Drugs of Abuse and Psychedelics

Understanding Addiction

Definition of Addiction

  • Addiction is a neuropsychological symptom characterized by a pervasive and intense urge to engage in maladaptive behaviors that provide immediate sensory rewards despite their harmful consequences.

    • Signs of Addiction:

    • Compulsive engagement in rewarding stimuli.

    • Preoccupation with rewarding stimuli.

    • Continued use despite negative effects.

    • Seeking immediate gratification.

Drug and Alcohol Addiction Statistics

  • More than 25% of illicit drug users suffer from addiction.

  • Around 140 million people consume alcohol in the USA, with over 20% experiencing addiction.

  • The economic cost of drug and alcohol addiction in the US reaches approximately $700 billion annually.

  • Drug addiction often coincides with a diagnosed mental illness over 50% of the time.

Risk Factors for Drug Addiction

  • Factors contributing to drug addiction include:

    • Childhood aggressive behavior.

    • Community economic status.

    • Impulsivity.

    • Age at first use (youth intake).

    • Mental illness.

    • Epigenetic influences.

    • Trauma exposure.

Psychoactive Drugs

Tolerance

  • Tolerance refers to a state where an individual becomes less responsive to a drug, necessitating increasing amounts to achieve the same effects.

    • This phenomenon significantly increases the risk of overdose.

Types of Drug Tolerance

  1. Metabolic Tolerance:

    • The body becomes more efficient at metabolizing and eliminating the drug, primarily involving liver enzymes and the cytochrome P450 system.

  2. Functional Tolerance:

    • Alterations in target tissue sensitivity to the drug, tied to changes in brain receptor configurations.

    • Mechanisms include:

      • Downregulation and desensitization of receptors.

  3. Conditioned or Learned Tolerance:

    • A learned association is established between drug tolerance and the environment where it develops.

    • A change in setting can elevate the likelihood of overdose, as the expected drug effects are not met in an unfamiliar context.

Cycle of Drug Addiction

Phases of Addiction Cycle

  • 1. Binge/Intoxication Phase

    • Associated with brain structures such as the dorsal striatum and ventral tegmental area.

    • All addictive substances primarily activate the mesolimbic pathway, leading to feelings of pleasure due to dopamine activation.

  • 2. Withdrawal/Negative Affect Phase

    • Linked with limbic circuitry, particularly the basal amygdala and central amygdala.

    • Withdrawal symptoms arise due to metabolic and neurochemical alterations.

  • 3. Preoccupation/Anticipation Phase

    • Involves the prefrontal cortex and hippocampus.

    • Responsible for the cognitive processes surrounding craving and anticipation of drug use.

Restoration Approaches

  • Strategies to restore executive control over drug use include pharmacological interventions and non-invasive brain stimulation techniques such as Transcranial Magnetic Stimulation (TMS) and transcranial direct current stimulation (tDCS).

Restore Response to Natural Rewards

  • Pharmacotherapies such as NK1 antagonists, oxytocin, pregnenolone, gabapentin, and topiramate aim to inhibit drug-reward pathways while enhancing natural reward responses.

Manage Withdrawal and Stress Response

  • Treatments for managing withdrawal and restoring balance include kappa-opioid receptor (KOR) antagonists and medications like lofexidine.

Neurochemical Basis of Addiction

Binge/Intoxication Neurocircuitry

  • Addiction can be traced through neurochemical pathways primarily involving dopamine signaling in response to addictive substances.

  • Key brain areas include the mesolimbic pathway, where dopamine neurons are activated, leading to reward and pleasure.

Withdrawal and Negative Affect Neurocircuitry

  • During withdrawal, neurochemical imbalances occur in limbic structures including the amygdala and extended amygdala.

  • Significant neurotransmitter changes during withdrawal include increased levels of corticotropin-releasing factor (CRF), norepinephrine, and dynorphin, among others.

  • Anti-stress neurotransmitter reductions, such as neuropeptide Y and oxytocin, further contribute to the negative affect during withdrawal.

The Role of Corticotropin-Releasing Factor (CRF)

  • CRF is involved in the body's stress response, linking physiological reactions during addiction, appetite regulation, and emotional states.

Allostasis Theory of Addiction

  • This theory suggests addiction alters brain mechanisms to maintain apparent reward function stability, leading to maladaptive changes in behavior and brain circuitry.

Habit Formation in Addiction

  • Continuous dopamine release can facilitate habit formation through adaptations in basal ganglia neural circuits.

Preoccupation and Anticipation Phase

Executive Control Circuitry

  • Involves the prefrontal cortex's function in regulating impulses and executive decision-making related to drug seeking behaviors, contrasting the impaired control observed in addiction.

