Chronic marijuana use can have an emetic effect. Patients shower or bathe in extremely hot water to relieve the symptoms.
Joseph G. Rella, MD
Department of Emergency Medicine, Division of Medical Toxicology, New York Presbyterian Hospital; Assistant Professor of Emergency Medicine, Weill Cornell Medical College, New York, NY
Address: Joseph G. Rella, MD, Department of Emergency Medicine, Division of Medical Toxicology, New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065; e-mail: firstname.lastname@example.org
ABSTRACTCannabis is widely used for a variety of reasons, and its changing legal status may foster more new users. Although the acute clinical effects of cannabis are generally benign, clinicians should be aware of health complications and testing limitations.
Clinicians may be encountering more cannabis users than before, and may be encountering users with complications hitherto unseen. Several trends may explain this phenomenon: the legal status of cannabis is changing, cannabis today is more potent than in the past, and enthusiasts are conjuring new ways to enjoy this substance.
This article discusses the history, pharmacology, and potential complications of cannabis use.
A LONG AND TANGLED HISTORY
Cannabis is a broad term that refers to the cannabis plant and its preparations, such as marijuana and hashish, as well as to a family of more than 60 bioactive substances called cannabinoids. It is the most commonly used illegal drug in the world, with an estimated 160 million users. Each year, about 2.4 million people in the United States use it for the first time.1,2
Cannabis has been used throughout the world for recreational and spiritual purposes for nearly 5,000 years, beginning with the fabled Celestial Emperors of China. The tangled history of cannabis in America began in the 17th century, when farmers were required by law to grow it as a fiber crop. It later found its way into the US Pharmacopeia for a wide range of indications. During the long prelude to Prohibition in the latter half of the 19th century, the US government became increasingly suspicious of mind-altering substances and began restricting its prescription in 1934, culminating in its designation by the US Food and Drug Administration as a schedule I controlled substance in 1970.
Investigation into the potential medical uses for the different chemicals within cannabis is ongoing, as is debate over its changing legality and usefulness to society. The apparent cognitive dissonance surrounding the use and advocacy of medical marijuana is beyond the scope of this review,3 which will instead restrict itself to what is known of the cannabinoids and to the recreational use of cannabis.
THC IS THE PRINCIPAL PSYCHOACTIVE MOLECULE
Delta-9 tetrahydrocannabinol (THC), first isolated in 1964, was identified as the principal psychoactive constituent of cannabis in 2002.4
Two G-protein–linked cannabinoid receptors cloned in the 1990s—CB1 and CB2—were found to be a part of a system of endocannabinoid receptors present throughout the body, from the brain to the immune system to the vas deferens.5 Both receptors inhibit cellular excitation by activating inwardly rectifying potassium channels. These receptors are mostly absent in the brainstem, which may explain why cannabis use rarely causes life-threatening autonomic dysfunction. Although the intoxicating effects of marijuana are mediated by CB1 receptors, the specific mechanisms underlying the cannabis “high” are unclear.6
CANNABINOIDS ARE LIPID-SOLUBLE
The rate of absorption of cannabinoids depends on the route of administration and the type of cannabis product used. When cannabis products are smoked, up to 35% of THC is available, and the average time to peak serum concentration is 8 minutes.7 The peak concentration depends on the dose.
On the other hand, when cannabis products (eg, nabilone, dronabinol) are ingested, absorption is unpredictable because THC is unstable in gastric acid and undergoes first-pass metabolism in the liver, which reduces the drug’s bioavailability. Up to 20% of an ingested dose of THC is absorbed, and the time to peak serum concentration averages between 2 and 4 hours. Consequently, many users prefer to smoke cannabis as a means to control the desired effects.
