Week 3 Forum:
The forum question for your consideration this week focuses on the legalization and decriminalization of drugs, including marijuana, in our society. Based on the readings from this week, and your reflections on your own beliefs, what is your perspective on the question of legalization of drugs, including marijuana?
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Legally Restricted Drugs in Our Society – Part II
This week, we turn to the very fascinating topics of hallucinogenic drugs and marijuana. Like some of the previous drugs we have studied, these drugs have existed in various natural forms for many thousands of years and, at various times in societies, have been held in high regard and, at other times, viewed with contempt and derision. It is interesting to note how societal norms, the practices of various religions, political and social movements, medical treatments, and expectations with regard to behavior all influence whether the manufacture, distribution, and use of these classes of drugs are deemed appropriate or not across societies. In fact, you can see the varying opinions that institutions and groups of individuals have held regarding this class of substances as they have been described as “mind expanding” to those who are accepting and “mind disrupting” by those who are alarmed by their use over the years. It is interesting to note that there has only been one documented fatality that can be ascribed to LSD ingestion since 1960.
Take a look at this 11-minute CrashCourse.com video on altered states as they relate to substance use and addiction. Discussion of hallucinogens begins about three-fourths through the presentation:
While there are thousands of naturally-occurring plants and fungi which can produce some perception-altering or hallucinogenic effects for those that consume them, this lesson will focus on the most prolific, widely know, and artificially manufactured of this class of drugs: lysergic acid diethylamide (LSD). In terms of effect per dose size, it is one of the most powerful psychoactive drugs known. Paradoxically, the toxicity (or degree to which it can be poisonous or directly harmful to the body) of this odorless, tasteless and colorless drug is relatively low. Its manufacture, distribution and use was made illegal in the United States in 1966. Hallucinogens, including LSD, are one of the eleven classes of substances covered by specific substance-related disorders in the Diagnostic and Statistical Manual of Mental Disorders.
How does a hallucinogen like LSD affect the brain and body?
Most hallucinogens are classified by the resemblance their molecules have to particular neurotransmitters in the brain. LSD is chemically similar to serotonin and affects receptors that are sensitive to this neurotransmitter. When taken orally, it is quickly absorbed into the bloodstream and begins to take effect in 30-60 minutes and reaches a peak potency in two to four hours. LSD is essentially eliminated from the system and the effect are gone within four to twelve hours of administration. Given its high degree of potency and low degree of toxicity, LSD has a fairly comfortable margin of safety. Recall that this margin is very different than that of heroin, where the range between an effective and a lethal dose can be quite narrow.
What are the behavioral patterns of hallucinogen, including LSD, use?
At the outset of use, LSD arouses the sympathetic nervous system. This results in an increase in heart rate and blood pressure, a dilation of the pupils, and a slightly raised body temperature. Individuals may report feelings of euphoria, restlessness, or tension release. Laughing or crying may be present, depending on the individual’s state of mind and the context in which the drug was administered. After 30 to 120 minutes, the user experiences the resultant “trip” of LSD. The typical symptoms of hallucinogen use include a wide variety of perceptual distortions, including visual images, altered body sense, the intermingling of auditory and visual sensations (called synthesia), and an altered sense of reality.
Individuals may report seeing vivid images while their eyes are closed, perception of a multi-level reality, a feeling of timelessness and separation of one’s mind from one’s body. Whether all of these phenomenon are characterized as “good” or “bad” by the user depends in large part of the individual’s expectations when taking LSD, the psychological health and well-being of the person, and the environmental setting in which it occurs. Fortunately, long-term psychiatric problems associated with LSD use are relatively uncommon.
What are the recommendations for individuals who come across someone having a “bad trip?” You are advised to remain calm and to encourage the affected individual to do the same. Any sudden movements or sense of panic on your part can unduly influence the individual into feeling the same way and incorporating that experience into their “trip.” You should provide reassurance that the situation is temporary and that you will remain with them until it is over and liken the experience to watching a TV program or movie. That is, it is outside them and not real. Finally, make sure the individual is in a quite environment that is not brightly lit. However, also make sure that they are not in total darkness, as the absence of visual stimuli tends to be associated with an increase in hallucinations.
