6.1.1 Basic Pharmacology and Epidemiology

Basic Pharmacology and Epidemiology of: Alcohol, Cannabis, Stimulants, Hallucinogens, Solvents and Nitrites, Ecstasy, Benzodiazepines, and Opiates

Alcohol:

Alcohol misuse is a significant public health concern, affecting millions of individuals worldwide. The basic pharmacology of alcohol, or ethanol, involves its absorption through the gastrointestinal tract, followed by distribution throughout the body and subsequent metabolism, primarily in the liver. Alcohol acts as a central nervous system (CNS) depressant by enhancing the inhibitory effects of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, and reducing the excitatory actions of glutamate. Additionally, alcohol increases the release of dopamine in the brain’s reward system, contributing to its reinforcing and addictive properties.

The epidemiology of alcohol misuse reveals a complex picture, with its prevalence varying across different age groups, genders, and geographical regions. According to the World Health Organization, approximately 3 million deaths worldwide each year are attributed to alcohol misuse, accounting for over 5% of the global burden of disease. Alcohol misuse is associated with numerous health risks, including liver cirrhosis, cardiovascular diseases, various types of cancer, and neuropsychiatric disorders. It also contributes to social issues such as domestic violence, workplace absenteeism, and motor vehicle accidents. Efforts to address alcohol misuse include public health policies, prevention programs, and treatment strategies that aim to reduce alcohol consumption and its associated harms.

Cannabis:

Cannabis misuse is a prevalent public health issue with a growing global impact. The basic pharmacology of cannabis centres on its primary psychoactive constituent, delta-9-tetrahydrocannabinol (THC). THC exerts its effects by binding to cannabinoid receptors (CB1 and CB2) in the endocannabinoid system, which is involved in regulating various physiological and cognitive processes. THC’s activation of CB1 receptors in the brain leads to characteristic psychoactive effects, such as euphoria, relaxation, and altered perception. It is important to note that cannabis also contains cannabidiol (CBD), a non-psychoactive compound that modulates THC’s effects and possesses potential therapeutic benefits.

The epidemiology of cannabis misuse reveals a complex landscape, with variations in prevalence across different age groups, genders, and regions. According to the United Nations Office on Drugs and Crime, cannabis is the most commonly used illicit drug worldwide, with an estimated 192 million users in 2018. Cannabis misuse is associated with several health risks, including cognitive impairments, mental health disorders such as anxiety and psychosis, respiratory issues, and the potential for addiction. The growing trend towards the legalization and decriminalization of cannabis in various countries presents new challenges in understanding and addressing the public health implications of its misuse. Efforts to tackle cannabis misuse involve a combination of prevention, education, and treatment programs aimed at reducing the negative consequences associated with its consumption.

Stimulants (Amphetamine, Cocaine, Phentermine, Diethylpropion, Pemoline etc.):

Stimulant misuse is a significant public health concern due to the wide range of substances involved and their potential for addiction and adverse effects. The basic pharmacology of stimulants, including amphetamine, cocaine, phentermine, diethylpropion, and pemoline, involves their action on monoamine neurotransmitters, such as dopamine, noradrenaline, and serotonin. These drugs increase the release and/or block the reuptake of these neurotransmitters, leading to increased extracellular concentrations and amplified neuronal signaling. Consequently, stimulant misuse can cause feelings of euphoria, increased energy, alertness, and heightened focus, but may also result in detrimental effects, such as cardiovascular complications, neurological damage, and psychiatric disorders.

The epidemiology of stimulant misuse shows considerable variation depending on the specific substance and the population studied. The World Drug Report 2021 indicates that approximately 19 million people used cocaine and 27 million people used amphetamines in 2019. Prescription stimulants, such as phentermine, diethylpropion, and pemoline, have also been misused, although the prevalence rates are generally lower than those of illicit stimulants. Addressing stimulant misuse requires a multifaceted approach, including prevention strategies, public education, and evidence-based treatment options for those struggling with addiction.

Stimulant	Legal Status	Primary Use	Duration of Effects	Addiction Potential
Amphetamine	Prescription / Controlled	ADHD, narcolepsy, obesity	4-6 hours	High
Cocaine	Illegal (Class A)	Recreational drug	15-90 minutes	High
Phentermine	Prescription / Controlled	Weight loss (short-term)	12-14 hours	Moderate
Diethylpropion	Prescription / Controlled	Weight loss (short-term)	6-8 hours	Moderate
Pemoline	Discontinued (in most markets)	ADHD (historically)	10-12 hours	Low

Hallucinogens:

Hallucinogen misuse is a public health concern due to the potential for adverse psychological effects and unpredictable reactions to these substances. Hallucinogens, such as LSD, psilocybin, and mescaline, primarily exert their effects through modulation of the serotonin system, particularly the 5-HT2A receptor subtype. Activation of these receptors alters sensory perception, cognition, and mood, leading to the characteristic hallucinations, distorted perceptions, and altered states of consciousness associated with these drugs. While hallucinogens generally have a lower risk of addiction compared to other classes of substances, their misuse can lead to dangerous situations and lasting psychological disturbances.

