Cannabis Compound Abuse 

Typically referred to as marijuana, cannabis has been used for medicinal purposes worldwide for thousands of years. Reports dating as early as 2700 BC refer to carbon-dated cannabis shoots, leaves, and fruits unearthed in the Yanghqi Tombs, Turpan District in Xinjiang, China. They are believed to have been used for ritual/medicinal purposes, given the Shamanistic identity of the entombed.

Cannabis was introduced to the Virginia colony of Jamestown in 1611 and to the Massachusetts Bay Colony in 1629. In 1619, the first American law related to marijuana was passed—it mandated that farmers grow Indian hempseed. Although primarily used as a source of fiber, cannabis was occasionally smoked. Cannabis began to be used medicinally and was grown by many American planters. From 1850-1942, it was listed in the US Pharmacopoeia, the official list of recognized medical drugs . Cannabis was marketed as extract or tincture by several pharmaceutical companies and used for ailments such as anxiety and lack of appetite.^[1]

Marijuana was legal in the United States until 1937, when Congress passed the Marijuana Tax Act, effectively making the drug illegal. Interestingly, the American Medical Association opposed the legislation at the time of its passage. As a result of the Comprehensive Drug Abuse Prevention and Control Act of 1970, marijuana was classified as a Schedule I drug, defined as a category of drugs not considered legitimate for medical use. Other Schedule I drugs include heroin, phencyclidine (PCP), and lysergic acid diethylamide (LSD).^[1]

The medicinal use of cannabis is currently the subject of intense legal debate in the United States, yet momentum appears to be building in support of the widespread legalization of marijuana for medicinal purposes. According to an April 2009 field poll, 56% of Californians expressed support for legalizing marijuana and taxing sale proceeds. In October 2009, Gallup reported that 44% of Americans favored legalization of marijuana.^[2]

At present time, 14 states have legalized the use of marijuana for medicinal use, yet a significant paradox continues to exist between state and federal law. Recent federal policy changes have attempted to redress these inconsistencies. In 2009, the Justice Department issued a federal medical marijuana policy memo to the Drug Enforcement Administration (DEA), Federal Bureau of Investigation (FBI), and US attorneys instructing prosecutors not to target medicinal marijuana patients and their providers for federal prosecution in states where medicinal marijuana has been legalized. In the summer of 2010, the Department of Veteran Affairs issued a department directive to "formally allow patients treated at its hospitals and clinics to use medical marijuana in states where it is legal, a policy clarification that veterans have sought for years."^[3]

Some states and countries have sought to decriminalize the use and possession of marijuana. In 2009, Massachusetts passed the Massachusetts Sensible Marijuana Policy, which reduced the penalties that individuals would have to pay and eliminated the offense from inclusion to the Criminal Offender Record Information (CORI) for minor marijuana offenses. Previously, this offense could be punishable with a fine of up to $1,000 and a maximum of 6 months in jail.

In the Netherlands, where the distribution of marijuana has been legalized, the effect of decriminalization has had little effect on the consumption rate of cannabis.^[4] In 2004, Reinarman et al looked at the consumption of marijuana rates between San Francisco and Amsterdam to see what effect decriminalization had on these different populations.^[5] The results showed that the consumption habits between the 2 populations were negligible. Little evidence has shown that the decriminalization of cannabis has changed the consumption habits of the populations involved.^[6]

While there is a rich history of anecdotal accounts of the benefits of marijuana and a long tradition of marijuana being used for a variety of ailments, the scientific literature in support of medicinal uses of marijuana is less substantial. Considered to be one of the first scientifically valid papers in support of marijuana’s medicinal benefit, in 2007, Dr. Donald Abrams and colleagues published the results of a randomized placebo-controlled trial examining the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. The authors concluded that smoked cannabis effectively relieved chronic neuropathic pain in HIV-associated sensory neuropathy and was well tolerated by patients. The pain relief was comparable to chronic neuropathic pain treated with oral drugs.^[7]

According to Harvard Medical School's April, 2010 edition of the Harvard Mental Health Letter:^[8]

Consensus exists that marijuana may be helpful in treating certain carefully defined medical conditions. In its comprehensive 1999 review, for example, the Institute of Medicine (IOM) concluded that marijuana may be modestly effective for pain relief (particularly nerve pain), appetite stimulation for people with AIDS wasting syndrome, and control of chemotherapy-related nausea and vomiting.

