disorders, psychiatric disorders, HIV, skin disorders, stomach disorders, cancer, and seizures. Moderate interaction occurs with disulfiram (Antabuse), causing agitation, trouble sleeping, and irritability. Fluoxetine (Prozac) also interacts with marijuana. Taking marijuana with fluoxetine may cause a hypomanic state, consisting of irritability, nervousness, jitteriness, and excitability. Marijuana may increase the risk of bleeding when taken with herbs and supplements that are Long-term health risks of marijuana use include immune system effects, cardiovascular effects, respiratory effects, reproductive effects, behavioral effects, and cancer. Marijuana use also puts users at risk for various types of accidents. Coinciding with the increasing rates of cannabis use due to medical marijuana has been the recognition of a new clinical condition known as cannabinoid hyperemesis syndrome. This syndrome is characterized by cyclic episodes of nausea and vomiting and abdominal pain. Despite the well-established antiemetic properties of marijuana, there is increasing evidence of its paradoxical effects on the gastrointestinal tract and central nervous system. The clinical course of cannabinoid hyperemesis syndrome consists of three phases: (1) prodromal, (2) hyperemetic, and (3) recovery phase. The hyperemetic phase usually ceases within 48 h after cessation of use, and treatment involves supportive therapy with fluid resuscitation and antiemetic medications. Patients often demonstrate the learned behavior of frequent hot bathing, which produces temporary cessation of nausea, vomiting, and abdominal pain [15, 16]. Marijuana affects the immune, cardiovascular, respiratory, and reproductive systems. It also has psychiatric/behavioral effects and can cause cancer. Motor vehicle accidents occur under the influence of marijuana . Immune System Long-term cannabis use can impair the immune system’s ability to fight off microbial and viral infections. Both animal and human studies have shown that marijuana impairs the ability of T-cells in the lungs’ immune defense system to fight off some infections . Cardiovascular System Users with preexisting coronary artery disease or cerebrovascular disease may experience 136 myocardial infarctions, congestive heart failure, or stroke. Peripheral vasodilatation causes postural hypotension, which may lead to dizziness or syncope. Cannabis arteritis is a very rare peripheral vascular disease similar to Buerger’s disease . Respiratory System The amount of tar in a marijuana cigarette is three times the amount in a tobacco cigarette, with one-third greater deposition in the respiratory tract. Chronic cannabis use is associated with bronchoconstriction, pharyngitis, sinusitis, bronchitis, squamous metaplasia of the tracheobronchial epithelium, and emphysema. Several case reports suggest a link between cannabis smoking and cancer of the oropharynx and tongue, nasal and sinus epithelium, and larynx. Some illegally obtained marijuana is contaminated with Aspergillus species, which can cause invasive pulmonary aspergillosis in immunocompromised users. Smoking marijuana may increase the risk of opportunistic infections among those who are HIV positive, although it does not seem to effect the development of AIDS or lower white cell counts [18, 19]. Reproductive System High doses of THC cause a drop in testosterone level, decreased sperm production, and compromised sperm motility and viability. THC alters the normal ovulatory cycle by decreasing follicle-stimulating hormone, luteinizing hormone, and prolactin secretion. It crosses the placenta and impairs placental development, fetal nourishment, and placental gas exchange. For this reason, it is implicated in low birth weight, growth restriction, preeclampsia, spontaneous miscarriage, and stillbirth. It also accumulates in breast milk. Children of chronic users (greater than five joints per week) were found to have lower verbal and memory scores at age 2 years . A possible increased risk of nonlymphoblastic leukemia, rhabdomyosarcoma, and astrocytoma 9 Cannabis Dependence exists in children whose mothers use cannabis during their pregnancies. Psychiatric/Behavioral Long-term use of marijuana also can lead to a series of attitude and personality changes known as “amotivational syndrome.” This syndrome is characterized by a diminished ability to carry out long-term plans, a sense of apathy, decreased attention to appearance and behavior, and decreased ability to concentrate for long periods of time. These changes can also include poor performance in school. Long-term marijuana use has been shown to cause a decline in IQ of up to eight points. Marijuana use can cause relationship problems and antisocial behavior, such as lying and stealing money. It leads to lower life satisfaction, financial difficulties, and a greater chance of being unemployed. Marijuana use has been shown to increase the risk of schizophrenia two fold in vulnerable individuals . Cancer Marijuana smoke contains some of the same cancer-causing compounds as tobacco, usually in higher concentrations. Someone who smokes five joints per day may be taking in as many cancercausing chemicals as someone who smokes a full pack of cigarettes every day. Cancer of the respiratory tract and lungs may be promoted by marijuana smoke, since it contains irritants and carcinogens. Tobacco smoke and marijuana smoke may work together to change the tissues that line the respiratory tract. Marijuana smoking could contribute to early development of head and neck cancer in