1.2 Brief Introductions into the Most Commonly Misused and Abused Drugs/Substances

While we all experience altered states of consciousness in the form of sleep on a regular basis, some people use drugs and other substances that result in altered states of consciousness as well. This section will present information relating to the use of various psychoactive drugs and problems associated with such use. This will be followed by brief descriptions of the effects of some of the more well-known drugs commonly used today.

SUBSTANCE USE DISORDERS

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is used by clinicians to diagnose individuals suffering from various psychological disorders. Drug use disorders are addictive disorders, and the criteria for specific substance (drug) use disorders are described in DSM-5. A person who has a substance use disorder often uses more of the substance than they originally intended to and continues to use that substance despite experiencing significant adverse consequences. In individuals diagnosed with a substance use disorder, there is a compulsive pattern of drug use that is often associated with both physical and psychological dependence.

Physical dependence involves changes in normal bodily functions—the user will experience withdrawal from the drug upon cessation of use. In contrast, a person who has psychological dependence has an emotional, rather than physical, need for the drug and may use the drug to relieve psychological distress. Tolerance is linked to physiological dependence, and it occurs when a person requires more and more drug to achieve effects previously experienced at lower doses. Tolerance can cause the user to increase the amount of drug used to a dangerous level—even to the point of overdose and death.

Drug withdrawal includes a variety of negative symptoms experienced when drug use is discontinued. These symptoms usually are opposite to the effects of the drug. For example, withdrawal from sedative drugs often produces unpleasant arousal and agitation. In addition to withdrawal, many individuals who are diagnosed with substance use disorders will also develop tolerance to these substances. Psychological dependence, or drug craving, is a recent addition to the diagnostic criteria for substance use disorder in DSM-5. This is an important factor because we can develop tolerance and experience withdrawal from any number of drugs that we do not abuse. In other words, physical dependence in and of itself is of limited utility in determining whether or not someone has a substance use disorder.

DRUG CATEGORIES

The effects of all psychoactive drugs occur through their interactions with our endogenous neurotransmitter systems. Many of these drugs, and their relationships, are shown in [link]. As you have learned, drugs can act as agonists or antagonists of a given neurotransmitter system. An agonist facilitates the activity of a neurotransmitter system, and antagonists impede neurotransmitter activity.

Alcohol and Other Depressants

Ethanol, which we commonly refer to as alcohol, is in a class of psychoactive drugs known as depressants (Figure 1.2.2 Drug Types). A depressant is a drug that tends to suppress central nervous system activity. Other depressants include barbiturates and benzodiazepines. These drugs share in common their ability to serve as agonists of the gamma-Aminobutyric acid (GABA) neurotransmitter system. Because GABA has a quieting effect on the brain, GABA agonists also have a quieting effect; these types of drugs are often prescribed to treat both anxiety and insomnia.

Acute alcohol administration results in a variety of changes to consciousness. At rather low doses, alcohol use is associated with feelings of euphoria. As the dose increases, people report feeling sedated. Generally, alcohol is associated with decreases in reaction time and visual acuity, lowered levels of alertness, and reduction in behavioural control. With excessive alcohol use, a person might experience a complete loss of consciousness and/or difficulty remembering events that occurred during a period of intoxication (McKim & Hancock, 2013). In addition, if a pregnant woman consumes alcohol, her infant may be born with a cluster of birth defects and symptoms collectively called fetal alcohol spectrum disorder (FASD) or fetal alcohol syndrome (FAS).

With repeated use of many central nervous system depressants, such as alcohol, a person becomes physically dependent upon the substance and will exhibit signs of both tolerance and withdrawal. Psychological dependence on these drugs is also possible. Therefore, the abuse potential of central nervous system depressants is relatively high.

Drug withdrawal is usually an aversive experience, and it can be a life-threatening process in individuals who have a long history of very high doses of alcohol and/or barbiturates. This is of such concern that people who are trying to overcome addiction to these substances should only do so under medical supervision.

Stimulants

Stimulants are drugs that tend to increase overall levels of neural activity. Many of these drugs act as agonists of the dopamine neurotransmitter system. Dopamine activity is often associated with reward and craving; therefore, drugs that affect dopamine neurotransmission often have abuse liability. Drugs in this category include cocaine, amphetamines (including methamphetamine), cathinones (i.e., bath salts), MDMA (ecstasy), nicotine, and caffeine.