Interestingly, compared to other illicit drugs that you have studies in this course, the threat of substance dependence with LSD use is comparatively low. Because of its highly level of potency, the body builds up a tolerance to the psychoactive effects of the drug faster than any other class of illicit drug. As such, one cannot remain in a hallucinogenic state for an extended period of time with successive dosing, unlike one can when using heroin, for example. In addition, while the hallucinogenic state can be quite pleasurable, individuals often characterize a six- to eight-hour sensory bombardment as quite exhausting and, oftentimes, unpredictable and nearly impossible to stop prematurely once it has begun. As such, there are some unique aspects of this experience that counter-condition the user to increase the frequency or amount of use over time.
Certainly an additional, negative aspect related to LSD use is the possibility of a flashback. The phenomenon of flashbacks is a relatively unique and typically unwanted byproduct of LSD abuse. This involves the transient recurrence of disturbances in an individual’s perception that previously occurred when an individual was intoxicated. In fact, the Diagnostic and Statistic Manual of Mental Disorders has a diagnosis for this condition: Hallucinogen Persisting Perception Disorder. The occurrence of flashbacks in individuals is estimated to be at five to thirty-five percent of users and can occur with not only habitual users but also individuals who have used LSD once. The exact mechanism by which this phenomenon occurs is not fully understood.
What challenges to “club drugs” like MDMA pose to individuals?
Another generation of synthetically produced hallucinogens have been produced which, unlike LSD, which works with serotonin receptors, work with the neurotransmitter norepinephrine. MDMA (3, 4-methylenedioxymethamphetamine), also known by its common street name Ecstasy, is technically a stimulant that also produces hallucinogenic effects on its user. It is used to elevate the mood of partygoers, create a feeling of connectedness to others, and provides a boost in energy that allows individuals to dance and stay awake through the night. Problems associated with the drug include impairment of memory, confusion, muscle tension, nausea, risk for liver damage, symptoms of anxiety and depression, insomnia, and paranoid thinking. Reduced sweating is one symptom that, in a hot club environment followed by hours of dancing, can create the risk for heat stroke or exhaustion.
Interested in learning more? Here’s a quick 2-minute video from ASAPScience.com on MDMA and its effects:
What does it mean to be substance dependent?
For the last few weeks, we have discussed a variety of illicit drugs that have the threat, when abused regularly, of leading to dependence. What does it mean to have cocaine dependence or hallucinogen dependence? Typically, dependence is formally diagnosed when a person’s symptoms indicate that he or she is persisting in their use of a drug despite significant problems in their life that are related to the use of the drug. Conducting a clinical interview with the individual where their drug use, work history, family life, social relationships, and other important life occurrences are reviewed will reveal a problematic pattern.
Over the course of a year, when at least three of the following symptoms are found, a consideration should be made as to whether the individual is drug dependent: (1) tolerance of the drug; (2) withdrawal symptoms and active attempts to avoid them; (3) a history of the drug being taken in increasingly larger doses and over long periods of time than would be intended; (4) attempts to cut down or stop using by the individual have been unsuccessful; (5) the individual spends a large portion of their waking hours in activities whose goal is obtaining, using, or recovering from the drug; (6) the drug use is to the extent that it has impaired the individual’s occupation, familial and social functioning in meaningful ways; and (7) despite the presence of physical and/or psychological problems stemming from its use, the individual continues to abuse the drug.
Certainly, some drugs are more prone to tolerance and/or withdrawal than others. For example, many people continue to smoke cigarettes or use other forms of nicotine as a way to avoid the negative withdrawal symptoms they might otherwise experience. By contrast, pronounced withdrawal symptoms are not as common with repeated use of hallucinogens. It is interesting to note that all classes of classically abused drugs that you will review in this course can result in a clinical diagnosis of dependence, except for the licit drug caffeine.