Cannabinoids are lipid-soluble. They accumulate in fatty tissue in a biphasic pattern, initially moving into highly vascularized tissue such as the liver before accumulating in less well-vascularized tissue such as fat. They are then slowly released from fatty tissue as the fat turns over. THC itself has a volume of distribution of about 2.5 to 3.5 L/kg. It crosses the placenta and enters breast milk.8
THC is metabolized by the cytochrome P450 system, primarily by the enzymes CYP2C9 and CYP3A4. Its primary metabolite, 11-hydroxy-delta-9 THC, is also active, but subsequent metabolism produces many other inactive metabolites. THC is eliminated in feces and urine, and its half-life ranges from 2 to nearly 60 hours.8
A LITTLE ABOUT PLANTS AND STREET NAMES
The plant from which THC and nearly a hundred other chemicals, including cannabinoids, are derived has been called many things over the years:
Hemp is a tall fibrous plant grown for rope and fabric that was used as legal tender in early America. In the mid-19th century, there were over 16 million acres of hemp plantations. Hemp contains very low THC concentrations.
Cannabis is an annual flowering herb that is predominantly diecious (ie, there are male and female plants). After a centuries-long debate among taxonomists, the two principal species are considered to be C sativa and C indica, although today many cannabis cultivars are grown by a great number of breeding enthusiasts.
THC levels in marijuana have increased from about 5% historically to over 30% in some samples today
Concentrations of THC vary widely among cannabis cultivars, ranging historically from around 5% to today’s highly selectively bred species containing more than 30%. Concentrations in seized cannabis have been measured as high as 37%, although the average is around 11%.9 This concentration is defined by the percent of THC per dried mass of plant material tested, usually via gas chromatography.
Hashish is a solid or resinous preparation of the trichomes, or glandular hairs, that grow on the cannabis plant, chiefly on its flowers. Various methods to separate the trichomes from the rest of the plant result in a powder called kief that is then compressed into blocks or bricks. THC concentrations as high as 66% have been measured in nondomestic sources of hashish.9
Hash oil is a further purification, produced by using solvents to dissolve the resin and by filtering out remaining plant material. Evaporating the solvent produces hash oil, sometimes called butane hash oil or honey oil. This process has recently led to an increasing number of home explosions, as people attempt to make the product themselves but do not take suitable precautions when using flammable solvents such as butane. THC concentrations as high as 81% have been measured in nondomestic sources of hash oil.9
Other names for hash oil are dab, wax, and budder. Cannabis enthusiasts refer to the use of hash oil as dabbing, which involves heating a small amount (dab) of the product using a variety of paraphernalia and inhaling the vapor.
IT’S ALL ABOUT GETTING HIGH
One user’s high is another user’s acute toxic effect
For recreational users, the experience has always been about being intoxicated—getting high. The psychological effects range broadly from positive to negative and vary both within and between users, depending on the dose and route of administration. Additional factors that influence the psychological effects include the social and physical settings of drug use and even the user’s expectations. One user’s high is another user’s acute toxic effect.
Although subjective reports of the cannabis experience vary greatly, it typically begins with a feeling of dizziness or lightheadedness followed by a relaxed calm and a feeling of being somewhat “disconnected.” There is a quickening of the sense of humor, described by some as a fatuous euphoria; often there is silly giggling. Awareness of the senses and of music may be increased. Appetite increases, and time seems to pass quickly. Eventually, the user becomes drowsy and experiences decreased attention and difficulty maintaining a coherent conversation. Slowed reaction time and decreased psychomotor activity may also occur. The user may drift into daydreams and eventually fall asleep.
Common negative acute effects of getting high can include mild to severe anxiety and feeling tense or agitated. Clumsiness, headache, and confusion are also possible. Lingering effects the following day may include dry mouth, dry eyes, fatigue, slowed thinking, and slowed recall.6
ACUTE PHYSICAL EFFECTS
Acute physical effects of cannabis use include a rapid onset of increased airway conductance, decreased intraocular pressure, and conjunctival injection. A single cannabis cigarette can also induce cardiovascular effects including a dose-dependent increase in heart rate and blood pressure. Chronic users, however, can experience a decreased heart rate, lower blood pressure, and postural hypotension.