Cocaine can be taken in multiple ways. While many users snort cocaine, intravenous injection and ingestion are also common. The freebase version of cocaine, known as crack, is a potent, smokable version of the drug. Like many other stimulants, cocaine agonizes the dopamine neurotransmitter system by blocking the re-uptake of dopamine in the neuronal synapse.

Dig Deeper: Crack Cocaine

Crack is often considered to be more addictive than cocaine itself because it is smokable and reaches the brain very quickly. Crack is often less expensive than other forms of cocaine; therefore, it tends to be a more accessible drug for individuals from impoverished segments of society. During the 1980s, many drug laws were rewritten to punish crack users more severely than cocaine users. This led to discriminatory sentencing with low-income, inner-city minority populations receiving the harshest punishments. The wisdom of these laws has recently been called into question, especially given research that suggests crack may not be more addictive than other forms of cocaine, as previously thought (Haasen & Krausz, 2001; Reinerman, 2007).

Amphetamines have a mechanism of action quite similar to cocaine in that they block the re-uptake of dopamine in addition to stimulating its release ([link]). While amphetamines are often abused, they are also commonly prescribed for children diagnosed with attention deficit hyperactivity disorder (ADHD). It may seem counterintuitive that stimulant medications are prescribed to treat a disorder that involves hyperactivity, but the therapeutic effect comes from increases in neurotransmitter activity within certain areas of the brain associated with impulse control.

In recent years, methamphetamine (meth) use has become increasingly widespread. Methamphetamine is a type of amphetamine that can be made from ingredients that are readily available (e.g., medications containing pseudoephedrine, a compound found in many over-the-counter cold and flu remedies). Despite recent changes in laws designed to make obtaining pseudoephedrine more difficult, methamphetamine continues to be an easily accessible and relatively inexpensive drug option (Shukla, Crump, & Chrisco, 2012).

The cocaine, amphetamine, cathinone, and MDMA users seek a euphoric high, feelings of intense elation and pleasure, especially in those users who take the drug via intravenous injection or smoking. Repeated use of these stimulants can have significant adverse consequences. Users can experience physical symptoms that include nausea, elevated blood pressure, and increased heart rate. In addition, these drugs can cause feelings of anxiety, hallucinations, and paranoia (Fiorentini et al., 2011). Normal brain functioning is altered after repeated use of these drugs. For example, repeated use can lead to overall depletion among the monoamine neurotransmitters (dopamine, norepinephrine, and serotonin). People may engage in the compulsive use of these stimulant substances in part to try to reestablish normal levels of these neurotransmitters (Jayanthi & Ramamoorthy, 2005; Rothman, Blough, & Baumann, 2007).

Caffeine is another stimulant drug. While it is probably the most commonly used drug in the world, the potency of this particular drug pales in comparison to the other stimulant drugs described in this section. Generally, people use caffeine to maintain increased levels of alertness and arousal. Caffeine is found in many common medicines (such as weight loss drugs), beverages, foods, and even cosmetics (Herman & Herman, 2013). While caffeine may have some indirect effects on dopamine neurotransmission, its primary mechanism of action involves antagonizing adenosine activity (Porkka-Heiskanen, 2011).

While caffeine is generally considered a relatively safe drug, high blood levels of caffeine can result in insomnia, agitation, muscle twitching, nausea, irregular heartbeat, and even death (Reissig, Strain, & Griffiths, 2009; Wolt, Ganetsky, & Babu, 2012). In 2012, Kromann and Nielson reported on a case study of a 40-year-old woman who suffered significant ill effects from her use of caffeine. The woman used caffeine in the past to boost her mood and to provide energy, but over the course of several years, she increased her caffeine consumption to the point that she was consuming three litres of soda each day. Although she had been taking a prescription antidepressant, her symptoms of depression continued to worsen and she began to suffer physically, displaying significant warning signs of cardiovascular disease and diabetes. Upon admission to an outpatient clinic for the treatment of mood disorders, she met all of the diagnostic criteria for substance dependence and was advised to dramatically limit her caffeine intake. Once she was able to limit her use to less than 12 ounces of soda a day, both her mental and physical health gradually improved. Despite the prevalence of caffeine use and a large number of people who confess to suffering from caffeine addiction, this was the first published description of soda dependence appearing in scientific literature.