Epidemiological data on hallucinogen misuse reveals that it is most common among adolescents and young adults, with usage patterns often reflecting experimentation and sporadic use rather than addiction. According to the World Drug Report 2021, approximately 21 million people aged 15-64 used hallucinogens in 2019. While the prevalence of hallucinogen misuse has remained relatively stable over the past decade, there has been a resurgence of interest in certain substances, such as psilocybin, due to their potential therapeutic benefits. Addressing hallucinogen misuse requires targeted prevention efforts, harm reduction strategies, and education on the potential risks and consequences associated with these substances.

Solvents and nitrates:

Solvents and nitrates represent two distinct categories of substances that are misused for their psychoactive effects. Solvent misuse, also known as inhalant abuse, typically involves inhaling volatile organic compounds found in everyday products, such as glue, paint thinner, and aerosol sprays. These substances are lipophilic and rapidly cross the blood-brain barrier, leading to a range of neurological effects, including euphoria, dizziness, and cognitive impairment. The exact mechanisms of action for solvents are not well understood, but they are thought to involve the modulation of neurotransmitter systems, particularly GABA and NMDA receptors, resulting in depressant-like effects.

Nitrates, including alkyl nitrites (e.g., “poppers”), are volatile substances that are inhaled for their vasodilatory effects and the associated brief, intense rush of euphoria. They act by releasing nitric oxide, which causes smooth muscle relaxation and a drop in blood pressure. Their misuse can lead to various health risks, including headaches, dizziness, and in rare cases, methemoglobinemia.

Epidemiologically, solvent and nitrate misuse are often associated with specific populations and contexts. Solvent misuse is more common among younger individuals and those in lower socioeconomic groups, partly due to the widespread availability and low cost of these substances. Nitrate misuse, on the other hand, is more prevalent among specific subpopulations, such as the LGBTQ+ community, particularly in the context of recreational drug use and sexual enhancement. Addressing the misuse of solvents and nitrates requires targeted prevention strategies, education on the potential health risks, and interventions aimed at reducing the accessibility and appeal of these substances.

Ecstasy:

Ecstasy, also known as MDMA (3,4-methylenedioxymethamphetamine), is a synthetic psychoactive substance that belongs to the class of phenethylamines. It is known for its unique combination of stimulant and hallucinogenic properties. The primary pharmacological action of MDMA involves the release and reuptake inhibition of neurotransmitters, specifically serotonin, dopamine, and noradrenaline. The elevated levels of these neurotransmitters in the brain result in feelings of euphoria, increased energy, heightened sensations, emotional warmth, and empathy towards others. Additionally, MDMA can induce mild perceptual changes and hallucinations due to its agonist action on certain serotonin receptors.

Epidemiologically, the misuse of ecstasy and related substances is often associated with specific social contexts and subcultures, particularly in electronic dance music and rave scenes. These substances are also misused in more casual settings, such as parties and clubs, due to their prosocial effects and the ability to enhance sensory experiences. Misuse of ecstasy and related substances can lead to various acute and long-term health risks, including hyperthermia, dehydration, electrolyte imbalances, neurotoxicity, and potential cognitive deficits.

Efforts to address the misuse of ecstasy and related substances involve harm reduction strategies, educational campaigns about potential risks, and the promotion of safe environments in contexts where these substances are commonly used. Additionally, research into the potential therapeutic uses of MDMA, such as its application in the treatment of post-traumatic stress disorder (PTSD), may contribute to a better understanding of its pharmacology and the development of evidence-based interventions for addressing misuse.

Benzodiazepines:

Benzodiazepines are a class of drugs that act as central nervous system depressants, used primarily to treat anxiety, insomnia, and seizures. They work by enhancing the effect of a neurotransmitter called gamma-aminobutyric acid (GABA), which slows down brain activity and produces a calming effect. However, benzodiazepines can be habit-forming and can lead to misuse, abuse, and addiction. The misuse of benzodiazepines can result in physical and psychological dependence, tolerance, and withdrawal symptoms when use is abruptly discontinued.

The epidemiology of benzodiazepine misuse shows that it is more common among individuals with a history of substance abuse, and mental illness, and those who use benzodiazepines for longer than recommended. Misuse of benzodiazepines can have serious health consequences, including overdose, respiratory depression, and cognitive impairment. It is important to use benzodiazepines only as prescribed and to avoid sharing them with others to prevent misuse and addiction.