These widely held beliefs in the medical community supporting the medicinal benefit of marijuana are starting to gain support in the form of rigorous empirical evidence demonstrating its clinical benefit and limited potential for harm. In 2012, the American Medical Association (AMA) published a landmark study that followed more than 5,000 patients longitudinally over 20 years. The results of the study were somewhat surprising. Although many had assumed that regular exposure to marijuana smoke would result in pulmonary function damage, similar to the deleterious effects seen with regular tobacco smoke exposure, the study convincingly demonstrated that regular exposure to marijuana smoke did not adversely affect lung function. Even more surprising, regular marijuana smokers demonstrated increased total lung function capacity.

The authors report, “Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”^[9]

The AMA is urging the federal government to change the classification of marijuana from a Schedule I drug to enable further clinical research on marijuana. Additionally, Harvard Mental Health Letter's authors point out that while marijuana works to relieve pain, suppress nausea, reduce anxiety, improve mood, and act as a sedative, the evidence that marijuana may be an effective treatment for psychiatric indications is inconclusive.^[8]

While marijuana may have medicinal benefits, its use can lead to abuse and dependence with concurrent morbidity, including impaired occupational and social functioning. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) recognizes the following 8 cannabis-associated disorders:^[10]

1. Cannabis dependence
2. Cannabis abuse
3. Cannabis intoxication
4. Cannabis intoxication delirium
5. Cannabis-induced psychotic disorder, with delusions
6. Cannabis-induced psychotic disorder, with hallucinations
7. Cannabis-induced anxiety disorder
8. Cannabis-related disorder not otherwise specified

An example of Cannabis sativa is shown in the image below.

Case study

Mr. X, a 19-year-old single white male presents complaining of apathy, lack of motivation, and an increasing sense of social isolation. He tried marijuana for the first time at age 15, when he was a junior in high school and quickly started smoking on a daily basis. He would spend nights and then days with friends, getting "stoned," experiencing the "giggles" and relishing the inevitable "munchies." He quickly noticed that smoking marijuana seemed to quell feelings of anxiety he experienced in social settings. Having graduated from high school a year earlier, he describes unfulfilled plans to attend college, which were foiled by his inability to submit the requisite applications. He describes half-hearted attempts to secure employment and now resides in the basement of his parent's house, supported by them. He describes a typical day in the following fashion:

Upon waking, usually in the late morning, he invariably takes a bong hit or smokes a joint, to "get going." Then he spends a significant amount of time preparing breakfast—he feels the marijuana heightens his culinary senses and he takes great joy in cooking and preparing a large meal.

Following breakfast he retires back to his room in the basement and spends the next several hours playing video games online. When he senses that he is slowing down and feeling sleepy, he’ll smoke more marijuana because it gives him more energy and improves his mood.

He’ll typically break from his immersion in the online gaming world for a late lunch, repeating his earlier efforts associated with breakfast. Occasionally, he’ll go to the local park to play basketball with the kids that are still in high school. Previously a successful athlete in high school, he feels like he’s lost a step and his reflexes on the court aren’t as quick as they used to be.

He has taken to selling a baseball card collection he painstakingly acquired when he was younger to raise money to pay for his marijuana and as that collection has dwindled he has started to grow marijuana in his basement. He describes his first efforts as generating a meager plant that bears a resemblance to the sad Christmas tree from Charlie Brown.