Nicotine is highly addictive, and the use of tobacco products is associated with increased risks of heart disease, stroke, and a variety of cancers. Nicotine exerts its effects through its interaction with acetylcholine receptors. Acetylcholine functions as a neurotransmitter in motor neurons. In the central nervous system, it plays a role in arousal and reward mechanisms. Nicotine is most commonly used in the form of tobacco products like cigarettes or chewing tobacco; therefore, there is a tremendous interest in developing effective smoking cessation techniques. To date, people have used a variety of nicotine replacement therapies in addition to various psychotherapeutic options in an attempt to discontinue their use of tobacco products. In general, smoking cessation programs may be effective in the short term, but it is unclear whether these effects persist (Cropley, Theadom, Pravettoni, & Webb, 2008; Levitt, Shaw, Wong, & Kaczorowski, 2007; Smedslund, Fisher, Boles, & Lichtenstein, 2004).

Opioids

An opioid is one of a category of drugs that includes heroin, morphine, methadone, and codeine. Opioids have analgesic properties; that is, they decrease pain. Humans have an endogenous opioid neurotransmitter system—the body makes small quantities of opioid compounds that bind to opioid receptors reducing pain and producing euphoria. Thus, opioid drugs, which mimic this endogenous painkilling mechanism, have an extremely high potential for abuse. Natural opioids, called opiates, are derivatives of opium, which is a naturally occurring compound found in the poppy plant. There are now several synthetic versions of opiate drugs (correctly called opioids) that have very potent painkilling effects, and they are often abused. There is multiple sponsored research that suggests the misuse and abuse of the prescription painkillers hydrocodone and oxycodone are significant public health concerns in Canada and worldwide.

Historically, heroin has been a major opioid drug of abuse ([link]). Heroin can be snorted, smoked, or injected intravenously. Like the stimulants described earlier, the use of heroin is associated with an initial feeling of euphoria followed by periods of agitation. Because heroin is often administered via intravenous injection, users often bear needle track marks on their arms and, like all abusers of intravenous drugs, have an increased risk for contraction of both tuberculosis and HIV.

Aside from their utility as analgesic drugs, opioid-like compounds are often found in cough suppressants, anti-nausea, and anti-diarrhea medications. Given that withdrawal from a drug often involves an experience opposite to the effect of the drug, it should be no surprise that opioid withdrawal resembles a severe case of the flu. While opioid withdrawal can be extremely unpleasant, it is not life-threatening (Julien, 2005). Still, people experiencing opioid withdrawal may be given methadone to make the withdrawal from the drug less difficult. Methadone is a synthetic opioid that is less euphorigenic than heroin and similar drugs. Methadone clinics help people who previously struggled with opioid addiction manage withdrawal symptoms through the use of methadone. Other drugs, including the opioid buprenorphine, have also been used to alleviate symptoms of opiate withdrawal.

Codeine is an opioid with relatively low potency. It is often prescribed for minor pain, and it is available over-the-counter in some other countries. Like all opioids, codeine does have abuse potential. In fact, abuse of prescription opioid medications is becoming a major concern worldwide (Aquina, Marques-Baptista, Bridgeman, & Merlin, 2009; Casati, Sedefov, & Pfeiffer-Gerschel, 2012).

Hallucinogens

A hallucinogen is one of a class of drugs that results in profound alterations in sensory and perceptual experiences ([link]). In some cases, users experience vivid visual hallucinations. It is also common for these types of drugs to cause hallucinations of body sensations (e.g., feeling as if you are a giant) and a skewed perception of the passage of time.

As a group, hallucinogens are incredibly varied in terms of the neurotransmitter systems they affect. Mescaline and LSD are serotonin agonists, and PCP (angel dust) and ketamine (an animal anesthetic) act as antagonists of the NMDA glutamate receptor. In general, these drugs are not thought to possess the same sort of abuse potential as other classes of drugs discussed in this section.

Dig Deeper: Medical Marijuana

Access to Medical Marijuana in Canada has regulations.  Cannabis Legalization and Regulation is legal in all Provinces and Territories.  The Cannabis Act creates a strict legal framework for controlling the production, distribution, sale, and possession of cannabis across Canada. The Cannabis Act

The Act aims to accomplish 3 goals:

• Keep cannabis out of the hands of youth
• Keep profits out of the pockets of criminals
• Protect public health and safety by allowing adults access to legal cannabis.