some people. Smoking marijuana has been linked to testicular cancer . Accidents Marijuana is the most common illegal drug reported in motor vehicle accidents. Fatal crashes involving marijuana use tripled during the previous decade. Marijuana also has been involved in other types of accidents [18, 21]. Synthetic Cannabinoids 137 Medical Use Cannabis indica ronabinol, Nabilone, and Nabiximols D Three medicinal products are derived from marijuana: dronabinol, nabilone, and nabiximols. The synthetic THC product dronabinol (Marinol) is for the control of nausea and vomiting caused by chemotherapeutic agents and for stimulating the appetite of AIDS patients. A DEA Schedule II drug, dronabinol, is supplied as a 2.5, 5, and 10 mg capsule. Originally cultivated in the United States, Cannabis indica, or “ganja,” is smoked as a form of marijuana. C. indica plants are short, dense plants, with broader, darker green leaves than the Cannabis sativa plant. The plant is commonly referred to as “skunk” (for the pungent odor it produces while growing), northern lights, early girl, and many other names. Nabilone (Cesamet) is used to treat severe nausea and vomiting caused by chemotherapy. Nabilone is a man-made drug similar to the natural substances found in marijuana. It works by decreasing the signals in the brain that lead to nausea and vomiting. Nabiximols (Sativex) is used to treat spasticity caused by multiple sclerosis. It is composed of two compounds found in marijuana—THC and cannabidiol (CBD)—which isn’t psychoactive. The drug, delivered through a vaporizer, is approved in 25 countries but isn’t available in the United States . Medical Marijuana Although several states have decriminalized marijuana, it remains an illegal substance under federal law. Depending on the state, patients may qualify for treatment with medical marijuana if they meet certain requirements and have one of the following conditions : • • • • • • • • • • Amyotrophic lateral sclerosis (ALS) Anorexia due to HIV/AIDS Chronic pain Crohn’s disease Epilepsy or seizures Glaucoma, although the American Academy of Ophthalmology doesn’t recommend medical marijuana Multiple sclerosis or severe muscle spasms Nausea, vomiting, or severe wasting associated with cancer treatment Terminal illness Tourette syndrome Cannabis indica and Cannabis sativa produce two greatly different effects. C. sativa produces a “high” effect, while C. indica produces a more relaxed, “stoned” effect. Cannabis indica contains a higher amount of THC than Cannabis sativa, causing the psychological effects to be heightened . Synthetic Cannabinoids Spice The synthetic cannabinoids, known as Spice or K2, are lab-synthesized liquid chemicals that mimic the effect of THC. The chemical ingredients of Spice are sprayed onto dried plant material, which consists of chopped up herbs in a mixture of colors including beige, cream red, and brown. The final product looks like colored marijuana or tobacco. In 2015, 3.10% of 8th graders, 4.30% of 10th graders, and 5.20% of 12th graders reported pastyear use of synthetic marijuana. Spice was first sold as a recreational drug in 2004 in the United Kingdom. By 2006, it had gained a considerable hold on the market, and the brand name Spice (along with another brand K2) had become a generic term for all synthetic cannabis. Some synthetic cannabinoids are 100 times more potent than THC. This has resulted in a number of significant side effects, including hypertension, blurred vision, myocardial infarction, vomiting, severe anxiety, paranoia, seizures, and hallucinations. In drug tests, the chemicals in synthetic marijuana are harder to detect than marijuana. 9 Cannabis Dependence 138 Spice is sold under a number of names, including Mojo, Scooby Snax, Black Mamba, and Annihilation. Vaping the liquid of synthetic marijuana using e-cigarette is a fast-rising trend. Most Spice manufacturers do not follow high manufacturing standards, many of the chemicals being produced in cheap basement laboratories. Chemical impurities carry additional, and possibly much greater, risks. Deaths have been associated with use of the drug. Spice is often sold as potpourri, room deodorizer, or incense, purporting to be an innocent product for scenting rooms and usually has the warning “Not for human consumption” on the packet. It is estimated that there are well over 200 synthetic cannabinoids sold on the street, with about 50 of them currently listed as DEA Schedule I drugs. Street names for synthetic cannabis include Spice, black mamba, K2, fake marijuana, and sexy monkey [25–27]. Hashish Hashish, or hash, is an extracted product from the cannabis plant that is composed of compressed or purified preparations of glandular resin hairs called trichomes. It is made from the resin, which is a secreted gum. Hashish may be solid or resinous depending on the preparation; pressed hashish is solid, whereas water-purified hashish is often a paste-like substance with varying hardness and pliability. Its color, most commonly light to dark brown, can vary from transparent to yellow, tan, black, or red depending on the process and amount of solvent left over. Hashish is usually smoked, but it also can be added to food and eaten. It may have 20–65% THC concentration. The name hashish comes from an Arabic word meaning “grass.” Massive hashish production for international trade originated in Morocco during the 1960s, where the cannabis plant was widely available. Northern India has a long social tradition in the production of hashish, known locally as charas. It is