He doesn’t understand why he no longer has a girlfriend or why it has become difficult to meet new girls. He seems perplexed by his last girlfriend's complaints that he had become boring and it seemed like he was "letting life pass him by." He reports that his parents seem to be growing increasingly frustrated with him and reports arguing with them over his marijuana use—they identify it as a problem, he disagrees. He no longer goes out at night and instead spends most of his time smoking, playing video games alone in his room in the basement.

He denies any difficulty sleeping, although he doesn’t remember dreaming anymore and can’t remember the last dream he had. He reports some cognitive difficulties associated with decreased ability to concentrate and some short-term memory problems. He reports feeling occasionally irritable when too much time passes in between smoking and feels that marijuana makes him less irritable. He is interested in being more social, more engaged and feeling like he is achieving his goals but seems unable to explain why he can’t accomplish what he sets out to.

He does not seem to appreciate that his heavy and chronic marijuana use is a significant cause of his symptoms. He indicates that overall he enjoys smoking marijuana and believes it makes it easier for him to enjoy his days, which have become more difficult lately as he appreciates the stark difference between the quality of life he is enjoying compared to his peers who are now working or attending college.

Cannabis contains several pharmacologically active substances, including delta-9-tetrahydrocannabinol (THC) and cannabidiol.

Pyrolysis of marijuana releases more than 100 substances that are subsequently inhaled with the smoke. 1-trans -delta-9-THC is thought to be the ingredient most responsible for the central nervous system effects of marijuana.

Another increasingly important constituent is cannabidiol. It is the constituent thought now to reduce many of the undesirable effects of THC; it significantly reduces the anxiety and psychotic-like symptoms that can be associated with THC. It is currently under investigation for use as an anxiolytic and antipsychotic. Double-blinded tests on volunteers have demonstrated its usefulness as an anxiolytic in anxiogenic test situations. Animal and human studies also suggest that it has a pharmacologic profile similar to atypical antipsychotics; as such, cannabis is being considered as an alternative effective treatment for schizophrenia.^[11] However, THC has been more extensively studied; therefore, much of our understanding of the physiological changes induced by marijuana is predicated on the binding and metabolism of THC.

Smoking is the most common and efficient means of ingestion, with the dose being titrated by the user through varying the depth and frequency of inhalation; thus, the delivery mechanism poses a challenge for cannabis as a medication. THC can also be extracted by fat-containing foods or dissolved in oil for pharmaceutical purposes.

Synthetic cannabinoids exist that are more potent and somewhat more water soluble. Currently, 2 medications containing synthetic THC are FDA approved.

• Dronabinol (Marinol): This drug is indicated for the treatment of anorexia associated with weight loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
• Nabilone (Cesamet): This drug is indicated for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

After intake, THC undergoes metabolism to an inactive metabolite (8-11-DiOH-THC) and also to a highly active metabolite (11-OH-delta-9-THC). The half-life of THC is approximately 4 hours. The long life of the active metabolite is explained by the incorporation of the compound in lipid storage depots and similar storage sites in muscle tissue. Thirty to 60% of THC, in all forms, is excreted in feces; the remaining amount is excreted in urine.

Delta-9-THC is believed to exert all of its effects on the brain via the cannabinoid 1 (CB1) receptor. High densities of CB1 receptors are found in the cerebral cortex (especially frontal), basal ganglia, cerebellum, anterior cingulate cortex, and hippocampus. They are relatively absent in the brainstem nuclei. Stimulation of these receptors causes monoamine and amino acid neurotransmitters to be released. Endogenous ligands for CB1 receptors include anandamide and 2-arachidonylglycerol—the endocannabinoids.

