Chapter 9

The British and Dutch East India Companies

• The first multinational corporations, active mainly from the 1600s to 1800s.

• Possessed significant power and military capacity to support their business interests.

• Key Commodities:

  • Tea, coffee, spices, and, in later years, opium.

Psychoactive Drugs in History

• Psychoactive substances have markedly influenced human civilization and neuroscience.

  • Major caffeine sources:

    • Coffee (Coffea arabica): Native to Northeast Africa.

    • Tea (Camellia sinensis): Native to East Asia.

    • Cacao (Theobroma cacao): Native to South and Central America, source of chocolate.

  • Other caffeine-containing plants: Kola (Cola acuminata), Guarana (Paullinia cupana), and Yerba mate (Ilex paraguariensis).

• Caffeine is recognized as the most widely consumed psychoactive substance globally.

Caffeine and Its Related Compounds

• Caffeine (1,3,7-trimethylxanthine)

  • Theophylline (1,3-dimethylxanthine): Found in tea.

  • Theobromine (3,7-dimethylxanthine): Found in cacao.

• Consumption methods include hot water extracts from various plant parts, kola nuts eaten intact, and cacao processed for chocolate.

• Commercial caffeine sources:

  • Introduced notably by Coca Cola in 1886, originally sourced from kola nuts.

  • Followed by Pepsi Cola in 1898 and later a rise in energy drinks with higher caffeine content.

Effects and Mechanism of Caffeine

• Caffeine acts as a stimulant on the central nervous system (CNS) and cardiovascular system:

  • Increases wakefulness and alertness.

  • Elevates heart rate and blood pressure.

• Molecular structure:

  • Similar to nucleotides of DNA (adenine and guanine).

  • Primarily synthesized from adenine and guanine precursors.

• Caffeine antagonizes adenosine receptors:

  • Adenosine’s normal function includes slowing heart rate and decreasing neuronal excitability.

  • Blocking these receptors leads to increased heart rate, vasoconstriction, and heightened CNS excitability.

Adenosine Receptors and Their Role

• Adenosine receptors are G-protein-coupled receptors (GPCRs) that modulate various physiological processes.

• Caffeine's action reduces the usual inhibition that adenosine provides, enhancing neuronal excitability and wakefulness.

Nicotine and Its Effects

• Tobacco (Nicotiana tabacum) is the primary psychoactive source; nicotine is the major constituent affecting the CNS:

  • Acts as an agonist at nicotinic acetylcholine receptors (nAChRs), with effects including relaxation, alertness, and focus.

  • Considered a poison, its properties protect the plant from herbivores.

  • Safety concerns include disruption of heart rhythm and respiration in cases of nicotine poisoning.

Alcohol and Sedative-Hypnotic Drugs

• Ethanol (ethyl alcohol) is the primary alcohol used recreationally, less toxic to humans than other organic alcohols.

  • Formed through fermentation, it has a spectrum of effects from mild relaxation to potential fatality at high doses.

• Sedative-hypnotics include barbiturates and benzodiazepines, used for various therapeutic effects:

  • Barbiturates: Phenobarbital, secobarbital, amobarbital, to treat anxiety and insomnia.

  • Benzodiazepines: Diazepam (Valium), chlordiazepoxide (Librium), and alprazolam (Xanax) for anxiety management.

Modern Anesthetics

• General anesthetics are potent sedative-hypnotics affecting CNS activity.

• Historical evolution from ethanol and diethyl ether to modern drugs such as halothane, desflurane, and sevoflurane.

• Most general anesthetics act by enhancing GABAergic activity, leading to varying degrees of sedation and inhibition.

Opium and Its Derivatives

• The opium poppy (Papaver somniferum) has been utilized for pain relief and relaxation over thousands of years.

  • Morphine, discovered by Friedrich Wilhelm Sertürner, was the first chemical isolated from a plant.

  • The discovery led to the emergence of a pharmaceutical industry focused on plant chemistry.

• Diacetylmorphine (Heroin), derived from morphine, was first synthesized by the Bayer Company.

• Various derivatives of opioids (e.g., hydrocodone, fentanyl) exhibit strong analgesic properties but also a high potential for addiction.

Discoveries in the 20th Century

• The identification of opioid receptors and endogenous opioids (endorphins) contributed to understanding pain management and addiction mechanisms.

• The coca plant yields cocaine, primarily causing stimulant effects.

  • Cocaine, first isolated in the mid-1800s, is linked with severe adverse effects including addiction and cardiovascular risks.

Amphetamines and Their Effects

• Amphetamine-related compounds affect norepinephrine and dopamine systems in the CNS similar to cocaine but with a different chemical structure.

• Common medications include Adderall and Ritalin, used for attention-related disorders.

Psychedelics and Their Impact

• Psychedelics (e.g., LSD, mescaline) alter perception and consciousness, offering therapeutic potential.

• The effects are heavily influenced by set (mental state) and setting (environment).

• Clinical research into psychedelics has revived since the 1990s, with promising results for mental health treatments.

Cannabis and Cannabinoids

• Cannabis (hemp) has historical roots with humans for psychoactive and medicinal uses.

• THC, the primary psychoactive component, interacts with cannabinoid (CB) receptors identified in the human nervous system.

  • Endocannabinoids like anandamide and 2-AG play roles in retrograde neurotransmission, influencing neural signaling and synaptic strength.

Overview of Key Concepts

• Psychoactive substances have diverse effects, heavily influencing culture and medicine.

• Strong potential for addiction exists across many classes of drugs, emphasizing the importance of understanding their mechanisms and effects for effective treatment and management.