 

What is the Difference Between Pharmacokinetics and Pharmacodynamics?  By Contagion_Live.  Elizabeth Dodds-Ashley, PharmD, MHS, at the Department of Medicine at Duke University School of Medicine, outlines the differences between Pharmacokinetics and Pharmacodynamics

Summary

Substance use disorder is defined in DSM-5 as a compulsive pattern of drug use despite negative consequences. Both physical and psychological dependence are important parts of this disorder. Alcohol, barbiturates, and benzodiazepines are central nervous system depressants that affect GABA neurotransmission. Cocaine, amphetamine, cathinone, and MDMA are all central nervous stimulants that agonize dopamine neurotransmission, while nicotine and caffeine affect acetylcholine and adenosine, respectively. Opiate drugs serve as powerful analgesics through their effects on the endogenous opioid neurotransmitter system, and hallucinogenic drugs cause pronounced changes in sensory and perceptual experiences. The hallucinogens are variable with regards to the specific neurotransmitter systems they affect.

Long Descriptions

Figure 1.2.1 Hallucinogens – The four main drug categories are “antipsychotics,” “stimulants,” “depressants,” and “hallucinogens.” The circle titled “Antipsychotics” includes the drug names “Haldol,” “Risperdal,” and “Seroquel.” The circle titled “Stimulants” contains a subcircle titled “Psychmotor stimulants” with the drug names “Amphetamines,” “Khat,” “Ritalin,” and “Cocaine.”

The “Stimulants” circle contains another subcircle titled “Methylxanthines” with the drug names “Caffeine,” “Theophylline,” and “Theobromine.” The circle titled “Depressants” contains a subcircle titled “Sedative Hypnotics” with the drug names “Alcohol,” “Barbituates,” “Ether,” and “GHB”; within that circle is a subcircle titled “Minor tranquilizers” with the drug names “Ativan,” “Valium,” and “Xanax.” “Nicotine” falls in the overlap between the “Stimulants” and “Depressants” circles.

The circle titled “Depressants” also contains a subcircle titled “Narcotic Analgesics” with the drug names “Opium,” “Codeine,” “Morphine,” “Heroin,” and “DXM.” “DXM” falls in the overlap between the “Depressants” circle and the “Dissociatives” subcircle of the “Hallucinogens” circle. The circle titled “Hallucinogens” contains a subcircle labeled “Dissociatives” including the drug names ”Ketamine,” “PCP,” “Nitrous,” “Amanitas,” and “Salvinorum.” Within that subcircle, “Ketamine,” “PCP,” and “Nitrous” overlap with with the “depressants” circle The circle titled “Hallucinogens” also contains a subcircle titled “Psychedelics” including the drug names “MDMA,” “Mescaline,” “LSD,” “Psilocybin,” “AMT,” “DMT,” and “Ibogaine.”

Within that subcircle, “MDMA,” “Mescaline,” “LSD,” “Psilocybin,” and “AMT” fall within the overlap between the “Hallucinogens” and “Stimulants” circles. “Ibogaine” falls within the overlap between the “Psychadelics” and “Dissociatives” subcircles. Outside of all subcircles, “Marijuana” falls within the overlap between the “Stimulants,” “Depressants,” and “Hallucinogens” circles.

Figure 1.2.2 – The channel has multiple receptor sites where alcohol, barbiturates, and benzodiazepines bind to exert their effects. The binding of these molecules opens the chloride channel, allowing negatively-charged chloride ions (Cl-) into the neuron’s cell body. Changing its charge in a negative direction pushes the neuron away from firing; thus, activating a GABA neuron has a quieting effect on the brain.

Figure 1.2.4 – The presynaptic cell contains two cylinder-shaped channels, one on each side near where it faces the postsynaptic cell. The postsynaptic cell contains several receptors, side-by-side across the area that faces the presynaptic cell. In the space between the two cells, there are both cocaine and dopamine molecules. One of the cocaine molecules attaches to one of the presynaptic cell’s channels.

This cocaine molecule is labelled “bound cocaine.” An X-shape is shown over the top of the bound cocaine and the channel to indicate that the cocaine does not enter the presynaptic cell. A dopamine molecule is shown inside of the presynaptic cell’s other channel. Arrows connect this dopamine molecule to several others inside of the presynaptic cell. More arrows connect to more dopamine molecules, tracing their paths from the channel into the presynaptic cell, and out into the space between the presynaptic cell and the postsynaptic cell. Arrows extend from two of the dopamine molecules in this in-between space to the postsynaptic cell’s receptors. Only the dopamine molecules are shown binding to the postsynaptic cell’s receptors.