Moving now to your study of marijuana, one of the most politicized drugs of the twentieth (and twenty-first) centuries. As a nice overview, review this quick four-minute SciShow.com video on the substance:
Marijuana is another example of a drug that has been similarly praised and demonized by different groups of people at different periods of time throughout our country’s history. Present across cultures for thousands of years, it is arguably the world’s oldest cultivated plant not used as a food source. The hardy plant from which this drug is derived is a bit of an anomaly; it produces symptoms akin to many other classes of drugs, but is unique unto itself. It produces some excitatory effects, but is not thought to be a stimulant; it produces some sedative effect, but is does not induce a stupor as could be seen with depressants; it produces some mild analgesic effects, but is not chemically related to opioids; it can produce mild hallucinations at high doses, but it not a hallucinogen like LSD. It should be noted that cannabis is one of the eleven classes of substances covered by specific substance-related disorders in the Diagnostic and Statistical Manual of Mental Disorders.
How does marijuana affect the brain?
The active ingredient of marijuana is the chemical compound delta-9-tetrahydrocannabinol (THC). When ingested, often through smoking, the THC stimulates specific neuronal receptors in areas of the brain that are associated with short-term memory and motor control. The degree to which THC affects the brain and produces the symptoms of intoxication depend heavily on the individual ingesting the drug and the experience they have in doing so. Regular marijuana smokers, when compared to novice users, inhale more deeply and hold the smoke in their lungs for a longer period of time, thereby allowing more of the THC to enter their bloodstream more quickly and with less consumption of marijuana than cigarettes, or “joints.” Further, chronic users will have residual THC in their system that elevates the total quantity of THC consumed with every new dose. When dosage levels are controlled, the phenomenon of tolerance is demonstrated with marijuana use, just like other illicit drugs you have studied in this course. More systematically, THC acts as an immune suppressant within the body, making a marijuana user more susceptible to infection and disease.
What are the behavioral symptoms of marijuana use?
Cannabis intoxication can involve feelings of grandiosity, euphoria, and inappropriate laughter, followed by sedation, lethargy and altered sensory perceptions. Short-term memory and judgment can be impaired as well as motor skills. At times, individuals using cannabis have reported the sensation that time is moving slowly. While some individuals believe that marijuana use is relatively harmless, a clinical level of psychological dependence can, in fact, develop. Habitual users commonly report cravings.
Whether with short-term or habitual use, withdrawal symptoms present themselves with the cessation of marijuana use. Symptoms include stomach discomfort, feelings of irritability, loss of appetite, and symptoms of anxiety. These symptoms can last for up to two days in duration. For those who use marijuana in a chronic fashion, withdrawal symptoms that mimic those of tobacco cessation are common as well. Nevertheless, all of these symptoms are certainly less pronounced or dangerous than the withdrawal symptoms one would experience from cessation of chronic heroin or alcohol abuse.
What are some of the factors behind the decriminalization and legalization of marijuana and its use as a medical treatment?
Marijuana regulated as medicine has been shown to be effective in the treatment of glaucoma and asthma, but it’s most efficacious use is in the treatment of nausea and weight loss secondary to the treatment of cancer. A growing number of states have legislatively approved marijuana for such uses under medical supervision, and the federal government has stopped using its resources to prosecute or restrict individuals’ use of marijuana for such purposes.
Current public policy in the United States has shifted dramatically from prior decades such that the possession of marijuana in small amounts in essentially decriminalized. That is, possession would be subject to a small fine but not otherwise viewed as a criminal offense requiring prosecution. A small number of states have legalized possession and a growing number of states have legislative bills forwarded for consideration each year. As you recall, history has shown that use of certain substances have been in and out in favor of society. Additionally, doctors for pain management commonly prescribe hydrocodone, codeine, and oxycodone while the opioid heroin is illegal to possess or use.
Botanical name: Cannabis sativa
Other common names: weed, pot, herb, bud, dope, spliff, reefer, grass, ganja, 420, chronic, Mary Jane, gangster, boom, skunk. There are over 200 street names for marijuana.
What is Marijuana?
Marijuana (cannabis) is a green, brown or gray mixture of dried, shredded leaves, stems, seeds and flowers of the hemp plant Cannabis sativa. Marijuana is used as a psychoactive (i.e. mind altering) recreational drug, for certain medical ailments and for religious and spiritual purposes. Sinsemilla, hash/hashish (resinous form) and hash oil (sticky black liquid) are stronger forms of marijuana.