believed to be the same plant resin that was burned in the religious ceremonies of ancient Persia. A 250–1000 mg ingestion of hashish can result in obtundation within 30 min. Street names for hashish include chocolate, hash, and shit [28, 29]. Hash Oil Hash oil is a resinous matrix produced by a solvent extraction of cannabis. A wide variety of solvents can be used for the extraction, such as chloroform, dichloromethane, ether, naphtha, benzene, butane, methanol, ethanol, isopropanol, and olive oil. One pound of marijuana yields from one-tenth to one-fifth of a pound of hash oil. It is a concentrated product with a high THC content, which generally varies between 20% and 60%, but can contain up to 80% THC. Hash oil is traditionally a dark, golden hue. Related “honey oil” is a specific type of hash oil made from the more potent parts of the cannabis plant. Hash oil is usually consumed by smoking, ingestion, or vaporization. Smoking or vaporizing hash oil is known as “dabbing” from the English verb to daub, which means “to smear with something adhesive.” Dabbing devices include special kinds of water pipes (“oil rigs”) and vaporizers similar in design to e-cigarettes. Anxiety or panic is the most common bad reaction, occurring during or shortly after smoking hash oil, or they can appear more gradually 1–2 h after an oral dose. These reactions usually resolve without medical intervention. Hash oil can cause tightness in chest, nausea, hypotension, tachycardia, dry mouth, and lethargy. Deaths have occurred. Flashbacks occasionally occur in which the original drug experience (usually dysphoria) is relieved weeks or months after use . Wax is a new marijuana product that looks and feels like lip balm and is as strong as 15–20 joints of marijuana. The marijuana concentrate is also referred to as butane hash oil, honey oil, budder, dabs, and 710 (spelled upside down is oil). It is easy to conceal in lip balm jars. It can be eaten or smoked using a bong or an e-cigarette. It is made Summary from the oils of marijuana plants. Highly flammable butane gas is used to extract the THC from the marijuana leaf and has resulted in home explosions, injuries, and deaths . Tolerance Repeated use over days to weeks induces considerable tolerance to the behavioral and psychological effects of cannabis. Regular marijuana smokers may require more potent cannabis or larger amounts of the drug to achieve the desired effects . Dependence Thirty percent of those who use marijuana may develop some degree of marijuana use disorder. People who begin using marijuana before the age of 18 are four to seven times more likely to develop a marijuana use disorder than those who begin smoking it in adulthood. Nine percent of people who use marijuana will become dependent on it, rising to about 17% in those who start using in their teens . Diagnosis of cannabis dependence is based on the DSM-5 criteria discussed in Chap. 1. Abstinence Syndrome On cessation of cannabis use, withdrawal symptoms may develop. Users most commonly experience cravings, irritability, mild tremor, anxiety, and sleep disturbances. Other symptoms may include restlessness, anorexia and weight loss, nausea, sweating, salivation, mild hyperthermia, and tremor . Overdose Symptoms Acute marijuana toxicity (bad trip) results in anxiety, agitation, difficulty with coordination, decreased muscle strength, postural hypotension, 139 headache, sweating, and lethargy. It also results in slurred speech, confusion, amnesia, delusions, and hallucinations. Treatment In 2012, there were over 450,000 emergency department visits in the United States related to use of marijuana. Treatment depends on the clinical presentation, the age of the patient, and the presence of other legal or illicit substances. Immediate management should be supportive, including cardiovascular and neurological monitoring and placement in a quiet room. Most episodes of marijuana toxicity remit fairly quickly. Gastric decontamination may be considered in children with an acute ingestion less than 2 h prior to presentation. Patients who are agitated or present with psychosis can be treated with a benzodiazepine . Summary Cannabis is a genus of flowering plant that includes three species—C. sativa, C. indica, and C. ruderalis. The male plant produces pollen, which pollinates the flowers of the female plant. Once pollinated, the female plant produces seeds. If the female plant is not pollinated, the buds and flowers continue to develop and produce THC, which is the major psychoactive substance in the cannabis plant. To produce a mood-altering effect, cannabis is used in three main forms: (1) marijuana, (2) hashish, and (3) hash oil. Long-term health risks of marijuana use include immune system effects, cardiovascular effects, respiratory effects, reproductive effects, behavioral effects, and cancer. Medical marijuana was legalized in California in 1996, and several other states have followed suit. Three medicinal products are derived from marijuana: dronabinol, nabilone, and nabiximols. Depending on the state, patients may qualify for treatment with medical marijuana if they meet certain requirements. 140 Cannabis indica, or “ganja,” is smoked as a form of marijuana. The synthetic cannabinoids, known as Spice or K2, are lab-synthesized liquid chemicals that mimic the effect of THC. Hashish, or hash, is an extracted product from the cannabis plant that is composed of compressed or purified preparations of glandular resin hairs called trichomes. 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