drugs of abuse

Substance Abuse

  • Definition: A pattern of harmful use of any substance for mood-altering purposes.

    • Substances include: Alcohol, illegal drugs, prescription medications, and some non-drug substances.

    • Abuse results from:

    • Using a substance in a manner that is not intended/recommended.

    • Using more than prescribed.

Categories of Drugs of Abuse

  • CNS Depressants:

    • Benzodiazepines

    • Barbiturates

  • CNS Stimulants:

    • Cocaine

    • Methamphetamine

  • Opioids:

    • Heroin

    • Prescription opioids

  • Anabolic steroids

  • Cannabinoids:

    • Marijuana

  • Tobacco

  • Alcohol

Diagnostic Criteria for Abuse and Dependence (DSM-V)

  • Criteria: A problematic pattern of substance use leading to clinically significant impairment or distress, as manifested by at least two of the following occurring within a 12-month period:

    1. Tolerance:

    • a) Need for markedly increased amounts of substance to achieve intoxication or desired effect.

    • b) Markedly diminished effect with continued use of the same amount of substance.

    1. Withdrawal:

    • a) Characteristic withdrawal syndrome for the substance.

    • b) Substance is taken to relieve/avoid withdrawal symptoms.

    1. Persistent desire or unsuccessful efforts to cut down or control substance use.

    2. Substance taken in larger amounts or over a longer period than intended.

    3. Important social, occupational, or recreational activities are given up or reduced due to substance use.

    4. A great deal of time spent obtaining substances, using substances, or recovering from its effects.

    5. Continued substance use despite persistent or recurrent social/interpersonal problems exacerbated by substance effects.

    6. Continued substance use despite knowledge of having a physical or psychological problem likely caused by substance use.

    7. Recurrent use in physically hazardous situations (e.g., drunk driving).

    8. Recurrent substance use resulting in failure to fulfill major role obligations at work, school, or home.

    9. Craving or a strong desire or urge to use alcohol or another substance.

Types of Tolerance

  • Innate: Genetically determined lack of sensitivity to the drug.

  • Pharmacokinetic: Changes in metabolism of the drug after repeat administration.

  • Pharmacodynamic: Adaptive changes in receptor activity due to the drug.

  • Conditioned tolerance: Reflexive adaptation to environmental cues.

  • Acute tolerance: Rapid tolerance after repeated use on a single occasion.

  • Reverse tolerance: Increased sensitivity to a drug due to previous use.

  • Cross-tolerance: Tolerance to other drugs in the same category.

Physical Dependence

  • Definition: Both physical and psychological effects from stopping a drug.

  • Characteristics:

    • Physical Dependence: State of biological adaptation resulting in a drug-specific withdrawal syndrome, produced by:

    • Abrupt cessation

    • Rapid dose reduction

    • Administration of an antagonist

  • Dependence syndrome: Need for the drug to maintain normal function.

    • Acute withdrawal syndrome: Lasts days.

    • Protracted withdrawal syndrome: Cravings can last for years.

Transition to Addiction

  • Stages of Addiction:

    1. Social - Recreational Use: The individual begins using drugs socially or for recreation.

    2. Intensified, Sustained Drug Use: Increased frequency, amount, and motivation to take drugs.

    3. Loss of Control: Drug use becomes the individual
      on

The Reward Pathway

  • Overview: A common feature of many drugs is the rewarding effect.

  • Activated through the mesolimbic dopaminergic pathway in the brain.

  • Key Structures:

    • Nucleus Accumbens (NAc)

    • Ventral Tegmental Area (VTA)

  • Mechanism: All drugs of abuse activate the mesolimbic dopamine pathway either directly or indirectly.

Nicotine

  • Mechanism of Action:

    • Activates dopamine reward pathway via presynaptic nicotinic receptors in the VTA.

    • This facilitates dopamine release.

    • Effects:

    • Central nicotinic receptors: anxiolytic effects, increased arousal, appetite suppression.

    • Peripheral nicotinic receptors: increase BP and smooth muscle contraction.

  • Withdrawal Symptoms:

    • Nicotinic (nAChR) receptors undergo rapid

    • Compensatory nAChR upregulation leads to a strong spontaneous withdrawal syndrome.

  • Effective Treatments:

    • Behavioral Therapies:

    • Cognitive Behavioral Therapy (CBT): teaches relapse-prevention skills.