According to the National Institute on Drug Abuse (NIDA), marijuana is the most abused drug in the US. Many states in the US have now legalized marijuana for medical or recreational use. However, according to federal law, the possession of marijuana (cannabis) is still illegal in the US, except within approved research settings.
How Does Marijuana Work?
The main active chemical in marijuana is THC (delta-9-tetrahydrocannabinol), the psychoactive ingredient. The highest concentrations of THC are found in the dried flowers, or buds. When marijuana smoke is inhaled, THC rapidly passes from the lungs into the bloodstream and is carried to the brain and other organs throughout the body. THC from the marijuana acts on specific receptors in the brain, called cannabinoid receptors, starting off a chain of cellular reactions that finally lead to the euphoria, or “high” that users experience. Feeling of a relaxed state, euphoria, and an enhanced sensory perception may occur. With higher THC levels in those who are not used to the effects, some people may feel anxious, paranoid, or have a panic attack.
Certain areas in the brain, such as the hippocampus, the cerebellum, the basal ganglia and the cerebral cortex, have a higher concentration of cannabinoid receptors. These areas influence memory, concentration, pleasure, coordination, sensory and time perception.1
Marijuana’s strength is correlated to the amount of THC it contains and the effects on the user depend on the strength or potency of the THC. Different strains will contain different levels of THC. In general, the THC content in marijuana has been increasing since the 1970s, when it contained roughly 10% THC. In 2015, as reported by Live Science, researchers from the American Chemical Society found levels of THC at roughly 30%.
There are many other chemicals found in marijuana, many of which may adversely affect health. Marijuana contains over 60 different cannabinoid compounds, and overall 400 different compounds have been identified in marijuana, including THC, cannabidiol (CBD), cannabinol, and β-caryophyllene, as noted by the National Institute of Drug Abuse (NIDA).
How is Marijuana Used?
Marijuana may be smoked as a cigarette (called a joint or a nail) or in a pipe or bong. It may be smoked in “blunts”, which are cigars that have been emptied of tobacco and refilled with marijuana, often in combination with another drug, such as crack. The “blunts” retain tobacco leaf used to wrap the cigar and therefore it combines marijuana’s active ingredients with nicotine and other harmful chemicals.
Some users also mix marijuana into food or use it to brew tea. In states that have now legalized sale of marijuana for recreational use, the marketing of edible products, such as cookies, brownies, and chocolates, are popular for those who prefer not to smoke the product.
Vaporizers are also popular for those who prefer not to inhale smoke. The devices concentrate the THC from the marijuana into a storage unit and the person then inhales the vapor, not the smoke. Some vaporizers use a liquid marijuana extract that can be extremely high in THC content, and can be dangerous to novice users, resulting in emergency room admissions.
Approved and Investigational Products
In the United States, the Controlled Substances Act (CSA) of 1990 classifies marijuana as a Schedule I substance, which states it has no approved medical use and a high potential for abuse. This Federal definition is highly controversial, and can limit marijuana’s availability for clinical research studies. However, many US states have legalized the use of marijuana for medical and/or recreational use. Prescription medicines containing synthetic cannabinoids (THC) are also available. Dronabinol, a pharmaceutical form of THC, and nabilone, a synthetic cannabinoid, are approved by the FDA to treat certain conditions. Marinol, generics (dronabinol capsules) – Classified as Schedule III Syndros (dronabinol liquid) – Classified as Schedule II Cesamet (nabilone capsules) – Classified as Schedule II
Syndros is a liquid form of dronabinol. Both dronabinol and nabilone are approved to treat patients receiving anti-cancer medicine (chemotherapy) who have nausea and vomiting, particularly patients who do not respond to other treatments.
Dronabinol (Marinol and Syndros) is also approved to treat anorexia (loss of appetite) associated with weight loss in patients with AIDS (Acquired Immune Deficiency Syndrome). Sativex (nabiximols)
Sativex (nabiximols) is not currently approved for use in the US, but is available in 30 countries outside the US, including Canada, the UK, Spain, Germany, Denmark, the Czech Republic, Sweden, and New Zealand. Sativex, an oral sublingual spray, is approved for use in multiple sclerosis (MS) spasticity. In Israel, Sativex is approved for the indications of MS spasticity and for chronic cancer pain. Sativex is composed of standardized extracts of THC and cannabidiol and is available as an oral mucosal spray formulation. Studies from Lakhan, et al report that THC and cannabidiol (CBD) provide therapeutic benefit for Multiple Sclerosis (MS) spasticity (muscle stiffness/spasm) symptoms.