Opiates:

Opiates are a class of drugs derived from opium poppy plants, which include prescription painkillers like oxycodone, hydrocodone, and fentanyl, as well as illegal drugs like heroin. They work by binding to receptors in the brain and spinal cord, which can result in pain relief, feelings of euphoria, and a decrease in anxiety. However, opiates can also lead to misuse, abuse, and addiction. The misuse of opiates can result in physical and psychological dependence, tolerance, and withdrawal symptoms when use is abruptly discontinued.

The epidemiology of opiate misuse shows that it is more common among individuals with a history of substance abuse, and mental illness, and those who use opiates for longer than recommended. Opiate misuse can have serious health consequences, including overdose, respiratory depression, and infectious diseases like HIV and hepatitis. It is important to use opiates only as prescribed and to avoid sharing them with others to prevent misuse and addiction. Treatment for opiate addiction may include medication-assisted therapy, behavioural therapy, and support groups.

Substance	Basic Pharmacology	Epidemiology
Alcohol	Acts on GABA-A receptors to enhance inhibition and reduce excitability in the brain. Increases dopamine release.	Worldwide, 75% of people aged 15 and over report drinking alcohol at least once in their lifetime. 14.5 million adults in the US had alcohol use disorder in 2019.
Cannabis	Binds to cannabinoid receptors in the brain, altering neurotransmitter release and producing psychoactive effects.	An estimated 192 million people worldwide use cannabis annually. 22% of 18-25-year-olds in the US report past-month cannabis use.
Stimulants	Increase dopamine and noradrenaline release in the brain, producing euphoria, increased energy, and alertness.	An estimated 21 million people worldwide use amphetamines annually. Cocaine use is highest in North America, with an estimated 5.5 million users.
Hallucinogens	Affect serotonin and other neurotransmitter systems, producing altered sensory perception and cognition.	An estimated 32 million people worldwide use hallucinogens annually. LSD use is highest in North America and Europe, with an estimated 1.3 million users in each region.
Solvents and nitrates	Produce rapid release of dopamine in the brain, producing euphoria and excitement.	An estimated 2.6 million people aged 12 or older in the US report past-year use of inhalants. Solvent use is highest in Africa, while nitrite use is highest in Europe.
Ecstasy and related substances	Increases serotonin, dopamine, and noradrenaline release in the brain, producing a combination of stimulant and psychedelic effects.	An estimated 20 million people worldwide use ecstasy annually. The UK has the highest prevalence of ecstasy use in Europe.
Benzodiazepines	Increase the activity of the neurotransmitter GABA in the brain, producing sedative, anxiolytic, and muscle relaxant effects.	Benzodiazepine prescribing rates have been increasing globally, and benzodiazepine misuse and dependence are common. The use of benzodiazepines has been linked to falls, traffic accidents, and mortality, particularly in older adults. Barbiturate use has declined since the introduction of benzodiazepines, but they are still used in anaesthesia and seizure management. Barbiturate misuse is associated with respiratory depression, overdose, and addiction. Barbiturate withdrawal can be life-threatening.
Opiates	Bind to opioid receptors in the brain and body, producing pain relief, sedation, and a sense of euphoria.	Opiate use has been associated with a range of negative health outcomes, including overdose, addiction, and infectious diseases (e.g. HIV, hepatitis C) associated with injection drug use. Opiate overdose deaths have been increasing globally, with a significant increase in deaths due to synthetic opioids such as fentanyl. Opiate misuse often begins with prescription pain medication, but many people who become dependent on opiates turn to illicit sources such as heroin.

References:

1. Alcohol: Rehm, J., & Shield, K. D. (2019). Global burden of alcohol use disorders and alcohol liver disease. Biomedicines, 7(4), 99.
2. Cannabis: Volkow, N. D., Compton, W. M., & Weiss, S. R. (2017). Adverse health effects of marijuana use. New England Journal of Medicine, 376(23), 2247-2256.
3. Stimulants: Compton, W. M., & Volkow, N. D. (2019). Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug and alcohol dependence, 34-41.
4. Hallucinogens: Halberstadt, A. L., & Geyer, M. A. (2018). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 142, 256-266.
5. Solvents and Nitrites: Fornazzari, L., Wilkinson, D. A., Kapur, B. M., & Carlen, P. L. (2018). Organic solvent abuse: epidemiology, clinical and imaging findings, and toxicology. Journal of medical toxicology, 14(2), 153-161.
6. Ecstasy and Related Substances: Parrott, A. C. (2013). MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in humans–no need for translation. British journal of pharmacology, 169(6), 1365-1377.
7. Benzodiazepines and Barbiturates: Lader, M. (2018). Benzodiazepine harm: how can it be reduced?. British Journal of Clinical Pharmacology, 84(6), 1129-1136.Opiates: Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Methadone maintenance therapy versus no opioid replacement therapy