    • Motivational Interviewing (MI): enhances motivation.

    • Mindfulness: teaches toleration of negative emotions including stress and cravings.

    • Medications:

    • Nicotine Replacement Therapy: replaces nicotine via less harmful formulations.

    • Bupropion: mechanism unknown, thought to increase dopamine in the CNS.

    • Varenicline: nicotinic receptor partial agonist that controls dopamine release.

    • Research indicates that smokers benefit more from a combination of behavioral treatment and medications.

Cannabinoids

  • Common Types/Names:

    • Cannabis (Cannabis Sativa)

  • Active Component: Delta-9-tetrahydrocannabinol (THC).

  • Subjective Effects:

    • Euphoria, relaxation, hallucinations

    • Toxic psychosis at high doses, leading to long-term psychosis.

  • Route of Administration:

    • Smoking or ingested/chronic use.

  • Abuse Profile:

    • Psychological dependence moderate, physiological dependence low.

    • Considered a gateway drug potentially leading to amotivational syndrome.

    • Currently, no medications specifically for the treatment of cannabis use disorder.

The Mechanism of Cannabinoids

  • Cholinergic and GABAergic Connection:

    • Cannabinoid receptors (CB1) inhibit GABAergic neurons in the VTA, leading to disinhibition and increased dopamine release in the NAc.

Cocaine

  • Common Types/Names:

    • Powdered cocaine (HCl) and freebase crack cocaine.

  • Route of Administration:

    • Intranasal (powdered), IV injection, smoked (freebase/crack).

  • Relative Abuse Potential:

    • 5/5

  • Abuse Profile:

    • High psychological dependence, high physiological dependence.

  • Receptor Activation:

    • Cocaine blocks reuptake transporters for dopamine, noradrenaline, and serotonin in the nucleus accumbens region.

  • Mechanism of Action:

    • Blocking of the dopamine transporter (DAT) increases dopamine levels in the NAc, contributing to its euphoric effects.

Amphetamines

  • Common Types/Names:

    • Amphetamine (speed), methamphetamine (crystal meth), Captagon.

  • Route of Administration:

    • Oral, duration of effects spanning several hours.

  • Relative Abuse Potential:

    • 5/5.

  • Abuse Profile:

    • High psychological and physiological dependence.

  • Mechanism of Action:

    • Amphetamines increase dopamine at presynaptic cleft by blocking DAT.

Amphetamine Effects at the Nucleus Accumbens

  • Amphetamines increase both noradrenaline and dopamine at the presynaptic cleft, resulting in increased release of neurotransmitters.

Psychostimulant Overdose Symptoms

  • Hyperthermia

  • Tachycardia

  • Hypertension

  • Possible death from heart failure, seizures, or respiratory depression.

Psychostimulant Withdrawal Symptoms

  • Difficulty concentrating

  • Slowed activity or physical fatigue (amphetamine crash).

Additional Symptoms of Withdrawal:

  • Bradycardia

  • Sleepiness

  • Dysphoria (inability to feel pleasure).

Treatment for Withdrawal:

  • No specific treatment available.

  • Propranolol may reduce cocaine withdrawal symptoms; Disulfiram used for alcohol dependency.

Methamphetamine

  • Common Types/Names: Meth, crystal meth.

  • Subjective Effects: Low doses lead to effects similar to amphetamines; high doses may result in psychosis, seizures, dysphoria, or hyperthermia.

  • Route of Administration: Smoked or by injection.

  • Abuse Potential: Highly addictive, with very high physiological and psychological dependence.

Withdrawal from Psychostimulants

  • Symptoms are typically the opposite of the drug's stimulating effects, including bradycardia, sleepiness, fatigue, dysphoria.

No specific medications approved for crystal meth withdrawal.

Symptomatic relief with antidepressants and diphenhydramine for insomnia/anhedonia.

Opioids

  • Common Types/Names:

    • Morphine, heroin, codeine.

  • Route of Administration: IV, oral, or smoked.

  • Subjective Effects:

  • Receptor Activation Related to Abuse: Activation of μ\mu-opioid receptors.

Long-Term Use of Heroin

  • Results in reduced life expectancy ( < 40 \text{ years}) and various health complications, such as:

    • Skin abscesses

    • Endocarditis

    • Pulmonary infections

    • Osteomyelitis

    • Hepatitis and AIDS.