GW Pharmaceuticals and Otsuka Pharmaceuticals announced results of three US Phase 3 trials in 2015 for the use of Sativex for the treatment of pain in patients with advanced cancer who experience inadequate analgesia during optimized chronic opioid therapy. According to the study results, Sativex did not meet the primary endpoint of demonstrating a statistically significant difference from placebo for pain control.
Epidiolex (cannabidiol or CBD), also from GW Pharmaceuticals, is a cannabinoid product FDA approved in June 2018 for the treatment of patients two years and older with seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome. Epidiolex comes as an oral solution.
These forms of epilepsy — Lennox-Gastaut syndrome and Dravet syndrome — are severe, rare, and begin in childhood. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana — CBD — and the first treatment for Dravet syndrome.
In pivotal Phase III studies with 516 patients with either seizure type, Epidiolex, as an adjunct with other seizure drugs, was shown to be effective in reducing the frequency of seizures when compared with placebo.
Common side effects with Epidiolex included sleepiness, diarrhea, sedation and lethargy, signs of possible liver damage, and decreased appetite, among others. It was rescheduled from a Schedule I controlled substance to a Schedule V controlled substance in September 2018 by the DEA. Medications listed in Schedule V have a proven medical use but a low potential for abuse.
Extent of Marijuana Use
Marijuana is reported as the most widely used illicit drug in the US, according to the 2016 National Survey on Drug Use and Health. In the past survey year (2016), 37.6 million people, or 13.9% of US adults reported using marijuana. In the same survey, past year marijuana use among adolescents aged 12 to 16 years dropped from 12.9% to 11.7% in males, but remained steady at 12.3% females. Overall, marijuana use was highest amongst the age group 18 to 25 years of age at 33%.
In the 2016 Monitoring the Future Survey, 22.5%, 14% and 5.4% of 12th, 10th, and 8th graders, respectively, reported marijuana use in the past year. Interestingly, 68.9% of high school seniors do not view regular marijuana smoking as harmful, but 68.5% say they disapprove of regular marijuana smoking.
Marijuana Side Effects
Side effects of marijuana use will be variable from person to person, depending upon strength and amount of marijuana used and if the user is occasionally or chronically exposed to THC. Side effects can be magnified in older people.
The short-term effects of marijuana or cannabinoid use include: increased heart rate low blood pressure, orthostatic hypotension muscle relaxation slowed digestion dizziness distorted perception (sights, sounds, time, touch) difficulty in thinking, memory, and problem solving loss of coordination and motor skills agitation, anxiety, confusion, panic, paranoia increased appetite dry mouth, dry eyes
Reaction time may be impaired while driving. NIDA research shows that drivers have slower reaction times, impaired judgment, and problems responding to signals and sounds if driving while under the influence of THC.
Panic attacks, paranoia and psychosis may occur acutely and be more common in psychiatric patients, a reported by Heller. For chronic users, the impact on memory and learning can last for days or weeks after its acute effects wear off, as noted by the NIDA. Marijuana, if purchased on the street, may be cut (or substituted) with substances that can lead to unknown, dangerous side effects.
THC in marijuana is strongly absorbed by fatty tissues in various organs. Generally, traces of THC can be detected by standard urine testing methods several days or more after a smoking session. In heavy chronic users, traces can sometimes be detected for weeks after they have stopped using marijuana.