DSM-IV Substance Dependence Criteria

  • The Diagnostic and Statistical Manual of Mental Disorders-IV outlines criteria for substance dependence, focusing on:

    • Preoccupation with obtaining the substance.

    • Withdrawal symptoms and their management.

    • Tolerance escalation.

    • Compromised social or occupational activities.

Drug Classifications

  • Stimulants: Activate the CNS, causing increased alertness, mood elevation, and appetite suppression.

  • Depressants: Inhibit CNS activity to produce calming effects, such as drowsiness and reduced anxiety.

  • Hallucinogens: Substances that alter perception significantly (the effects discussed further in dedicated sections).

Alcohol: An Overview

Characteristics and Effects

  • Production: Derived from the fermentation of grains and sugars.

  • Category: Depressant.

  • Significant neurotransmitter interactions, particularly with GABA systems.

Effects Based on Dosage

  • Low Doses: Induce euphoria, analgesia, increased sociability.

  • High Doses: Can lead to loss of coordination, memory impairment, unconsciousness, and death.

Withdrawal Symptoms

  • Symptoms include: nausea, vomiting, hallucinations, and delirium tremens; severe cases can result in death during withdrawal.

Benzodiazepines

Overview and Effects

  • Common names: “benzos, zannies.”

  • Includes: chlordiazepoxide, diazepam, alprazolam.

  • Mechanism: GABAA receptor agonists producing anxiolytic effects.

Withdrawal Symptoms

  • Common Symptoms:

    • Sleep disturbances, increased tension and anxiety, panic attacks, cravings, etc.

  • Severe Symptoms: Hallucinations, seizures, and increased risk of suicidal ideation; length of withdrawal varies based on duration of use.

Marijuana

General Information

  • Common names: “pot, weed, ganja.”

  • Active compound: tetrahydrocannabinol (THC); effects vary widely based on dosage and method of use.

  • Routes of Administration: Smoking, vaping, ingestion.

Cocaine

Characteristics and Routes

  • Common names: “blow, rail, line.”

  • Extracted from the coca plant; acts primarily as a stimulant.

Dosage Effects

  • Low Doses: Euphoria, sexual arousal, and increased heart rate.

  • High Doses: Physical effects such as formication (skin crawling sensation) and increased risk of heart attack.

Crack Cocaine

Overview

  • Definition: Freebase form of cocaine that can be smoked; higher bioavailability than powdered cocaine.

  • Route of administration: smoking.

Amphetamines

Overview

  • Examples: methyphenidate, Adderall, Benzedrine.

  • Function: Stimulates release of dopamine, norepinephrine, and serotonin in the mesolimbic pathway.

Methamphetamine

Characteristics

  • Slang: “speed, ice.”

  • Features neurotoxicity and is often associated with severe psychological effects.

  • Routes of administration: inhalation and intravenous.

Opiates

Overview

  • Common examples: heroin, morphine, methadone, fentanyl.

  • Mechanism: Activate mu-opioid receptors, leading to euphoria and analgesic effects.

Withdrawal Timeline

  • Symptoms include chills, body aches, abdominal pain, and long-lasting psychological effects post withdrawal.

  • The timeline can span several weeks post last use.

Psychedelics

Historical Context

  • Psychedelics saw a significant cultural revolution in the 1960s but have remained controversial.

Contemporary Psychedelics

  • The market for psychedelics is expected to grow significantly, with projected revenue reaching $7.1 billion by 2032 at a CAGR of 10.9% (2023-2032).

Psychedelic Class Features

  1. Psilocybin:

    • Mechanism: 5HT2A agonist leading to feelings of euphoria and altered perception.

  2. DMT: a short-acting psychedelic associated with intense experiences.

  3. LSD: Known for visual hallucinations, ego disturbance, has a variety of psychological effects.

  4. MDMA: Significant serotonic release leading to euphoria and enhanced sociability.

  5. Ketamine: Dissociative properties that can alleviate depression and provide unique near-death type experiences.

Efficacy and Research on Psychedelics

  • There is ongoing research regarding the therapeutic potential of psychedelics for various conditions, including PTSD and anxiety disorders.

  • Effects reported in animals suggest potential for social enhancement behaviors post-treatment.

Important Considerations

  • Safety and Environment: Use should ideally be supervised by medical professionals, especially in individuals with a history of psychological issues.

  • Research remains inconclusive on whether the psychedelic experience itself is necessary for therapeutic outcomes.

  • Physical dependence on psychedelics is low as indicated by animal studies on self-administration.

Conclusion

  • The potential of psychedelics in mental health treatment remains a subject for further rigorous research and clinical testing, acknowledging their history and evolving societal perceptions.