Opioid Overdose Treatment

  • Antagonists Used: Naloxone or Naltrexone.

  • Signs of Intoxication:

    • Pinpoint pupils

    • Decreased consciousness

    • Decreased body temperature

    • Coma

    • Respiratory depression, common in overdose deaths.

Opioid and Methadone

  • Methadone:

    • Long half-life, less euphoria, leading to lower overdose potential.

    • Often leads to methadone dependency and prevents withdrawal symptoms.

  • Buprenorphine: Partial μ\mu receptor agonist with minimal withdrawal symptoms.

Benzodiazepines - CNS Depressants

  • Common Types/Names:

    • Chlordiazepoxide (Librium), Diazepam (Valium), Clonazepam (Rivotril).

  • Subjective Effects:

    • Anti-anxiety effects, muscle relaxation, sedation, and euphoria.

  • Route of Administration: Oral.

  • Relative Abuse Potential: 3/5.

  • Abuse Profile: High physiological and psychological dependence.

Therapeutic Use of Benzodiazepines

  • Used as anti-anxiety drugs, anticonvulsants, and anesthetics.

  • Dependence can develop during long-term clinical use; hence, only short courses of 2-3 weeks are recommended.

  • Must be discontinued gradually, tapering the dose to avoid rebound anxiety, insomnia, and seizures from high doses.

Alcohol - CNS Depressant

  • Common Types: Various alcoholic drinks.

  • Subjective Effects: Impaired coordination, increased self-confidence, aggression, anxiolytic effects, and impaired intellectual capacity.

  • Route of Administration: Oral.

  • Relative Abuse Potential: 3/5.

  • Abuse Profile: Highly physically addictive with strong physical dependence, leading to withdrawal symptoms like hangovers.

Alcoholism Statistics

  • Lifetime Prevalence of Alcohol Dependence: 10-14%.

  • Gender Disparity: 3 times more common in men than women.

  • Development of dependence typically requires prolonged and chronic use.

Mechanism of Alcohol Effects

  • Ethanol blocks NMDA receptors, decreasing cellular excitation.

    • Binds to GABAAGABA_A receptors, increasing inhibitory circuits.

Chronic Alcoholism Effects

  • Leads to peripheral neuropathy, chronic gastritis, impaired testicular steroid synthesis, fatty liver disease, hepatitis, necrosis, and fibrosis of the liver (cirrhosis).

Treatment for Alcohol Withdrawal

  • For Seizures and Anxiety: Long-acting benzodiazepines (e.g., Lorazepam).

  • For Hallucinations and Delirium: Haloperidol.

  • For Alcohol-Related Pancreatitis: Pancreatic enzyme supplementation.

Long-Term Treatment and Preventing Relapse

  • Disulfiram: An acetaldehyde dehydrogenase inhibitor leading to flushing, headache, nausea, and vomiting due to the accumulation of acetaldehyde.

Hallucinogens (Psychedelic Agents)

  • LSD: Does not cause toxic fatalities but can lead to fatal accidents and suicides.

  • Effects: Distorted vision, auditory perception, unpleasant hallucinations, and paranoid delusions.

  • Flashbacks and can induce long-term psychosis.

Hallucinogens and Addictiveness

  • Animals do not self-administer hallucinogens, indicating they may not be rewarding. LSD does not evoke dopamine release.

  • Mechanism: Critical action may increase glutamate release in the cortex via a presynaptic effect on 5−HT2A5-HT_{2A} receptors.

MDMA (Methylenedioxymethamphetamine)

  • Common Types/Names: Ecstasy.

  • Subjective Effects: Diminished aggression, increased sociability, sense of empathy, diminished anxiety, extreme mood lift with euphoria, jaw clenching, visual hallucinations.

  • Route of Administration: Oral.

  • Relative Abuse Potential: 1/5.

  • Abuse Profile: Moderate psychological dependence.

  • Mechanism of Action: Causes serotonin release and blocks serotonin reuptake.

Effects and Risks of MDMA

  • Overdose Symptoms: Increased risk of acute harm, including hyperthermia, seizures, and liver and renal failure.

  • Chronic Use Effects: Associated with sleep disturbances, depression, anxiety, impulsivity, increased aggression, memory impairments, and "mid-week blues" due to serotonin depletion.