Frequency

United States

• Marijuana remains the most commonly used illicit drug, with 14.6 million persons reporting use in the past month.^[12]
• The National Institute on Drug Abuse reported in January 2010 that while historically drug use, including marijuana, has declined since the 1990s among 8th, 10th, and 12th graders, the prevalence rates of marijuana use in 2009 were the same as they were 5 years prior.^[13]
• Throughout their lifetime, approximately 9% of the American adult population has met criteria for a cannabis use disorder.^[14]

International

An estimated 65 million European adults have used marijuana at least once and it is widely accepted that it is the most frequently used illicit substance in Western countries.^[15]

Mortality/Morbidity

Cannabis consumption has never directly resulted in mortality and no fatalities have been documented that identify cannabis consumption as the etiologic agent. However, cannabis consumption has been associated with multifactorial deaths, including marijuana-related accidents and deaths attributed to abuse of alcohol and other illicit substances.^[16]

Studies using simulated driving and flying situations have shown that the use of cannabis has a profound effect on estimations of time and distance and causes impairment of attention and short-term memory. These effects are still discernible 24-48 hours after use of the drug. A linear relationship is noted between level of impairment and serum/saliva THC level in tasks necessary for driving, such as perceptual motor control, motor impulsivity, and cognitive function.

Cannabis dependence is associated with morbidity, including impaired occupational and social functioning. Cannabis use can be comorbid with the presence of other psychiatric disorders, characterized by a disordered thought process, perceptual disturbances, or symptoms of anxiety. When marijuana is believed to be the etiologic agent, clinicians may diagnose a cannabis-induced disorder.

Psychotic symptoms represent a significant morbidity associated with cannabis use in select patients. While cannabis and the development of psychosis have been linked, this link is not without considerable controversy and understandably there are differing perspectives on whether this relationship is indeed causal, temporal, or coincidental. Given marijuana's clinical benefits, some have argued that patients diagnosed with psychotic disorders gravitate toward self-medicating with marijuana for these effects while others have advanced the view that marijuana can help precipitate the onset of psychosis in those who are genetically vulnerable. A recent study examining this controversial topic concluded that marijuana use can play a "catalytic role" in the onset of psychosis as demonstrated by cannabis use being associated with an association of an earlier age at on onset of psychosis treatment. Unfortunately, this study is not without limitations.^[17]

Another recent article examining this topic observed patients over 10 years and reached some similar conclusions. This study appears to provide additional evidence supporting the hypothesis that cannabis use is associated with an earlier age of onset of psychosis. However, the authors' findings complicate the debate further regarding the potential role of cannabis as an etiologic agent versus its use as self-medication by patients with psychotic symptoms. The authors note that there is a bidirectional relationship between psychosis and cannabis use; cannabis exposure predicted psychosis severity and those with more severe psychotic symptoms were more likely to use cannabis in the future.^[18]

A study conducted in Germany stated that the use of cannabis in adolescence is a risk factor for the development of incident psychotic symptoms.^[19]

This study was not without significant limitations; the study ignored the impact of genetic inheritability as a risk factor in the development of psychosis, the impact of confounding risk factors associated with other drug use (eg, PCP, methamphetamine), and the authors’ assumption that transient psychotic experiences were a surrogate for clinically relevant psychosis.

A meta-analysis examining 83 different studies reached similar conclusions, reporting that cannabis use was associated with an earlier age of onset of psychosis. Unfortunately despite a dearth of evidence, the authors argued that this temporal association supported their personal view that marijuana was an etiological risk factor for the development of psychosis.^[20] The exact role that marijuana plays in the development of psychosis and whether or not it has any causal role remains a matter of debate and controversy.

Race

Given how widespread cannabis use is globally, across cultures, race is not a significant risk factor associated with cannabis use nor does it represent a useful criteria for identifying acute or chronic marijuana users. However, a recent study in California demonstrated a significant disparity in arrest rates for users of marijuana based on race. According to the report, from 2004-2008, in Sacramento and San Francisco Counties, black residents were arrested for marijuana possession 4 times as often as white residents. In Los Angeles County, the disparity was more than 3 to 1.^[21]

A report looking at factors that could predict transition from abuse to dependence provided additional epidemiological data. According to the authors, rates of cannabis use were higher among white males.^[22]

Sex

Being male increases the odds of reporting past month cannabis use (10.2% vs 6.1% in 2005).^[12]

Age

Use, abuse, and dependence on marijuana tends to cut across demographics, including age.