In a personal communication, colleagues in Colorado—where recreational use of cannabis was legalized in 2012—described a sharp increase (from virtually none) in the number of adults presenting to the emergency department with cannabis intoxication since 2012. Their patients experienced palpitations, light-headedness, and severe ataxia lasting as long as 12 hours, possibly reflecting the greater potency of current cannabis products. Most of these patients required only supportive care.
Acute effects of cannabis include increased airway conductance, decreased intraocular pressure, and conjunctival injection
Other acute adverse cardiovascular reactions that have been reported include atrial fibrillation, ventricular tachycardia, and a fivefold increased risk of myocardial infarction in the 60 minutes following cannabis use, which subsequently drops sharply to baseline levels.10 Investigations into the cardiovascular effects of cannabis are often complicated by concurrent use of other drugs such as tobacco or cocaine. Possible mechanisms of injury include alterations in coronary microcirculation or slowed coronary flow. In fact, one author found that cannabis users with a history of myocardial infarction had a risk of death 4.2 times higher than users with no history of myocardial infarction.11,12
In children, acute toxicity has been reported from a variety of exposures to cannabis and hashish, including a report of an increase in pediatric cannabis exposures following the changes in Colorado state laws.13 Most of these patients had altered mental status ranging from drowsiness to coma; one report describes a child who experienced a first-time seizure. These patients unfortunately often underwent extensive evaluations such as brain imaging and lumbar puncture, and mechanical ventilation to protect the airway. Earlier consideration of cannabis exposure in these patients might have limited unnecessary testing. Supportive care is usually all that is needed, and most of these patients fully recover.13–17
Cannabinoids cause a variety of adverse effects, but the ultimate risk these changes pose to human health has been difficult to calculate. Long-term studies are confounded by possible inaccuracies of patient self-reporting of cannabis use, poor control of covariates, and disparate methodologies.
For more than a century, cannabis use has been reported to cause both acute psychotic symptoms and persistent psychotic disorders.18 But the strength of this relationship is modest. Cannabis is more likely a component cause that, in addition to other factors (eg, specific genetic polymorphisms), contributes to the risk of schizophrenia. Individuals with prodromal symptoms and those who have experienced discrete episodes of psychosis related to cannabis use should be discouraged from using cannabis and cannabinoids.19–21
Mounting evidence implicates chronic cannabis use as a cause of long-term medical problems
Mounting evidence implicates chronic cannabis use as a cause of long-term medical problems including chronic bronchitis,22 elevated rates of myocardial infarction and dysrhythmias,11 bone loss,23 and cancers at eight different sites including the lung, head, and neck.24 In view of these chronic effects, healthcare providers should caution their patients about cannabis use, as we do about other drugs such as tobacco.
WITHDRAWAL SYNDROME RECOGNIZED
Until recently, neither clinicians nor users recognized a withdrawal syndrome associated with chronic use of cannabis, probably because this syndrome is not as severe as withdrawal from other controlled substances such as opioids or sedative-hypnotics. A number of studies, however, have reported subtle cannabis withdrawal symptoms that are similar to those associated with tobacco withdrawal.
As such, the fifth and latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)25 characterized withdrawal from cannabis use in 2013. The DSM-5 criteria require cessation of heavy or prolonged use of cannabis (ie, daily or almost daily over a period of at least a few months) and three or more of the following withdrawal symptoms:
Medical treatment of cannabis withdrawal has included a range of antidepressants, mood stabilizers, and alpha-2-adrenergic agonists, all of which have limited success.26 Symptoms of cannabis withdrawal tend to be most intense soon after cessation and decline over the next few weeks.27
Chronic marijuana use can have an emetic effect. Patients shower or bathe in extremely hot water to relieve the symptoms.