Long-term abuse of marijuana may lead to dependence in some people. McKenna, et al have reported on the addicting potential of marijuana, noting that “it is an erroneous belief widely held by the general public, and among many physicians, that marijuana is not addicting.” However, not all people will become addicted to marijuana and the effects can be psychological in some patients. Withdrawal symptoms can occur upon abrupt cessation of the drug, including: anxiety agitation tremulousness elevation of vital signs insomnia irritability
Marijuana also may affect mental health. Studies show that use may increase the risk of developing psychosis (a severe mental disorder in which there is a loss of contact with reality) including false ideas about what is happening (delusions) and seeing or hearing things that aren’t there (hallucinations), particularly if you carry a genetic vulnerability to the disease. Also, rates of marijuana use are often higher in people with symptoms of depression or anxiety, as reported by the NIDA. There have been no reports of THC overdose leading to death.
Marijuana Effects on the Heart
Shortly after smoking marijuana the heart rate increases drastically and may remain elevated for up to 3 hours. This effect may be enhanced if other drugs are taken with marijuana. One study from Mittleman, et al has suggested that the risk of heart attack may increase by up to 4.8-fold in the first hour after smoking marijuana. The effect may be due to the increased heart rate, as well as altered heart rhythms. The risk of heart attack may be greater in those with specific risk factors such as patients with high blood pressure, heart arrhythmia, or other cardiac disease.
Harvard Health also reports that the risk of a heart attack is several times higher in the hour after smoking marijuana than it would be normally, and this should be a red flag for anyone with a history of heart disease. The risk of stroke may be increased, as well.
Marijuana Effects on the Lungs
After smoking marijuana, the bronchial passage relaxes and becomes enlarged. Marijuana smoke contains many of the same cancer-causing chemicals found in cigarette smoke, often in greater quantities, as reported by Mehmedic and colleagues. Both types of smoke contain cancer-causing nitrosamines, polycyclic aromatic hydrocarbons, vinyl chlorides, and phenol per research reported by Martinasek. Studies have shown that marijuana smoke contains 50 to 70 percent more carcinogenic hydrocarbons than tobacco smoke, and is an irritant to the lungs. Marijuana users tend to inhale more deeply and hold their breath longer than tobacco smokers do, which further increases lung exposure to carcinogenic smoke.
People who smoke marijuana often have the same respiratory problems as cigarette smokers. These individuals may have daily cough and phlegm, symptoms of chronic bronchitis, shortness of breath, chest tightness, wheezing and more frequent chest colds. They are also at greater risk of getting lung infections like pneumonia, as reported by the NIDA.
A 2016 systematic review of the respiratory effects of inhalational marijuana from Martinasek, et al indicates that there is a risk of lung cancer from inhalational marijuana as well as an association between inhalational marijuana and spontaneous pneumothorax, emphysema, or COPD. In the review, eight of the 12 studies indicated an increased risk of lung cancer from cannabis use or cases indicating lung cancer occurrence.
Drug Interactions With Marijuana Combining marijuana with other CNS depressant drugs that also cause drowsiness or sedation (such as alcohol, barbiturates, sedating antihistamines, anti-anxiety medications, opiate pain killers, etc) can magnify the drowsiness. DO NOT drive if you are under the influence of marijuana, alcohol or any sedating drug. A study from Hartman, et al shows that low doses of alcohol can significantly elevate the concentrations of THC in the blood. Marijuana use can raise the heart rate (tachycardia) and may be dangerous if used with other drugs that may also increase the heart rate. People with cardiovascular disease should avoid marijuana use. The cannabinoids in marijuana (THC, cannabidiol) can affect liver enzymes and may alter the blood levels and effects of medications. Drug interactions are often unpredictable or undocumented with marijuana and extreme caution should be exercised.
Effects During Pregnancy and Breastfeeding
Marijuana is also the most common illicit drug used during pregnancy, in roughly 2% to 5% of women. According to a 2017 updated report published by the American College of Obstetricians and Gynecologists (ACOG) entitled Marijuana Use During Pregnancy and Lactation, 34% to 60% of marijuana users continue use during pregnancy, with many women believing that use is relatively safe. These numbers could rise as more states continue to legalize marijuana for medicinal or recreational purposes. Due to possible adverse effects of marijuana on the fetus, ACOG recommends that marijuana should be avoided during pregnancy.
Any drug of abuse can affect a mother’s health. It can be difficult to determine the effects of marijuana on a baby’s health because women who use marijuana often use other substances, such as alcohol, nicotine, or drugs of abuse. THC appears to cross the placenta, according to Davies et
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